[see Use in Specific Populations ( 8.4) and Clinical Studies ( 14.2)]

Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following:

To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

[see Indications and Usage ( 1.1) and Clinical Pharmacology ( 12.3)]

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="49%"/> <col width="50%"/> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd> DUE TO THE INDICATED ORGANISMS [see Indications and usage ( 1.1) </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Infection <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Recommended Dose/Duration of Therapy</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Community-acquired pneumonia Pharyngitis/tonsillitis (second-line therapy) <br/> Skin/skin structure (uncomplicated) <br/> </td><td align="center" class="Botrule Rrule">500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Acute bacterial exacerbations of chronic obstructive pulmonary disease <br/> </td><td align="center" class="Botrule Rrule">500 mg once daily for 3 days <br/> OR <br/> 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Acute bacterial sinusitis <br/> </td><td align="center" class="Botrule Rrule">500 mg once daily for 3 days <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Genital ulcer disease (chancroid) <br/> </td><td align="center" class="Botrule Rrule">One single 1 gram dose <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Non-gonococcal urethritis and cervicitis <br/> </td><td align="center" class="Botrule Rrule">One single 1 gram dose <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Gonococcal urethritis and cervicitis <br/> </td><td align="center" class="Botrule Rrule">One single 2 gram dose <br/> </td> </tr> </tbody> </table></div>

Azithromycin tablets can be taken with or without food.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="28%"/> <col width="71%"/> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd> DUE TO THE INDICATED ORGANISMS [see Indications and Usage ( 1.2)] </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Infection <a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">Recommended Dose/Duration of Therapy</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Acute otitis media <br/> </td><td align="left" class="Botrule Rrule">30 mg/kg as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg/day on Days 2 through 5. <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Acute bacterial sinusitis <br/> </td><td align="left" class="Botrule Rrule">10 mg/kg once daily for 3 days. <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Community-acquired pneumonia <br/> </td><td align="left" class="Botrule Rrule">10 mg/kg as a single dose on Day 1 followed by 5 mg/kg once daily on Days 2 through 5. <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Pharyngitis/tonsillitis <br/> </td><td align="left" class="Botrule Rrule">12 mg/kg once daily for 5 days. <br/> </td> </tr> </tbody> </table></div>

1see dosing tables below for maximum doses evaluated by indication 

Azithromycin for oral suspension can be taken with or without food.

<div class="scrollingtable"><table class="Noautorules" width="103%"> <caption> <span>PEDIATRIC DOSAGE GUIDELINES FOR OTITIS MEDIA, ACUTE BACTERIAL SINUSITIS, AND COMMUNITY-ACQUIRED PNEUMONIA (Age 6 months and above, [see Use in Specific Populations ( <a href="#ID98">8.4</a>)] ) Based on Body Weight </span> </caption> <col width="21%"/> <col width="8%"/> <col width="10%"/> <col width="11%"/> <col width="10%"/> <col width="15%"/> <col width="21%"/> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>Effectiveness of the 3-day or 1-day regimen in pediatric patients with community-acquired pneumonia has not been established. </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="7"><span class="Bold">OTITIS MEDIA AND COMMUNITY-ACQUIRED PNEUMONIA: (5-Day Regimen) <a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a></span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Dosing Calculated on 10 mg/kg/day Day 1 and 5 mg/kg/day Days 2 to 5.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule" colspan="2"><span class="Bold">100 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" colspan="2"><span class="Bold">200 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mL per Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mg per Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days</span> <br/> <span class="Bold">2 to 5</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days</span> <br/> <span class="Bold">2 to 5</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td align="center" class="Botrule Rrule">1.25mL; <br/> (¼ tsp) <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL <br/> </td><td align="center" class="Botrule Rrule">150 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">5 mL; (1tsp) <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">300 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">20 <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">5 mL; <br/>  (1 tsp) <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">600 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">30 <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL; (1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">3.75 mL; (¾ tsp) <br/> </td><td align="center" class="Botrule Rrule">22.5 mL <br/> </td><td align="center" class="Botrule Rrule">900 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">10 mL; <br/>  (2 tsp) <br/> </td><td align="center" class="Botrule Rrule">5 mL; <br/>  (1 tsp) <br/> </td><td align="center" class="Botrule Rrule">30 mL <br/> </td><td align="center" class="Botrule Rrule">1200 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">50 and above <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">12.5mL; (2½ tsp) <br/> </td><td align="center" class="Botrule Rrule">6.25 mL; (1¼ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="95%"> <col width="22%"/> <col width="14%"/> <col width="12%"/> <col/> <col width="22%"/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>Effectiveness of the 5-day or 1-day regimen in pediatric patients with acute bacterial sinusitis has not been established.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">OTITIS MEDIA AND ACUTE BACTERIAL SINUSITIS: (3-Day Regimen) <a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a></span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Dosing Calculated on 10 mg/kg/day.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">100 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">200 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mL per Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mg per Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days 1 to 3</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days 1 to 3</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; <br/>  (1/2 tsp) <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL <br/> </td><td align="center" class="Botrule Rrule">150 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">5 mL; <br/> (1 tsp) <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">300 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">20 <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">5 mL <br/> (1 tsp) <br/> </td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">600 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">30 <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL <br/> (1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">22.5 mL <br/> </td><td align="center" class="Botrule Rrule">900 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">10 mL <br/>  (2 tsp) <br/> </td><td align="center" class="Botrule Rrule">30 mL <br/> </td><td align="center" class="Botrule Rrule">1200 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">50 and above <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">12.5 mL <br/>  (2 ½ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="30%"/> <col width="24%"/> <col width="28%"/> <col width="15%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="4"><span class="Bold">OTITIS MEDIA: (1-Day Regimen)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="4"><span class="Bold">Dosing Calculated on 30 mg/kg as a single dose.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">200 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mL per Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mg per</span> <br/> <span class="Bold">Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">1-Day Regimen</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">3.75 mL;(3/4 tsp) <br/> </td><td align="center" class="Botrule Rrule">3.75 mL <br/> </td><td align="center" class="Botrule Rrule">150 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">7.5 mL;(1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">7.5 mL <br/> </td><td align="center" class="Botrule Rrule">300 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">20 <br/> </td><td align="center" class="Botrule Rrule">15 mL;(3 tsp) <br/> </td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">600 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">30 <br/> </td><td align="center" class="Botrule Rrule">22.5 mL;(4½ tsp) <br/> </td><td align="center" class="Botrule Rrule">22.5 mL <br/> </td><td align="center" class="Botrule Rrule">900 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td align="center" class="Botrule Rrule">30 mL;(6 tsp) <br/> </td><td align="center" class="Botrule Rrule">30 mL <br/> </td><td align="center" class="Botrule Rrule">1200 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">50 and above <br/> </td><td align="center" class="Botrule Rrule">37.5 mL;(7½ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> </tbody> </table></div>

The safety of re-dosing azithromycin in pediatric patients who vomit after receiving 30 mg/kg as a single dose has not been established. In clinical studies involving 487 patients with acute otitis media given a single 30 mg/kg dose of azithromycin, 8 patients who vomited within 30 minutes of dosing were re-dosed at the same total dose.

Pharyngitis/Tonsillitis:The recommended dose of azithromycin for children with pharyngitis/tonsillitis is 12 mg/kg once daily for 5 days. (See chart below.)

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>PEDIATRIC DOSAGE GUIDELINES FOR PHARYNGITIS/TONSILLITIS (Age 2 years and above, [see Use in Specific Populations ( <a href="#ID98">8.4</a>)] ) Based on Body Weight </span> </caption> <col width="15%"/> <col width="24%"/> <col width="33%"/> <col width="26%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="4"><span class="Bold">PHARYNGITIS/TONSILLITIS: (5-Day Regimen)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="4"><span class="Bold">Dosing Calculated on 12 mg/kg/day for 5 days.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">200 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mL per Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mg per Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1 to 5</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td align="center" class="Botrule Rrule">12.5 mL <br/> </td><td align="center" class="Botrule Rrule">500 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">17 <br/> </td><td align="center" class="Botrule Rrule">5 mL; (1 tsp) <br/> </td><td align="center" class="Botrule Rrule">25 mL <br/> </td><td align="center" class="Botrule Rrule">1000 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">25 <br/> </td><td align="center" class="Botrule Rrule">7.5 mL; (1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">33 <br/> </td><td align="center" class="Botrule Rrule">10 mL; (2 tsp) <br/> </td><td align="center" class="Botrule Rrule">50 mL <br/> </td><td align="center" class="Botrule Rrule">2000 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td align="center" class="Botrule Rrule">12.5 mL; (2½ tsp) <br/> </td><td align="center" class="Botrule Rrule">62.5 mL <br/> </td><td align="center" class="Botrule Rrule">2500 mg <br/> </td> </tr> </tbody> </table></div>

Constituting instructions for Azithromycin Oral Suspension 300, 600, 900, 1200 mg bottles. The table below indicates the volume of water to be used for constitution:

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col/> <col/> <col/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Amount of water to be added</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Total volume after constitution (azithromycin content)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Azithromycin concentration after constitution</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">9 mL (300 mg) <br/> </td><td align="center" class="Botrule Rrule">15 mL (300 mg) <br/> </td><td align="center" class="Botrule Rrule">100 mg/5 mL <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">9 mL (600 mg) <br/> </td><td align="center" class="Botrule Rrule">15 mL (600 mg) <br/> </td><td align="center" class="Botrule Rrule">200 mg/5 mL <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">12 mL (900 mg) <br/> </td><td align="center" class="Botrule Rrule">22.5 mL (900 mg) <br/> </td><td align="center" class="Botrule Rrule">200 mg/5 mL <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">15 mL (1200 mg) <br/> </td><td align="center" class="Botrule Rrule">30 mL (1200 mg) <br/> </td><td align="center" class="Botrule Rrule">200 mg/5 mL <br/> </td> </tr> </tbody> </table></div>

Shake well before each use. Oversized bottle provides shake space. Keep tightly closed.

After mixing, store suspension at 5° to 30°C (41° to 86°F) and use within 10 days. Discard after full dosing is completed.

Azithromycin for oral suspension USP, 100 mg/ 5mL or 200 mg/5 mL [each teaspoonful (5 mL) contains Azithromycin Dihydrate equivalent to Azithromycin USP, 100 mg or 200 mg] is supplied in bottles.

{ "type": "p", "children": [], "text": "\nAzithromycin for oral suspension USP, 100 mg/ 5mL or 200 mg/5 mL [each teaspoonful (5 mL) contains Azithromycin Dihydrate equivalent to Azithromycin USP, 100 mg or 200 mg] is supplied in bottles." }

Azithromycin for oral suspension, USP is white to light pink granular powder filled in translucent HDPE bottle with child-resistant cap and after constitution with water contains a red colored flavored suspension.

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, USP is white to light pink granular powder filled in translucent HDPE bottle with child-resistant cap and after constitution with water contains a red colored flavored suspension." }

Azithromycin for oral suspension is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug.

Azithromycin for oral suspension is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported in patients on azithromycin therapy. [seeContraindications ( 4.1)]

Fatalities have been reported. Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is presently unknown.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that allergic symptoms may reappear when symptomatic therapy has been discontinued.

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:

Elderly patients may be more susceptible to drug-associated effects on the QT interval.

Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. The five-day cardiovascular mortality observed in these studies ranged from 20 to 400 per million azithromycin treatment courses. This potential risk was noted to be greater during the first five days of azithromycin use and does not appear to be limited to those patients with preexisting cardiovascular diseases. The data in these observational studies are insufficient to establish or exclude a causal relationship between acute cardiovascular death and azithromycin use. Consider balancing this potential risk with treatment benefits when prescribing azithromycin.

Clostridioides difficile-associated diarrhea has been reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficilecause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Azithromycin, at the recommended dose, should not be relied upon to treat syphilis. Antibacterial agents used to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate testing for gonorrhea performed at the time of diagnosis. Appropriate antibacterial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.

Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious adverse reactions of angioedema and cholestatic jaundice were reported. Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related adverse reactions. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related adverse reactions was 0.6%. In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related adverse reactions was approximately 1%. Most of the adverse reactions leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. [seeClinical Studies ( 14.2)]

Adults

Multiple-dose regimens: Overall, the most common treatment-related adverse reactions in adult patients receiving multiple-dose regimens of azithromycin were related to the gastrointestinal system with diarrhea/loose stools (4 to 5%), nausea (3%), and abdominal pain (2 to 3%) being the most frequently reported.

No other adverse reactions occurred in patients on the multiple-dose regimens of azithromycin with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following:

Cardiovascular:Palpitations, chest pain.

Gastrointestinal:Dyspepsia, flatulence, vomiting, melena, and cholestatic jaundice.

Genitourinary:Monilia, vaginitis, and nephritis.

Nervous System:Dizziness, headache, vertigo, and somnolence.

General:Fatigue.

Allergic:Rash, pruritus, photosensitivity, and angioedema.

Single 1-gram dose regimen:

Overall, the most common adverse reactions in patients receiving a single-dose regimen of 1 gram of azithromycin were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen.

Adverse reactions that occurred in patients on the single 1-gram dosing regimen of azithromycin with a frequency of 1% or greater included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), and vaginitis (1%).

Single 2-gram dose regimen:

Overall, the most common adverse reactions in patients receiving a single 2-gram dose of azithromycin were related to the gastrointestinal system. Adverse reactions that occurred in patients in this study with a frequency of 1% or greater included nausea (18%), diarrhea/loose stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%), and dizziness (1%). The majority of these complaints were mild in nature.

Pediatric Patients

Single and Multiple-dose regimens: The types of adverse reactions in pediatric patients were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in pediatric patients.

Acute Otitis Media:For the recommended total dosage regimen of 30 mg/kg, the most frequent adverse reactions (≥1%) attributed to treatment were diarrhea, abdominal pain, vomiting, nausea, and rash. [seeDosage and Administration ( 2) and Clinical Studies ( 14.2)]

The incidence, based on dosing regimen, is described in the table below:

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="21%"/> <col width="14%"/> <col width="24%"/> <col width="16%"/> <col width="13%"/> <col width="9%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Dosage Regimen</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Diarrhea %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Abdominal Pain %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Vomiting %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Nausea %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Rash %</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">1-day <br/> </td><td align="center" class="Botrule Rrule">4.3% <br/> </td><td align="center" class="Botrule Rrule">1.4% <br/> </td><td align="center" class="Botrule Rrule">4.9% <br/> </td><td align="center" class="Botrule Rrule">1% <br/> </td><td align="center" class="Botrule Rrule">1% <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">3-day <br/> </td><td align="center" class="Botrule Rrule">2.6% <br/> </td><td align="center" class="Botrule Rrule">1.7% <br/> </td><td align="center" class="Botrule Rrule">2.3% <br/> </td><td align="center" class="Botrule Rrule">0.4% <br/> </td><td align="center" class="Botrule Rrule">0.6% <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5-day <br/> </td><td align="center" class="Botrule Rrule">1.8% <br/> </td><td align="center" class="Botrule Rrule">1.2% <br/> </td><td align="center" class="Botrule Rrule">1.1% <br/> </td><td align="center" class="Botrule Rrule">0.5% <br/> </td><td align="center" class="Botrule Rrule">0.4% <br/> </td> </tr> </tbody> </table></div>

Community-Acquired Pneumonia:For the recommended dosage regimen of 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5, the most frequent adverse reactions attributed to treatment were diarrhea/loose stools, abdominal pain, vomiting, nausea, and rash.

The incidence is described in the table below:

<div class="scrollingtable"><table class="Noautorules" width="104%"> <col width="17%"/> <col width="26%"/> <col width="20%"/> <col width="13%"/> <col width="11%"/> <col width="10%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Dosage Regimen</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Diarrhea/Loose stools %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Abdominal Pain %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Vomiting %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Nausea %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Rash %</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5-day <br/> </td><td align="center" class="Botrule Rrule">5.8% <br/> </td><td align="center" class="Botrule Rrule">1.9% <br/> </td><td align="center" class="Botrule Rrule">1.9% <br/> </td><td align="center" class="Botrule Rrule">1.9% <br/> </td><td align="center" class="Botrule Rrule">1.6% <br/> </td> </tr> </tbody> </table></div>

Pharyngitis/Tonsillitis:For the recommended dosage regimen of 12 mg/kg on Days 1 to 5, the most frequent adverse reactions attributed to treatment were diarrhea, vomiting, abdominal pain, nausea, and headache.

The incidence is described in the table below:

<div class="scrollingtable"><table class="Noautorules" width="104%"> <col width="17%"/> <col width="13%"/> <col width="20%"/> <col width="13%"/> <col width="11%"/> <col width="8%"/> <col width="15%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Dosage Regimen</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Diarrhea %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Abdominal Pain %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Vomiting %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Nausea %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Rash %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Headache %</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5-day <br/> </td><td align="center" class="Botrule Rrule">5.4% <br/> </td><td align="center" class="Botrule Rrule">3.4% <br/> </td><td align="center" class="Botrule Rrule">5.6% <br/> </td><td align="center" class="Botrule Rrule">1.8% <br/> </td><td align="center" class="Botrule Rrule">0.7% <br/> </td><td align="center" class="Botrule Rrule">1.1% <br/> </td> </tr> </tbody> </table></div>

With any of the treatment regimens, no other adverse reactions occurred in pediatric patients treated with azithromycin with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following:

Cardiovascular:Chest pain.

Gastrointestinal:Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools, and oral moniliasis.

Hematologic and Lymphatic:Anemia and leukopenia.

Nervous System:Headache (otitis media dosage), hyperkinesia, dizziness, agitation, nervousness, and insomnia.

General:Fever, face edema, fatigue, fungal infection, malaise, and pain.

Allergic:Rash and allergic reaction.

Respiratory:Cough, pharyngitis, pleural effusion, and rhinitis.

Skin and Appendages:Eczema, fungal dermatitis, pruritus, sweating, urticaria, and vesiculobullous rash.

Special Senses:Conjunctivitis.

The following adverse reactions have been identified during post-approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported with azithromycin during the postmarketing period in adult and/or pediatric patients for which a causal relationship may not be established include:

Allergic:Arthralgia, edema, urticaria, and angioedema.

Cardiovascular:Arrhythmias including ventricular tachycardia and hypotension. There have been reports of QT prolongation, torsades de pointesand cardiovascular death.

Gastrointestinal:Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and reports of tongue discoloration.

General:Asthenia, paresthesia, fatigue, malaise, and anaphylaxis

Genitourinary:Interstitial nephritis and acute renal failure and vaginitis.

Hematopoietic:Thrombocytopenia.

Liver/Biliary:Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure. [seeWarnings and Precautions ( 5.2)]

Nervous System:Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation, and syncope.

Psychiatric:Aggressive reaction and anxiety.

Skin/Appendages:Pruritus serious skin reactions including erythema multiforme, AGEP, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and DRESS.

Special Senses:Hearing disturbances including hearing loss, deafness and/or tinnitus, and reports of taste/smell perversion and/or loss.

Adults:

Clinically significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows: with an incidence of greater than 1%: decreased hemoglobin, hematocrit, lymphocytes, neutrophils, and blood glucose; elevated serum creatine phosphokinase, potassium, ALT, GGT, AST, BUN, creatinine, blood glucose, platelet count, lymphocytes, neutrophils, and eosinophils; with an incidence of less than 1%: leukopenia, neutropenia, decreased sodium, potassium, platelet count, elevated monocytes, basophils, bicarbonate, serum alkaline phosphatase, bilirubin, LDH, and phosphate. The majority of subjects with elevated serum creatinine also had abnormal values at baseline. When follow-up was provided, changes in laboratory tests appeared to be reversible.

In multiple-dose clinical trials involving more than 5000 patients, four patients discontinued therapy because of treatment-related liver enzyme abnormalities and one because of a renal function abnormality.

Pediatric Patients:

One, Three, and Five-Day Regimens

Laboratory data collected from comparative clinical trials employing two 3-day regimens (30 mg/kg or 60 mg/kg in divided doses over 3 days), or two 5-day regimens (30 mg/kg or 60 mg/kg in divided doses over 5 days) were similar for regimens of azithromycin and all comparators combined, with most clinically significant laboratory abnormalities occurring at incidences of 1 to 5%. Laboratory data for patients receiving 30 mg/kg as a single dose were collected in one single center trial. In that trial, an absolute neutrophil count between 500 cells/mm 3to 1,500 cells/mm 3was observed in 10/64 patients receiving 30 mg/kg as a single dose, 9/62 patients receiving 30 mg/kg given over 3 days, and 8/63 comparator patients. No patient had an absolute neutrophil count <500 cells/mm 3.

In multiple-dose clinical trials involving approximately 4,700 pediatric patients, no patients discontinued therapy because of treatment-related laboratory abnormalities.

Co-administration of nelfinavir at steady-state with a single oral dose of azithromycin resulted in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. [seeAdverse Reactions ( 6)]

Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.

Interactions with digoxin, colchicine or phenytoin have not been reported in clinical trials with azithromycin. No specific drug interaction studies have been performed to evaluate potential drug-drug interactions. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin, colchicine or phenytoin are used with azithromycin careful monitoring of patients is advised.

Risk Summary

Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Developmental toxicity studies with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to 4, 2, and 2 times, respectively, an adult human daily dose of 500 mg based on body surface area. Decreased viability and delayed development were observed in the offspring of pregnant rats administered azithromycin from day 6 of pregnancy through weaning at a dose equivalent to 4 times an adult human daily dose of 500 mg based on body surface area (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with azithromycin use in pregnant women. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.

Animal Data

Azithromycin administered during the period of organogenesis did not cause fetal malformations in rats and mice at oral doses up to 200 mg/kg/day (moderately maternally toxic). Based on body surface area, this dose is approximately 4 (rats) and 2 (mice) times an adult human daily dose of 500 mg. In rabbits administered azithromycin at oral doses of 10, 20, and 40 mg/kg/day during organogenesis, reduced maternal body weight and food consumption were observed in all groups; no evidence of fetotoxicity or teratogenicity was observed at these doses, the highest of which is estimated to be 2 times an adult human daily dose of 500 mg based on body surface area.

In a pre- and postnatal development study, azithromycin was administered orally to pregnant rats from day 6 of pregnancy until weaning at doses of 50 or 200 mg/kg/day. Maternal toxicity (reduced food consumption and body weight gain; increased stress at parturition) was observed at the higher dose. Effects in the offspring were noted at 200 mg/kg/day during the postnatal development period (decreased viability, delayed developmental landmarks). These effects were not observed in a pre- and postnatal rat study when up to 200 mg/kg/day of azithromycin was given orally beginning on day 15 of pregnancy until weaning.

Risk Summary

Azithromycin is present in human milk (see Data). Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin (see Clinical Considerations). There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for azithromycin and any potential adverse effects on the breastfed infant from azithromycin or from the underlying maternal condition.

Clinical Considerations

Advise women to monitor the breastfed infant for diarrhea, vomiting, or rash.

Data

Azithromycin breastmilk concentrations were measured in 20 women after receiving a single 2 g oral dose of azithromycin during labor. Breastmilk samples collected on days 3 and 6 postpartum as well as 2 and 4 weeks postpartum revealed the presence of azithromycin in breastmilk up to 4 weeks after dosing. In another study, a single dose of azithromycin 500 mg was administered intravenously to 8 women prior to incision for cesarean section. Breastmilk (colostrum) samples obtained between 12 and 48 hours after dosing revealed that azithromycin persisted in breastmilk up to 48 hours.

[see Clinical Pharmacology ( 12.3), Indications and Usage ( 1.2), and Dosage and Administration ( 2.2)]

Safety and effectiveness in the treatment of pediatric patients with acute otitis media, acute bacterial sinusitis and community-acquired pneumonia under 6 months of age have not been established. Use of azithromycin for the treatment of acute bacterial sinusitis and community-acquired pneumonia in pediatric patients (6 months of age or greater) is supported by adequate and well-controlled trials in adults.

Pharyngitis/Tonsillitis:Safety and effectiveness in the treatment of pediatric patients with pharyngitis/tonsillitis under 2 years of age have not been established.

In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4,949) and 3% of patients (144/4,949) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients. [seeWarnings and Precautions ( 5.4)]

Adverse reactions experienced at higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea, and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required.

