Amiodarone injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. Amiodarone also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with amiodarone, patients may be transferred to oral amiodarone therapy [see Dosage and Administration (2)].

{ "type": "p", "children": [], "text": "\nAmiodarone injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. Amiodarone also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with amiodarone, patients may be transferred to oral amiodarone therapy [see Dosage and Administration (2)]." }

Use amiodarone for acute treatment until the patient's ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but amiodarone may be safely administered for longer periods if necessary.

{ "type": "p", "children": [], "text": "Use amiodarone for acute treatment until the patient's ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but amiodarone may be safely administered for longer periods if necessary." }

Amiodarone shows considerable interindividual variation in response. Although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose is essential. The recommended starting dose of amiodarone is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:

{ "type": "p", "children": [], "text": "\nAmiodarone shows considerable interindividual variation in response. Although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose is essential. The recommended starting dose of amiodarone is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:" }

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 1: AMIODARONE DOSE RECOMMENDATIONS:  FIRST 24 HOURS </span> </caption> <col width="23%"/> <col width="18%"/> <col width="57%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Toprule" valign="top"> <br/> </td><td align="left" class="Toprule" valign="top"><span class="Bold"></span> <br/> </td><td align="left" class="Toprule" valign="top"> <br/> </td> </tr> <tr> <td align="left" valign="top"><span class="Bold"> Loading infusions</span> <br/> </td><td align="left" valign="top"><span class="Bold"><span class="Italics">First</span></span><span class="Bold"> Rapid:</span> <br/> </td><td align="left" valign="top"><span class="Bold"> 150 mg over the FIRST 10 minutes (15 mg/min).</span>   <br/> Add 3 mL of amiodarone (150 mg) to 100 mL D<span class="Sub">5</span>W <br/> (concentration = 1.5 mg/mL). Infuse 100 mL over 10 minutes.<br/> </td> </tr> <tr> <td valign="top"></td><td align="left" valign="top"> <br/> <span class="Bold"><span class="Italics">Followed by</span></span><span class="Bold"> Slow:</span> <br/> </td><td align="left" valign="top"> <br/> <span class="Bold"> 360 mg over the NEXT 6 hours (1 mg/min). </span> <br/> Add 18 mL of amiodarone (900 mg) to 500 mL D<span class="Sub">5</span>W <br/> (concentration = 1.8 mg/mL). Infuse 200 mL at a rate of 0.556 mL/min.<br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule" valign="top"><span class="Bold"> Maintenance infusion</span> <br/> </td><td class="Botrule" valign="top"></td><td align="left" class="Botrule" valign="top"><span class="Bold"> 540 mg over the REMAINING 18 hours (0.5 mg/min</span> ).<br/> Decrease the rate of the slow loading infusion to 0.278 mL/min.<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span> Table 1: AMIODARONE DOSE RECOMMENDATIONS:  FIRST 24 HOURS </span>\n</caption>\n<col width=\"23%\"/>\n<col width=\"18%\"/>\n<col width=\"57%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"left\" class=\"Toprule\" valign=\"top\">\n<br/>\n</td><td align=\"left\" class=\"Toprule\" valign=\"top\"><span class=\"Bold\"></span>\n<br/>\n</td><td align=\"left\" class=\"Toprule\" valign=\"top\">\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" valign=\"top\"><span class=\"Bold\"> Loading infusions</span>\n<br/>\n</td><td align=\"left\" valign=\"top\"><span class=\"Bold\"><span class=\"Italics\">First</span></span><span class=\"Bold\"> Rapid:</span>\n<br/>\n</td><td align=\"left\" valign=\"top\"><span class=\"Bold\"> 150 mg over the FIRST 10 minutes (15 mg/min).</span>   <br/> Add 3 mL of amiodarone (150 mg) to 100 mL D<span class=\"Sub\">5</span>W <br/> (concentration = 1.5 mg/mL). Infuse 100 mL over 10 minutes.<br/>\n</td>\n</tr>\n<tr>\n<td valign=\"top\"></td><td align=\"left\" valign=\"top\">\n<br/>\n<span class=\"Bold\"><span class=\"Italics\">Followed by</span></span><span class=\"Bold\"> Slow:</span>\n<br/>\n</td><td align=\"left\" valign=\"top\">\n<br/>\n<span class=\"Bold\"> 360 mg over the NEXT 6 hours (1 mg/min). </span>\n<br/> Add 18 mL of amiodarone (900 mg) to 500 mL D<span class=\"Sub\">5</span>W <br/> (concentration = 1.8 mg/mL). Infuse 200 mL at a rate of 0.556 mL/min.<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule\" valign=\"top\"><span class=\"Bold\"> Maintenance infusion</span>\n<br/>\n</td><td class=\"Botrule\" valign=\"top\"></td><td align=\"left\" class=\"Botrule\" valign=\"top\"><span class=\"Bold\"> 540 mg over the REMAINING 18 hours (0.5 mg/min</span> ).<br/> Decrease the rate of the slow loading infusion to 0.278 mL/min.<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

After the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) utilizing a concentration of 1 to 6 mg/mL (Use a central venous catheter for amiodarone concentrations greater than 2 mg/mL). The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression.

{ "type": "p", "children": [], "text": "\nAfter the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) utilizing a concentration of 1 to 6 mg/mL (Use a central venous catheter for amiodarone concentrations greater than 2 mg/mL). The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression. " }

In the event of breakthrough episodes of VF or hemodynamically unstable VT, use 150 mg supplemental infusions of amiodarone (mixed in 100 mL of D5W and infused over 10 minutes to minimize the potential for hypotension). 

{ "type": "p", "children": [], "text": "In the event of breakthrough episodes of VF or hemodynamically unstable VT, use 150 mg supplemental infusions of amiodarone (mixed in 100 mL of D5W and infused over 10 minutes to minimize the potential for hypotension).  " }

The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. Do not exceed an initial infusion rate of 30 mg/min.

{ "type": "p", "children": [], "text": "The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. Do not exceed an initial infusion rate of 30 mg/min." }

Based on the experience from clinical studies of intravenous amiodarone, a maintenance infusion of up to 0.5 mg/min can be continued for 2 to 3 weeks regardless of the patient's age, renal function, or left ventricular function. There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks.

{ "type": "p", "children": [], "text": "Based on the experience from clinical studies of intravenous amiodarone, a maintenance infusion of up to 0.5 mg/min can be continued for 2 to 3 weeks regardless of the patient's age, renal function, or left ventricular function. There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks." }

The surface properties of solutions containing injectable amiodarone are altered such that the drop size may be reduced. This reduction may lead to underdosage of the patient by up to 30% if drop counter infusion sets are used. Amiodarone must be delivered by a volumetric infusion pump.