{ "type": "p", "children": [], "text": "\nAdverse reactions experienced at higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea, and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required." }

Azithromycin for oral suspension, USP contain the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl) oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C 38H 72N 2O 12and its molecular weight is 749. Azithromycin dihydrate, USP has the following structural formula:

{ "type": "p", "children": [], "text": "\nAzithromycin for oral suspension, USP contain the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl) oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C\n \n 38H\n \n 72N\n \n 2O\n \n 12and its molecular weight is 749. Azithromycin dihydrate, USP has the following structural formula:\n\n " }

Azithromycin dihydrate, USP, is a white or almost white powder with a molecular formula of C 38H 72N 2O 12.2H 2O and a molecular weight of 785.02. It is freely soluble in anhydrous ethanol and in methylene chloride and practically insoluble in water.

{ "type": "p", "children": [], "text": "\nAzithromycin dihydrate, USP, is a white or almost white powder with a molecular formula of C\n \n 38H\n \n 72N\n \n 2O\n \n 12.2H\n \n 2O and a molecular weight of 785.02. It is freely soluble in anhydrous ethanol and in methylene chloride and practically insoluble in water.\n\n " }

Azithromycin for oral suspension, USP is supplied in bottles containing azithromycin dihydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle and the following inactive ingredients: sucrose; trisodium phosphate anhydrous, hydroxypropyl cellulose; xanthan gum; FD&C Red #40; cherry flavor, ripe banana flavor. After constitution, each 5 mL of suspension contains 100 mg or 200 mg of azithromycin.

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, USP is supplied in bottles containing azithromycin dihydrate powder equivalent to 300 mg, 600 mg, 900 mg, or 1200 mg azithromycin per bottle and the following inactive ingredients: sucrose; trisodium phosphate anhydrous, hydroxypropyl cellulose; xanthan gum; FD&C Red #40; cherry flavor, ripe banana flavor. After constitution, each 5 mL of suspension contains 100 mg or 200 mg of azithromycin." }

Azithromycin is a macrolide antibacterial drug. [seeMicrobiology ( 12.4)]

Based on animal models of infection, the antibacterial activity of azithromycin appears to correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for certain pathogens ( S. pneumoniaeand S. aureus). The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with azithromycin.

Cardiac Electrophysiology

QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with oral azithromycin (500 mg, 1000 mg, and 1500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1000 mg and 1500 mg azithromycin, respectively.

Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC 0–72=4.3 (1.2) mcg∙hr/mL; C max=0.5 (0.2) mcg/mL; T max=2.2 (0.9) hours. Two azithromycin 250 mg tablets are bioequivalent to a single 500 mg tablet.

In a two-way crossover study, 12 adult healthy volunteers (6 males, 6 females) received 1500 mg of azithromycin administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2 to 5) or 3 days (500 mg per day for days 1 to 3). Due to limited serum samples on day 2 (3-day regimen) and days 2 to 4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC 0–∞for the fitted concentration profile was comparable between the 5-day and 3-day regimens.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col/> <col/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-5" name="footnote-5">*</a> </dt> <dd>Total AUC for the entire 3-day and 5-day regimens. </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold">3-Day Regimen</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold">5-Day Regimen</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Pharmacokinetic Parameter [mean (SD)]</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 3</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 5</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">C <span class="Sub">max</span>(serum, mcg/mL) <br/> </td><td align="center" class="Botrule Rrule">0.44 (0.22) <br/> </td><td align="center" class="Botrule Rrule">0.54 (0.25) <br/> </td><td align="center" class="Botrule Rrule">0.43 (0.20) <br/> </td><td align="center" class="Botrule Rrule">0.24 (0.06) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Serum AUC <span class="Sub">0–∞</span>(mcg∙hr/mL) <br/> </td><td align="center" class="Botrule Rrule" colspan="2">17.4 (6.2) <a class="Sup" href="#footnote-5" name="footnote-reference-5">*</a> <br/> </td><td align="center" class="Botrule Rrule" colspan="2">14.9 (3.1) <a class="Sup" href="#footnote-5">*</a> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Serum T <span class="Sub">1/2</span> <br/> </td><td align="center" class="Botrule Rrule" colspan="2">71.8 hr <br/> </td><td align="center" class="Botrule Rrule" colspan="2">68.9 hr <br/> </td> </tr> </tbody> </table></div>

Absorption

The absolute bioavailability of azithromycin 250 mg capsules is 38%.

In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high fat meal, food was shown to increase C maxby 23% but had no effect on AUC.

When azithromycin oral suspension was administered with food to 28 adult healthy male subjects, C maxincreased by 56% and AUC was unchanged.

Distribution

The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL.

The antibacterial activity of azithromycin is pH related and appears to be reduced with decreasing pH. However, the extensive distribution of drug to tissues may be relevant to clinical activity.

Azithromycin has been shown to penetrate into human tissues, including skin, lung, tonsil, and cervix. Extensive tissue distribution was confirmed by examination of additional tissues and fluids (bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder). As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical significance of these tissue concentration data is unknown.

Following a regimen of 500 mg on the first day and 250 mg daily for 4 days, very low concentrations were noted in cerebrospinal fluid (less than 0.01 mcg/mL) in the presence of non-inflamed meninges.

Metabolism

In vitroand in vivostudies to assess the metabolism of azithromycin have not been performed.

Elimination

Plasma concentrations of azithromycin following single 500 mg oral and IV doses declined in a polyphasic pattern resulting in a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hr. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues. Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.

Specific Populations

Patients with Renal Impairment 

Azithromycin pharmacokinetics was investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1 g dose of azithromycin (4 × 250 mg capsules), mean C maxand AUC 0–120increased by 5.1% and 4.2%, respectively, in subjects with mild to moderate renal impairment (GFR 10 to 80 mL/min) compared to subjects with normal renal function (GFR >80 mL/min). The mean C maxand AUC 0–120increased 61% and 35%, respectively, in subjects with severe renal impairment (GFR <10 mL/min) compared to subjects with normal renal function (GFR >80 mL/min).

Patients with Hepatic Impairment

The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established.

Male and Female Patients

There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender.

Geriatric Patients

Pharmacokinetic parameters in older volunteers (65 to 85 years old) were similar to those in young adults (18 to 40 years old) for the 5-day therapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen. [seeGeriatric Use ( 8.5)]

Pediatric Patients

In two clinical studies, azithromycin for oral suspension was dosed at 10 mg/kg on day 1, followed by 5 mg/kg on days 2 through 5 in two groups of pediatric patients (aged 1 year to 5 years and 5 years to 15 years, respectively). The mean pharmacokinetic parameters on day 5 were C max=0.216 mcg/mL, T max=1.9 hr, and AUC 0–24=1.822 mcg∙hr/mL for the 1 year to 5-year-old group and were C max=0.383 mcg/mL, T max=2.4 hr, and AUC 0–24=3.109 mcg∙hr/mL for the 5 year to 15-year-old group.

In another study, 33 pediatric patients received doses of 12 mg/kg/day (maximum daily dose 500 mg) for 5 days, of whom 31 patients were evaluated for azithromycin pharmacokinetics following a low fat breakfast. In this study, azithromycin concentrations were determined over a 24 hr period following the last daily dose. Patients weighing above 41.7 kg received the maximum adult daily dose of 500 mg. Seventeen patients (weighing 41.7 kg or less) received a total dose of 60 mg/kg. The following table shows pharmacokinetic data in the subset of pediatric patients who received a total dose of 60 mg/kg.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="57%"/> <col width="42%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Pharmacokinetic Parameter</span> <br/> <span class="Bold">[mean (SD)]</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">5-Day Regimen</span> <br/> <span class="Bold">(12 mg/kg for 5 days)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">N</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">17</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">C <span class="Sub">max</span>(mcg/mL) <br/> </td><td align="center" class="Botrule Rrule">0.5 (0.4) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">T <span class="Sub">max</span>(hr) <br/> </td><td align="center" class="Botrule Rrule">2.2 (0.8) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">AUC <span class="Sub">0–24</span>(mcg∙hr/mL) <br/> </td><td align="center" class="Botrule Rrule">3.9 (1.9) <br/> </td> </tr> </tbody> </table></div>

Single dose pharmacokinetics of azithromycin in pediatric patients given doses of 30 mg/kg have not been studied. [seeDosage and Administration ( 2)]

Drug Interaction Studies

Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 2.

Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin.

Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the C maxand AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2. [seeDrug Interactions ( 7.3)]

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 1 Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Azithromycin</span> </caption> <col/> <col/> <col width="19%"/> <col width="4%"/> <col width="17%"/> <col/> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>- 90% Confidence interval not reported</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2"><span class="Bold">Co-administered Drug</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" rowspan="2"><span class="Bold">Dose of</span> <br/> <span class="Bold">Co-administered Drug</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" rowspan="2"><span class="Bold">Dose of Azithromycin</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" rowspan="2"><span class="Bold">n</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold">Ratio (with/without azithromycin) of</span> <br/> <span class="Bold">Co-administered Drug Pharmacokinetic Parameters (90% CI); No Effect = 1</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Rrule"><span class="Bold">Mean C <span class="Sub">max</span></span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Mean AUC</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Atorvastatin <br/> </td><td align="center" class="Botrule Rrule">10 mg/day for 8 days <br/> </td><td align="center" class="Botrule Rrule">500 mg/day orally on days 6 to 8 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">0.83 <br/> (0.63 to 1.08) <br/> </td><td align="center" class="Botrule Rrule">1.01 <br/> (0.81 to 1.25) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Carbamazepine <br/> </td><td align="center" class="Botrule Rrule">200 mg/day for 2 days, then 200 mg twice a day for 18 days <br/> </td><td align="center" class="Botrule Rrule">500 mg/day orally for days 16 to 18 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">0.97 <br/> (0.88 to 1.06) <br/> </td><td align="center" class="Botrule Rrule">0.96 <br/> (0.88 to 1.06) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Cetirizine <br/> </td><td align="center" class="Botrule Rrule">20 mg/day for 11 days <br/> </td><td align="center" class="Botrule Rrule">500 mg orally on day 7, then 250 mg/day on days 8 to 11 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">1.03 <br/> (0.93 to 1.14) <br/> </td><td align="center" class="Botrule Rrule">1.02 <br/> (0.92 to 1.13) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Didanosine <br/> </td><td align="center" class="Botrule Rrule">200 mg orally twice a day for 21 days <br/> </td><td align="center" class="Botrule Rrule">1,200 mg/day orally on days <br/>  8 to 21 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">1.44 <br/> (0.85 to 2.43) <br/> </td><td align="center" class="Botrule Rrule">1.14 <br/> (0.83 to 1.57) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Efavirenz <br/> </td><td align="center" class="Botrule Rrule">400 mg/day for 7 days <br/> </td><td align="center" class="Botrule Rrule">600 mg orally on day 7 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">1.04 <a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a> <br/> </td><td align="center" class="Botrule Rrule">0.95 <a class="Sup" href="#footnote-6">*</a> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Fluconazole <br/> </td><td align="center" class="Botrule Rrule">200 mg orally single dose <br/> </td><td align="center" class="Botrule Rrule">1,200 mg orally single dose <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">1.04 <br/> (0.98 to 1.11) <br/> </td><td align="center" class="Botrule Rrule">1.01 <br/> (0.97 to 1.05) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Indinavir <br/> </td><td align="center" class="Botrule Rrule">800 mg three times a day for 5 days <br/> </td><td align="center" class="Botrule Rrule">1,200 mg orally on day 5 <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">0.96 <br/> (0.86 to 1.08) <br/> </td><td align="center" class="Botrule Rrule">0.90 <br/> (0.81 to 1) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Midazolam <br/> </td><td align="center" class="Botrule Rrule">15 mg orally on day 3 <br/> </td><td align="center" class="Botrule Rrule">500 mg/day orally for 3 days <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">1.27 <br/> (0.89 to 1.81) <br/> </td><td align="center" class="Botrule Rrule">1.26 <br/> (1.01 to 1.56) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Nelfinavir <br/> </td><td align="center" class="Botrule Rrule">750 mg three times a day for 11 days <br/> </td><td align="center" class="Botrule Rrule">1,200 mg orally on day 9 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">0.90 <br/> (0.81 to 1.01) <br/> </td><td align="center" class="Botrule Rrule">0.85 <br/> (0.78 to 0.93) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Sildenafil <br/> </td><td align="center" class="Botrule Rrule">100 mg on days <br/> 1 and 4 <br/> </td><td align="center" class="Botrule Rrule">500 mg/day orally for 3 days <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">1.16 <br/> (0.86 to 1.57) <br/> </td><td align="center" class="Botrule Rrule">0.92 <br/> (0.75 to 1.12) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Theophylline <br/> </td><td align="center" class="Botrule Rrule">4 mg/kg IV on days 1, 11, 25 <br/> </td><td align="center" class="Botrule Rrule">500 mg orally on day 7, 250 mg/day on days 8 to 11 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">1.19 <br/> (1.02 to 1.40) <br/> </td><td align="center" class="Botrule Rrule">1.02 <br/> (0.86 to 1.22) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Theophylline <br/> </td><td align="center" class="Botrule Rrule">300 mg orally twice a day for 15 days <br/> </td><td align="center" class="Botrule Rrule">500 mg orally on day 6, then 250 mg/day on days <br/> 7 to 10 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">1.09 <br/> (0.92 to 1.29) <br/> </td><td align="center" class="Botrule Rrule">1.08 <br/> (0.89 to 1.31) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Triazolam <br/> </td><td align="center" class="Botrule Rrule">0.125 mg on day 2 <br/> </td><td align="center" class="Botrule Rrule">500 mg orally on day 1, then 250 mg/day on day 2 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">1.06* <br/> </td><td align="center" class="Botrule Rrule">1.02* <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Trimethoprim/ <br/> Sulfamethoxazole <br/> </td><td align="center" class="Botrule Rrule">160 mg/800 mg/day orally for 7 days <br/> </td><td align="center" class="Botrule Rrule">1,200 mg orally on day 7 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">0.85 <br/> (0.75 to 0.97)/0.90 <br/> (0.78 to 1.03) <br/> </td><td align="center" class="Botrule Rrule">0.87 <br/> (0.80 to 0.95/0.96 <br/> (0.88 to 1.03) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Zidovudine <br/> </td><td align="center" class="Botrule Rrule">500 mg/day orally for 21 days <br/> </td><td align="center" class="Botrule Rrule">600 mg/day orally for14 days <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">1.12 <br/> (0.42 to 3.02) <br/> </td><td align="center" class="Botrule Rrule">0.94 <br/> (0.52 to 1.70) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Zidovudine <br/> </td><td align="center" class="Botrule Rrule">500 mg/day orally for 21 days <br/> </td><td align="center" class="Botrule Rrule">1,200 mg/day orally for 14 days <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">1.31 <br/> (0.43 to 3.97) <br/> </td><td align="center" class="Botrule Rrule">1.30 <br/> (0.69 to 2.43) <br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="113%"> <caption> <span>Table 2 Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs. [see Drug Interactions ( <a href="#ID84">7</a>) ] </span> </caption> <col width="12%"/> <col width="29%"/> <col width="14%"/> <col/> <col/> <col/> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-7" name="footnote-7">*</a> </dt> <dd>- 90% Confidence interval not reported</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2"><span class="Bold">Co-administered Drug</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" rowspan="2"><span class="Bold">Dose of</span> <br/> <span class="Bold">Co-administered Drug</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" rowspan="2"><span class="Bold">Dose of Azithromycin</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" rowspan="2"><span class="Bold">n</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold">Ratio (with/without co-administered drug) of Azithromycin Pharmacokinetic Parameters (90% CI); No Effect = 1</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Rrule"><span class="Bold">Mean C <span class="Sub">max</span></span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Mean AUC</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Efavirenz <br/> </td><td align="center" class="Botrule Rrule">400 mg/day for 7 days <br/> </td><td align="center" class="Botrule Rrule">600 mg orally on day 7 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">1.22 <br/> (1.04 to 1.42) <br/> </td><td align="center" class="Botrule Rrule">0.92 <a class="Sup" href="#footnote-7" name="footnote-reference-7">*</a> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Fluconazole <br/> </td><td align="center" class="Botrule Rrule">200 mg orally single dose <br/> </td><td align="center" class="Botrule Rrule">1,200 mg orally single dose <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">0.82 <br/> (0.66 to 1.02) <br/> </td><td align="center" class="Botrule Rrule">1.07 <br/> (0.94 to 1.22) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Nelfinavir <br/> </td><td align="center" class="Botrule Rrule">750 mg three times a day for 11 days <br/> </td><td align="center" class="Botrule Rrule">1,200 mg orally on day 9 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">2.36 <br/> (1.77 to 3.15) <br/> </td><td align="center" class="Botrule Rrule">2.12 <br/> (1.80 to 2.50) <br/> </td> </tr> </tbody> </table></div>

Mechanism of Action

Azithromycin acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit.

Resistance

Azithromycin demonstrates cross resistance with erythromycin. The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides, and streptogramin B (MLS Bphenotype).

Antimicrobial Activity

Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitroand in clinical infections. [seeIndications and Usage ( 1)]

Gram-Positive Bacteria

Staphylococcus aureus

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenes

Gram-Negative Bacteria

Haemophilus ducreyi

Haemophilus influenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

Other Bacteria

Chlamydophila pneumoniae

Chlamydia trachomatis

Mycoplasma pneumoniae

The following in vitrodata are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitrominimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for azithromycin against isolates of similar genus or organism group. However, the efficacy of azithromycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

Gram-Positive Bacteria

Beta-hemolytic streptococci (Groups C, F, G)

Viridans group streptococci

Gram-Negative Bacteria

Bordetella pertussis

Legionella pneumophila

Anaerobic Bacteria

Prevotella bivia

Peptostreptococcus species

Other Bacteria

Ureaplasma urealyticum

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. In fertility studies conducted in male and female rats, oral administration of azithromycin for 64 to 66 days (males) or 15 days (females) prior to and during cohabitation resulted in decreased pregnancy rate at 20 and 30 mg/kg/day when both males and females were treated with azithromycin. This minimal effect on pregnancy rate (approximately 12% reduction compared to concurrent controls) did not become more pronounced when the dose was increased from 20 to 30 mg/kg/day (approximately 0.4 to 0.6 times the adult daily dose of 500 mg based on body surface area) and it was not observed when only one animal in the mated pair was treated. There were no effects on any other reproductive parameters, and there were no effects on fertility at 10 mg/kg/day. The relevance of these findings to patients being treated with azithromycin at the doses and durations recommended in the prescribing information is uncertain.

Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) in dogs and rats treated with azithromycin at doses which, expressed on the basis of body surface area, are similar to or less than the highest recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 mcg/mL (1.6 times the observed C maxof 0.821 mcg/mL at the adult dose of 2 g). Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1 mcg/mL (1.2 times the observed C maxof 0.821 mcg/mL at the adult dose of 2 g). Phospholipidosis was also observed in neonatal rats dosed for 18 days at 30 mg/kg/day, which is less than the pediatric dose of 60 mg/kg based on the surface area. It was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 mcg/mL, approximately 1.5 times the C maxof 1.27 mcg/mL at the pediatric dose. Phospholipidosis has been observed in neonatal dogs (10 mg/kg/day) at maximum mean whole blood concentrations of 3.54 mcg/mL, approximately 3 times the pediatric dose C max. The significance of these findings for animals and for humans is unknown.

Acute Bacterial Exacerbations of Chronic Bronchitis

In a randomized, double-blind controlled clinical trial of acute exacerbation of chronic bronchitis (AECB), azithromycin (500 mg once daily for 3 days) was compared with clarithromycin (500 mg twice daily for 10 days). The primary endpoint of this trial was the clinical cure rate at Days 21 to 24. For the 304 patients analyzed in the modified intent-to-treat analysis at the Days 21 to 24 visit, the clinical cure rate for 3 days of azithromycin was 85% (125/147) compared to 82% (129/157) for 10 days of clarithromycin.

The following outcomes were the clinical cure rates at the Days 21 to 24 visit for the bacteriologically evaluable patients by pathogen:

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col/> <col/> <col/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Pathogen</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Azithromycin (3 Days)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Clarithromycin (10 Days)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">S. pneumoniae</span> <br/> </td><td align="center" class="Botrule Rrule">29/32 (91%) <br/> </td><td align="center" class="Botrule Rrule">21/27 (78%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">H. influenzae</span> <br/> </td><td align="center" class="Botrule Rrule">12/14 (86%) <br/> </td><td align="center" class="Botrule Rrule">14/16 (88%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">M. catarrhalis</span> <br/> </td><td align="center" class="Botrule Rrule">11/12 (92%) <br/> </td><td align="center" class="Botrule Rrule">12/15 (80%) <br/> </td> </tr> </tbody> </table></div>

Acute Bacterial Sinusitis

In a randomized, double-blind, double-dummy controlled clinical trial of acute bacterial sinusitis, azithromycin (500 mg once daily for 3 days) was compared with amoxicillin/clavulanate (500/125 mg three times a day for 10 days). Clinical response assessments were made at Day 10 and Day 28. The primary endpoint of this trial was prospectively defined as the clinical cure rate at Day 28. For the 594 patients analyzed in the modified intent to treat analysis at the Day 10 visit, the clinical cure rate for 3 days of azithromycin was 88% (268/303) compared to 85% (248/291) for 10 days of amoxicillin/clavulanate. For the 586 patients analyzed in the modified intent to treat analysis at the Day 28 visit, the clinical cure rate for 3 days of azithromycin was 71.5% (213/298) compared to 71.5% (206/288), with a 97.5% confidence interval of –8.4 to 8.3, for 10 days of amoxicillin/clavulanate.

In an open label, non-comparative study requiring baseline transantral sinus punctures, the following outcomes were the clinical success rates at the Day 7 and Day 28 visits for the modified intent to treat patients administered 500 mg of azithromycin once daily for 3 days with the following pathogens:

Clinical Success Rates of Azithromycin (500 mg per day for 3 Days)

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col/> <col/> <col/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Pathogen</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Day 7</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Day28</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">S. pneumoniae</span> <br/> </td><td align="center" class="Botrule Rrule">23/26 (88%) <br/> </td><td align="center" class="Botrule Rrule">21/25 (84%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">H. influenzae</span> <br/> </td><td align="center" class="Botrule Rrule">28/32 (87%) <br/> </td><td align="center" class="Botrule Rrule">24/32 (75%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">M. catarrhalis</span> <br/> </td><td align="center" class="Botrule Rrule">14/15 (93%) <br/> </td><td align="center" class="Botrule Rrule">13/15 (87%) <br/> </td> </tr> </tbody> </table></div>

From the perspective of evaluating pediatric clinical trials, Days 11 to 14 were considered on-therapy evaluations because of the extended half-life of azithromycin. Days 11 to 14 data are provided for clinical guidance. Days 24 to 32 evaluations were considered the primary test of cure endpoint.

Pharyngitis/Tonsillitis

In three double-blind controlled studies, conducted in the United States, azithromycin (12 mg/kg once a day for 5 days) was compared to penicillin V (250 mg three times a day for 10 days) in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci(GABHS or S. pyogenes). Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success (i.e., cure and improvement) and bacteriologic efficacy rates (for the combined evaluable patient with documented GABHS):

<div class="scrollingtable"><table class="Noautorules" width="98%"> <caption> <span>Three U.S. Streptococcal Pharyngitis Studies Azithromycin vs. Penicillin V EFFICACY RESULTS</span> </caption> <col width="55%"/> <col width="23%"/> <col width="21%"/> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Day 14</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Day 30</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Bold">Bacteriologic Eradication:</span> <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Azithromycin <br/> </td><td align="center" class="Botrule Rrule">323/340 (95%) <br/> </td><td align="center" class="Botrule Rrule">255/330 (77%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Penicillin V <br/> </td><td align="center" class="Botrule Rrule">242/332 (73%) <br/> </td><td align="center" class="Botrule Rrule">206/325 (63%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Bold">Clinical Success (cure plus improvement):</span> <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Azithromycin <br/> </td><td align="center" class="Botrule Rrule">336/343 (98%) <br/> </td><td align="center" class="Botrule Rrule">310/330 (94%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Penicillin V <br/> </td><td align="center" class="Botrule Rrule">284/338 (84%) <br/> </td><td align="center" class="Botrule Rrule">241/325 (74%) <br/> </td> </tr> </tbody> </table></div>

Approximately 1% of azithromycin-susceptible S. pyogenesisolates were resistant to azithromycin following therapy.

Acute Otitis Media

Efficacy using azithromycin given over 5 days (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5).

Trial 1

In a double-blind, controlled clinical study of acute otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5) was compared to amoxicillin/clavulanate potassium (4:1). For the 553 patients who were evaluated for clinical efficacy, the clinical success rate (i.e., cure plus improvement) at the Day 11 visit was 88% for azithromycin and 88% for the control agent. For the 521 patients who were evaluated at the Day 30 visit, the clinical success rate was 73% for azithromycin and 71% for the control agent.

Trial 2

In a non-comparative clinical and microbiologic trial performed in the United States, where significant rates of beta-lactamase producing organisms (35%) were found, 131 patients were evaluable for clinical efficacy. The combined clinical success rate (i.e., cure and improvement) at the Day 11 visit was 84% for azithromycin. For the 122 patients who were evaluated at the Day 30 visit, the clinical success rate was 70% for azithromycin.

Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. The following clinical success rates were obtained from the evaluable group:

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col/> <col/> <col/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Pathogen</span> <br/> </td><td class="Botrule Rrule Toprule"></td><td class="Botrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule"></td><td align="center" class="Botrule Rrule"><span class="Bold">Day 11</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 30</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule"></td><td align="center" class="Botrule Rrule"><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Azithromycin</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">S. pneumoniae</span> <br/> </td><td align="center" class="Botrule Rrule">61/74 (82%) <br/> </td><td align="center" class="Botrule Rrule">40/56 (71%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">H. influenzae</span> <br/> </td><td align="center" class="Botrule Rrule">43/54 (80%) <br/> </td><td align="center" class="Botrule Rrule">30/47 (64%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">M. catarrhalis</span> <br/> </td><td align="center" class="Botrule Rrule">28/35 (80%) <br/> </td><td align="center" class="Botrule Rrule">19/26 (73%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">S. pyogenes</span> <br/> </td><td align="center" class="Botrule Rrule">11/11 (100%) <br/> </td><td align="center" class="Botrule Rrule">7/7 (100%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Overall <br/> </td><td align="center" class="Botrule Rrule">177/217 (82%) <br/> </td><td align="center" class="Botrule Rrule">97/137 (73%) <br/> </td> </tr> </tbody> </table></div>

Trial 3

In another controlled comparative clinical and microbiologic study of otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5) was compared to amoxicillin/clavulanate potassium (4:1). This study utilized two of the same investigators as Protocol 2 (above), and these two investigators enrolled 90% of the patients in Protocol 3. For this reason, Protocol 3 was not considered to be an independent study. Significant rates of beta-lactamase producing organisms (20%) were found. Ninety-two (92) patients were evaluable for clinical and microbiologic efficacy. The combined clinical success rate (i.e., cure and improvement) of those patients with a baseline pathogen at the Day 11 visit was 88% for azithromycin vs. 100% for control; at the Day 30 visit, the clinical success rate was 82% for azithromycin vs. 80% for control.

Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. At the Day 11 and Day 30 visits, the following clinical success rates were obtained from the evaluable group:

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold">Day 11</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2"><span class="Bold">Day 30</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Bold">Pathogen</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Control</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Control</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">S. pneumoniae</span> <br/> </td><td align="center" class="Botrule Rrule">25/29 (86%) <br/> </td><td align="center" class="Botrule Rrule">26/26 (100%) <br/> </td><td align="center" class="Botrule Rrule">22/28 (79%) <br/> </td><td align="center" class="Botrule Rrule">18/22 (82%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">H. influenzae</span> <br/> </td><td align="center" class="Botrule Rrule">9/11 (82%) <br/> </td><td align="center" class="Botrule Rrule">9/9 (100%) <br/> </td><td align="center" class="Botrule Rrule">8/10 (80%) <br/> </td><td align="center" class="Botrule Rrule">6/8 (75%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">M. catarrhalis</span> <br/> </td><td align="center" class="Botrule Rrule">7/7 (100%) <br/> </td><td align="center" class="Botrule Rrule">5/5 (100%) <br/> </td><td align="center" class="Botrule Rrule">5/5 (100%) <br/> </td><td align="center" class="Botrule Rrule">2/3 (66%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">S. pyogenes</span> <br/> </td><td align="center" class="Botrule Rrule">2/2 (100%) <br/> </td><td align="center" class="Botrule Rrule">5/5 (100%) <br/> </td><td align="center" class="Botrule Rrule">2/2 (100%) <br/> </td><td align="center" class="Botrule Rrule">4/4 (100%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Overall <br/> </td><td align="center" class="Botrule Rrule">43/49 (88%) <br/> </td><td align="center" class="Botrule Rrule">45/45 (100%) <br/> </td><td align="center" class="Botrule Rrule">37/45 (82%) <br/> </td><td align="center" class="Botrule Rrule">30/37 (81%) <br/> </td> </tr> </tbody> </table></div>

Efficacy using azithromycin given over 3 days (10 mg/kg/day).

Trial 4

In a double-blind, controlled, randomized clinical study of acute otitis media in pediatric patients from 6 months to 12 years of age, azithromycin (10 mg/kg per day for 3 days) was compared to amoxicillin/clavulanate potassium (7:1) in divided doses q12h for 10 days. Each patient received active drug and placebo matched for the comparator.

For the 366 patients who were evaluated for clinical efficacy at the Day 12 visit, the clinical success rate (i.e., cure plus improvement) was 83% for azithromycin and 88% for the control agent. For the 362 patients who were evaluated at the Days 24 to 28 visit, the clinical success rate was 74% for azithromycin and 69% for the control agent.

Efficacy using azithromycin 30 mg/kg given as a single dose

Trial 5

A double-blind, controlled, randomized trial was performed at nine clinical centers. Pediatric patients from 6 months to 12 years of age were randomized 1:1 to treatment with either azithromycin (given at 30 mg/kg as a single dose on Day 1) or amoxicillin/clavulanate potassium (7:1), divided q12h for 10 days. Each child received active drug, and placebo matched for the comparator.

Clinical response (Cure, Improvement, Failure) was evaluated at End of Therapy (Days 12 to 16) and Test of Cure (Days 28 to 32). Safety was evaluated throughout the trial for all treated subjects. For the 321 subjects who were evaluated at End of Treatment, the clinical success rate (cure plus improvement) was 87% for azithromycin, and 88% for the comparator. For the 305 subjects who were evaluated at Test of Cure, the clinical success rate was 75% for both azithromycin and the comparator.

Trial 6

In a non-comparative clinical and microbiological trial, 248 patients from 6 months to 12 years of age with documented acute otitis media were dosed with a single oral dose of azithromycin (30 mg/kg on Day 1).

For the 240 patients who were evaluable for clinical modified Intent-to-Treat (MITT) analysis, the clinical success rate (i.e., cure plus improvement) at Day 10 was 89% and for the 242 patients evaluable at Days 24 to 28, the clinical success rate (cure) was 85%.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col/> <col/> <col/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Presumed Bacteriologic Eradication</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule"></td><td align="center" class="Botrule Rrule"><span class="Bold">Day 10</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days 24 to 28</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">S. pneumoniae</span> <br/> </td><td align="center" class="Botrule Rrule">70/76 (92%) <br/> </td><td align="center" class="Botrule Rrule">67/76 (88%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">H. influenzae</span> <br/> </td><td align="center" class="Botrule Rrule">30/42 (71%) <br/> </td><td align="center" class="Botrule Rrule">28/44 (64%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Italics">M. catarrhalis</span> <br/> </td><td align="center" class="Botrule Rrule">10/10 (100%) <br/> </td><td align="center" class="Botrule Rrule">10/10 (100%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Overall <br/> </td><td align="center" class="Botrule Rrule">110/128 (86%) <br/> </td><td align="center" class="Botrule Rrule">105/130 (81%) <br/> </td> </tr> </tbody> </table></div>

Azithromycin for oral suspension USP, 100 mg/ 5mL or 200 mg/5 mL [each teaspoonful (5 mL) contains Azithromycin Dihydrate equivalent to Azithromycin USP, 100 mg or 200 mg] is supplied in bottles.

{ "type": "p", "children": [], "text": "\nAzithromycin for oral suspension USP, 100 mg/ 5mL or 200 mg/5 mL [each teaspoonful (5 mL) contains Azithromycin Dihydrate equivalent to Azithromycin USP, 100 mg or 200 mg] is supplied in bottles." }

Azithromycin for oral suspension, USP is white to light pink granular powder filled in translucent HDPE bottle with child-resistant cap and after constitution with water contains a red colored flavored suspension.

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, USP is white to light pink granular powder filled in translucent HDPE bottle with child-resistant cap and after constitution with water contains a red colored flavored suspension." }

Azithromycin for oral suspension, USP is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension in bottles as follows:

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, USP is supplied to provide 100 mg/5 mL or 200 mg/5 mL suspension in bottles as follows:" }

<div class="scrollingtable"><table class="Noautorules" width="60%"> <col/> <col/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Azithromycin contents per bottle</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">NDC</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">300 mg (15 mL bottle) <br/> </td><td align="left" class="Botrule Rrule">70710-1457-1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">600 mg (15 mL bottle) <br/> </td><td align="left" class="Botrule Rrule">70710-1458-2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">900 mg (22.5 mL bottle) <br/> </td><td align="left" class="Botrule Rrule">70710-1459-2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">1200 mg (30 mL bottle) <br/> </td><td align="left" class="Botrule Rrule">70710-1460-2 <br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"60%\">\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Azithromycin contents per bottle</span>\n<br/>\n</td><td align=\"left\" class=\"Botrule Rrule Toprule\"><span class=\"Bold\">NDC</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">300 mg (15 mL bottle) \n <br/>\n</td><td align=\"left\" class=\"Botrule Rrule\">70710-1457-1 \n <br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">600 mg (15 mL bottle) \n <br/>\n</td><td align=\"left\" class=\"Botrule Rrule\">70710-1458-2 \n <br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">900 mg (22.5 mL bottle) \n <br/>\n</td><td align=\"left\" class=\"Botrule Rrule\">70710-1459-2 \n <br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\">1200 mg (30 mL bottle) \n <br/>\n</td><td align=\"left\" class=\"Botrule Rrule\">70710-1460-2 \n <br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

[see Dosage and Administration ( 2)] for constitution instructions with each bottle type.

{ "type": "p", "children": [], "text": "\n[see Dosage and Administration (\n \n 2)]\n \n for constitution instructions with each bottle type.\n\n " }

Azithromycin for oral suspension, USP is supplied with child-resistant closure.

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, USP is supplied with child-resistant closure." }

Storage:Store dry powder at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15ºC to 30ºC (59ºF to 86ºF) [See USP Controlled Room Temperature]. Store constituted suspension between 5°C to 30°C (41°F to 86°F) and discard when full dosing is completed.

{ "type": "p", "children": [], "text": "\nStorage:Store dry powder at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15ºC to 30ºC (59ºF to 86ºF) [See USP Controlled Room Temperature]. Store constituted suspension between 5°C to 30°C (41°F to 86°F) and discard when full dosing is completed.\n\n " }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "\nAdvise the patient to read the FDA-approved patient labeling (Patient Information)." }

General Patient Counseling

{ "type": "p", "children": [], "text": "\nGeneral Patient Counseling\n" }

Azithromycin for oral suspension can be taken with or without food.

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension can be taken with or without food." }

Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and azithromycin simultaneously.

{ "type": "p", "children": [], "text": "Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and azithromycin simultaneously." }

The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur.

{ "type": "p", "children": [], "text": "The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur." }

Direct parents or caregivers to contact their physician if vomiting and irritability with feeding occurs in the infant.

{ "type": "p", "children": [], "text": "Direct parents or caregivers to contact their physician if vomiting and irritability with feeding occurs in the infant." }

Patients should be counseled that antibacterial drugs including Azithromycin for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Azithromycin for oral suspension is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Azithromycin for oral suspension or other antibacterial drugs in the future.

{ "type": "p", "children": [], "text": "Patients should be counseled that antibacterial drugs including Azithromycin for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Azithromycin for oral suspension is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Azithromycin for oral suspension or other antibacterial drugs in the future." }

Diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible.

{ "type": "p", "children": [], "text": "Diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible." }

Manufactured by:

{ "type": "p", "children": [], "text": "\nManufactured by:\n" }

Zydus Lifesciences Ltd.

{ "type": "p", "children": [], "text": "\nZydus Lifesciences Ltd.\n" }

Baddi, India.

{ "type": "p", "children": [], "text": "Baddi, India." }

Distributed by:

{ "type": "p", "children": [], "text": "\nDistributed by:\n" }

Zydus Pharmaceuticals USA Inc.

{ "type": "p", "children": [], "text": "\nZydus Pharmaceuticals USA Inc.\n" }

Pennington, NJ 08534

{ "type": "p", "children": [], "text": "Pennington, NJ 08534" }

Rev.: 01/23

{ "type": "p", "children": [], "text": "Rev.: 01/23" }

Azithromycin ( ay zith" roe mye' sin) for Oral Suspension, USP

{ "type": "p", "children": [], "text": "\nAzithromycin ( ay zith\" roe mye' sin) for Oral Suspension, USP\n" }

Read this Patient Information leaflet before you start taking azithromycin for oral suspension. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

{ "type": "p", "children": [], "text": "Read this Patient Information leaflet before you start taking azithromycin for oral suspension. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment." }

What is azithromycin for oral suspension?

{ "type": "p", "children": [], "text": "\nWhat is azithromycin for oral suspension?\n" }

Azithromycin for oral suspension is a macrolide antibiotic prescription medicine used in adults 18 years or older to treat certain infections caused by certain germs called bacteria. These bacterial infections include:

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension is a macrolide antibiotic prescription medicine used in adults 18 years or older to treat certain infections caused by certain germs called bacteria. These bacterial infections include:" }

{ "type": "ul", "children": [ "acute worsening of chronic bronchitis", "acute sinus infection", "community-acquired pneumonia", "infected throat or tonsils", "skin infections", "infections of the urethra or cervix", "genital ulcers in men" ], "text": "" }

Azithromycin for oral suspension is also used in children to treat:

{ "type": "p", "children": [], "text": "\nAzithromycin for oral suspension is also used in children to treat:" }

{ "type": "ul", "children": [ "ear infections", "community-acquired pneumonia", "infected throat or tonsils" ], "text": "" }

Azithromycin should not be taken by people who cannot tolerate oral medications because they are very ill or have certain other risk factors including:

{ "type": "p", "children": [], "text": "\nAzithromycin should not be taken by people who cannot tolerate oral medications because they are very ill or have certain other risk factors including:" }

{ "type": "ul", "children": [ "have cystic fibrosis", "have hospital acquired infections", "have known or suspected bacteria in the blood", "need to be in the hospital", "are elderly", "have any medical problems that can lower the ability of the immune system to fight infections" ], "text": "" }

Azithromycin for oral suspension is not for viral infections such as the common cold.

{ "type": "p", "children": [], "text": "\nAzithromycin for oral suspension is not for viral infections such as the common cold." }

It is not known if Azithromycin for oral suspension is safe and effective for genital ulcers in women.

{ "type": "p", "children": [], "text": "It is not known if Azithromycin for oral suspension is safe and effective for genital ulcers in women." }

It is not known if Azithromycin for oral suspension is safe and effective for children with ear infections, sinus infections, and community-acquired pneumonia under 6 months of age.

{ "type": "p", "children": [], "text": "It is not known if Azithromycin for oral suspension is safe and effective for children with ear infections, sinus infections, and community-acquired pneumonia under 6 months of age." }

It is not known if Azithromycin for oral suspension is safe and effective for infected throat or tonsils in children under 2 years of age.

{ "type": "p", "children": [], "text": "It is not known if Azithromycin for oral suspension is safe and effective for infected throat or tonsils in children under 2 years of age." }

Who should not take azithromycin for oral suspension?

{ "type": "p", "children": [], "text": "\nWho should not take azithromycin for oral suspension?\n" }

Do not take azithromycin for oral suspension if you:

{ "type": "p", "children": [], "text": "\nDo not take azithromycin for oral suspension if you:\n" }

{ "type": "ul", "children": [ "have had a severe allergic reaction to certain antibiotics known as macrolides or ketolides including azithromycin and erythromycin.", "have a history of cholestatic jaundice or hepatic dysfunction that happened with the use of azithromycin." ], "text": "" }

What should I tell my healthcare provider before taking azithromycin for oral suspension?

{ "type": "p", "children": [], "text": "\nWhat should I tell my healthcare provider before taking azithromycin for oral suspension?\n" }

Before you take azithromycin for oral suspension, tell your healthcare provider if you:

{ "type": "p", "children": [], "text": "\nBefore you take azithromycin for oral suspension, tell your healthcare provider if you:\n" }

{ "type": "ul", "children": [ "have pneumonia", "have cystic fibrosis", "have known or suspected bacteremia (bacterial infection in the blood)", "have liver or kidney problems", "have an irregular heartbeat, especially a problem called \"QT prolongation\"", "have a problem that causes muscle weakness (myasthenia gravis)", "have any other medical problems", "are pregnant or plan to become pregnant. It is not known if azithromycin for oral suspension will harm your unborn baby.", "are breastfeeding or plan to breastfeed. Azithromycin has been reported to pass into breast milk. Talk to your healthcare provider about the best way to feed your baby while you take azithromycin for oral suspension." ], "text": "" }

Contact your healthcare provider immediately if you are giving azithromycin for oral suspension to a young child (less than 6 weeks of age) and he or she vomits or becomes irritable when fed.

{ "type": "p", "children": [], "text": "\nContact your healthcare provider immediately if you are giving azithromycin for oral suspension to a young child (less than 6 weeks of age) and he or she vomits or becomes irritable when fed." }

Tell your healthcare provider about all the medicines you take,including prescription and non-prescription medicines, vitamins, and herbal supplements.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take,including prescription and non-prescription medicines, vitamins, and herbal supplements.\n\n " }

Azithromycin for oral suspension and other medicines may affect each other causing side effects. Azithromycin for oral suspension may affect the way other medicines work, and other medicines may affect how azithromycin for oral suspension works.

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension and other medicines may affect each other causing side effects. Azithromycin for oral suspension may affect the way other medicines work, and other medicines may affect how azithromycin for oral suspension works." }

Especially tell your healthcare provider if you take:

{ "type": "p", "children": [], "text": "Especially tell your healthcare provider if you take:" }

{ "type": "ul", "children": [ "nelfinavir", "a blood thinner (warfarin)", "digoxin", "phenytoin", "colchicine", "an antacid that contains aluminum or magnesium" ], "text": "" }

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

{ "type": "p", "children": [], "text": "\nKnow the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine." }

How should I take azithromycin for oral suspension?

{ "type": "p", "children": [], "text": "\nHow should I take azithromycin for oral suspension?\n" }

{ "type": "ul", "children": [ "Take azithromycin for oral suspension exactly as your healthcare provider tells you to take it.", "Azithromycin for oral suspension can be taken with or without food.", "If you take azithromycin for oral suspension, shake the bottle well just before you take it.", "Do not skip any doses of azithromycin for oral suspension or stop taking it, even if you begin to feel better, until you finish your prescribed treatment unless you have a serious allergic reaction or your healthcare provider tells you to stop taking azithromycin for oral suspension. \"\n \n SeeWhat are the possible side effects of azithromycin for oral suspension?\"If you skip doses, or do not complete the total course of azithromycin for oral suspension your treatment may not work as well and your infection may be harder to treat. Taking all of your azithromycin for oral suspension doses will help lower the chance that the bacteria will become resistant to azithromycin for oral suspension.\n \n ", "If the bacteria becomes resistant to azithromycin, azithromycin for oral suspension and other antibiotic medicines may not work for you in the future.", "If you take too much azithromycin for oral suspension, call your healthcare provider or get medical help right away." ], "text": "" }

What are the possible side effects of azithromycin for oral suspension?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of azithromycin for oral suspension?\n" }

Azithromycin for oral suspension can cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nAzithromycin for oral suspension can cause serious side effects, including:\n" }

{ "type": "ul", "children": [ "\nSerious allergic reactions.Allergic reactions can happen in people taking azithromcyin the active ingredient in azithromycin for oral suspension, even after only 1 dose. Stop taking azithromycin for oral suspension and get emergency medical help right away if you have any of the following symptoms of a severe allergic reaction:\n \n \ntrouble breathing or swallowing\nswelling of the lips, tongue, face\nthroat tightness, hoarseness\nrapid heartbeat\nfaintness\nskin rash (hives)\nnew onset of fever and swollen lymph nodes\n\n" ], "text": "" }

Stop taking azithromycin for oral suspension at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to azithromycin for oral suspension.

{ "type": "p", "children": [], "text": "\nStop taking azithromycin for oral suspension at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to azithromycin for oral suspension." }

{ "type": "ul", "children": [ "\nLiver damage (hepatotoxicity).Hepatotoxicity can happen in people who take azithromycin for oral suspension. Call your healthcare provider right away if you have unexplained symptoms such as:\n \n \nnausea or vomiting\nstomach pain\nfever\nweakness\nabdominal pain or tenderness\nitching\nunusual tiredness\nloss of appetite\nchange in the color of your bowel movements\ndark colored urine\nyellowing of your skin or of the whites of your eyes\n\n" ], "text": "" }

Stop taking azithromycin for oral suspension and tell your healthcare provider right away if you have yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to azithromycin for oral suspension (a liver problem).

{ "type": "p", "children": [], "text": "\nStop taking azithromycin for oral suspension and tell your healthcare provider right away if you have yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to azithromycin for oral suspension (a liver problem)." }

          Serious heart rhythm changesthat can be life-threatening, including heart stopping (cardiac arrest), QT prolongation, torsades de pointes,feeling that your heart is pounding or racing (palpitations), chest discomfort, or irregular heartbeat.

{ "type": "p", "children": [], "text": "         \n \n Serious heart rhythm changesthat can be life-threatening, including heart stopping (cardiac arrest), QT prolongation, torsades de pointes,feeling that your heart is pounding or racing (palpitations), chest discomfort, or irregular heartbeat.\n" }

{ "type": "ul", "children": [ "Tell your healthcare provider right away if you or your child feel a fast or irregular heartbeat, get dizzy or faint. Azithromycin for oral suspension may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people:\n \n \nwho are elderly\nwith a family history of prolonged QT interval\nwith low blood potassium\nwho take certain medicines to control heart rhythm (antiarrhythmics)\n\n", "\nWorsening of myasthenia gravis (a problem that causes muscle weakness).\n" ], "text": "" }

Certain antibiotics like azithromycin for oral suspension may cause worsening of myasthenia gravis symptoms including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

{ "type": "p", "children": [], "text": "\nCertain antibiotics like azithromycin for oral suspension may cause worsening of myasthenia gravis symptoms including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems." }

{ "type": "ul", "children": [ "\nDiarrhea.Tell your healthcare provider right away if you have watery diarrhea, diarrhea that does not go away, or bloody stools. You may experience cramping and a fever. This could happen after you have finished your azithromycin for oral suspension.\n \n " ], "text": "" }

The most common side effects of azithromycin for oral suspension include:

{ "type": "p", "children": [], "text": "\nThe most common side effects of azithromycin for oral suspension include:" }

{ "type": "ul", "children": [ "nausea", "stomach pain", "vomiting" ], "text": "" }

These are not all the possible side effects of azithromycin for oral suspension. Tell your healthcare provider about any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "\nThese are not all the possible side effects of azithromycin for oral suspension. Tell your healthcare provider about any side effect that bothers you or that does not go away." }

Call your doctor for medical advice about side effects. You may report side effects to FDA at

{ "type": "p", "children": [], "text": "Call your doctor for medical advice about side effects. You may report side effects to FDA at" }

1-800-FDA-1088.

{ "type": "p", "children": [], "text": "1-800-FDA-1088." }

How should I store azithromycin for oral suspension?

{ "type": "p", "children": [], "text": "\nHow should I store azithromycin for oral suspension?\n" }

{ "type": "ul", "children": [ "Azithromycin for oral suspension comes in child-resistant package.", "Store azithromycin for oral suspension at 41°F to 86°F (5°C to 30°C).", "Keep azithromycin for oral suspension in a tightly closed container.", "Safely throw away any medicine that is out of date or no longer needed." ], "text": "" }

Keep azithromycin for oral suspension and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep azithromycin for oral suspension and all medicines out of the reach of children.\n" }

General information about the safe and effective use of azithromycin for oral suspension.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of azithromycin for oral suspension.\n" }

Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use azithromycin for oral suspension for a condition for which it was not prescribed. Do not give azithromycin for oral suspension to other people, even if they have the same symptoms you have. It may harm them.