{ "type": "p", "children": [], "text": "The surface properties of solutions containing injectable amiodarone are altered such that the drop size may be reduced. This reduction may lead to underdosage of the patient by up to 30% if drop counter infusion sets are used. Amiodarone must be delivered by a volumetric infusion pump." }

Administer amiodarone, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration.

{ "type": "p", "children": [], "text": "Administer amiodarone, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration." }

Intravenous amiodarone loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Intravenous amiodarone loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death [see Warnings and Precautions (5.3)]." }

Intravenous amiodarone concentrations greater than 3 mg/mL in D5W have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, do not exceed amiodarone concentrations of 2 mg/mL, unless a central venous catheter is used [see Adverse Reactions (6.2)].

{ "type": "p", "children": [], "text": "Intravenous amiodarone concentrations greater than 3 mg/mL in D5W have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, do not exceed amiodarone concentrations of 2 mg/mL, unless a central venous catheter is used [see Adverse Reactions (6.2)].\n" }

Amiodarone infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W. Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation.

{ "type": "p", "children": [], "text": "Amiodarone infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W. Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation." }

Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, but all of the clinical experience has been with PVC tubing and the concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect dosing in these studies.

{ "type": "p", "children": [], "text": "Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, but all of the clinical experience has been with PVC tubing and the concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect dosing in these studies. " }

Amiodarone has been found to leach out plasticizers, including DEHP [di-(2- ethylhexyl)phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing amiodarone at higher concentrations and lower flow rates than provided in DOSAGE AND ADMINISTRATION. Polysorbate 80, a component of amiodarone injection, is also known to leach DEHP from PVC [see Description (11)].

{ "type": "p", "children": [], "text": "Amiodarone has been found to leach out plasticizers, including DEHP [di-(2- ethylhexyl)phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing amiodarone at higher concentrations and lower flow rates than provided in DOSAGE AND ADMINISTRATION. Polysorbate 80, a component of amiodarone injection, is also known to leach DEHP from PVC [see Description (11)]." }

Amiodarone does not need to be protected from light during administration.

{ "type": "p", "children": [], "text": "Amiodarone does not need to be protected from light during administration." }

NOTE: Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit - solution should be clear.

{ "type": "p", "children": [], "text": "NOTE: Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit - solution should be clear." }

CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.

{ "type": "p", "children": [], "text": "CAUTION: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete." }

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 2: AMIODARONE HCl SOLUTION STABILITY </span> </caption> <col width="20%"/> <col width="21%"/> <col width="14%"/> <col width="42%"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule" valign="top"></td><td align="center" class="Toprule"> Concentration<br/> </td><td class="Toprule" valign="top"></td><td class="Toprule" valign="top"></td> </tr> <tr> <td align="center"> Solution<br/> </td><td align="center"> (mg/mL)<br/> </td><td align="center"> Container<br/> </td><td align="center"> Comments<br/> </td> </tr> <tr> <td align="left" valign="top"> 5% Dextrose in Water (D5W) <br/> </td><td align="center" valign="top"> 1 to 6<br/> </td><td align="center" valign="top"> PVC<br/> </td><td align="left" valign="top"> Physically compatible, with amiodarone loss <br/> &lt;10% at 2 hours at room temperature.<br/> </td> </tr> <tr> <td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td> </tr> <tr class="Last"> <td align="left" class="Botrule"> 5% Dextrose in Water (D5W) <br/> </td><td align="center" class="Botrule" valign="top"> 1 to 6<br/> </td><td align="center" class="Botrule" valign="top"> Polyolefin, Glass<br/> </td><td align="left" class="Botrule" valign="top"> Physically compatible, with no amiodarone loss <br/> at 24 hours at room temperature.<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span> Table 2: AMIODARONE HCl SOLUTION STABILITY </span>\n</caption>\n<col width=\"20%\"/>\n<col width=\"21%\"/>\n<col width=\"14%\"/>\n<col width=\"42%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Toprule\" valign=\"top\"></td><td align=\"center\" class=\"Toprule\"> Concentration<br/>\n</td><td class=\"Toprule\" valign=\"top\"></td><td class=\"Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td align=\"center\"> Solution<br/>\n</td><td align=\"center\"> (mg/mL)<br/>\n</td><td align=\"center\"> Container<br/>\n</td><td align=\"center\"> Comments<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" valign=\"top\"> 5% Dextrose in Water (D5W) <br/>\n</td><td align=\"center\" valign=\"top\"> 1 to 6<br/>\n</td><td align=\"center\" valign=\"top\"> PVC<br/>\n</td><td align=\"left\" valign=\"top\"> Physically compatible, with amiodarone loss <br/> &lt;10% at 2 hours at room temperature.<br/>\n</td>\n</tr>\n<tr>\n<td valign=\"top\"></td><td valign=\"top\"></td><td valign=\"top\"></td><td valign=\"top\"></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule\"> 5% Dextrose in Water (D5W) <br/>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\"> 1 to 6<br/>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\"> Polyolefin, Glass<br/>\n</td><td align=\"left\" class=\"Botrule\" valign=\"top\"> Physically compatible, with no amiodarone loss <br/> at 24 hours at room temperature.<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Admixture Incompatibility

{ "type": "p", "children": [], "text": "\nAdmixture Incompatibility\n" }

Amiodarone in D5W Injection forms precipitates with the drugs shown in Table 3. If co-administration of the following drugs is necessary, use separate intravenous administration lines.

{ "type": "p", "children": [], "text": "Amiodarone in D5W Injection forms precipitates with the drugs shown in Table 3. If co-administration of the following drugs is necessary, use separate intravenous administration lines." }