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use azithromycin for oral suspension for a condition for which it was not prescribed. Do not give azithromycin for oral suspension to other people, even if they have the same symptoms you have. It may harm them." }

This Patient Information leaflet summarizes the most important information about azithromycin for oral suspension. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about azithromycin for oral suspension that is written for health professionals.

{ "type": "p", "children": [], "text": "This Patient Information leaflet summarizes the most important information about azithromycin for oral suspension. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about azithromycin for oral suspension that is written for health professionals." }

For more information, go to Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

{ "type": "p", "children": [], "text": "For more information, go to Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch." }

What are the ingredients in  azithromycin for oral suspension?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in \n \n azithromycin for oral suspension?\n" }

Azithromycin for oral suspension

{ "type": "p", "children": [], "text": "\nAzithromycin for oral suspension\n" }

Active ingredient: Azithromycin dihydrate, USP

{ "type": "p", "children": [], "text": "Active ingredient: Azithromycin dihydrate, USP" }

Inactive ingredients: sucrose; trisodium phosphate anhydrous, hydroxypropyl cellulose; xanthan gum; FD&C Red #40; cherry flavor, ripe banana flavor.

{ "type": "p", "children": [], "text": "Inactive ingredients: sucrose; trisodium phosphate anhydrous, hydroxypropyl cellulose; xanthan gum; FD&C Red #40; cherry flavor, ripe banana flavor." }

This Patient Information has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "\nThis Patient Information has been approved by the U.S. Food and Drug Administration.\n" }

Manufactured by:

{ "type": "p", "children": [], "text": "\nManufactured by:\n" }

Cadila Healthcare Limited

{ "type": "p", "children": [], "text": "\nCadila Healthcare Limited\n" }

Baddi, India.

{ "type": "p", "children": [], "text": "Baddi, India." }

Distributed by:

{ "type": "p", "children": [], "text": "\nDistributed by:\n" }

Zydus Pharmaceuticals USA Inc.

{ "type": "p", "children": [], "text": "\nZydus Pharmaceuticals USA Inc.\n" }

Pennington, NJ 08534

{ "type": "p", "children": [], "text": "Pennington, NJ 08534" }

Rev.: 03/22

{ "type": "p", "children": [], "text": "Rev.: 03/22" }

NDC 70710-1457-1

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Azithromycin for oral suspension, 300 mg

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100 mg/5 mL

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Rx only

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Zydus

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NDC 70710-1458-2

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Azithromycin for oral suspension, 600 mg

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, 600 mg" }

200 mg/5 mL

{ "type": "p", "children": [], "text": "200 mg/5 mL" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

Zydus

{ "type": "p", "children": [], "text": "Zydus" }

NDC 70710-1459-2

{ "type": "p", "children": [], "text": "\nNDC 70710-1459-2" }

Azithromycin for oral suspension, 900 mg

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, 900 mg" }

200 mg/5 mL

{ "type": "p", "children": [], "text": "200 mg/5 mL" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

Zydus

{ "type": "p", "children": [], "text": "Zydus" }

NDC 70710-1460-2

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Azithromycin for oral suspension, 1200 mg

{ "type": "p", "children": [], "text": "Azithromycin for oral suspension, 1200 mg" }

200 mg/5 mL

{ "type": "p", "children": [], "text": "200 mg/5 mL" }

Rx only

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Zydus

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due to Chlamydophila pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, or Streptococcus pneumoniae in patients who require initial intravenous therapy.

due to Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma hominis in patients who require initial intravenous therapy. If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial agent with anaerobic activity should be administered in combination with Azithromycin.

Azithromycin for Injection, USP should be followed by azithromycin the oral route as required [see Dosage and Administration (2)].

To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

The recommended dose of Azithromycin for Injection, USP for the treatment of adult patients with community-acquired pneumonia due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for at least two days. Intravenous therapy should be followed by azithromycin by the oral route at a single, daily dose of 500 mg, administered as two 250-mg tablets to complete a 7- to 10-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response.

The recommended dose of Azithromycin for Injection, USP for the treatment of adult patients with pelvic inflammatory disease due to the indicated organisms is 500 mg as a single daily dose by the intravenous route for one or two days. Intravenous therapy should be followed by azithromycin by the oral route at a single, daily dose of 250 mg to complete a 7-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response.

The infusate concentration and rate of infusion for Azithromycin for Injection, USP should be 2 mg/mL over 1 hour. Azithromycin for Injection, USP should not be given as a bolus or as an intramuscular injection.

Reconstitution

Instructions for Use

These instructions for use should be made available to the individuals who perform the reconstitution steps.

Parenteral drug products should be inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solution should be discarded.

To Open

Peel overwrap at corner and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container:

(Use Aseptic Technique)

<div class="scrollingtable"><table width="100%"> <col width="100%"/> <tbody class="Headless"> <tr class="First Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">To Reconstitute the Drug</span> </p> <dl> <dt>•</dt> <dd>Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.</dd> <dt>•</dt> <dd>With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (See Figure 5.)</dd> <dt>•</dt> <dd> <span class="Bold">Pull the inner cap from the drug vial. (See Figure 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.</span> </dd> <dt>•</dt> <dd>Mix container contents thoroughly and use within the specified time.</dd> <dt>•</dt> <dd>Look through the bottom of the vial to verify that the stopper has been removed and complete mixing has occurred. (See Figure 7.)</dd> </dl> <p>If the rubber stopper is not removed from the vial and medication is not released on the first attempt, the inner cap may be manipulated back into the rubber stopper without removing the drug vial from the diluent container. Repeat steps 3 through 5.</p> <p>           <a name="id-998419767"></a><img alt="Figure 5" src="/dailymed/image.cfm?name=azithromycin-05.jpg&amp;setid=d2f4907f-b952-403b-229e-cc5b8327a773"/>                 <a name="id608083621"></a><img alt="Figure 6" src="/dailymed/image.cfm?name=azithromycin-06.jpg&amp;setid=d2f4907f-b952-403b-229e-cc5b8327a773"/>                        <a name="id-420646035"></a><img alt="Figure 7" src="/dailymed/image.cfm?name=azithromycin-07.jpg&amp;setid=d2f4907f-b952-403b-229e-cc5b8327a773"/></p> </td> </tr> </tbody> </table></div>

Dilute this solution further prior to administration as instructed below.

Dilution

Azithromycin for Injection, USP ADD-Vantage® vials must be diluted prior to IV administration with the ADD-Vantage® diluent container [see Dosage and Administration (2.3)]. The ADD-Vantage® vial should be joined with a 250 mL ADD-Vantage® flexible diluent container (5% dextrose injection, 0.9% sodium chloride injection or 0.45% sodium chloride injection).

It is recommended that a 500-mg dose of Azithromycin for Injection, diluted as above, be infused over a period of not less than 60 minutes.

Other intravenous substances, additives, or medications should not be added to Azithromycin for Injection, or infused simultaneously through the same intravenous line.

Preparation for Administration

(Use Aseptic Technique)

WARNING: Do not use flexible container in series connections.

Storage

When diluted according to the instructions (2 mg/mL), Azithromycin for Injection is stable for 24 hours at or below room temperature (30°C or 86°F), or for 7 days if stored under refrigeration (5°C or 41°F).

Azithromycin for Injection is supplied as white to off-white lyophilized powder in a single-dose ADD-Vantage® vial equivalent to 500 mg of azithromycin for intravenous administration.

{ "type": "p", "children": [], "text": "Azithromycin for Injection is supplied as white to off-white lyophilized powder in a single-dose ADD-Vantage® vial equivalent to 500 mg of azithromycin for intravenous administration." }

Azithromycin for Injection is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drugs.

Azithromycin for Injection is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported in patients on azithromycin therapy [see Contraindications (4.1)].

Fatalities have been reported. Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is unknown at present.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that the allergic symptoms may reappear after symptomatic therapy has been discontinued.

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation, which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:

Elderly patients may be more susceptible to drug-associated effects on the QT interval.

Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. The five-day cardiovascular mortality observed in these studies ranged from 20 to 400 per million azithromycin treatment courses. This potential risk was noted to be greater during the first five days of azithromycin use and does not appear to be limited to those patients with preexisting cardiovascular diseases. The data in these observational studies are insufficient to establish or exclude a causal relationship between acute cardiovascular death and azithromycin use. Consider balancing this potential risk with treatment benefits when prescribing azithromycin.

Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Azithromycin for Injection and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile and surgical evaluation should be instituted as clinically indicated.

Exacerbations of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Azithromycin for Injection should be reconstituted and diluted as directed and administered as an intravenous infusion over not less than 60 minutes [see Dosage and Administration (2)].

Local IV site reactions have been reported with the intravenous administration of azithromycin. The incidence and severity of these reactions were the same when 500 mg azithromycin was given over 1 hour (2 mg/mL as 250 mL infusion) or over 3 hours (1 mg/mL as 500 mL infusion) [see Adverse Reactions (6)]. All volunteers who received infusate concentrations above 2 mg/mL experienced local IV site reactions and, therefore, higher concentrations should be avoided.

Prescribing Azithromycin for Injection in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials of intravenous azithromycin for community-acquired pneumonia, in which 2 to 5 IV doses were given, the reported adverse reactions were mild to moderate in severity and were reversible upon discontinuation of the drug. The majority of patients in these trials had one or more co-morbid diseases and were receiving concomitant medications. Approximately 1.2% of the patients discontinued intravenous Azithromycin for Injection therapy, and a total of 2.4% discontinued azithromycin therapy by either the intravenous or oral route because of clinical or laboratory side effects.

In clinical trials conducted in patients with pelvic inflammatory disease, in which 1 to 2 IV doses were given, 2% of women who received monotherapy with azithromycin and 4% who received azithromycin plus metronidazole discontinued therapy due to clinical side effects.

Clinical adverse reactions leading to discontinuations from these studies were gastrointestinal (abdominal pain, nausea, vomiting, diarrhea) and rashes; laboratory side effects leading to discontinuation were increases in transaminase levels and/or alkaline phosphatase levels.

Overall, the most common adverse reactions associated with treatment in adult patients who received IV/Oral Azithromycin in studies of community-acquired pneumonia were related to the gastrointestinal system with diarrhea/loose stools (4.3%), nausea (3.9%), abdominal pain (2.7%) and vomiting (1.4%) being the most frequently reported.

Approximately 12% of patients experienced a side effect related to the intravenous infusion; most common were pain at the injection site (6.5%) and local inflammation (3.1%).

The most common adverse reactions associated with treatment in adult women who received IV/Oral Azithromycin in trials of pelvic inflammatory disease were related to the gastrointestinal system. Diarrhea (8.5%) and nausea (6.6%) were most commonly reported, followed by vaginitis (2.8%), abdominal pain (1.9%), anorexia (1.9%), rash and pruritus (1.9%). When azithromycin was co-administered with metronidazole in these trials, a higher proportion of women experienced adverse reactions of nausea (10.3%), abdominal pain (3.7%), vomiting (2.8%), infusion site reaction, stomatitis, dizziness, or dyspnea (all at 1.9%).

Adverse reactions that occurred with a frequency of 1% or less included the following:

Gastrointestinal: Dyspepsia, flatulence, mucositis, oral moniliasis and gastritis. Nervous system: Headache, somnolence. Allergic: Bronchospasm. Special senses: Taste perversion.

The following adverse reactions have been identified during post-approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported with azithromycin during the postmarketing period in adult and/or pediatric patients for which a causal relationship may not be established include:

Allergic: Arthralgia, edema, urticaria and angioedema. Cardiovascular: Arrhythmias including ventricular tachycardia and hypotension. There have been reports of QT prolongation, torsades de pointes, and cardiovascular death. Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and reports of tongue discoloration. General: Asthenia, paresthesia, fatigue, malaise and anaphylaxis (including fatalities). Genitourinary: Interstitial nephritis and acute renal failure and vaginitis. Hematopoietic: Thrombocytopenia. Liver/biliary: Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure [see Warnings and Precautions (5.2)]. Nervous system: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation and syncope. Psychiatric: Aggressive reaction and anxiety. Skin/appendages: Pruritus, serious skin reactions including, erythema multiforme, AGEP, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS. Special senses: Hearing disturbances including hearing loss, deafness and/or tinnitus and reports of taste/smell perversion and/or loss.

Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows:

When follow-up was provided, changes in laboratory tests appeared to be reversible.

In multiple-dose clinical trials involving more than 750 patients treated with azithromycin (IV/Oral), less than 2% of patients discontinued azithromycin therapy because of treatment-related liver enzyme abnormalities.

Co-administration of nelfinavir at steady-state with a single oral dose of azithromycin resulted in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted [see Adverse Reactions (6)].

Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.

Interactions with digoxin, colchicine or phenytoin have not been reported in clinical trials with azithromycin. No specific drug interaction studies have been performed to evaluate potential drug-drug interaction. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin, colchicine or phenytoin are used with azithromycin careful monitoring of patients is advised.

Risk Summary

Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Developmental toxicity studies with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to 4, 2, and 2 times, respectively, an adult human daily dose of 500 mg based on body surface area. Decreased viability and delayed development were observed in the offspring of pregnant rats administered azithromycin from day 6 of pregnancy through weaning at a dose equivalent to 4 times an adult human daily dose of 500 mg based on body surface area (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

Available data from published observational studies, case series and case reports over several decades do not suggest an increased risk for major birth defects, miscarriage or adverse maternal or fetal outcomes with azithromycin use in pregnant women. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.

Animal Data

Reproductive and developmental toxicology studies have not been conducted using IV administration of azithromycin to animals. Azithromycin administered during the period of organogenesis did not cause fetal malformations in rats and mice at oral doses up to 200 mg/kg/day (moderately maternally toxic). Based on body surface area, this dose is approximately 4 (rats) and 2 (mice) times an adult human daily dose of 500 mg. In rabbits administered azithromycin at oral doses of 10, 20 and 40 mg/kg/day during organogenesis, reduced maternal body weight and food consumption were observed in all groups; no evidence of fetotoxicity or teratogenicity was observed at these doses, the highest of which is estimated to be 2 times an adult human daily dose of 500 mg based on body surface area.

In a pre- and postnatal development study, azithromycin was administered orally to pregnant rats from day 6 of pregnancy until weaning at doses of 50 or 200 mg/kg/day. Maternal toxicity (reduced food consumption and body weight gain; increased stress at parturition) was observed at the higher dose. Effects in the offspring were noted at 200 mg/kg/day during the postnatal development period (decreased viability, delayed developmental landmarks). These effects were not observed in a pre- and postnatal rat study when up to 200 mg/kg/day of azithromycin was given orally beginning on day 15 of pregnancy until weaning.

Risk Summary

Azithromycin is present in human milk (see Clinical Considerations). Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin (see Clinical Considerations). There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for azithromycin and any potential adverse effects on the breastfed infant from azithromycin or from the underlying maternal condition.

Clinical Considerations

Advise women to monitor the breastfed infant for diarrhea, vomiting, or rash.

Data

Azithromycin breastmilk concentrations were measured in 20 women after receiving a single 2 g oral dose of azithromycin during labor. Breastmilk samples collected on days 3 and 6 postpartum as well as 2 and 4 weeks postpartum revealed the presence of azithromycin in breastmilk up to 4 weeks after dosing. In another study, a single dose of azithromycin 500 mg was administered intravenously to 8 women prior to incision for cesarean section. Breastmilk (colostrum) samples obtained between 12 and 48 hours after dosing revealed that azithromycin persisted in breastmilk up to 48 hours.

Safety and effectiveness of azithromycin for injection in children or adolescents under 16 years have not been established. In controlled clinical studies, azithromycin has been administered to pediatric patients (age 6 months to 16 years) by the oral route. For information regarding the use of azithromycin for oral suspension in the treatment of pediatric patients, [see Indications and Usage (1) and Dosage and Administration (2)] of the prescribing information for Azithromycin for oral suspension 100 mg/5 mL and 200 mg/5 mL bottles.

Pharmacokinetic studies with intravenous azithromycin have not been performed in older volunteers. Pharmacokinetics of azithromycin following oral administration in older volunteers (65–85 years old) were similar to those in younger volunteers (18–40 years old) for the 5-day therapeutic regimen.

In multiple-dose clinical trials of intravenous azithromycin in the treatment of community-acquired pneumonia, 45% of patients (188/414) were at least 65 years of age and 22% of patients (91/414) were at least 75 years of age. No overall differences in safety were observed between these subjects and younger subjects in terms of adverse reactions, laboratory abnormalities and discontinuations. Similar decreases in clinical response were noted in azithromycin- and comparator-treated patients with increasing age.

Azithromycin for Injection contains 114 mg (4.96 mEq) of sodium per vial. At the usual recommended doses, patients would receive 114 mg (4.96 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. The total sodium content from dietary and non-dietary sources may be clinically important with regard to such diseases as congestive heart failure.

Elderly patients may be more susceptible to development of torsades de pointes arrhythmia than younger patients [see Warnings and Precautions (5.4)].

Adverse reactions experienced in higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required.

{ "type": "p", "children": [], "text": "Adverse reactions experienced in higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required." }

Azithromycin for Injection, USP contains the active ingredient azithromycin, an azalide, a subclass of macrolide antibiotics, for intravenous injection. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-hepta-methyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C38H72N2O12, and its molecular weight is 749. Azithromycin has the following structural formula:

{ "type": "p", "children": [], "text": "Azithromycin for Injection, USP contains the active ingredient azithromycin, an azalide, a subclass of macrolide antibiotics, for intravenous injection. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-hepta-methyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C38H72N2O12, and its molecular weight is 749. Azithromycin has the following structural formula:" }

Azithromycin, as the monohydrate, is a white crystalline powder with a molecular formula of C38H72N2O12 ∙ H2O and a molecular weight of 767.

{ "type": "p", "children": [], "text": "Azithromycin, as the monohydrate, is a white crystalline powder with a molecular formula of C38H72N2O12 ∙ H2O and a molecular weight of 767." }

Azithromycin for Injection, USP consists of azithromycin monohydrate and the following inactive ingredients: anhydrous citric acid and sodium hydroxide. Sodium hydroxide is added to adjust the pH. Azithromycin for Injection, USP is supplied as white to off-white lyophilized powder in a single-dose ADD-Vantage® vial for intravenous administration only after reconstitution, according to directions in the Dosage and Administration section. Each ADD-Vantage® vial contains azithromycin monohydrate equivalent to 500 mg azithromycin, 392 mg anhydrous citric acid and sodium hydroxide for pH adjustment.

{ "type": "p", "children": [], "text": "Azithromycin for Injection, USP consists of azithromycin monohydrate and the following inactive ingredients: anhydrous citric acid and sodium hydroxide. Sodium hydroxide is added to adjust the pH. Azithromycin for Injection, USP is supplied as white to off-white lyophilized powder in a single-dose ADD-Vantage® vial for intravenous administration only after reconstitution, according to directions in the Dosage and Administration section. Each ADD-Vantage® vial contains azithromycin monohydrate equivalent to 500 mg azithromycin, 392 mg anhydrous citric acid and sodium hydroxide for pH adjustment." }

Azithromycin is a macrolide antibacterial drug [see Microbiology (12.4)].

Based on animal models of infection, the antibacterial activity of azithromycin appears to correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for certain pathogens (S. pneumoniae and S. aureus). The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with azithromycin.

Cardiac Electrophysiology

QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1,000 mg) alone or in combination with oral azithromycin (500 mg, 1,000 mg, and 1,500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1,000 mg and 1,500 mg azithromycin, respectively.

Since the mean Cmax of azithromycin following a 500 mg IV dose given over 1 hour is higher than the mean Cmax of azithromycin following the administration of a 1,500 mg oral dose, it is possible that QTc may be prolonged to a greater extent with IV azithromycin at close proximity to a one hour infusion of 500 mg.

In patients hospitalized with community-acquired pneumonia receiving single daily one-hour intravenous infusions for 2 to 5 days of 500-mg azithromycin at a concentration of 2 mg/mL, the mean Cmax ± S.D. achieved was 3.63 ± 1.60 mcg/mL, while the 24-hour trough level was 0.20 ± 0.15 mcg/mL and the AUC24 was 9.60 ± 4.80 mcg∙h/mL.

The mean Cmax, 24-hour trough and AUC24 values were 1.14 ± 0.14 mcg/mL, 0.18 ± 0.02 mcg/mL and 8.03 ±0.86 mcg∙ h/mL, respectively, in normal volunteers receiving a 3-hour intravenous infusion of 500 mg azithromycin at a concentration of 1 mg/mL. Similar pharmacokinetic values were obtained in patients hospitalized with community-acquired pneumonia who received the same 3-hour dosage regimen for 2–5 days.

<div class="scrollingtable"><table width="100%"> <col width="15%"/> <col width="14%"/> <col width="14%"/> <col width="8%"/> <col width="8%"/> <col width="8%"/> <col width="8%"/> <col width="8%"/> <col width="8%"/> <col width="8%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="10" valign="top"><span class="Sup">a</span> 500 mg (2 mg/mL) for 2-5 days in community-acquired pneumonia patients.<br/> <span class="Sup">b</span> 500 mg (1 mg/mL) for 5 days in healthy subjects.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" rowspan="2" valign="top"> <p class="First"> <span class="Bold">Infusion Concentration, Duration</span> </p> </td><td align="center" class="Botrule Lrule Toprule" colspan="9" valign="bottom"> <p class="First"> <span class="Bold">Time after starting the infusion (hr)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">  </span> <br/> <span class="Bold">0.5</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">1</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">2</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">3</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">4</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">6</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">8</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">12</span> </p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First"> <span class="Bold">  </span> <br/> <span class="Bold">24</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">2 mg/mL, 1 hr<span class="Sup">a</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">2.98 ±1.12</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">3.63 ±1.73</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.60 ±0.31</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.40 ±0.23</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.33 ±0.16</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.26 ±0.14</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.27 ±0.15</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.20 ±0.12</p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First">0.20 ±0.15</p> </td> </tr> <tr class="Last"> <td class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">1 mg/mL, 3 hr<span class="Sup">b</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.91 ±0.13</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">1.02 ±0.11</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">1.14 ±0.13</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">1.13 ±0.16</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.32 ±0.05</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.28 ±0.04</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.27 ±0.03</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0.22 ±0.02</p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First">0.18 ±0.02</p> </td> </tr> </tbody> </table></div>

Comparison of the plasma pharmacokinetic parameters following the 1st and 5th daily doses of 500 mg intravenous azithromycin showed only an 8% increase in Cmax but a 61% increase in AUC24 reflecting a threefold rise in C24 trough levels.

Following single-oral doses of 500 mg azithromycin (two 250 mg capsules) to 12 healthy volunteers, Cmax, trough level and AUC24 were reported to be 0.41 mcg/mL, 0.05 mcg/mL and 2.6 mcg∙h/mL, respectively. These oral values are approximately 38%, 83% and 52% of the values observed following a single 500-mg I.V. 3-hour infusion (Cmax: 1.08 mcg/mL, trough: 0.06 mcg/mL and AUC24: 5 mcg∙h/mL). Thus, plasma concentrations are higher following the intravenous regimen throughout the 24-hour interval.

Distribution

The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL.

Tissue concentrations have not been obtained following intravenous infusions of azithromycin, but following oral administration in humans azithromycin has been shown to penetrate into tissues, including skin, lung, tonsil and cervix.

Tissue levels were determined following a single oral dose of 500-mg azithromycin in 7 gynecological patients. Approximately 17 hours after dosing, azithromycin concentrations were 2.7 mcg/g in ovarian tissue, 3.5 mcg/g in uterine tissue and 3.3 mcg/g in salpinx. Following a regimen of 500 mg on the first day followed by 250 mg daily for 4 days, concentrations in the cerebrospinal fluid were less than 0.01 mcg/mL in the presence of non-inflamed meninges.

Metabolism

In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.

Elimination

Plasma concentrations of azithromycin following single 500-mg oral and IV doses declined in a polyphasic pattern with a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68 hours. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues.