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 3: Y-SITE INJECTION INCOMPATIBILITY </span> </caption> <col width="48%"/> <col width="22%"/> <col width="28%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3"> <p class="First Footnote">D<span class="Sub">5</span>W = Dextrose 5% in Sterile Water, NS = Normal Saline</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> Drug<br/> </td><td align="center" class="Botrule Toprule" valign="top"> Vehicle<br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> Amiodarone<br/> Concentration<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Aminophylline<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W; NS<br/> </td><td align="center" class="Rrule" valign="top"> 4 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Amoxicillin Sodium-Clavulanic Acid <br/> </td><td align="center" valign="top"> Unknown<br/> </td><td align="center" class="Rrule" valign="top"> 12.5 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Ampicillin Sodium-Sulbactam Sodium<br/> </td><td align="center" valign="top"> NS<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Argatroban<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 1.8 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Bivalirudin<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 4 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Cefamandole Nafate<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 4 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Cefazolin Sodium<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 4 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Ceftazidime<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Digoxin<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Furosemide (10 mg/mL)<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Mezlocillin Sodium<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 4 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Heparin Sodium<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> --<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Imipenem-Cilastin Sodium<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Magnesium Sulfate (500 mg/mL)<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Micafungin<br/> </td><td align="center" valign="top"> NS<br/> </td><td align="center" class="Rrule" valign="top"> 4 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Piperacillin Sodium - TazobactamSodium<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Potassium Phosphates<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Sodium Bicarbonate<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 3 mg/mL<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Sodium Nitroprusside<br/> </td><td align="center" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Rrule" valign="top"> 1.5, 6 and 15 mg/mL<br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule" valign="top"> Sodium Phosphates<br/> </td><td align="center" class="Botrule" valign="top"> D<span class="Sub">5</span>W<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 6 mg/mL<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span> Table 3: Y-SITE INJECTION INCOMPATIBILITY </span>\n</caption>\n<col width=\"48%\"/>\n<col width=\"22%\"/>\n<col width=\"28%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"3\">\n<p class=\"First Footnote\">D<span class=\"Sub\">5</span>W = Dextrose 5% in Sterile Water, NS = Normal Saline</p>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"> Drug<br/>\n</td><td align=\"center\" class=\"Botrule Toprule\" valign=\"top\"> Vehicle<br/>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\"> Amiodarone<br/> Concentration<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Aminophylline<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W; NS<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 4 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Amoxicillin Sodium-Clavulanic Acid <br/>\n</td><td align=\"center\" valign=\"top\"> Unknown<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 12.5 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Ampicillin Sodium-Sulbactam Sodium<br/>\n</td><td align=\"center\" valign=\"top\"> NS<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Argatroban<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 1.8 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Bivalirudin<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 4 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Cefamandole Nafate<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 4 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Cefazolin Sodium<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 4 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Ceftazidime<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Digoxin<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Furosemide (10 mg/mL)<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Mezlocillin Sodium<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 4 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Heparin Sodium<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> --<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Imipenem-Cilastin Sodium<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Magnesium Sulfate (500 mg/mL)<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Micafungin<br/>\n</td><td align=\"center\" valign=\"top\"> NS<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 4 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Piperacillin Sodium - TazobactamSodium<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Potassium Phosphates<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Sodium Bicarbonate<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 3 mg/mL<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" valign=\"top\"> Sodium Nitroprusside<br/>\n</td><td align=\"center\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 1.5, 6 and 15 mg/mL<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Botrule Lrule\" valign=\"top\"> Sodium Phosphates<br/>\n</td><td align=\"center\" class=\"Botrule\" valign=\"top\"> D<span class=\"Sub\">5</span>W<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> 6 mg/mL<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Intravenous to Oral Transition

{ "type": "p", "children": [], "text": "\nIntravenous to Oral Transition\n" }

Patients whose arrhythmias have been suppressed by amiodarone may be switched to oral amiodarone. The optimal dose for changing from intravenous to oral administration of amiodarone will depend on the dose of intravenous amiodarone already administered, as well as the bioavailability of oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients. See package insert for oral amiodarone.

{ "type": "p", "children": [], "text": "Patients whose arrhythmias have been suppressed by amiodarone may be switched to oral amiodarone. The optimal dose for changing from intravenous to oral administration of amiodarone will depend on the dose of intravenous amiodarone already administered, as well as the bioavailability of oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients. See package insert for oral amiodarone." }

Since grapefruit juice is known to inhibit CYP3A-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, do not drink grapefruit juice during treatment with oral amiodarone [see Drug Interactions (7)].

{ "type": "p", "children": [], "text": "Since grapefruit juice is known to inhibit CYP3A-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, do not drink grapefruit juice during treatment with oral amiodarone [see Drug Interactions (7)]." }

Table 4 provides suggested doses of oral amiodarone to be initiated after varying durations of amiodarone administration. These recommendations are made on the basis of a similar total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone.

{ "type": "p", "children": [], "text": "Table 4 provides suggested doses of oral amiodarone to be initiated after varying durations of amiodarone administration. These recommendations are made on the basis of a similar total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone." }

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 4: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS INFUSION </span> </caption> <col width="47%"/> <col width="52%"/> <tfoot> <tr class="First"> <td align="left" colspan="2"> <p class="First Footnote"># Assuming a 720 mg/day infusion (0.5 mg/min).</p> </td> </tr> <tr class="Last"> <td align="left" colspan="2"> <p class="First Footnote">* Intravenous amiodarone is not intended for maintenance treatment.</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> Duration of <br/> Amiodarone Infusion<span class="Sup">#</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> Initial Daily Dose of<br/> Oral Amiodarone<br/> </td> </tr> <tr> <td align="center" class="Lrule" valign="top"> &lt; 1 week<br/> </td><td align="center" class="Rrule" valign="top"> 800 to 1600 mg<br/> </td> </tr> <tr> <td align="center" class="Lrule" valign="top"> 1 to 3 weeks<br/> </td><td align="center" class="Rrule" valign="top"> 600 to 800 mg<br/> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule" valign="top"> &gt; 3 weeks*<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 400 mg<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span> Table 4: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS INFUSION </span>\n</caption>\n<col width=\"47%\"/>\n<col width=\"52%\"/>\n<tfoot>\n<tr class=\"First\">\n<td align=\"left\" colspan=\"2\">\n<p class=\"First Footnote\"># Assuming a 720 mg/day infusion (0.5 mg/min).</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" colspan=\"2\">\n<p class=\"First Footnote\">* Intravenous amiodarone is not intended for maintenance treatment.</p>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"> Duration of <br/> Amiodarone Infusion<span class=\"Sup\">#</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\"> Initial Daily Dose of<br/> Oral Amiodarone<br/>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule\" valign=\"top\"> &lt; 1 week<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 800 to 1600 mg<br/>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule\" valign=\"top\"> 1 to 3 weeks<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"top\"> 600 to 800 mg<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule\" valign=\"top\"> &gt; 3 weeks*<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> 400 mg<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Injection, 50 mg/mL

{ "type": "p", "children": [], "text": "\nInjection, 50 mg/mL" }

Amiodarone is contraindicated in patients with:

{ "type": "p", "children": [], "text": "\nAmiodarone is contraindicated in patients with:" }

{ "type": "ul", "children": [ "Known hypersensitivity to any of the components of Amiodarone Injection, including iodine. Hypersensitivity reactions may involve rash, angioedema, cutaneous/mucosal hemorrhage (bleeding), fever, arthralgias (joint pains), eosinophilia (abnormal blood counts), uritcaria (hives), thrombotic thrombocytopenic purpura, or severe periarteritis (inflammation around blood vessels).", "Cardiogenic shock.", "Marked sinus bradycardia.", "Second- or third-degree atrio-ventricular (AV) block unless a functioning pacemaker is available." ], "text": "" }

Hypotension is the most common adverse reaction seen with intravenous amiodarone. In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with intravenous amiodarone. Clinically significant hypotension during infusions was seen most often in the first several hours of treatment and was not dose related, but appeared to be related to the rate of infusion. Hypotension necessitating alterations in intravenous amiodarone therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients.

Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion. Monitor the initial rate of infusion closely and do not exceed the recommended rate [see Dosage and Administration (2)].

In some cases, hypotension may be refractory and result in a fatal outcome [see Adverse Reactions (6.2)].

In 90 (4.9%) of 1836 patients in clinical trials, drug-related bradycardia that was not dose-related occurred while they were receiving intravenous amiodarone for life-threatening VT/VF. Treat bradycardia by slowing the infusion rate or discontinuing amiodarone. In some patients, a pacemaker is required. Despite such measures, bradycardia was progressive and terminal in 1 patient during the controlled trials. Treat patients with a known predisposition to bradycardia or AV block with amiodarone in a setting where a temporary pacemaker is available.

Elevations of blood hepatic enzyme values [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)] are commonly seen in patients with immediately life-threatening VT/VF. Interpreting elevated AST activity can be difficult because the values may be elevated in patients who have had recent myocardial infarction, congestive heart failure, or multiple electrical defibrillations. Approximately 54% of patients receiving intravenous amiodarone in clinical studies had baseline liver enzyme elevations, and 13% had clinically significant elevations. In 81% of patients with both baseline and on-therapy data available, the liver enzyme elevations either improved during therapy or remained at baseline levels. Baseline abnormalities in hepatic enzymes are not a contraindication to treatment. Elevated bilirubin levels have been reported in patients administered intravenous amiodarone.

Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of intravenous amiodarone [see Dosage and Administration (2)].

In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential benefit of amiodarone therapy. Carefully monitor patients receiving amiodarone for evidence of progressive hepatic injury. In such cases, consider reducing the rate of administration or withdrawing amiodarone.

Like all antiarrhythmic agents, amiodarone may cause a worsening of existing arrhythmias or precipitate a new arrhythmia sometimes leading to fatal outcomes [see Adverse Reactions (6.2)]. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation, by intravenous amiodarone, of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving intravenous amiodarone, TdP or new-onset VF occurred infrequently (less than 2%). Monitor patients for QTc prolongation during infusion with amiodarone. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent.

Correct hypokalemia, hypomagnesemia or hypocalcemia whenever possible before initiating treatment with amiodarone, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics and laxatives.

Amiodarone causes thyroid dysfunction in some patients, which may lead to potentially fatal breakthrough or exacerbated arrhythmias.

Early-onset Pulmonary Toxicity

There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings have included pulmonary infiltrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure or death.

ARDS

Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy.

Pulmonary Fibrosis

There have been reports of early development of pulmonary fibrosis (within 1 to 3 months) following initiation of amiodarone treatment. Only 1 of more than 1000 patients treated with intravenous amiodarone in clinical studies developed pulmonary fibrosis. In that patient, the condition was diagnosed 3 months after treatment with intravenous amiodarone, during which time the patient received oral amiodarone. Pulmonary toxicity is a well-recognized complication of long-term amiodarone use (see package insert for oral amiodarone).

Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment, have been reported in patients treated with oral amiodarone or intravenous amiodarone. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. Perform an ophthalmic examination if symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision. Re-evaluate the necessity of amiodarone therapy if optic neuropathy or neuritis is suspected. Perform regular ophthalmic examination, including fundoscopy and slit-lamp examination, during administration of amiodarone.

Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Amiodarone is also a potential source of large amounts of inorganic iodine and can cause either hypothyroidism or hyperthyroidism. Evaluate thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid-function tests may persist for months following amiodarone withdrawal.

There have been postmarketing reports of thyroid nodules/thyroid cancer in patients treated with amiodarone. In some instances hyperthyroidism was also present.

Hyperthyroidism and Thyrotoxicosis

Amiodarone causes hyperthyroidism in about 2% of patients. Thyrotoxicosis and arrhythmia with fatal outcome has been reported in the presence of pre-existing hyperthyroidism even following a single intravenous amiodarone dose. Consider the possibility of hyperthyroidism if any new signs of arrhythmia appear.

Hyperthyroidism may result from iodine load (type 1 amiodarone-induced thyrotoxicosis [type 1 AIT]; in particular in patients with underlying autonomous thyroid nodules or latent Grave's disease). Hyperthyroidism may also result from direct amiodarone-induced destructive thyroiditis that occurs in individuals with no underlying thyroid disease (type 2 AIT), resulting in the release of preformed thyroid hormone into the bloodstream from damaged thyroid follicular epithelium. Mixed forms of hyperthyroidism as a result of both pathogenic mechanisms (excessive thyroid hormone production and thyroid destruction) can also occur. The risk of hyperthyroidism may be higher among patients with prior inadequate dietary iodine intake.

Identify hyperthyroidism by relevant clinical signs and symptoms, subnormal serum levels of thyroid stimulating hormone (TSH), abnormally elevated serum free T4, and elevated or normal serum T3. Since arrhythmia breakthroughs may accompany amiodarone-induced hyperthyroidism, aggressive medical treatment is indicated, including, if possible, dose reduction or withdrawal of amiodarone. Amiodarone hyperthyroidism may be followed by a transient period of hypothyroidism.

The institution of antithyroid drugs, β-adrenergic blockers or temporary corticosteroid therapy may be necessary. The action of antithyroid drugs may be especially delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. Radioactive iodine therapy is not recommended because of the low radioiodine uptake associated with amiodarone-induced hyperthyroidism.

When aggressive treatment of amiodarone-induced thyrotoxicosis has failed or amiodarone cannot be discontinued because it is the only drug effective against the resistant arrhythmia, surgical management may be an option. Experience with thyroidectomy as a treatment for amiodarone-induced thyrotoxicosis is limited, and this form of therapy could induce thyroid storm. Therefore, surgical and anesthetic management require careful planning.

Hypothyroidism

Hypothyroidism has been reported in 2 to 10% of patients receiving amiodarone and may be primary or subsequent to resolution of preceding amiodarone-induced hyperthyroidism. This condition may be identified by clinical symptoms and elevated serum TSH levels. Cases of severe hypothyroidism and myxedema coma, sometimes fatal, have been reported in association with amiodarone therapy. In some clinically hypothyroid amiodarone-treated patients, free thyroxine index values may be normal. Manage hypothyroidism by reducing the dose of or discontinuing amiodarone and considering the need for thyroid hormone supplement.

Amiodarone can cause fetal harm when administered to a pregnant woman. Fetal exposure may increase the potential for adverse experiences including cardiac, thyroid, neurodevelopmental, neurological and growth effects in neonates. Inform the patient of the potential hazard to the fetus if amiodarone is administered during pregnancy or if the patient becomes pregnant while taking amiodarone [see Pregnancy (8.1)].

Perform close perioperative monitoring in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction defects of halogenated inhalational anesthetics.