In a multiple-dose study in 12 normal volunteers utilizing a 500-mg (1 mg/mL) one-hour intravenous-dosage regimen for five days, the amount of administered azithromycin dose excreted in urine in 24 hours was about 11% after the 1st dose and 14% after the 5th dose. These values are greater than the reported 6% excreted unchanged in urine after oral administration of azithromycin. Biliary excretion is a major route of elimination for unchanged drug, following oral administration.

Specific Populations

Patients with Renal Impairment

Azithromycin pharmacokinetics were investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1,000-mg dose of azithromycin, mean Cmax and AUC0–120 increased by 5.1% and 4.2%, respectively in subjects with mild to moderate renal impairment (GFR 10 to 80 mL/min) compared to subjects with normal renal function (GFR >80 mL/min). The mean Cmax and AUC0–120 increased 61% and 35%, respectively in subjects with severe renal impairment (GFR <10 mL/min) compared to subjects with normal renal function (GFR >80 mL/min).

Patients with Hepatic Impairment

The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established.

Male and Female Patients

There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender.

Geriatric Patients

Pharmacokinetic studies with intravenous azithromycin have not been performed in older volunteers. Pharmacokinetics of azithromycin following oral administration in older volunteers (65–85 years old) were similar to those in younger volunteers (18–40 years old) for the 5-day therapeutic regimen [see Geriatric Use (8.5)].

Pediatric Patients

Pharmacokinetic studies with intravenous azithromycin have not been performed in children.

Drug Interaction Studies

Drug interaction studies were performed with oral azithromycin and other drugs likely to be co-administered. The effects of co-administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 2.

Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin.

Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the Cmax and AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2 [see Drug Interactions (7.3)].

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1. Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Azithromycin</span> </caption> <col width="19%"/> <col width="20%"/> <col width="20%"/> <col width="5%"/> <col width="18%"/> <col width="20%"/> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>- 90% Confidence interval not reported</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Co-administered Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of </span> <br/> <span class="Bold">Co-administered Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of </span> <br/> <span class="Bold">Azithromycin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Ratio (with/without azithromycin) of </span> </p> <p> <span class="Bold">Co-administered Drug Pharmacokinetic </span> </p> <p> <span class="Bold">Parameters (90% CI); No Effect = 1</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Mean C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First"> <span class="Bold">Mean AUC</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Atorvastatin</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">10 mg/day for 8 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg/day orally on days 6-8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.83</p> <p>(0.63 to 1.08)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.01</p> <p>(0.81 to 1.25)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Carbamazepine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">200 mg/day for 2 days, then 200 mg twice a day for 18 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg/day orally for days 16-18</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.97</p> <p>(0.88 to 1.06)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">0.96</p> <p>(0.88 to 1.06)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Cetirizine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">20 mg/day for 11 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg orally on day 7, then 250 mg/day on days 8-11</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.03</p> <p>(0.93 to 1.14)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.02</p> <p>(0.92 to 1.13)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Didanosine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">200 mg orally twice a day for 21 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,200 mg/day orally</p> <p>on days 8-21</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.44</p> <p>(0.85 to 2.43)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.14</p> <p>(0.83 to 1.57)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Efavirenz</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">400 mg/day for 7 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">600 mg orally on day 7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.04<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">0.95<a class="Sup" href="#footnote-1">*</a> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Fluconazole</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">200 mg orally single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,200 mg orally single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.04</p> <p>(0.98 to 1.11)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.01</p> <p>(0.97 to 1.05)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Indinavir</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">800 mg three times a day for 5 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,200 mg orally on day 5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.96</p> <p>(0.86 to 1.08)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">0.9</p> <p>(0.81 to 1)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Midazolam</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">15 mg orally on day 3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg/day orally for 3 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.27</p> <p>(0.89 to 1.81)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.26</p> <p>(1.01 to 1.56)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Nelfinavir</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">750 mg three times a day for 11 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,200 mg orally on day 9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.9</p> <p>(0.81 to 1.01)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">0.85</p> <p>(0.78 to 0.93)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Sildenafil</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">100 mg on days 1 and 4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg/day orally for 3 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.16</p> <p>(0.86 to 1.57)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">0.92</p> <p>(0.75 to 1.12)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Theophylline</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4 mg/kg IV on days 1, 11, 25</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg orally on day 7,</p> <p>250 mg/day on days</p> <p>8-11</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.19</p> <p>(1.02 to 1.4)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.02</p> <p>(0.86 to 1.22)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Theophylline</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">300 mg orally twice a day for 15 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg orally on day 6, then 250 mg/day on days 7-10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.09</p> <p>(0.92 to 1.29)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.08</p> <p>(0.89 to 1.31)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Triazolam</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.125 mg on day 2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg orally on day 1,</p> <p>then 250 mg/day on day 2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.06<a class="Sup" href="#footnote-1">*</a> </p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.02<a class="Sup" href="#footnote-1">*</a> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Trimethoprim/</p> <p>Sulfamethoxazole</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">160 mg/800 mg/day orally for 7 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,200 mg orally on day 7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.85</p> <p>(0.75 to 0.97)/</p> <p>0.9</p> <p>(0.78 to 1.03)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">0.87</p> <p>(0.8 to 0.95)/</p> <p>0.96</p> <p>(0.88 to 1.03)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="top"> <p class="First">Zidovudine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg/day orally for 21 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">600 mg/day orally for 14 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.12</p> <p>(0.42 to 3.02)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">0.94</p> <p>(0.52 to 1.7)</p> </td> </tr> <tr class="Last"> <td class="Botrule Rrule" valign="top"> <p class="First">Zidovudine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg/day orally for 21 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1,200 mg/day orally for 14 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.31</p> <p>(0.43 to 3.97)</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1.3</p> <p>(0.69 to 2.43)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2. Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs [see <a href="#_RefID_83b2fb0a-2f21-4048-88ce-bd5cdfce9">Drug Interactions (7.3)</a>].</span> </caption> <col width="18%"/> <col width="17%"/> <col width="17%"/> <col width="5%"/> <col width="22%"/> <col width="22%"/> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>- 90% Confidence interval not reported</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Co-administered Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of </span> <br/> <span class="Bold">Co-administered Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Azithromycin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">n</span> </p> </td><td align="center" class="Botrule Lrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Ratio (with/without co-administered drug) of Azithromycin Pharmacokinetic Parameters (90% CI); No Effect = 1</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Mean C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Mean AUC</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First">Efavirenz</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">400 mg/day for 7 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">600 mg orally on day 7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">14</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">1.22</p> <p>(1.04 to 1.42)</p> </td><td align="center" class="Botrule Lrule Toprule" valign="middle"> <p class="First">0.92<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First">Fluconazole</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">200 mg orally single dose</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">1,200 mg orally single dose</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">18</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">0.82</p> <p>(0.66 to 1.02)</p> </td><td align="center" class="Botrule Lrule Toprule" valign="middle"> <p class="First">1.07</p> <p>(0.94 to 1.22)</p> </td> </tr> <tr class="Last"> <td class="Botrule Rrule Toprule" valign="middle"> <p class="First">Nelfinavir</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">750 mg three times a day for 11 days</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">1,200 mg orally on day 9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">14</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">2.36</p> <p>(1.77 to 3.15)</p> </td><td align="center" class="Botrule Lrule Toprule" valign="middle"> <p class="First">2.12</p> <p>(1.80 to 2.5)</p> </td> </tr> </tbody> </table></div>

Mechanism of Action

Azithromycin acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit.

Resistance

Azithromycin demonstrates cross-resistance with erythromycin. The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides and streptogramin B (MLSB phenotype).

Antimicrobial Activity

Azithromycin has been shown to be active against the following microorganisms, both in vitro and in clinical infections. [see Indications and Usage (1)]

Gram-positive Bacteria                                                     Other Bacteria

Staphylococcus aureus                                                        Chlamydophila pneumoniae Streptococcus pneumoniae                                                  Chlamydia trachomatis                                                                                              Mycoplasma hominis Gram-negative Bacteria                                                    Mycoplasma pneumoniae

Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Legionella pneumophila

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for azithromycin against isolates of similar genus or organism group. However, the efficacy of azithromycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="50%"/> <col width="50%"/> <tbody class="Headless"> <tr> <td valign="top"> <p class="First"> <span class="Bold">Aerobic Gram-Positive Bacteria</span> <br/> <span class="Italics">Streptococci</span> (Groups C, F, G)<br/> <span class="Italics">Viridans</span> group <span class="Italics">streptococci</span> </p> </td><td valign="top"></td> </tr> <tr> <td valign="top"></td><td valign="top"> <p class="First"> <span class="Bold">Anaerobic Bacteria </span> <br/> <span class="Italics">Peptostreptococcus</span> species<br/> <span class="Italics">Prevotella bivia</span> </p> </td> </tr> <tr> <td valign="top"></td><td valign="top"> <p class="First"> <span class="Bold">Other Bacteria</span> <br/> <span class="Italics">Ureaplasma urealyticum</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Gram-Negative Bacteria</span> <br/> <span class="Italics">Bordetella pertussis</span> </p> </td><td valign="top"></td> </tr> </tbody> </table></div>

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. In fertility studies conducted in male and female rats, oral administration of azithromycin for 64 to 66 days (males) or 15 days (females) prior to and during cohabitation resulted in decreased pregnancy rate at 20 and 30 mg/kg/day when both males and females were treated with azithromycin. This minimal effect on pregnancy rate (approximately 12% reduction compared to concurrent controls) did not become more pronounced when the dose was increased from 20 to 30 mg/kg/day (approximately 0.4 to 0.6 times the adult daily dose of 500 mg based on body surface area) and it was not observed when only one animal in the mated pair was treated. There were no effects on any other reproductive parameters and there were no effects on fertility at 10 mg/kg/day. The relevance of these findings to patients being treated with azithromycin at the doses and durations recommended in the prescribing information is uncertain.

Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats and dogs given multiple oral doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen and/or pancreas) in dogs and rats treated with azithromycin at doses which, expressed on the basis of body surface area, are similar to or less than the highest recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 mcg/mL (1.6 times the observed Cmax of 0.821 mcg/mL at the adult dose of 2 g.) Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1 mcg/mL (1.2 times the observed Cmax of 0.821 mcg/mL at the adult dose of 2 g).

Phospholipidosis was also observed in neonatal rats dosed for 18 days at 30 mg/kg/day, which is less than the pediatric dose of 60 mg/kg based on body surface area. It was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 mcg/mL, approximately 1.5 times the Cmax of 1.27 mcg/mL at the pediatric dose. Phospholipidosis has been observed in neonatal dogs (10 mg/kg/day) at maximum mean whole blood concentrations of 3.54 mcg/mL, approximately 3 times the pediatric dose Cmax. The significance of the findings for animals and for humans is unknown.

In a controlled trial of community-acquired pneumonia performed in the U.S., azithromycin (500 mg as a single daily dose by the intravenous route for 2 to 5 days, followed by 500 mg/day by the oral route to complete 7 to 10 days therapy) was compared to cefuroxime (2,250 mg/day in three divided doses by the intravenous route for 2 to 5 days followed by 1,000 mg/day in two divided doses by the oral route to complete 7 to 10 days therapy), with or without erythromycin. For the 291 patients who were evaluable for clinical efficacy, the clinical outcome rates, i.e., cure, improved, and success (cure + improved) among the 277 patients seen at 10 to 14 days post-therapy were as follows:

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <col width="28%"/> <col width="38%"/> <col width="35%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Clinical Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Azithromycin</span> </p> </td><td align="center" class="Botrule Lrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Comparator</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First">Cure</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">46%</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">44%</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First">Improved</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">32%</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">30%</p> </td> </tr> <tr class="Last"> <td class="Botrule Rrule" valign="middle"> <p class="First">Success (Cure + Improved)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">78%</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">74%</p> </td> </tr> </tbody> </table></div>

In a separate, uncontrolled clinical and microbiological trial performed in the U.S., 94 patients with community-acquired pneumonia who received azithromycin in the same regimen were evaluable for clinical efficacy. The clinical outcome rates, i.e., cure, improved and success (cure + improved) among the 84 patients seen at 10 to 14 days post-therapy were as follows:

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <col width="47%"/> <col width="53%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Clinical Outcome</span> </p> </td><td align="center" class="Botrule Lrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Azithromycin</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First">Cure</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">60%</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First">Improved</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">29%</p> </td> </tr> <tr class="Last"> <td class="Botrule Rrule" valign="middle"> <p class="First">Success (Cure + Improved)</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">89%</p> </td> </tr> </tbody> </table></div>

Microbiological determinations in both trials were made at the pre-treatment visit and, where applicable, were reassessed at later visits. Serological testing was done on baseline and final visit specimens. The following combined presumptive bacteriological eradication rates were obtained from the evaluable groups:

Combined Bacteriological Eradication Rates for Azithromycin:

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <col width="49%"/> <col width="26%"/> <col width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top"><span class="Sup">a</span>   Nineteen of twenty-four patients (79%) with positive blood cultures for <span class="Italics">S. pneumoniae </span>were cured (intent-to-treat analysis) with eradication of the pathogen.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">(at last completed visit)</span> </p> </td><td align="center" class="Botrule Lrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Azithromycin</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Italics">S. pneumoniae</span> </p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First">64/67</p> </td><td align="center" class="Botrule" valign="bottom"> <p class="First">(96%)<span class="Sup">a</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Italics">H. influenzae</span> </p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First">41/43</p> </td><td align="center" class="Botrule" valign="bottom"> <p class="First">(95%)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Italics">M. catarrhalis</span> </p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First">9/10</p> </td><td align="center" class="Botrule" valign="bottom"> <p class="First">(90%)</p> </td> </tr> <tr class="Last"> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Italics">S. aureus</span> </p> </td><td align="center" class="Botrule Lrule" valign="bottom"> <p class="First">9/10</p> </td><td align="center" class="Botrule" valign="bottom"> <p class="First">(90%)</p> </td> </tr> </tbody> </table></div>

The presumed bacteriological outcomes at 10 to 14 days post-therapy for patients treated with azithromycin with evidence (serology and/or culture) of atypical pathogens for both trials were as follows:

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <col width="29%"/> <col width="18%"/> <col width="18%"/> <col width="18%"/> <col width="18%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Evidence of Infection</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Total</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Cure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Improved</span> </p> </td><td align="center" class="Botrule Lrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Cure + Improved</span> </p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Italics">Mycoplasma pneumoniae</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">18</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">11 (61%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">5 (28%)</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">16 (89%)</p> </td> </tr> <tr> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Italics">Chlamydia pneumoniae</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">34</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">15 (44%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">13 (38%)</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">28 (82%)</p> </td> </tr> <tr class="Last"> <td class="Botrule Rrule" valign="middle"> <p class="First"> <span class="Italics">Legionella pneumophila</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">16</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">5 (31%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">8 (50%)</p> </td><td align="center" class="Botrule Lrule" valign="middle"> <p class="First">13 (81%)</p> </td> </tr> </tbody> </table></div>

Azithromycin for Injection, USP is supplied as white to off-white lyophilized powder in a single-dose ADD-Vantage® vial equivalent to 500 mg of azithromycin for intravenous administration.

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These are packaged as follows:

{ "type": "p", "children": [], "text": "These are packaged as follows:" }

<div class="scrollingtable"><table width="100%"> <col width="50%"/> <col width="50%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Unit of Sale</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">Concentration</span></th> </tr> </thead> <tbody> <tr class="First Last"> <td class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">NDC 0409-0144-11</span> <br/>Tray containing 10 single-dose ADD-Vantage<span class="Sup">®</span> vials</p> </td><td class="Botrule Rrule Toprule" valign="middle"> <p class="First">500 mg/vial</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"50%\"/>\n<col width=\"50%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Botrule Lrule Rrule Toprule\" valign=\"middle\"><span class=\"Bold\">Unit of Sale</span></th><th align=\"left\" class=\"Botrule Rrule Toprule\" valign=\"middle\"><span class=\"Bold\">Concentration</span></th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">NDC 0409-0144-11</span>\n<br/>Tray containing 10 single-dose ADD-Vantage<span class=\"Sup\">®</span> vials</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"middle\">\n<p class=\"First\">500 mg/vial</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Store the lyophilized cake at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

{ "type": "p", "children": [], "text": "Store the lyophilized cake at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]" }

Patients should be informed of the following serious and potentially serious adverse reactions that have been associated with Azithromycin for Injection:

{ "type": "p", "children": [], "text": "Patients should be informed of the following serious and potentially serious adverse reactions that have been associated with Azithromycin for Injection:" }

Diarrhea: Inform patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should notify their physician as soon as possible.

{ "type": "p", "children": [], "text": "\nDiarrhea: Inform patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should notify their physician as soon as possible.\n" }

Distributed by Hospira, Inc., Lake Forest, IL 60045 USA

{ "type": "p", "children": [], "text": "Distributed by Hospira, Inc., Lake Forest, IL 60045 USA" }

LAB-1012-7.0

{ "type": "p", "children": [], "text": "LAB-1012-7.0" }

Single-doseADD-Vantage® Vial

{ "type": "p", "children": [], "text": "Single-doseADD-Vantage® Vial" }

NDC 0409-0144-21Rx only

{ "type": "p", "children": [], "text": "NDC 0409-0144-21Rx only" }

Azithromycinfor Injection, USP

{ "type": "p", "children": [], "text": "Azithromycinfor Injection, USP" }

500 mg/vial

{ "type": "p", "children": [], "text": "500 mg/vial" }

For Intravenous Use

{ "type": "p", "children": [], "text": " For Intravenous Use" }

Sterile

{ "type": "p", "children": [], "text": "Sterile" }

Distributed by Hospira, Inc.Lake Forest, IL 60045 USA

{ "type": "p", "children": [], "text": "Distributed by Hospira, Inc.Lake Forest, IL 60045 USA" }

Hospira

{ "type": "p", "children": [], "text": "Hospira" }

10 Single-dose ADD-Vantage® VialsRx only

{ "type": "p", "children": [], "text": "10 Single-dose ADD-Vantage® VialsRx only" }

NDC 0409-0144-11Contains 10 of NDC 0409-0144-21

{ "type": "p", "children": [], "text": "NDC 0409-0144-11Contains 10 of NDC 0409-0144-21" }

Azithromycinfor Injection, USP

{ "type": "p", "children": [], "text": "Azithromycinfor Injection, USP" }

500 mg/vial

{ "type": "p", "children": [], "text": "500 mg/vial" }

For Intravenous Use

{ "type": "p", "children": [], "text": " For Intravenous Use " }

Sterile

{ "type": "p", "children": [], "text": "Sterile" }

500 mg/vial

{ "type": "p", "children": [], "text": "500 mg/vial" }

Hospira

{ "type": "p", "children": [], "text": "Hospira" }

Azithromycin tablets are a macrolide antibacterial drug indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. Recommended dosages and durations of therapy in adult and pediatric patient populations vary in these indications. [see DOSAGE AND ADMINISTRATION ( 2)]

[see USE IN SPECIFIC POPULATIONS ( 8.4) and CLINICAL STUDIES ( 14.2)]

Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following:

To reduce the development of drug-resistant bacteria and maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

[see INDICATIONS AND USAGE ( 1.1) and CLINICAL PHARMACOLOGY ( 12.3)]

<div class="scrollingtable"><table class="Noautorules" width="0"> <caption> <span></span> </caption> <col width="247"/> <col width="385"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Infection*</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">Recommended Dose/Duration of Therapy</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Community-acquired pneumonia Pharyngitis/tonsillitis (second-line therapy) Skin/skin structure (uncomplicated) <br/> </td><td align="left" class="Botrule Rrule">500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Acute bacterial exacerbations of chronic obstructive pulmonary disease <br/> </td><td align="left" class="Botrule Rrule">500 mg once daily for 3 days <br/> OR <br/> 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Acute bacterial sinusitis <br/> </td><td align="left" class="Botrule Rrule">500 mg once daily for 3 days <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Genital ulcer disease (chancroid) <br/> </td><td align="left" class="Botrule Rrule">One single 1 gram dose <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Non-gonococcal urethritis and cervicitis <br/> </td><td align="left" class="Botrule Rrule">One single 1 gram dose <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Gonococcal urethritis and cervicitis <br/> </td><td align="left" class="Botrule Rrule">One single 2 gram dose <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="2">*DUE TO THE INDICATED ORGANISMS <span class="Italics">[see INDICATIONS AND USAGE ( <a href="#ID134">1.1</a>)] </span> <br/> </td> </tr> </tbody> </table></div>

Azithromycin tablets can be taken with or without food.

<div class="scrollingtable"><table width="100%"> <col width="30%"/> <col width="70%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Infection</span><span class="Bold">* </span> <br/> </td><td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Recommended </span><span class="Bold">Dose</span><span class="Bold">/</span><span class="Bold">Duration </span><span class="Bold">of </span><span class="Bold">Therapy </span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Acute otitis media  <br/> </td><td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">30 mg/kg as a single dose or 10 mg/kg once daily for 3 days or 10 mg/kg as a single dose on Day 1 followed by 5 mg/kg/day on Days 2 through 5.  <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Acute bacterial sinusitis  <br/> </td><td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">10 mg/kg once daily for 3 days.  <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Community-acquired pneumonia  <br/> </td><td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">10 mg/kg as a single dose on Day 1 followed by 5 mg/kg once daily on Days 2 through 5.  <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Pharyngitis/tonsillitis  <br/> </td><td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">12 mg/kg once daily for 5 days.  <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" colspan="2" valign="middle">*DUE TO THE INDICATED ORGANISMS [see INDICATIONS AND USAGE ( <a href="#ID136">1.2</a>)] </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule" colspan="2" valign="middle"><span class="Italics"><span class="Sup">1</span>  </span><span class="Italics">see </span><span class="Italics">dosing </span><span class="Italics">tables </span><span class="Italics">below </span><span class="Italics">for </span><span class="Italics">maximum </span><span class="Italics">doses </span><span class="Italics">evaluated </span><span class="Italics">by </span><span class="Italics">indication </span> <br/> </td> </tr> </tbody> </table></div>

Azithromycin for oral suspension can be taken with or without food.