Advise patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone.

Anaphylactic/anaphylactoid reactions have been reported with intravenous amiodarone including shock (sometimes fatal), cardiac arrest, and the following manifestations: hypotension, tachycardia, hypoxia, cyanosis, rash, flushing, hyperhidrosis and cold sweat.

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 a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received intravenous amiodarone for at least one week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks, without an increased incidence of severe adverse reactions. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days.

The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse reactions. The most common adverse reactions leading to discontinuation of intravenous amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%).

Table 5 lists the most common (incidence ≥2%) adverse reactions during intravenous amiodarone therapy considered at least possibly drug-related. These data were collected in clinical trials involving 1836 patients with life-threatening VT/VF. Data from all assigned treatment groups are pooled because none of the adverse reactions appeared to be dose-related.

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 5: ADVERSE REACTIONS IN PATIENTS RECEIVING INTRAVENOUS AMIODARONE IN CONTROLLED AND OPEN-LABEL STUDIES (≥ 2% INCIDENCE) </span> </caption> <col width="29%"/> <col width="9%"/> <col width="12%"/> <col width="12%"/> <col width="13%"/> <col width="9%"/> <col width="12%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> Study Event</span> <br/> </td><td align="center" class="Botrule Toprule" colspan="2" valign="top"><span class="Bold"> Controlled</span> <br/> <span class="Bold"> Studies</span> <br/> <span class="Bold"> (n = 814)</span> <br/> </td><td align="center" class="Botrule Toprule" colspan="2" valign="top"><span class="Bold"> Open-Label</span> <br/> <span class="Bold"> Studies</span> <br/> <span class="Bold"> (n = 1022)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"><span class="Bold"> Total</span> <br/> <span class="Bold"> (n = 1836)</span> <br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"><span class="Bold"> Body as a whole</span> <br/> </td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Fever<br/> </td><td align="center" valign="top"> 24<br/> </td><td align="center" valign="top"> (2.9%)<br/> </td><td align="center" valign="top"> 13<br/> </td><td align="center" valign="top"> (1.2%)<br/> </td><td align="center" valign="top"> 37<br/> </td><td align="center" class="Rrule" valign="top"> (2.0%)<br/> </td> </tr> <tr> <td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="left" class="Lrule" valign="top"><span class="Bold"> Cardiovascular System</span> <br/> </td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Bradycardia<br/> </td><td align="center" valign="top"> 49<br/> </td><td align="center" valign="top"> (6%)<br/> </td><td align="center" valign="top"> 41<br/> </td><td align="center" valign="top"> (4%)<br/> </td><td align="center" valign="top"> 90<br/> </td><td align="center" class="Rrule" valign="top"> (4.9%)<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Congestive heart failure<br/> </td><td align="center" valign="top"> 18<br/> </td><td align="center" valign="top"> (2.2%)<br/> </td><td align="center" valign="top"> 21<br/> </td><td align="center" valign="top"> (2%)<br/> </td><td align="center" valign="top"> 39<br/> </td><td align="center" class="Rrule" valign="top"> (2.1%)<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Heart arrest<br/> </td><td align="center" valign="top"> 29<br/> </td><td align="center" valign="top"> (3.5%)<br/> </td><td align="center" valign="top"> 26<br/> </td><td align="center" valign="top"> (2.5%)<br/> </td><td align="center" valign="top"> 55<br/> </td><td align="center" class="Rrule" valign="top"> (2.9%)<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Hypotension<br/> </td><td align="center" valign="top"> 165<br/> </td><td align="center" valign="top"> (20.2%)<br/> </td><td align="center" valign="top"> 123<br/> </td><td align="center" valign="top"> (12%)<br/> </td><td align="center" valign="top"> 288<br/> </td><td align="center" class="Rrule" valign="top"> (15.6%)<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Ventricular tachycardia<br/> </td><td align="center" valign="top"> 15<br/> </td><td align="center" valign="top"> (1.8%)<br/> </td><td align="center" valign="top"> 30<br/> </td><td align="center" valign="top"> (2.9%)<br/> </td><td align="center" valign="top"> 45<br/> </td><td align="center" class="Rrule" valign="top"> (2.4%)<br/> </td> </tr> <tr> <td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="left" class="Lrule" valign="top"><span class="Bold"> Digestive System</span> <br/> </td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Liver function tests abnormal<br/> </td><td align="center" valign="top"> 35<br/> </td><td align="center" valign="top"> (4.2%)<br/> </td><td align="center" valign="top"> 29<br/> </td><td align="center" valign="top"> (2.8%)<br/> </td><td align="center" valign="top"> 64<br/> </td><td align="center" class="Rrule" valign="top"> (3.4%)<br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule" valign="top"> Nausea<br/> </td><td align="center" class="Botrule" valign="top"> 29<br/> </td><td align="center" class="Botrule" valign="top"> (3.5%)<br/> </td><td align="center" class="Botrule" valign="top"> 43<br/> </td><td align="center" class="Botrule" valign="top"> (4.2%)<br/> </td><td align="center" class="Botrule" valign="top"> 72<br/> </td><td align="center" class="Botrule Rrule" valign="top"> (3.9%)<br/> </td> </tr> </tbody> </table></div>

Other adverse reactions reported in less than 2% of patients receiving intravenous amiodarone in controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.

The following adverse reactions have been reported in the post-marketing experience during or in close temporal relationship to intravenous amiodarone administration. 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.

Blood and Lymphatic System Disorders: pancytopenia, neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia, and agranulocytosis.

Cardiac Disorders: sinus node dysfunction (sinus arrest, sinoatrial block), intraventricular conduction disorders including bundle branch block and infra-HIS block, bradycardia (sometimes fatal), ventricular extrasystoles, and antegrade conduction via an accessory pathway.

Endocrine Disorders: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Eye Disorders: visual field defect and blurred vision.

Gastrointestinal Disorders: pancreatitis.

General Disorders and Administration Site Conditions: infusion site reactions, including thrombosis, phlebitis, thrombophlebitis, cellulitis, pain, induration, edema, inflammation, urticaria, pruritus, erythema, pigment changes, hypoesthesia, skin sloughing, extravasation possibly leading to venous/infusion site necrosis, intravascular amiodarone deposition/mass (developed in the superior vena cava around a central venous catheter after long-term [28 days] amiodarone therapy administered through a central line), and granuloma.

Hepatobiliary Disorders: cholestasis, cirrhosis, jaundice, alkaline phosphatase and blood lactate dehydrogenase increase.

Musculoskeletal and Connective Tissue Disorders: myopathy, muscle weakness, rhabdomyolysis, muscle spasms, and back pain.

Neoplasms Benign, Malignant and Unspecified (incl Cysts and Polyps) Disorders: thyroid nodules/thyroid cancer.