<div class="scrollingtable"><table class="Noautorules" width="624"> <caption> <span>PEDIATRIC DOSAGE GUIDELINES FOR OTITIS MEDIA, ACUTE BACTERIAL SINUSITIS, AND COMMUNITY-ACQUIRED PNEUMONIA (Age 6 months and above, [see USE IN SPECIFIC POPULATIONS (8.4)] ) Based on Body Weight</span> </caption> <col width="78"/> <col width="90"/> <col width="90"/> <col width="100"/> <col width="104"/> <col width="78"/> <col width="84"/> <tfoot> <tr> <td align="left" colspan="7"> <p class="First Footnote"> <span class="Bold">*</span>Effectiveness of the 3-day or 1-day regimen in pediatric patients with community-acquired pneumonia has not been established. </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="7"><span class="Bold">OTITIS MEDIA AND COMMUNITY-ACQUIRED PNEUMONIA: (5-Day Regimen)*</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Dosing Calculated on 10 mg/kg/day Day 1 and 5 mg/kg/day Days 2 to 5.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule" colspan="2"><span class="Bold">100 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" colspan="2"><span class="Bold">200 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mL per Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mg per Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days 2 to 5</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days 2 to 5</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td align="center" class="Botrule Rrule">1.25 mL;(¼ tsp) <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL <br/> </td><td align="center" class="Botrule Rrule">150 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">5 mL; (1tsp) <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">300 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">20 <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">5 mL; (1 tsp) <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">600 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">30 <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL; (1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">3.75 mL; (¾ tsp) <br/> </td><td align="center" class="Botrule Rrule">22.5 mL <br/> </td><td align="center" class="Botrule Rrule">900 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">10 mL; (2 tsp) <br/> </td><td align="center" class="Botrule Rrule">5 mL;(1 tsp) <br/> </td><td align="center" class="Botrule Rrule">30 mL <br/> </td><td align="center" class="Botrule Rrule">1200 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">50 and above <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">12.5 mL; (2½ tsp) <br/> </td><td align="center" class="Botrule Rrule">6.25 mL; (1¼ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="617"> <caption> <span></span> </caption> <col width="102"/> <col width="128"/> <col width="120"/> <col width="144"/> <col width="123"/> <tfoot> <tr> <td align="left" colspan="5"> <p class="First Footnote"> <span class="Bold">*</span>Effectiveness of the 5-day or 1-day regimen in pediatric patients with acute bacterial sinusitis has not been established. </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="5"><span class="Bold">OTITIS MEDIA AND ACUTE BACTERIAL SINUSITIS: (3-Day Regimen)*</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Dosing Calculated on 10 mg/kg/day.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">100 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">200 mg/5 mL</span> <br/> </td><td class="Rrule"></td><td class="Rrule"></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days 1 to 3</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Days 1 to 3</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Total mL per</span> <br/> <span class="Bold">Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Total mg per Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (1/2 tsp) <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL <br/> </td><td align="center" class="Botrule Rrule">150 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">5 mL; (1 tsp) <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">300 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">20 <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">5 mL (1 tsp) <br/> </td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">600 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">30 <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">7.5 mL (1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">22.5 mL <br/> </td><td align="center" class="Botrule Rrule">900 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">10 mL (2 tsp) <br/> </td><td align="center" class="Botrule Rrule">30 mL <br/> </td><td align="center" class="Botrule Rrule">1200 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">50 and above <br/> </td><td class="Botrule Rrule"></td><td align="center" class="Botrule Rrule">12.5 mL (2 ½ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table class="Noautorules" width="617"> <caption> <span></span> </caption> <col width="120"/> <col width="173"/> <col width="190"/> <col width="134"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="4"><span class="Bold">OTITIS MEDIA: (1-Day Regimen)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="4"><span class="Bold">Dosing Calculated on 30 mg/kg as a single dose.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">200 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mL per Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mg per Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">1-Day Regimen</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">3.75 mL;(3/4 tsp) <br/> </td><td align="center" class="Botrule Rrule">3.75 mL <br/> </td><td align="center" class="Botrule Rrule">150 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">7.5 mL;(1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">7.5 mL <br/> </td><td align="center" class="Botrule Rrule">300 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">20 <br/> </td><td align="center" class="Botrule Rrule">15 mL;(3 tsp) <br/> </td><td align="center" class="Botrule Rrule">15 mL <br/> </td><td align="center" class="Botrule Rrule">600 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">30 <br/> </td><td align="center" class="Botrule Rrule">22.5 mL;(4½ tsp) <br/> </td><td align="center" class="Botrule Rrule">22.5 mL <br/> </td><td align="center" class="Botrule Rrule">900 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td align="center" class="Botrule Rrule">30 mL;(6 tsp) <br/> </td><td align="center" class="Botrule Rrule">30 mL <br/> </td><td align="center" class="Botrule Rrule">1200 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">50 and above <br/> </td><td align="center" class="Botrule Rrule">37.5 mL;(7½ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> </tbody> </table></div>

The safety of re-dosing azithromycin in pediatric patients who vomit after receiving 30 mg/kg as a single dose has not been established. In clinical studies involving 487 patients with acute otitis media given a single 30 mg/kg dose of azithromycin, 8 patients who vomited within 30 minutes of dosing were re-dosed at the same total dose.

Pharyngitis/Tonsillitis

The recommended dose of azithromycin for children with pharyngitis/tonsillitis is 12 mg/kg once daily for 5 days. (See chart below.)

<div class="scrollingtable"><table class="Noautorules" width="617"> <caption> <span>PEDIATRIC DOSAGE GUIDELINES FOR PHARYNGITIS/TONSILLITIS (Age 2 years and above, [see USE IN SPECIFIC POPULATIONS (8.4)] ) Based on Body Weight</span> </caption> <col width="120"/> <col width="173"/> <col width="190"/> <col width="134"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="4"><span class="Bold">PHARYNGITIS/TONSILLITIS: (5-Day Regimen)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="4"><span class="Bold">Dosing Calculated on 12 mg/kg/day for 5 days.</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Weight</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">200 mg/5 mL</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mL per Treatment Course</span> <br/> </td><td align="center" class="Botrule Rrule" rowspan="2"><span class="Bold">Total mg per Treatment Course</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Kg</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">Day 1 to 5</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">2.5 mL; (½ tsp) <br/> </td><td align="center" class="Botrule Rrule">12.5 mL <br/> </td><td align="center" class="Botrule Rrule">500 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">17 <br/> </td><td align="center" class="Botrule Rrule">5 mL; (1 tsp) <br/> </td><td align="center" class="Botrule Rrule">25 mL <br/> </td><td align="center" class="Botrule Rrule">1000 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">25 <br/> </td><td align="center" class="Botrule Rrule">7.5 mL; (1½ tsp) <br/> </td><td align="center" class="Botrule Rrule">37.5 mL <br/> </td><td align="center" class="Botrule Rrule">1500 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">33 <br/> </td><td align="center" class="Botrule Rrule">10 mL; (2 tsp) <br/> </td><td align="center" class="Botrule Rrule">50 mL <br/> </td><td align="center" class="Botrule Rrule">2000 mg <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">40 <br/> </td><td align="center" class="Botrule Rrule">12.5 mL; (2½ tsp) <br/> </td><td align="center" class="Botrule Rrule">62.5 mL <br/> </td><td align="center" class="Botrule Rrule">2500 mg <br/> </td> </tr> </tbody> </table></div>

Constituting instructions for azithromycin oral suspension 300, 600, 900, 1200 mg bottles. The table below indicates the volume of water to be used for constitution:

<div class="scrollingtable"><table width="100%"> <col width="25%"/> <col width="36%"/> <col width="39%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Amount </span><span class="Bold">of </span><span class="Bold">water </span><span class="Bold">to </span><span class="Bold">be </span><span class="Bold">added </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Total </span><span class="Bold">volume </span><span class="Bold">after </span><span class="Bold">constitution </span><span class="Bold">(</span><span class="Bold">azithromycin </span><span class="Bold">content</span><span class="Bold">) </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Azithromycin </span><span class="Bold">concentration </span><span class="Bold">after </span><span class="Bold">constitution </span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">9 mL (300 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">15 mL (300 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">100 mg/5 mL  <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">9 mL (600 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">15 mL (600 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">200 mg/5 mL  <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">12 mL (900 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">22.5 mL (900 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">200 mg/5 mL  <br/> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">15 mL (1200 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">30 mL (1200 mg)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">200 mg/5 mL  <br/> </td> </tr> </tbody> </table></div>

Shake well before each use. Oversized bottle provides shake space. Keep tightly closed.

After mixing, store suspension at 5° to 30°C (41° to 86°F) and use within 10 days. Discard after full dosing is completed.

Azithromycin Tablets, 250 mg are supplied as pink, oval shaped film-coated tablets, engraved with "LU" on one side and "L04" on the other side containing azithromycin dihydrate equivalent to 250 mg of azithromycin USP.

Azithromycin Tablets, 500 mg are supplied as pink, oval shaped film-coated tablets, engraved with "LU" on one side and "L05" on the other side containing azithromycin dihydrate equivalent to 500 mg of azithromycin USP.

Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide drug.

Azithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin.

Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported in patients on azithromycin therapy. [see CONTRAINDICATIONS ( 4.1)]

Fatalities have been reported. Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment. The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is presently unknown.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that allergic symptoms may reappear when symptomatic therapy has been discontinued.

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported. Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen with treatment with macrolides, including azithromycin. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin. Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including:

Elderly patients may be more susceptible to drug-associated effects on the QT interval.

Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. The five-day cardiovascular mortality observed in these studies ranged from 20 to 400 per million azithromycin treatment courses. This potential risk was noted to be greater during the first five days of azithromycin use and does not appear to be limited to those patients with preexisting cardiovascular diseases. The data in these observational studies are insufficient to establish or exclude a causal relationship between acute cardiovascular death and azithromycin use. Consider balancing this potential risk with treatment benefits when prescribing Azithromycin tablets.

Clostridioides difficile-associated diarrhea has been reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficilecause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy.

Azithromycin, at the recommended dose, should not be relied upon to treat syphilis. Antibacterial agents used to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually transmitted urethritis or cervicitis should have a serologic test for syphilis and appropriate testing for gonorrhea performed at the time of diagnosis. Appropriate antibacterial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.

Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious adverse reactions of angioedema and cholestatic jaundice were reported. Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related adverse reactions. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related adverse reactions was 0.6%. In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related adverse reactions was approximately 1%. Most of the adverse reactions leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. [see CLINICAL STUDIES ( 14.2)]

Adults

Multiple-dose regimens: Overall, the most common treatment-related adverse reactions in adult patients receiving multiple-dose regimens of azithromycin were related to the gastrointestinal system with diarrhea/loose stools (4 to 5%), nausea (3%), and abdominal pain (2 to 3%) being the most frequently reported.

No other adverse reactions occurred in patients on the multiple-dose regimens of azithromycin with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following:

Cardiovascular:

Palpitations, chest pain.

Gastrointestinal:

Dyspepsia, flatulence, vomiting, melena, and cholestatic jaundice.

Genitourinary:

Monilia, vaginitis, and nephritis.

Nervous System:

Dizziness, headache, vertigo, and somnolence.

General:

Fatigue.

Allergic:

Rash, pruritus, photosensitivity, and angioedema.

Single 1-gram dose regimen:

Overall, the most common adverse reactions in patients receiving a single-dose regimen of 1 gram of azithromycin were related to the gastrointestinal system and were more frequently reported than in patients receiving the multiple-dose regimen.

Adverse reactions that occurred in patients on the single 1-gram dosing regimen of azithromycin with a frequency of 1% or greater included diarrhea/loose stools (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), and vaginitis (1%).

Single 2-gram dose regimen:

Overall, the most common adverse reactions in patients receiving a single 2-gram dose of azithromycin were related to the gastrointestinal system. Adverse reactions that occurred in patients in this study with a frequency of 1% or greater included nausea (18%), diarrhea/loose stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%), and dizziness (1%). The majority of these complaints were mild in nature.

Pediatric Patients

Single and Multiple-dose regimens: The types of adverse reactions in pediatric patients were comparable to those seen in adults, with different incidence rates for the dosage regimens recommended in pediatric patients.

Acute Otitis Media:

For the recommended total dosage regimen of 30 mg/kg, the most frequent adverse reactions (≥1%) attributed to treatment were diarrhea, abdominal pain, vomiting, nausea, and rash. [see DOSAGE AND ADMINISTRATION ( 2) and CLINICAL STUDIES ( 14.2)]  

The incidence, based on dosing regimen, is described in the table below:

<div class="scrollingtable"><table width="100%"> <col width="12%"/> <col width="15%"/> <col width="21%"/> <col width="16%"/> <col width="16%"/> <col width="20%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Dosage </span><span class="Bold">Regimen</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Diarrhea </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Abdominal </span><span class="Bold">Pain </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Vomiting </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Nausea </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Rash </span><span class="Bold">%</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">1-day <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">4.3% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.4% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">4.9% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.0% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.0% <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">3-day <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2.6% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.7% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2.3% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.4% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.6% <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">5-day <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.8% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.2% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.1% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.5% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.4% <br/> </td> </tr> </tbody> </table></div>

Community-Acquired Pneumonia:

For the recommended dosage regimen of 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5, the most frequent adverse reactions attributed to treatment were diarrhea/loose stools, abdominal pain, vomiting, nausea, and rash.

The incidence is described in the table below:

<div class="scrollingtable"><table width="100%"> <col width="18%"/> <col width="23%"/> <col width="20%"/> <col width="15%"/> <col width="13%"/> <col width="11%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Dosage </span><span class="Bold">Regimen</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Diarrhea</span><span class="Bold">/</span><span class="Bold">Loose </span><span class="Bold">stools </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Abdominal </span><span class="Bold">Pain </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Vomiting </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Nausea </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Rash </span><span class="Bold">%</span> <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">5-day <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5.8% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.9% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.9% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.9% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.6% <br/> </td> </tr> </tbody> </table></div>

Pharyngitis/Tonsillitis:

For the recommended dosage regimen of 12 mg/kg on Days 1 to 5, the most frequent adverse reactions attributed to treatment were diarrhea, vomiting, abdominal pain, nausea, and headache.

The incidence is described in the table below:

<div class="scrollingtable"><table width="99%"> <col width="13%"/> <col width="15%"/> <col width="20%"/> <col width="14%"/> <col width="13%"/> <col width="10%"/> <col width="14%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Dosage </span><span class="Bold">Regimen</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Diarrhea </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Abdominal </span><span class="Bold">Pain </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Vomiting </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Nausea </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Rash </span><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Headache </span><span class="Bold">%</span> <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">5-day <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5.4% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">3.4% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5.6% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.8% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.7% <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.1% <br/> </td> </tr> </tbody> </table></div>

With any of the treatment regimens, no other adverse reactions occurred in pediatric patients treated with azithromycin with a frequency greater than 1%. Adverse reactions that occurred with a frequency of 1% or less included the following:

Cardiovascular:

Chest pain.

Gastrointestinal:

Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools, and oral moniliasis.

Hematologic and Lymphatic:

Anemia and leukopenia.

Nervous System:

Headache (otitis media dosage), hyperkinesia, dizziness, agitation, nervousness, and insomnia.

General:

Fever, face edema, fatigue, fungal infection, malaise, and pain.

Allergic:

Rash and allergic reaction.

Respiratory:

Cough, pharyngitis, pleural effusion, and rhinitis.

Skin and Appendages:

Eczema, fungal dermatitis, pruritus, sweating, urticaria, and vesiculobullous rash.

Special Senses:

Conjunctivitis.

The following adverse reactions have been identified during post-approval use of azithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported with azithromycin during the postmarketing period in adult and/or pediatric patients for which a causal relationship may not be established include:

Allergic:

Arthralgia, edema, urticaria, and angioedema.

Cardiovascular:

Arrhythmias including ventricular tachycardia and hypotension. There have been reports of QT prolongation, torsades de pointes and cardiovascular death.

Gastrointestinal:

Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and reports of tongue discoloration.

General:

Asthenia, paresthesia, fatigue, malaise, and anaphylaxis.

Genitourinary:

Interstitial nephritis and acute renal failure and vaginitis.

Hematopoietic:

Thrombocytopenia.

Liver/Biliary:

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure. [ see WARNINGS AND PRECAUTIONS ( 5.2)]

Nervous System:

Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation, and syncope.

Psychiatric:

Aggressive reaction and anxiety.

Skin/Appendages:

Pruritus serious skin reactions including erythema multiforme, AGEP, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and DRESS

Special Senses:

Hearing disturbances including hearing loss, deafness and/or tinnitus, and reports of taste/smell perversion and/or loss.

Adults

Clinically significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows: with an incidence of greater than 1%: decreased hemoglobin, hematocrit, lymphocytes, neutrophils, and blood glucose; elevated serum creatine phosphokinase, potassium, ALT, GGT, AST, BUN, creatinine, blood glucose, platelet count, lymphocytes, neutrophils, and eosinophils; with an incidence of less than 1%: leukopenia, neutropenia, decreased sodium, potassium, platelet count, elevated monocytes, basophils, bicarbonate, serum alkaline phosphatase, bilirubin, LDH, and phosphate. The majority of subjects with elevated serum creatinine also had abnormal values at baseline. When follow-up was provided, changes in laboratory tests appeared to be reversible.

In multiple-dose clinical trials involving more than 5000 patients, four patients discontinued therapy because of treatment-related liver enzyme abnormalities and one because of a renal function abnormality.

Pediatric Patients

One, Three, and Five Day Regimens:

Laboratory data collected from comparative clinical trials employing two 3-day regimens (30 mg/kg or 60 mg/kg in divided doses over 3 days), or two 5-day regimens (30 mg/kg or 60 mg/kg in divided doses over 5 days) were similar for regimens of azithromycin and all comparators combined, with most clinically significant laboratory abnormalities occurring at incidences of 1 to 5%. Laboratory data for patients receiving 30 mg/kg as a single dose were collected in one single center trial. In that trial, an absolute neutrophil count between 500 to 1500 cells/mm 3was observed in 10/64 patients receiving 30 mg/kg as a single dose, 9/62 patients receiving 30 mg/kg given over 3 days, and 8/63 comparator patients. No patient had an absolute neutrophil count <500 cells/mm 3.

In multiple-dose clinical trials involving approximately 4700 pediatric patients, no patients discontinued therapy because of treatment-related laboratory abnormalities.

Co-administration of nelfinavir at steady-state with a single oral dose of azithromycin resulted in increased azithromycin serum concentrations. Although a dose adjustment of azithromycin is not recommended when administered in combination with nelfinavir, close monitoring for known adverse reactions of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted. [see ADVERSE REACTIONS ( 6)]

Spontaneous postmarketing reports suggest that concomitant administration of azithromycin may potentiate the effects of oral anticoagulants such as warfarin, although the prothrombin time was not affected in the dedicated drug interaction study with azithromycin and warfarin. Prothrombin times should be carefully monitored while patients are receiving azithromycin and oral anticoagulants concomitantly.

Interactions with digoxin, colchicine or phenytoin have not been reported in clinical trials with azithromycin. No specific drug interaction studies have been performed to evaluate potential drug-drug interaction. However, drug interactions have been observed with other macrolide products. Until further data are developed regarding drug interactions when digoxin, colchicine or phenytoin are used with azithromycin careful monitoring of patients is advised.

Risk Summary

Available data from published literature and postmarketing experience over several decades with azithromycin use in pregnant women have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Developmental toxicity studies with azithromycin in rats, mice, and rabbits showed no drug-induced fetal malformations at doses up to 4, 2, and 2 times, respectively, an adult human daily dose of 500 mg based on body surface area. Decreased viability and delayed development were observed in the offspring of pregnant rats administered azithromycin from day 6 of pregnancy through weaning at a dose equivalent to 4 times an adult human daily dose of 500 mg based on body surface area (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data:

Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with azithromycin use in pregnant women. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.

Animal Data:

Azithromycin administered during the period of organogenesis did not cause fetal malformations in rats and mice at oral doses up to 200 mg/kg/day (moderately maternally toxic). Based on body surface area, this dose is approximately 4 (rats) and 2 (mice) times an adult human daily dose of 500 mg. In rabbits administered azithromycin at oral doses of 10, 20, and 40 mg/kg/day during organogenesis, reduced maternal body weight and food consumption were observed in all groups; no evidence of fetotoxicity or teratogenicity was observed at these doses, the highest of which is estimated to be 2 times an adult human daily dose of 500 mg based on body surface area.

In a pre-and postnatal development study, azithromycin was administered orally to pregnant rats from day 6 of pregnancy until weaning at doses of 50 or 200 mg/kg/day. Maternal toxicity (reduced food consumption and body weight gain; increased stress at parturition) was observed at the higher dose. Effects in the offspring were noted at 200 mg/kg/day during the postnatal development period (decreased viability, delayed developmental landmarks). These effects were not observed in a pre-and postnatal rat study when up to 200 mg/kg/day of azithromycin was given orally beginning on day 15 of pregnancy until weaning.

Risk Summary

Azithromycin is present in human milk (see Data). Non-serious adverse reactions have been reported in breastfed infants after maternal administration of azithromycin (see Clinical Considerations). There are no available data on the effects of azithromycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for azithromycin and any potential adverse effects on the breastfed infant from azithromycin or from the underlying maternal condition.

Clinical Considerations

Advise women to monitor the breastfed infant for diarrhea, vomiting, or rash.

Data

Azithromycin breastmilk concentrations were measured in 20 women after receiving a single 2 g oral dose of azithromycin during labor. Breastmilk samples collected on days 3 and 6 postpartum as well as 2 and 4 weeks postpartum revealed the presence of azithromycin in breastmilk up to 4 weeks after dosing. In another study, a single dose of azithromycin 500 mg was administered intravenously to 8 women prior to incision for cesarean section. Breastmilk (colostrum) samples obtained between 12 and 48 hours after dosing revealed that azithromycin persisted in breastmilk up to 48 hours.

[see CLINICAL PHARMACOLOGY ( 12.3), INDICATIONS AND USAGE ( 1.2), and DOSAGE AND ADMINISTRATION ( 2.2)]

Safety and effectiveness in the treatment of pediatric patients with acute otitis media, acute bacterial sinusitis and community-acquired pneumonia under 6 months of age have not been established. Use of azithromycin for the treatment of acute bacterial sinusitis and community-acquired pneumonia in pediatric patients (6 months of age or greater) is supported by adequate and well-controlled trials in adults.

Pharyngitis/Tonsillitis

Safety and effectiveness in the treatment of pediatric patients with pharyngitis/tonsillitis under 2 years of age have not been established.

In multiple-dose clinical trials of oral azithromycin, 9% of patients were at least 65 years of age (458/4949) and 3% of patients (144/4949) were at least 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients . [see WARNINGS AND PRECAUTIONS ( 5.4)]  

Adverse reactions experienced at higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea, and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required.

{ "type": "p", "children": [], "text": "\nAdverse reactions experienced at higher than recommended doses were similar to those seen at normal doses particularly nausea, diarrhea, and vomiting. In the event of overdosage, general symptomatic and supportive measures are indicated as required." }

Azithromycin tablets USP contain the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl) oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C 38H 72N 2O 12, and its molecular weight is 749.00. Azithromycin has the following structural formula:

{ "type": "p", "children": [], "text": "\nAzithromycin tablets USP contain the active ingredient azithromycin, a macrolide antibacterial drug, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl) oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is C\n \n 38H\n \n 72N\n \n 2O\n \n 12, and its molecular weight is 749.00. Azithromycin has the following structural formula:\n\n " }

Azithromycin, as the dihydrate, is a white to almost white crystalline powder with a molecular formula of C 38H 72N 2O 12•2H 2O and a molecular weight of 785.02.

{ "type": "p", "children": [], "text": "\nAzithromycin, as the dihydrate, is a white to almost white crystalline powder with a molecular formula of C\n \n 38H\n \n 72N\n \n 2O\n \n 12•2H\n \n 2O and a molecular weight of 785.02.\n\n " }

Azithromycin is supplied as tablets containing azithromycin dihydrate equivalent to either 250 mg or 500 mg azithromycin and the following inactive ingredients: croscarmellose sodium, dibasic calcium phosphate, hydroxypropyl methyl cellulose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, titanium dioxide, triacetin and D&C Red #30.

{ "type": "p", "children": [], "text": "Azithromycin is supplied as tablets containing azithromycin dihydrate equivalent to either 250 mg or 500 mg azithromycin and the following inactive ingredients: croscarmellose sodium, dibasic calcium phosphate, hydroxypropyl methyl cellulose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, titanium dioxide, triacetin and D&C Red #30." }

Organic Impurities Test Pending.

{ "type": "p", "children": [], "text": "Organic Impurities Test Pending." }

Azithromycin is a macrolide antibacterial drug. [see Microbiology ( 12.4)]

Based on animal models of infection, the antibacterial activity of azithromycin appears to correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for certain pathogens ( S. pneumoniaeand S. aureus). The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with azithromycin.

Cardiac Electrophysiology

QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with oral azithromycin (500 mg, 1000 mg, and 1500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration- dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1000 mg and 1500 mg azithromycin, respectively.

Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC 0-72=4.3 (1.2) mcg·hr/mL; C max=0.5 (0.2) mcg/mL; T max=2.2 (0.9) hours. Two azithromycin 250 mg tablets are bioequivalent to a single 500 mg tablet.

In a two-way crossover study, 12 adult healthy volunteers (6 males, 6 females) received 1500 mg of azithromycin administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2 to 5) or 3 days (500 mg per day for days 1 to 3). Due to limited serum samples on day 2 (3-day regimen) and days 2 to 4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC 0-∞for the fitted concentration profile was comparable between the 5-day and 3-day regimens.

<div class="scrollingtable"><table width="100%"> <col width="32%"/> <col width="16%"/> <col width="18%"/> <col width="17%"/> <col width="17%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="5"> <p class="First Footnote">*Total AUC for the entire 3-day and 5-day regimens. <br/> </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="1" valign="top"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">3</span><span class="Bold">-</span><span class="Bold">Day </span><span class="Bold">Regimen </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">5</span><span class="Bold">-</span><span class="Bold">Day </span><span class="Bold">Regimen </span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Pharmacokinetic </span><span class="Bold">Parameter </span><span class="Bold">[</span><span class="Bold">mean </span><span class="Bold">(</span><span class="Bold">SD</span><span class="Bold">)] </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">1 </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">3 </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">1 </span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">5 </span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top">C <span class="Sub">m</span><span class="Sub">a</span><span class="Sub">x</span> (serum, mcg/mL)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.44 (0.22)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.54 (0.25)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.43 (0.20)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.24 (0.06)  <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="1" valign="top">Serum AUC  <span class="Sub">0</span><span class="Sub">-</span><span class="Sub">∞</span> (mcg·hr/mL)  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top">17.4 (6.2)*  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top">14.9 (3.1)*  <br/> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="1" valign="top">Serum T  <span class="Sub">1</span><span class="Sub">/</span><span class="Sub">2</span>  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top">71.8 hr  <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top">68.9 hr  <br/> </td> </tr> </tbody> </table></div>

Absorption

The absolute bioavailability of azithromycin 250 mg capsules is 38%.