Nervous System Disorders: intracranial pressure increased, pseudotumor cerebri, tremor, dizziness and hypoesthesia.

Psychiatric Disorders: confusional state, hallucination, disorientation, and delirium.

Renal and Urinary Disorders: acute renal failure (sometimes fatal), renal impairment, renal insufficiency, and blood creatinine increased.

Reproductive Disorders and Breast Disorders: Epididymitis

Respiratory, Thoracic and Mediastinal Disorders: interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia (possibly fatal), pulmonary alveolar hemorrhage, pulmonary phospholipidoisis, pleural effusion, bronchospasm, dyspnea, cough, hemoptysis, wheezing, and hypoxia.

Skin and Subcutaneous Tissue Disorders: toxic epidermal necrolysis (sometimes fatal), Stevens-Johnson syndrome, exfoliative dermatitis, erythema multiforme, skin cancer, pruritus, angioedema, and urticaria.

Vascular Disorders: vasculitis and flushing.

Drugs prolonging the QT interval: Co-administration of drugs prolonging the QT interval (such as class I and III antiarrhythmics, lithium, certain phenothiazines, tricyclic antidepressants, certain fluoroquinolone and macrolide antibiotics, azole antifungals, halogenated inhalation anesthetic agents) increases the risk of Torsade de Pointes. In general, avoid concomitant use of drugs that prolong the QT interval [see Warnings and Precautions (5.4)].

Drugs that slow heart rate: Concomitant use of drugs with depressant effects on the sinus and AV nodes (e.g., digoxin, beta blockers, verapamil, diltiazem, ivabradine, clonidine) can potentiate the electrophysiologic and hemodynamic effects of amiodarone, resulting in bradycardia, sinus arrest, and AV block. Monitor heart rate in patients on amiodarone and concomitant drugs that slow heart rate.

Effect of other drugs on amiodarone

Amiodarone is metabolized to the active metabolite desethylamiodarone (DEA) by the cytochrome P450 (CYP450) enzyme group, specifically CYP3A and CYP2C8.

Amiodarone has the potential for interactions with drugs or substances that may be substrates, inhibitors or inducers of CYP450 enzymes (e.g., inhibitors such as protease inhibitors, grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals and inducers such as St. John's Wort) or P-glycoprotein. In view of the long and variable half- life of amiodarone, potential for drug interactions exists not only with concomitant medications but also with drugs administered after discontinuation of amiodarone [see Clinical Pharmacology (12.3)].

Patients should avoid grapefruit juice beverages while taking amiodarone because exposure to amiodarone is significantly increased [see Clinical Pharmacology (12.3)].

Effect of amiodarone on other drugs

Amiodarone and DEA are inhibitors of P-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A [see Clinical Pharmacology (12.3)].

Antiarrhythmics: The metabolism of quinidine, procainamide, and flecainide can be inhibited by amiodarone. In general, initiate any added antiarrhythmic drug at a lower than usual dose and monitor the patient carefully.

During transfer to oral amiodarone, reduce the dose levels of previously administered antiarrhythmic agents by 30 to 50% several days after the addition of oral amiodarone. Review the continued need for the other antiarrhythmic agent after the effects of amiodarone have been established, and attempt discontinuation [see Clinical Pharmacology (12.3)].

Digoxin: In patients receiving digoxin therapy, administration of oral amiodarone results in an increase in serum digoxin concentration. Reduce dose of digoxin by half or discontinue digoxin. If digitalis treatment is continued, monitor serum levels closely and observe patients for clinical evidence of toxicity [see Clinical Pharmacology (12.3)].

HMG-CoA Reductase Inhibitors: Limit the dose of simvastatin in patients on amiodarone to 20 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as amiodarone may increase the plasma concentration of these drugs.

Anticoagulants: Potentiation of warfarin-type (CYP2C9 and CYP3A substrate) anticoagulant response is almost always seen in patients receiving amiodarone and can result in serious or fatal bleeding. Since the concomitant administration of warfarin with amiodarone increases INR by 100% after 3 to 4 days, reduce the dose of the anticoagulant by one-third to one-half, and monitor INR closely.

Cyclosporine (CYP3A substrate) administered in combination with oral amiodarone has been reported to produce persistently elevated plasma concentrations of cyclosporine resulting in elevated creatinine, despite reduction in dose of cyclosporine. Monitor cyclosporine drug levels and renal function in patients taking both drugs.

Increased steady-state levels of phenytoin during concomitant therapy with amiodarone have been reported. Monitor phenytoin levels in patients taking both drugs.

Postmarketing cases of symptomatic bradycardia, some requiring pacemaker insertion and at least one fatal, have been reported when ledipasvir/sofosbuvir or sofosbuvir with simeprevir were initiated in patients on amiodarone. Bradycardia generally occurred within hours to days, but in some cases up to 2 weeks after initiating antiviral treatment. Bradycardia generally resolved after discontinuation of antiviral treatment. The mechanism for this effect is unknown. Monitor heart rate in patients taking or recently discontinuing amiodarone when starting antiviral treatment.

Pregnancy Category D [see Warnings and Precautions (5.8)].

Teratogenic Effects

Amiodarone and desethylamiodarone cross the placenta.

Reported risks include:

Amiodarone has caused a variety of adverse effects in animals.

Amiodarone was given intravenously to rabbits at dosages of 5, 10, or 25 mg/kg per day (about 0.1, 0.3, and 0.7 times the human intravenous maintenance dose of 0.5 mg/min on a body surface area basis), during gestation days 8 to 16 (organogenesis). The incidence of maternal deaths increased with increasing dose and occurred in all treated groups, and controls. Mean fetal weights were significantly decreased in the low and middle dose groups and embryotoxicity (as manifested by fewer full- term fetuses and increased resorptions) occurred at dosages of 10 mg/kg and above. There were no significant differences in the number of minor fetal abnormalities and no major fetal abnormalities were observed.

Amiodarone was administered by continuous intravenous infusion to rats at dosages of 25, 50, or 100 mg/kg per day (about 0.3, 0.7, and 1.3 times the human intravenous maintenance dose of 0.5 mg/min on a body surface area basis) during gestation days 8 to 16 (organogenesis). Maternal toxicity (manifest as reduced weight gain and food consumption) and embryotoxicity (manifest as increased resorptions, decreased live litter size and fetal body weights, and delayed sternal and metacarpal ossification) were observed in the 100 mg/kg group. The delayed ossification was reversible and related to decreased fetal weight. Fetal thyroid tissues appeared normal in all groups.

Nonteratogenic Effects

Very high concentrations of amiodarone and desethylamiodarone may be found in testes. Elevated follicle-stimulating hormone and luteinizing hormone levels, suggestive of testicular dysfunction, have been reported in men on long-term amiodarone treatment.

While planning pregnancy after discontinuation of amiodarone treatment, consider the long half-life of amiodarone and its metabolite DEA.

It is not known whether the use of amiodarone during labor or delivery has any immediate or delayed adverse effects. Preclinical studies in rodents have not shown any effect on the duration of gestation or on parturition.

Amiodarone and one of its major metabolites, desethylamiodarone (DEA), are excreted in human milk, suggesting that breast-feeding could expose the nursing infant to a significant dose of the drug. Nursing offspring of lactating rats administered amiodarone have demonstrated reduced viability and reduced body weight gains. The risk of exposing the infant to amiodarone must be weighed against the potential benefit of arrhythmia suppression in the mother. Advise the mother to discontinue nursing.

The safety and effectiveness of amiodarone in pediatric patients have not been established; therefore, the use of amiodarone in pediatric patients is not recommended. In a pediatric trial of 61 patients, aged 30 days to 15 years, hypotension (36%), bradycardia (20%), and AV block (15%) were common dose-related adverse reactions and were severe or life-threatening in some cases. Injection site reactions were seen in 5 (25%) of the 20 patients receiving intravenous amiodarone through a peripheral vein irrespective of dose regimen. 

Amiodarone injection contains the preservative benzyl alcohol [see Description (11)]. There have been reports of fatal "gasping syndrome" in neonates (children less than one month of age) following the administration of intravenous solutions containing the preservative benzyl alcohol. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse.

Clinical studies of amiodarone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Carefully consider dose selection in an elderly patient. In general, start at the low end of the dosing range in the elderly to reflect the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

There have been cases, some fatal, of amiodarone overdose. Effects of an inadvertent overdose of intravenous amiodarone include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity. Treat hypotension and cardiogenic shock by slowing the infusion rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion. Bradycardia and AV block may require temporary pacing. Monitor hepatic enzyme concentrations closely. Neither amiodarone nor DEA is dialyzable.

{ "type": "p", "children": [], "text": "\nThere have been cases, some fatal, of amiodarone overdose. Effects of an inadvertent overdose of intravenous amiodarone include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity. Treat hypotension and cardiogenic shock by slowing the infusion rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion. Bradycardia and AV block may require temporary pacing. Monitor hepatic enzyme concentrations closely. Neither amiodarone nor DEA is dialyzable." }

Amiodarone injection contains amiodarone HCl (C25H29I2NO3•HCl), a class III antiarrhythmic drug. Amiodarone HCl is (2-butyl-3-benzo-furanyl)[4-[2- (diethylamino)ethoxy]-3,5-diiodophenyl]methanone hydrochloride.

{ "type": "p", "children": [], "text": "\nAmiodarone injection contains amiodarone HCl (C25H29I2NO3•HCl), a class III antiarrhythmic drug. Amiodarone HCl is (2-butyl-3-benzo-furanyl)[4-[2- (diethylamino)ethoxy]-3,5-diiodophenyl]methanone hydrochloride." }

Amiodarone HCl has the following structural formula:

{ "type": "p", "children": [], "text": "Amiodarone HCl has the following structural formula: " }

Amiodarone HCl is a white to slightly yellow crystalline powder, and is very slightly soluble in water. It has a molecular weight of 681.78 and contains 37.3% iodine by weight. Amiodarone injection is a sterile clear, pale-yellow micellar solution visually free from particulates. Each milliliter of the amiodarone formulation contains 50 mg of amiodarone HCl USP, 20.2 mg of benzyl alcohol, 100 mg of polysorbate 80, and water for injection.

{ "type": "p", "children": [], "text": "\nAmiodarone HCl is a white to slightly yellow crystalline powder, and is very slightly soluble in water. It has a molecular weight of 681.78 and contains 37.3% iodine by weight. Amiodarone injection is a sterile clear, pale-yellow micellar solution visually free from particulates. Each milliliter of the amiodarone formulation contains 50 mg of amiodarone HCl USP, 20.2 mg of benzyl alcohol, 100 mg of polysorbate 80, and water for injection." }

Amiodarone injection contains polysorbate 80, which is known to leach di-(2- ethylhexyl)phthalate (DEHP) from polyvinylchloride (PVC) [(see Dosage and Administration (2)].

{ "type": "p", "children": [], "text": "Amiodarone injection contains polysorbate 80, which is known to leach di-(2- ethylhexyl)phthalate (DEHP) from polyvinylchloride (PVC) [(see Dosage and Administration (2)].\n" }

Amiodarone is generally considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, amiodarone exerts a noncompetitive antisympathetic action. One of its main effects, with prolonged administration, is to lengthen the cardiac action potential, a class III effect. The negative chronotropic effect of amiodarone in nodal tissues is similar to the effect of class IV drugs. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness. The antisympathetic action and the block of calcium and potassium channels are responsible for the negative dromotropic effects on the sinus node and for the slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node. Its vasodilatory action can decrease cardiac workload and consequently myocardial oxygen consumption.

Intravenous amiodarone administration prolongs intranodal conduction (Atrial-His, AH) and refractoriness of the atrioventricular node (ERP AVN), but has little or no effect on sinus cycle length (SCL), refractoriness of the right atrium and right ventricle (ERP RA and ERP RV), repolarization (QTc), intraventricular conduction (QRS), and infra-nodal conduction (His-ventricular, HV). A comparison of the electrophysiologic effects of intravenous amiodarone and oral amiodarone is shown in the table below.

<div class="scrollingtable"><table width="100%"> <caption> <span> Table 6: EFFECTS OF INTRAVENOUS AND ORAL AMIODARONE ON ELECTROPHYSIOLOGIC PARAMETERS </span> </caption> <col width="20%"/> <col width="10%"/> <col width="10%"/> <col width="9%"/> <col width="8%"/> <col width="8%"/> <col width="10%"/> <col width="10%"/> <col width="11%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="9"> <p class="First Footnote">↔   No change</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"> Formulation<br/> </td><td align="left" class="Botrule Toprule" valign="top"> SCL<br/> </td><td align="left" class="Botrule Toprule" valign="top"> QRS<br/> </td><td align="left" class="Botrule Toprule" valign="top"> QTc<br/> </td><td align="left" class="Botrule Toprule" valign="top"> AH<br/> </td><td align="left" class="Botrule Toprule" valign="top"> HV<br/> </td><td align="left" class="Botrule Toprule" valign="top"> ERP RA<br/> </td><td align="left" class="Botrule Toprule" valign="top"> ERP RV<br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"> ERP AVN<br/> </td> </tr> <tr> <td align="left" class="Lrule" valign="top"> Intravenous<br/> </td><td align="center" valign="top"> ↔<br/> </td><td align="center" valign="top"> ↔<br/> </td><td align="center" valign="top"> ↔<br/> </td><td align="center" valign="top"> ↑<br/> </td><td align="center" valign="top"> ↔<br/> </td><td align="center" valign="top"> ↔<br/> </td><td align="center" valign="top"> ↔<br/> </td><td align="center" class="Rrule" valign="top"> ↑<br/> </td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule" valign="top"> Oral<br/> </td><td align="center" class="Botrule" valign="top"> ↑<br/> </td><td align="center" class="Botrule" valign="top"> ↔<br/> </td><td align="center" class="Botrule" valign="top"> ↑<br/> </td><td align="center" class="Botrule" valign="top"> ↑<br/> </td><td align="center" class="Botrule" valign="top"> ↔<br/> </td><td align="center" class="Botrule" valign="top"> ↑<br/> </td><td align="center" class="Botrule" valign="top"> ↑<br/> </td><td align="center" class="Botrule Rrule" valign="top"> ↑<br/> </td> </tr> </tbody> </table></div>