In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high fat meal, food was shown to increase

C maxby 23% but had no effect on AUC.

When azithromycin oral suspension was administered with food to 28 adult healthy male subjects, C maxincreased by 56% and AUC was unchanged.

Distribution

The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg/mL to 7% at 2 mcg/mL.

The antibacterial activity of azithromycin is pH related and appears to be reduced with decreasing pH, However, the extensive distribution of drug to tissues may be relevant to clinical activity.

Azithromycin has been shown to penetrate into human tissues, including skin, lung, tonsil, and cervix. Extensive tissue distribution was confirmed by examination of additional tissues and fluids (bone, ejaculum, prostate, ovary, uterus, salpinx, stomach, liver, and gallbladder). As there are no data from adequate and well-controlled studies of azithromycin treatment of infections in these additional body sites, the clinical significance of these tissue concentration data is unknown.

Following a regimen of 500 mg on the first day and 250 mg daily for 4 days, very low concentrations were noted in cerebrospinal fluid (less than 0.01 mcg/mL) in the presence of noninflamed meninges.

Metabolism

In vitroand in vivostudies to assess the metabolism of azithromycin have not been performed.

Elimination

Plasma concentrations of azithromycin following single 500 mg oral and IV doses declined in a polyphasic pattern resulting in a mean apparent plasma clearance of 630 mL/min and terminal elimination half-life of 68hr. The prolonged terminal half-life is thought to be due to extensive uptake and subsequent release of drug from tissues. Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.

Specific Populations

Patients with Renal Impairment:

Azithromycin pharmacokinetics was investigated in 42 adults (21 to 85 years of age) with varying degrees of renal impairment. Following the oral administration of a single 1.0 g dose of azithromycin (4 x 250 mg capsules), mean C maxand AUC 0-120increased by 5.1% and 4.2%, respectively, in subjects with mild to moderate renal impairment (GFR 10 to 80 mL/min) compared to subjects with normal renal function (GFR >80 mL/min). The mean C maxand AUC 0-120increased 61% and 35%, respectively, in subjects with severe renal impairment (GFR <10 mL/min) compared to subjects with normal renal function (GFR >80 mL/min).

Patients with Hepatic Impairment:  

The pharmacokinetics of azithromycin in subjects with hepatic impairment has not been established.

Male and Female Patients:

There are no significant differences in the disposition of azithromycin between male and female subjects. No dosage adjustment is recommended based on gender.

Geriatric Patients: 

Pharmacokinetic parameters in older volunteers (65 to 85 years old) were similar to those in young adults (18 to 40 years old) for the 5-day therapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen. [see Geriatric Use ( 8.5)]

Pediatric Patients: 

In two clinical studies, azithromycin for oral suspension was dosed at 10 mg/kg on day 1, followed by 5 mg/kg on days 2 through 5 in two groups of pediatric patients (aged 1 to 5 years and 5 to 15 years, respectively). The mean pharmacokinetic parameters on day 5 were C max=0.216 mcg/mL, T max=1.9 hr, and AUC 0-24=1.822 mcg·hr/mL for the 1 to 5-year-old group and were C max=0.383 mcg/mL, T max=2.4 hr, and AUC 0-24=3.109 mcg·hr/mL for the 5 to 15-year-old group.

In another study, 33 pediatric patients received doses of 12 mg/kg/day (maximum daily dose 500 mg) for 5 days, of whom 31 patients were evaluated for azithromycin pharmacokinetics following a low fat breakfast. In this study, azithromycin concentrations were determined over a 24 hr period following the last daily dose. Patients weighing above 41.7 kg received the maximum adult daily dose of 500 mg. Seventeen patients (weighing 41.7 kg or less) received a total dose of 60 mg/kg. The following table shows pharmacokinetic data in the subset of pediatric patients who received a total dose of 60 mg/kg.

<div class="scrollingtable"><table width="100%"> <col width="52%"/> <col width="48%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Pharmacokinetic </span><span class="Bold">Parameter </span><span class="Bold"> <br/> </span><span class="Bold">[</span><span class="Bold">mean </span><span class="Bold">(</span><span class="Bold">SD</span><span class="Bold">)]</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">5</span><span class="Bold">-</span><span class="Bold">Day </span><span class="Bold">Regimen </span><span class="Bold"> <br/> </span><span class="Bold">(</span><span class="Bold">12 </span><span class="Bold">mg</span><span class="Bold">/</span><span class="Bold">kg </span><span class="Bold">for </span><span class="Bold">5 </span><span class="Bold">days</span><span class="Bold">)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">N</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">17</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">C <span class="Sub">m</span><span class="Sub">a</span><span class="Sub">x</span> (mcg/mL) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.5 (0.4) <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">T <span class="Sub">m</span><span class="Sub">a</span><span class="Sub">x</span> (hr) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2.2 (0.8) <br/> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">AUC  <span class="Sub">0</span><span class="Sub">-</span><span class="Sub">2</span><span class="Sub">4</span>(mcg⋅hr/mL) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">3.9 (1.9) <br/> </td> </tr> </tbody> </table></div>

Single dose pharmacokinetics of azithromycin in pediatric patients given doses of 30 mg/kg have not been studied. [see DOSAGE AND ADMINISTRATION ( 2)]  

Drug Interaction Studies

Drug interaction studies were performed with azithromycin and other drugs likely to be co-administered. The effects of co -administration of azithromycin on the pharmacokinetics of other drugs are shown in Table 1 and the effects of other drugs on the pharmacokinetics of azithromycin are shown in Table 2.

Co-administration of azithromycin at therapeutic doses had a modest effect on the pharmacokinetics of the drugs listed in Table 1. No dosage adjustment of drugs listed in Table 1 is recommended when co-administered with azithromycin.

Co-administration of azithromycin with efavirenz or fluconazole had a modest effect on the pharmacokinetics of azithromycin. Nelfinavir significantly increased the C maxand AUC of azithromycin. No dosage adjustment of azithromycin is recommended when administered with drugs listed in Table 2. [see DRUG INTERACTIONS ( 7.3)]  

<div class="scrollingtable"><table width="100%"> <col width="15%"/> <col width="18%"/> <col width="24%"/> <col width="7%"/> <col width="19%"/> <col width="17%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6"> <p class="First Footnote">* -90% Confidence interval not reported <br/> </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="6" valign="middle"><span class="Bold">Table </span><span class="Bold">1</span><span class="Bold">. </span><span class="Bold">Drug </span><span class="Bold">Interactions</span><span class="Bold">: </span><span class="Bold">Pharmacokinetic </span><span class="Bold">Parameters </span><span class="Bold">for </span><span class="Bold">Co</span><span class="Bold">-</span><span class="Bold">administered </span><span class="Bold">Drugs </span><span class="Bold">in </span><span class="Bold">the </span><span class="Bold">Presence </span><span class="Bold">of </span><span class="Bold">Azithromycin</span> <br/> </td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">Co</span><span class="Bold">-</span><span class="Bold">administered </span><span class="Bold">Drug</span> <br/> </td><td align="center" class="Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">Dose </span><span class="Bold">of </span><span class="Bold">Co</span><span class="Bold">-</span><span class="Bold">administered </span><span class="Bold">Drug</span> <br/> </td><td align="center" class="Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">Dose </span><span class="Bold">of </span><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Lrule Rrule Toprule" colspan="1" valign="middle">n <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">Ratio </span><span class="Bold">(</span><span class="Bold">with</span><span class="Bold">/</span><span class="Bold">without </span><span class="Bold">azithromycin</span><span class="Bold">) </span><span class="Bold">of </span><span class="Bold"> <br/> </span><span class="Bold">Co</span><span class="Bold">-</span><span class="Bold">administered </span><span class="Bold">Drug </span><span class="Bold">Pharmacokinetic </span><span class="Bold">Parameters </span><span class="Bold">(</span><span class="Bold">90</span><span class="Bold">% </span><span class="Bold">CI</span><span class="Bold">); </span><span class="Bold">No </span><span class="Bold">Effect </span><span class="Bold">= </span><span class="Bold">1</span><span class="Bold">.</span><span class="Bold">00</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Mean </span><span class="Bold">C <span class="Sub">m</span><span class="Sub">a</span><span class="Sub">x</span></span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Mean </span><span class="Bold">AUC</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Atorvastatin <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">10 mg/day for 8 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg/day orally on days 6 to 8 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.83  <br/> (0.63 to 1.08) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.01  <br/> (0.81 to 1.25) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Carbamazepine <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">200 mg/day for 2 days, then 200 mg twice a day for 18 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg/day orally for days 16 to 18 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">7 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.97  <br/> (0.88 to 1.06) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.96  <br/> (0.88 to 1.06) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Cetirizine <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">20 mg/day for 11 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg orally on day 7, then 250 mg/day on days 8 to 11 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">14 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.03  <br/> (0.93 to 1.14) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.02  <br/> (0.92 to 1.13) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Didanosine <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">200 mg orally twice a day for 21 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1200 mg/day orally on days 8 to 21 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">6 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.44  <br/> (0.85 to 2.43) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.14  <br/> (0.83 to 1.57) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Efavirenz <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">400 mg/day for 7 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">600 mg orally on day 7 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">14 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.04* <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.95* <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Fluconazole <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">200 mg orally single dose <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1200 mg orally single dose <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">18 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.04  <br/> (0.98 to 1.11) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.01  <br/> (0.97 to 1.05) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Indinavir <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">800 mg three times a day for 5 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1200 mg orally on day 5 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">18 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.96  <br/> (0.86 to 1.08) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.90  <br/> (0.81 to 1.00) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Midazolam <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">15 mg orally on day 3 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg/day orally for 3 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.27  <br/> (0.89 to 1.81) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.26  <br/> (1.01 to 1.56) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Nelfinavir <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">750 mg three times a day for 11 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1,200 mg orally on day 9 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">14 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.90  <br/> (0.81 to 1.01) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.85  <br/> (0.78 to 0.93) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Sildenafil <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">100 mg on days 1 and 4 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg/day orally for 3 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.16  <br/> (0.86 to 1.57) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.92  <br/> (0.75 to 1.12) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Theophylline <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">4 mg/kg IV on days 1, 11, 25 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg orally on day 7, 250 mg/day on days 8 to 11 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">10 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.19  <br/> (1.02 to 1.40) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.02  <br/> (0.86 to 1.22) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Theophylline <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">300 mg orally twice a day for 15 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg orally on day 6, then 250 mg/day on days 7 to 10 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">8 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.09  <br/> (0.92 to 1.29) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.08  <br/> (0.89 to 1.31) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Triazolam <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.125 mg on day 2 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg orally on day 1, then 250 mg/day on day 2 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.06* <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.02* <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Trimethoprim/ Sulfamethoxazole <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">160 mg/800 mg/day orally for 7 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1200 mg orally on day 7 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.85 <br/> (0.75 to 0.97)/0.90 (0.78 to 1.03) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.87 (0.80 to 0.95/0.96  <br/> (0.88 to 1.03) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Zidovudine <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg/day orally for 21 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">600 mg/day orally for 14 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.12 <br/> (0.42 to 3.02) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.94  <br/> (0.52 to 1.70) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Zidovudine <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">500 mg/day orally for 21 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1200 mg/day orally for 14 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">4 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.31  <br/> (0.43 to 3.97) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.30  <br/> (0.69 to 2.43) <br/> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="101%"> <col width="15%"/> <col width="21%"/> <col width="23%"/> <col width="8%"/> <col width="17%"/> <col width="17%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="6"> <p class="First Footnote">* -90% Confidence interval not reported <br/> </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="6" valign="middle">Table 2. Drug Interactions: Pharmacokinetic Parameters for Azithromycin in the Presence of Co-administered Drugs. [see DRUG INTERACTIONS ( <a href="#ID209">7</a>)] </td> </tr> <tr> <td align="left" class="Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">Co</span><span class="Bold">-</span><span class="Bold">administered </span><span class="Bold">Drug</span> <br/> </td><td align="center" class="Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">Dose </span><span class="Bold">of </span><span class="Bold">Co</span><span class="Bold">-</span><span class="Bold">administered </span><span class="Bold">Drug</span> <br/> </td><td align="center" class="Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">Dose </span><span class="Bold">of </span><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">n</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">Ratio </span><span class="Bold">(</span><span class="Bold">with</span><span class="Bold">/</span><span class="Bold">without </span><span class="Bold">co</span><span class="Bold">-</span><span class="Bold">administered </span><span class="Bold">drug</span><span class="Bold">) </span><span class="Bold">of </span><span class="Bold">Azithromycin </span><span class="Bold">Pharmacokinetic </span><span class="Bold">Parameters </span><span class="Bold"> <br/> </span><span class="Bold">(</span><span class="Bold">90</span><span class="Bold">% </span><span class="Bold">CI</span><span class="Bold">); </span><span class="Bold">No </span><span class="Bold">Effect </span><span class="Bold">= </span><span class="Bold">1</span><span class="Bold">.</span><span class="Bold">00</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Mean </span><span class="Bold">C <span class="Sub">m</span><span class="Sub">a</span><span class="Sub">x</span></span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Mean </span><span class="Bold">AUC</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Efavirenz <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">400 mg/day for 7 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">600 mg orally on day 7 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">14 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.22  <br/> (1.04 to 1.42) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.92* <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Fluconazole <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">200 mg orally single dose <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1,200 mg orally single dose <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">18 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">0.82  <br/> (0.66 to 1.02) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1.07  <br/> (0.94 to 1.22) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Nelfinavir <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">750 mg three times a day for 11 days <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">1,200 mg orally on day 9 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">14 <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2.36  <br/> (1.77 to 3.15) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2.12  <br/> (1.80 to 2.50) <br/> </td> </tr> </tbody> </table></div>

Mechanism of Action

Azithromycin acts by binding to the 23S rRNA of the 50S ribosomal subunit of susceptible microorganisms inhibiting bacterial protein synthesis and impeding the assembly of the 50S ribosomal subunit.

Resistance

Azithromycin demonstrates cross resistance with erythromycin. The most frequently encountered mechanism of resistance to azithromycin is modification of the 23S rRNA target, most often by methylation. Ribosomal modifications can determine cross resistance to other macrolides, lincosamides, and streptogramin B (MLS Bphenotype).

Antimicrobial Activity

Azithromycin has been shown to be active against most isolates of the following microorganisms, both in vitroand in clinical infections. [see INDICATIONS AND USAGE ( 1)]  

Gram-Positive Bacteria

Staphylococcus aureus

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenes

Gram-Negative Bacteria

Haemophilus ducreyi

Haemophilus influenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

Other Bacteria

Chlamydophila pneumoniae

Chlamydia trachomatis

Mycoplasma pneumoniae

The following in vitrodata are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitrominimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for azithromycin against isolates of similar genus or organism group. However, the efficacy of azithromycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

Gram-Positive Bacteria

Beta-hemolytic streptococci (Groups C, F, G)

Viridans group streptococci

Gram-Negative Bacteria

Bordetella pertussis

Legionella pneumophila

Anaerobic Bacteria

Prevotella bivia

Peptostreptococcus species

Other Bacteria

Ureaplasma urealyticum

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. In fertility studies conducted in male and female rats, oral administration of azithromycin for 64 to 66 days (males) or 15 days (females) prior to and during cohabitation resulted in decreased pregnancy rate at 20 and 30 mg/kg/day when both males and females were treated with azithromycin. This minimal effect on pregnancy rate (approximately 12% reduction compared to concurrent controls) did not become more pronounced when the dose was increased from 20 to 30 mg/kg/day (approximately 0.4 to 0.6 times the adult daily dose of 500 mg based on body surface area) and it was not observed when only one animal in the mated pair was treated. There were no effects on any other reproductive parameters, and there were no effects on fertility at 10 mg/kg/day. The relevance of these findings to patients being treated with azithromycin at the doses and durations recommended in the prescribing information is uncertain.

Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) in dogs and rats treated with azithromycin at doses which, expressed on the basis of body surface area, are similar to or less than the highest recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (50 mg/kg/day dose) at the observed maximal plasma concentration of 1.3 mcg/mL (1.6 times the observed C maxof 0.821 mcg/mL at the adult dose of 2 g). Similarly, it has been shown in the dog (10 mg/kg/day dose) at the observed maximal serum concentration of 1 mcg/mL (1.2 times the observed C maxof 0.821 mcg/mL at the adult dose of 2 g). Phospholipidosis was also observed in neonatal rats dosed for 18 days at 30 mg/kg/day, which is less than the pediatric dose of 60 mg/kg based on the surface area. It was not observed in neonatal rats treated for 10 days at 40 mg/kg/day with mean maximal serum concentrations of 1.86 mcg/mL, approximately 1.5 times the C maxof 1.27 mcg/mL at the pediatric dose. Phospholipidosis has been observed in neonatal dogs (10 mg/kg/day) at maximum mean whole blood concentrations of 3.54 mcg/mL, approximately 3 times the pediatric dose C max. The significance of these findings for animals and for humans is unknown.

Acute Bacterial Exacerbations of Chronic Bronchitis

In a randomized, double-blind controlled clinical trial of acute exacerbation of chronic bronchitis (AECB), azithromycin (500 mg once daily for 3 days) was compared with clarithromycin (500 mg twice daily for 10 days). The primary endpoint of this trial was the clinical cure rate at Days 21 to 24. For the 304 patients analyzed in the modified intent-to-treat analysis at the Days 21 to 24 visit, the clinical cure rate for 3 days of azithromycin was 85% (125/147) compared to 82% (129/157) for 10 days of clarithromycin.

The following outcomes were the clinical cure rates at the Days 21 to 24 visit for the bacteriologically evaluable patients by pathogen:

<div class="scrollingtable"><table width="100%"> <col width="18%"/> <col width="49%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Pathogen</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Azithromycin </span><span class="Bold">(</span><span class="Bold">3 </span><span class="Bold">Days</span><span class="Bold">)</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Clarithromycin </span><span class="Bold">(</span><span class="Bold">10 </span><span class="Bold">Days</span><span class="Bold">)</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">S</span><span class="Italics">. </span><span class="Italics">pneumoniae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">29/32 (91%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">21/27 (78%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">H</span><span class="Italics">. </span><span class="Italics">influenzae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12/14 (86%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">14/16 (88%) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">M</span><span class="Italics">. </span><span class="Italics">catarrhalis</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">11/12 (92%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12/15 (80%) <br/> </td> </tr> </tbody> </table></div>

Acute Bacterial Sinusitis

In a randomized, double-blind, double-dummy controlled clinical trial of acute bacterial sinusitis, azithromycin (500 mg once daily for 3 days) was compared with amoxicillin/clavulanate (500/125 mg three times a day for 10 days). Clinical response assessments were made at Day 10 and Day 28. The primary endpoint of this trial was prospectively defined as the clinical cure rate at Day 28. For the 594 patients analyzed in the modified intent to treat analysis at the Day 10 visit, the clinical cure rate for 3 days of azithromycin was 88% (268/303) compared to 85% (248/291) for 10 days of amoxicillin/clavulanate. For the 586 patients analyzed in the modified intent to treat analysis at the Day 28 visit, the clinical cure rate for 3 days of azithromycin was 71.5% (213/298) compared to 71.5% (206/288), with a 97.5% confidence interval of –8.4 to 8.3, for 10 days of amoxicillin/clavulanate.

In an open label, non-comparative study requiring baseline transantral sinus punctures, the following outcomes were the clinical success rates at the Day 7 and Day 28 visits for the modified intent to treat patients administered 500 mg of azithromycin once daily for 3 days with the following pathogens:

<div class="scrollingtable"><table width="100%"> <caption> <span>Clinical Success Rates of Azithromycin (500 mg per day for 3 Days)</span> </caption> <col width="24%"/> <col width="45%"/> <col width="31%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Pathogen</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">7</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">28</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">S</span><span class="Italics">. </span><span class="Italics">pneumoniae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">23/26 (88%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">21/25 (84%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">H</span><span class="Italics">. </span><span class="Italics">influenzae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">28/32 (87%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">24/32 (75%) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">M</span><span class="Italics">. </span><span class="Italics">catarrhalis</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">14/15 (93%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">13/15 (87%) <br/> </td> </tr> </tbody> </table></div>

From the perspective of evaluating pediatric clinical trials, Days 11 to 14 were considered on-therapy evaluations because of the extended half-life of azithromycin. Days 11 to 14 data are provided for clinical guidance. Days 24 to 32 evaluations were considered the primary test of cure endpoint.

Pharyngitis/Tonsillitis

In three double-blind controlled studies, conducted in the United States, azithromycin (12 mg/kg once a day for 5 days) was compared to penicillin V (250 mg three times a day for 10 days) in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci(GABHS or S. pyogenes). Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success (i.e., cure and improvement) and bacteriologic efficacy rates (for the combined evaluable patient with documented GABHS):

<div class="scrollingtable"><table width="99%"> <caption> <span>Three U.S. Streptococcal Pharyngitis Studies Azithromycin vs. Penicillin V EFFICACY RESULTS</span> </caption> <col width="47%"/> <col width="29%"/> <col width="23%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">14</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">30</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Bacteriologic </span><span class="Bold">Eradication</span><span class="Bold">:</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Azithromycin <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">323/340 (95%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">255/330 (77%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Penicillin V <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">242/332 (73%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">206/325 (63%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Clinical </span><span class="Bold">Success </span><span class="Bold">(</span><span class="Bold">cure </span><span class="Bold">plus </span><span class="Bold">improvement</span><span class="Bold">):</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Azithromycin <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">336/343 (98%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">310/330 (94%) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Penicillin V <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">284/338 (84%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">241/325 (74%) <br/> </td> </tr> </tbody> </table></div>

Approximately 1% of azithromycin-susceptible S. pyogenesisolates were resistant to azithromycin following therapy.

Acute Otitis Media

Efficacy using azithromycin given over 5 days(10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5):

Trial 1

In a double-blind, controlled clinical study of acute otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5) was compared to amoxicillin/clavulanate potassium (4:1). For the 553 patients who were evaluated for clinical efficacy, the clinical success rate (i.e., cure plus improvement) at the Day 11 visit was 88% for azithromycin and 88% for the control agent. For the 521 patients who were evaluated at the Day 30 visit, the clinical success rate was 73% for azithromycin and 71% for the control agent.

Trial 2

In a non-comparative clinical and microbiologic trial performed in the United States, where significant rates of beta-lactamase producing organisms (35%) were found, 131 patients were evaluable for clinical efficacy. The combined clinical success rate (i.e., cure and improvement) at the Day 11 visit was 84% for azithromycin. For the 122 patients who were evaluated at the Day 30 visit, the clinical success rate was 70% for azithromycin.

Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. The following clinical success rates were obtained from the evaluable group:

<div class="scrollingtable"><table width="100%"> <col width="37%"/> <col width="30%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">11</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">30</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Pathogen</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Azithromycin</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">S</span><span class="Italics">. </span><span class="Italics">pneumoniae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">61/74 (82%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">40/56 (71%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">H</span><span class="Italics">. </span><span class="Italics">influenzae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">43/54 (80%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">30/47 (64%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">M</span><span class="Italics">. </span><span class="Italics">catarrhalis</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">28/35 (80%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">19/26 (73%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">S</span><span class="Italics">. </span><span class="Italics">pyogenes</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">11/11 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">7/7 (100%) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Overall <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">177/217 (82%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">97/137 (73%) <br/> </td> </tr> </tbody> </table></div>

Trial 3

In another controlled comparative clinical and microbiologic study of otitis media performed in the United States, azithromycin (10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5) was compared to amoxicillin/clavulanate potassium (4:1). This study utilized two of the same investigators as Protocol 2 (above), and these two investigators enrolled 90% of the patients in Protocol 3. For this reason, Protocol 3 was not considered to be an independent study. Significant rates of beta-lactamase producing organisms (20%) were found. Ninety-two (92) patients were evaluable for clinical and microbiologic efficacy. The combined clinical success rate (i.e., cure and improvement) of those patients with a baseline pathogen at the Day 11 visit was 88% for azithromycin vs. 100% for control; at the Day 30 visit, the clinical success rate was 82% for azithromycin vs. 80% for control.

Microbiologic determinations were made at the pre-treatment visit. Microbiology was not reassessed at later visits. At the Day 11 and Day 30 visits, the following clinical success rates were obtained from the evaluable group:

<div class="scrollingtable"><table width="100%"> <col width="31%"/> <col width="18%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" colspan="1" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">Day </span><span class="Bold">11</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"><span class="Bold">Day </span><span class="Bold">30</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Pathogen</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Control</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Azithromycin</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Control</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">S</span><span class="Italics">. </span><span class="Italics">pneumoniae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">25/29 (86%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">26/26 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">22/28 (79%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">18/22 (82%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">H</span><span class="Italics">. </span><span class="Italics">influenzae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">9/11 (82%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">9/9 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">8/10 (80%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">6/8 (75%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">M</span><span class="Italics">. </span><span class="Italics">catarrhalis</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">7/7 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5/5 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5/5 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2/3 (66%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">S</span><span class="Italics">. </span><span class="Italics">pyogenes</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2/2 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5/5 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">2/2 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">4/4 (100%) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Overall <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">43/49 (88%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">45/45 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">37/45 (82%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">30/37 (81%) <br/> </td> </tr> </tbody> </table></div>

Efficacy using azithromycin given over 3 days(10 mg/kg/day):

Trial 4

In a double-blind, controlled, randomized clinical study of acute otitis media in pediatric patients from 6 months to 12 years of age, azithromycin (10 mg/kg per day for 3 days) was compared to amoxicillin/clavulanate potassium (7:1) in divided doses q12h for 10 days. Each patient received active drug and placebo matched for the comparator.

For the 366 patients who were evaluated for clinical efficacy at the Day 12 visit, the clinical success rate (i.e., cure plus improvement) was 83% for azithromycin and 88% for the control agent. For the 362 patients who were evaluated at the Days 24 to 28 visit, the clinical success rate was 74% for azithromycin and 69% for the control agent.

Efficacy using azithromycin 30 mg/kg given as a single dose:

Trial 5

A double-blind, controlled, randomized trial was performed at nine clinical centers. Pediatric patients from 6 months to 12 years of age were randomized 1:1 to treatment with either azithromycin (given at 30 mg/kg as a single dose on Day 1) or amoxicillin/clavulanate potassium (7:1), divided q12h for 10 days. Each child received active drug, and placebo matched for the comparator.

Clinical response (Cure, Improvement, Failure) was evaluated at End of Therapy (Days 12 to 16) and Test of Cure (Days 28 to 32). Safety was evaluated throughout the trial for all treated subjects. For the 321 subjects who were evaluated at End of Treatment, the clinical success rate (cure plus improvement) was 87% for azithromycin, and 88% for the comparator. For the 305 subjects who were evaluated at Test of Cure, the clinical success rate was 75% for both azithromycin and the comparator.

Trial 6

In a non-comparative clinical and microbiological trial, 248 patients from 6 months to 12 years of age with documented acute otitis media were dosed with a single oral dose of azithromycin (30 mg/kg on Day 1).

For the 240 patients who were evaluable for clinical modified Intent-to-Treat (MITT) analysis, the clinical success rate (i.e., cure plus improvement) at Day 10 was 89% and for the 242 patients evaluable at Days 24 to 28, the clinical success rate (cure) was 85%.

<div class="scrollingtable"><table width="100%"> <col width="22%"/> <col width="39%"/> <col width="39%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="middle"><span class="Bold">Presumed </span><span class="Bold">Bacteriologic </span><span class="Bold">Eradication</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Day </span><span class="Bold">10</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Days </span><span class="Bold">24</span><span class="Bold">-</span><span class="Bold">28</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">S</span><span class="Italics">. </span><span class="Italics">pneumoniae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">70/76 (92%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">67/76 (88%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">H</span><span class="Italics">. </span><span class="Italics">influenzae</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">30/42 (71%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">28/44 (64%) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Italics">M</span><span class="Italics">. </span><span class="Italics">catarrhalis</span> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">10/10 (100%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">10/10 (100%) <br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle">Overall <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">110/128 (86%) <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">105/130 (81%) <br/> </td> </tr> </tbody> </table></div>

Azithromycin tablets USP are supplied in the following strengths and package configurations:

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Azithromycin tablets USP, 250 mg are supplied as pink, oval shaped film-coated tablets, engraved with "LU" on one side and "L04" on the other side containing azithromycin dihydrate equivalent to 250 mg of azithromycin USP.

{ "type": "p", "children": [], "text": "Azithromycin tablets USP, 250 mg are supplied as pink, oval shaped film-coated tablets, engraved with \"LU\" on one side and \"L04\" on the other side containing azithromycin dihydrate equivalent to 250 mg of azithromycin USP." }

These are packaged in

{ "type": "p", "children": [], "text": "These are packaged in" }

NDC: 70518-4356-00

{ "type": "p", "children": [], "text": "NDC: 70518-4356-00" }

PACKAGING: 30 in 1 BLISTER PACK

{ "type": "p", "children": [], "text": "PACKAGING: 30 in 1 BLISTER PACK" }

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]." }

Repackaged and Distributed By:

{ "type": "p", "children": [], "text": "Repackaged and Distributed By:" }

Remedy Repack, Inc.

{ "type": "p", "children": [], "text": "Remedy Repack, Inc." }

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

{ "type": "p", "children": [], "text": "625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762" }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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General Patient Counseling

{ "type": "p", "children": [], "text": "\nGeneral Patient Counseling\n" }

Azithromycin tablets can be taken with or without food.

{ "type": "p", "children": [], "text": "Azithromycin tablets can be taken with or without food." }

Patients should also be cautioned not to take aluminum-and magnesium-containing antacids and azithromycin simultaneously.

{ "type": "p", "children": [], "text": "Patients should also be cautioned not to take aluminum-and magnesium-containing antacids and azithromycin simultaneously." }

The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur.

{ "type": "p", "children": [], "text": "The patient should be directed to discontinue azithromycin immediately and contact a physician if any signs of an allergic reaction occur." }

Direct parents or caregivers to contact their physician if vomiting and irritability with feeding occurs in the infant.

{ "type": "p", "children": [], "text": "Direct parents or caregivers to contact their physician if vomiting and irritability with feeding occurs in the infant." }

Patients should be counseled that antibacterial drugs including azithromycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When azithromycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by azithromycin or other antibacterial drugs in the future.

{ "type": "p", "children": [], "text": "Patients should be counseled that antibacterial drugs including azithromycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When azithromycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of the therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by azithromycin or other antibacterial drugs in the future." }

Diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible.

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LUPIN are registered trademarks of Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "LUPIN are registered trademarks of Lupin Pharmaceuticals, Inc." }

Repackaged By / Distributed By: RemedyRepack Inc.

{ "type": "p", "children": [], "text": "Repackaged By / Distributed By: RemedyRepack Inc." }

625 Kolter Drive, Indiana, PA 15701

{ "type": "p", "children": [], "text": "625 Kolter Drive, Indiana, PA 15701" }

(724) 465-8762

{ "type": "p", "children": [], "text": "(724) 465-8762" }

Patient Information

{ "type": "p", "children": [], "text": "\nPatient Information\n" }

Azithromycin (ay-ZITH-roe-MYE-sin) Tablets USP

{ "type": "p", "children": [], "text": "\nAzithromycin (ay-ZITH-roe-MYE-sin) Tablets USP\n" }

Read this Patient Information leaflet before you start taking azithromycin tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

{ "type": "p", "children": [], "text": "Read this Patient Information leaflet before you start taking azithromycin tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment." }

What are azithromycin tablets?

{ "type": "p", "children": [], "text": "\nWhat are azithromycin tablets?\n" }

Azithromycin tablets are a macrolide antibiotic prescription medicine used in adults 18 years or older to treat certain infections caused by certain germs called bacteria. These bacterial infections include:

{ "type": "p", "children": [], "text": "Azithromycin tablets are a macrolide antibiotic prescription medicine used in adults 18 years or older to treat certain infections caused by certain germs called bacteria. These bacterial infections include:" }

{ "type": "ul", "children": [ "acute worsening of chronic bronchitis", "acute sinus infection", "community-acquired pneumonia", "infected throat or tonsils", "skin infections", "infections of the urethra or cervix", "genital ulcers in men" ], "text": "" }

Azithromycin tablets are also used in children to treat:

{ "type": "p", "children": [], "text": "Azithromycin tablets are also used in children to treat:" }

{ "type": "ul", "children": [ "ear infections", "community-acquired pneumonia", "infected throat or tonsils" ], "text": "" }

Azithromycin should not be taken by people who cannot tolerate oral medications because they are very ill or have certain other risk factors including:

{ "type": "p", "children": [], "text": "Azithromycin should not be taken by people who cannot tolerate oral medications because they are very ill or have certain other risk factors including:" }

{ "type": "ul", "children": [ "have cystic fibrosis", "have hospital acquired infections", "have known or suspected bacteria in the blood", "need to be in the hospital", "are elderly", "have any medical problems that can lower the ability of the immune system to fight infections" ], "text": "" }

Azithromycin tablets are not for viral infections such as the common cold.

{ "type": "p", "children": [], "text": "Azithromycin tablets are not for viral infections such as the common cold." }

It is not known if azithromycin tablets are safe and effective for genital ulcers in women.

{ "type": "p", "children": [], "text": "It is not known if azithromycin tablets are safe and effective for genital ulcers in women." }

It is not known if azithromycin tablets are safe and effective for children with ear infections, sinus infections, and community-acquired pneumonia under 6 months of age.

{ "type": "p", "children": [], "text": "It is not known if azithromycin tablets are safe and effective for children with ear infections, sinus infections, and community-acquired pneumonia under 6 months of age." }

It is not known if azithromycin tablets are safe and effective for infected throat or tonsils in children under 2 years of age.

{ "type": "p", "children": [], "text": "It is not known if azithromycin tablets are safe and effective for infected throat or tonsils in children under 2 years of age." }

Who should not take azithromycin tablets?

{ "type": "p", "children": [], "text": "\nWho should not take azithromycin tablets?\n" }

Do not take azithromycin tablets if you:

{ "type": "p", "children": [], "text": "\nDo not take azithromycin tablets if you:\n" }

{ "type": "ul", "children": [ "have had a severe allergic reaction to certain antibiotics known as macrolides or ketolides including azithromycin and erythromycin.", "have a history of cholestatic jaundice or hepatic dysfunction that happened with the use of azithromycin." ], "text": "" }

What should I tell my healthcare provider before taking azithromycin tablets?

{ "type": "p", "children": [], "text": "\nWhat should I tell my healthcare provider before taking azithromycin tablets?\n" }

Before you take azithromycin tablets, tell your healthcare provider if you:

{ "type": "p", "children": [], "text": "\nBefore you take azithromycin tablets, tell your healthcare provider if you:\n" }

{ "type": "ul", "children": [ "have pneumonia", "have cystic fibrosis", "have known or suspected bacteremia (bacterial infection in the blood)", "have liver or kidney problems", "have an irregular heartbeat, especially a problem called \"QT prolongation\"", "have a problem that causes muscle weakness (myasthenia gravis)", "have any other medical problems", "are pregnant or plan to become pregnant. It is not known if azithromycin tablets will harm your unborn baby.", "are breastfeeding or plan to breastfeed. Azithromycin has been reported to pass into breast milk. Talk to your healthcare provider about the best way to feed your baby while you take azithromycin tablets." ], "text": "" }

Contact your healthcare provider immediately if you are giving azithromycin tablets to a young child (less than 6 weeks of age) and he or she vomits or becomes irritable when fed.

{ "type": "p", "children": [], "text": "Contact your healthcare provider immediately if you are giving azithromycin tablets to a young child (less than 6 weeks of age) and he or she vomits or becomes irritable when fed." }

Tell your healthcare provider about all the medicines you take,including prescription and non-prescription medicines, vitamins, and herbal supplements.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take,including prescription and non-prescription medicines, vitamins, and herbal supplements.\n " }

Azithromycin tablets and other medicines may affect each other causing side effects. Azithromycin tablets may affect the way other medicines work, and other medicines may affect how azithromycin tablets works.

{ "type": "p", "children": [], "text": "Azithromycin tablets and other medicines may affect each other causing side effects. Azithromycin tablets may affect the way other medicines work, and other medicines may affect how azithromycin tablets works." }

Especially tell your healthcare provider if you take:

{ "type": "p", "children": [], "text": "Especially tell your healthcare provider if you take:" }

{ "type": "ul", "children": [ " nelfinavir", " a blood thinner (warfarin)", " digoxin", " colchicine", " phenytoin", " an antacid that contains aluminum or magnesium" ], "text": "" }

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

{ "type": "p", "children": [], "text": "Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine." }

How should I take azithromycin tablets?

{ "type": "p", "children": [], "text": "\nHow should I take azithromycin tablets?\n" }

{ "type": "ul", "children": [ "Take azithromycin tablets exactly as your healthcare provider tells you to take it.", "Azithromycin tablets can be taken with or without food.", "Do not skip any doses of azithromycin tablets or stop taking it, even if you begin to feel better, until you finish your prescribed treatment unless you have a serious allergic reaction or your healthcare provider tells you to stop taking azithromycin tablets. \n \"See What are the possible side effects of azithromycin tablets?\"If you skip doses, or do not complete the total course of azithromycin tablets your treatment may not work as well and your infection may be harder to treat. Taking all of your azithromycin tablets doses will help lower the chance that the bacteria will become resistant to azithromycin tablets.\n ", "If the bacteria becomes resistant to azithromycin, azithromycin tablets and other antibiotic medicines may not work for you in the future.", "If you take too much azithromycin tablets, call your healthcare provider or get medical help right away." ], "text": "" }

What are the possible side effects of azithromycintablets?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of azithromycintablets?\n" }

Azithromycin tablets can cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nAzithromycin tablets can cause serious side effects, including:\n" }

• Serious allergic reactions.Allergic reactions can happen in people taking azithromycin tablets the active ingredient in azithromycin tablets, even after only 1 dose. Stop taking azithromycin tablets and get emergency medical help right away if you have any of the following symptoms of a severe allergic reaction:

{ "type": "p", "children": [], "text": "\n• Serious allergic reactions.Allergic reactions can happen in people taking azithromycin tablets the active ingredient in azithromycin tablets, even after only 1 dose. Stop taking azithromycin tablets and get emergency medical help right away if you have any of the following symptoms of a severe allergic reaction:\n " }

° trouble breathing or swallowing

{ "type": "p", "children": [], "text": " ° trouble breathing or swallowing" }

° swelling of the lips, tongue, face

{ "type": "p", "children": [], "text": " ° swelling of the lips, tongue, face" }

° throat tightness, hoarseness

{ "type": "p", "children": [], "text": " ° throat tightness, hoarseness" }

° rapid heartbeat

{ "type": "p", "children": [], "text": " ° rapid heartbeat" }

° faintness

{ "type": "p", "children": [], "text": " ° faintness" }

° skin rash (hives)

{ "type": "p", "children": [], "text": " ° skin rash (hives)" }

° new onset of fever and swollen lymph nodes

{ "type": "p", "children": [], "text": " ° new onset of fever and swollen lymph nodes" }

Stop taking azithromycin tablets at the first sign of a skin rash and call your healthcare provider.

{ "type": "p", "children": [], "text": "Stop taking azithromycin tablets at the first sign of a skin rash and call your healthcare provider." }

Skin rash may be a sign of a more serious reaction to azithromycin tablets.

{ "type": "p", "children": [], "text": "Skin rash may be a sign of a more serious reaction to azithromycin tablets." }

•Liver damage (hepatotoxicity).Hepatotoxicity can happen in people who take azithromycin tablets. Call your healthcare provider right away if you have unexplained symptoms such as:

{ "type": "p", "children": [], "text": "\n•Liver damage (hepatotoxicity).Hepatotoxicity can happen in people who take azithromycin tablets. Call your healthcare provider right away if you have unexplained symptoms such as:\n " }

° nausea or vomiting

{ "type": "p", "children": [], "text": " ° nausea or vomiting" }

° stomach pain

{ "type": "p", "children": [], "text": " ° stomach pain" }

° fever

{ "type": "p", "children": [], "text": " ° fever" }

° weakness

{ "type": "p", "children": [], "text": " ° weakness" }

° abdominal pain or tenderness

{ "type": "p", "children": [], "text": " ° abdominal pain or tenderness" }

° itching

{ "type": "p", "children": [], "text": " ° itching" }

° unusual tiredness

{ "type": "p", "children": [], "text": " ° unusual tiredness" }

° loss of appetite

{ "type": "p", "children": [], "text": " ° loss of appetite" }

° change in the color of your bowel movements

{ "type": "p", "children": [], "text": " ° change in the color of your bowel movements" }

° dark colored urine

{ "type": "p", "children": [], "text": " ° dark colored urine" }

° yellowing of your skin or of the whites of your eyes

{ "type": "p", "children": [], "text": " ° yellowing of your skin or of the whites of your eyes" }

Stop taking azithromycin tablets and tell your healthcare provider right away if you have yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to azithromycin tablets (a liver problem).

{ "type": "p", "children": [], "text": "Stop taking azithromycin tablets and tell your healthcare provider right away if you have yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to azithromycin tablets (a liver problem)." }

• Serious heart rhythm changes that can be life-threatening, including heart stopping (cardiac arrest), QT prolongation, torsades de pointes, feeling that your heart is pounding or racing (palpitations), chest discomfort, or irregular heartbeat.

{ "type": "p", "children": [], "text": "• \n Serious heart rhythm changes that can be life-threatening, including heart stopping (cardiac arrest), QT prolongation, torsades de pointes, feeling that your heart is pounding or racing (palpitations), chest discomfort, or irregular heartbeat.\n" }

Tell your healthcare provider right away if you or your child feel a fast or irregular heartbeat, get dizzy or faint. Azithromycin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people:

{ "type": "p", "children": [], "text": "Tell your healthcare provider right away if you or your child feel a fast or irregular heartbeat, get dizzy or faint. Azithromycin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people:" }

° who are elderly

{ "type": "p", "children": [], "text": " ° who are elderly" }

° with a family history of prolonged QT interval

{ "type": "p", "children": [], "text": " ° with a family history of prolonged QT interval" }

° with low blood potassium

{ "type": "p", "children": [], "text": " ° with low blood potassium" }

° who take certain medicines to control heart rhythm (antiarrhythmics)

{ "type": "p", "children": [], "text": " ° who take certain medicines to control heart rhythm (antiarrhythmics)" }

• Worsening of myasthenia gravis (a problem that causes muscle weakness).

{ "type": "p", "children": [], "text": "• \n Worsening of myasthenia gravis (a problem that causes muscle weakness).\n" }

Certain antibiotics like azithromycin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

{ "type": "p", "children": [], "text": "Certain antibiotics like azithromycin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems." }

• Diarrhea.Tell your healthcare provider right away if you have watery diarrhea, diarrhea that does not go away, or bloody stools. You may experience cramping and a fever. This could happen after you have finished your azithromycin tablets.

{ "type": "p", "children": [], "text": "• \n Diarrhea.Tell your healthcare provider right away if you have watery diarrhea, diarrhea that does not go away, or bloody stools. You may experience cramping and a fever. This could happen after you have finished your azithromycin tablets.\n " }

The most common side effects of azithromycin tablets include:

{ "type": "p", "children": [], "text": "The most common side effects of azithromycin tablets include:" }

•nausea

{ "type": "p", "children": [], "text": " •nausea" }

•stomach pain

{ "type": "p", "children": [], "text": " •stomach pain" }

•vomiting

{ "type": "p", "children": [], "text": " •vomiting" }

These are not all the possible side effects of azithromycin tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "These are not all the possible side effects of azithromycin tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away." }

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

{ "type": "p", "children": [], "text": "Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088." }

How should I store azithromycin tablets?

{ "type": "p", "children": [], "text": "\nHow should I store azithromycin tablets?\n" }

{ "type": "ul", "children": [ "Store azithromycin tablets at 15° to 30°C (59° to 86°F).", "Safely throw away any medicine that is out of date or no longer needed." ], "text": "" }

Keep azithromycin tablets and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep azithromycin tablets and all medicines out of the reach of children.\n" }

General information about the safe and effective use of azithromycin tablets.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of azithromycin tablets.\n" }

Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use azithromycin tablets for a condition for which it was not prescribed. Do not give azithromycin tablets to other people, even if they have the same symptoms you have. It may harm them.

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use azithromycin tablets for a condition for which it was not prescribed. Do not give azithromycin tablets to other people, even if they have the same symptoms you have. It may harm them." }

This Patient Information leaflet summarizes the most important information about azithromycin tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about azithromycin tablets that is written for health professionals.

{ "type": "p", "children": [], "text": "This Patient Information leaflet summarizes the most important information about azithromycin tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about azithromycin tablets that is written for health professionals." }

For more information, go to www.lupinpharmaceuticals.com or call 1-800-399-2561

{ "type": "p", "children": [], "text": "For more information, go to www.lupinpharmaceuticals.com or call 1-800-399-2561" }

What are the ingredients in azithromycin tablets?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in azithromycin tablets?\n" }

Azithromycin Tablets:

{ "type": "p", "children": [], "text": "\nAzithromycin Tablets:\n" }

Active ingredient: azithromycin dihydrate

{ "type": "p", "children": [], "text": "Active ingredient: azithromycin dihydrate" }

Inactive ingredients: croscarmellose sodium, dibasic calcium phosphate, hydroxypropyl methyl cellulose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, titanium dioxide, triacetin and D & C Red #30.

{ "type": "p", "children": [], "text": "Inactive ingredients: croscarmellose sodium, dibasic calcium phosphate, hydroxypropyl methyl cellulose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, titanium dioxide, triacetin and D & C Red #30." }

How to open the blister:

{ "type": "p", "children": [], "text": "\nHow to open the blister:\n" }

This Patient Information has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "\nThis Patient Information has been approved by the U.S. Food and Drug Administration.\n" }

Repackaged and Distributed By:

{ "type": "p", "children": [], "text": "Repackaged and Distributed By:" }

Remedy Repack, Inc.

{ "type": "p", "children": [], "text": "Remedy Repack, Inc." }

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

{ "type": "p", "children": [], "text": "625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762" }

DRUG: azithromycin

{ "type": "p", "children": [], "text": "DRUG: azithromycin" }

GENERIC: azithromycin

{ "type": "p", "children": [], "text": "GENERIC: azithromycin" }

DOSAGE: TABLET, FILM COATED

{ "type": "p", "children": [], "text": "DOSAGE: TABLET, FILM COATED" }

ADMINSTRATION: ORAL

{ "type": "p", "children": [], "text": "ADMINSTRATION: ORAL" }

NDC: 70518-4356-0

{ "type": "p", "children": [], "text": "NDC: 70518-4356-0" }

COLOR: pink

{ "type": "p", "children": [], "text": "COLOR: pink" }

SHAPE: OVAL

{ "type": "p", "children": [], "text": "SHAPE: OVAL" }

SCORE: No score

{ "type": "p", "children": [], "text": "SCORE: No score" }

SIZE: 14 mm

{ "type": "p", "children": [], "text": "SIZE: 14 mm" }

IMPRINT: LU;L04

{ "type": "p", "children": [], "text": "IMPRINT: LU;L04" }

PACKAGING: 30 in 1 BLISTER PACK

{ "type": "p", "children": [], "text": "PACKAGING: 30 in 1 BLISTER PACK" }

ACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "ACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "AZITHROMYCIN DIHYDRATE 250mg in 1" ], "text": "" }

INACTIVE INGREDIENT(S):

{ "type": "p", "children": [], "text": "INACTIVE INGREDIENT(S):" }

{ "type": "ul", "children": [ "CALCIUM PHOSPHATE, DIBASIC, ANHYDROUS", "CROSCARMELLOSE SODIUM", "D&C RED NO. 30", "HYPROMELLOSE 2910 (15 MPA.S)", "LACTOSE MONOHYDRATE", "MAGNESIUM STEARATE", "SODIUM LAURYL SULFATE", "TITANIUM DIOXIDE", "TRIACETIN" ], "text": "" }