At higher doses (>10 mg/kg) of intravenous amiodarone, prolongation of the ERP RV and modest prolongation of the QRS have been seen. These differences between oral and IV administration suggest that the initial acute effects of intravenous amiodarone may be predominately focused on the AV node, causing an intranodal conduction delay and increased nodal refractoriness due to slow channel blockade (class IV activity) and noncompetitive adrenergic antagonism (class II activity).

Intravenous amiodarone has been reported to produce negative inotropic and vasodilatory effects in animals and humans. In clinical studies of patients with refractory VF or hemodynamically unstable VT, treatment-emergent, drug-related hypotension occurred in 288 of 1836 patients (16%) treated with intravenous amiodarone. No correlations were seen between the baseline ejection fraction and the occurrence of clinically significant hypotension during infusion of intravenous amiodarone.

No data are available on the activity of DEA in humans, but in animals, it has significant electrophysiologic and antiarrhythmic effects generally similar to amiodarone itself. DEA's precise role and contribution to the antiarrhythmic activity of oral amiodarone are not certain. The development of maximal ventricular class III effects after oral amiodarone administration in humans correlates more closely with DEA accumulation over time than with amiodarone accumulation. On the other hand, after intravenous amiodarone administration, there is evidence of activity well before significant concentrations of DEA are attained [see Clinical Trials (14)].

Disposition:

Amiodarone exhibits complex disposition characteristics after intravenous administration. Peak serum concentrations after single 5 mg/kg 15-minute intravenous infusions in healthy subjects range between 5 and 41 mg/L. Peak concentrations after 10-minute infusions of 150 mg intravenous amiodarone in patients with ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT) range between 7 and 26 mg/L. Due to rapid distribution, serum concentrations decline to 10% of peak values within 30 to 45 minutes after the end of the infusion. In clinical trials, after 48 hours of continued infusions (125, 500 or 1000 mg/day) plus supplemental (150 mg) infusions (for recurrent arrhythmias), amiodarone mean serum concentrations between 0.7 to 1.4 mg/L were observed (n=260).

Metabolism:

N-desethylamiodarone (DEA) is the major active metabolite of amiodarone in humans.  DEA serum concentrations above 0.05 mg/L are not usually seen until after several days of continuous infusion but with prolonged therapy reach approximately the same concentration as amiodarone. Amiodarone is metabolized to DEA by the cytochrome P450 (CYP450) enzyme group, specifically cytochrome CYP3A and CYP2C8.  The CYP3A isoenzyme is present in both the liver and intestines. The highly variable systemic availability of oral amiodarone may be attributed to large interindividual variability in CYP3A activity.

Distribution/Elimination:

From in vitro studies, the protein binding of amiodarone is >96%. Amiodarone and DEA cross the placenta and both appear in breast milk. Neither amiodarone nor DEA is dialyzable.

Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine. In studies in healthy subjects following single intravenous administration (5 mg/kg of amiodarone over 15 min), the plasma concentration vs. time profile could be characterized by linear sum of four exponential terms with terminal elimination half-lives (t½) of 9 to 36 days for amiodarone and 9 to 30 days for DEA. The clearance of amiodarone and DEA ranged between 63 to 231 mL/hr/kg and 140 to 400 ml/h/kg, respectively. In clinical studies of 2 to 7 days, clearance of amiodarone after intravenous administration in patients with VT and VF ranged between 220 and 440 mL/hr/kg.

Special Populations:

Effect of Age: The pharmacokinetics of amiodarone and DEA are affected by age. Normal subjects over 65 years of age show lower clearances (about 100 mL/hr/kg) than younger subjects (about 150 mL/hr/kg) and an increase in t½ from about 20 to 47 days.

Effect of Gender: Pharmacokinetics of amiodarone and DEA are similar in males and females.

Renal Impairment: Renal disease does not influence the pharmacokinetics of amiodarone or DEA.

Hepatic Impairment: After a single dose of intravenous amiodarone to cirrhotic patients, significantly lower Cmax and average concentration values are seen for DEA, but mean amiodarone levels are unchanged.

Cardiac Disease: In patients with severe left ventricular dysfunction, the pharmacokinetics of amiodarone are not significantly altered but the terminal elimination t½ of DEA is prolonged.

Although no dosage adjustment for patients with renal, hepatic, or cardiac abnormalities has been defined during chronic treatment with oral amiodarone, close clinical monitoring is prudent for elderly patients and those with severe left ventricular dysfunction.

Exposure-Response: There is no established relationship between drug concentration and therapeutic response for short-term intravenous use.

Drug Interactions:

Effect of other drugs on amiodarone:

Cimetidine inhibits CYP3A and can increase serum amiodarone levels.

Grapefruit juice given to healthy volunteers increased amiodarone AUC by 50% and Cmax by 84%, resulting in increased plasma levels of amiodarone.

Cholestyramine reduces enterohepatic circulation of amiodarone thereby increasing its elimination. This results in reduced amiodarone serum levels and half-life.

Effect of amiodarone on other drugs:

Amiodarone taken concomitantly with quinidine increases the quinidine serum concentration by 33% after two days. Amiodarone taken concomitantly with procainamide for less than seven days increases plasma concentrations of procainamide and n-acetyl procainamide by 55% and 33%, respectively.

Loratadine, a non-sedating antihistaminic, is metabolized primarily by CYP3A and its metabolism can be inhibited by amiodarone.

Metabolism of lidocaine can be inhibited by amiodarone. Sinus bradycardia has been reported with oral amiodarone in combination with lidocaine (CYP3A substrate) given for local anesthesia. Seizure, associated with increased lidocaine concentrations, has been reported with concomitant administration of intravenous amiodarone.

Amiodarone can inhibit the metabolismof macrolide/ketolide antibiotics (except for azithromycin) and systemic azole antifungal drugs.

Amiodarone taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day.

Dextromethorphan is a substrate for both CYP2D6 and CYP3A. Amiodarone inhibits CYP2D6. Chronic (> 2 weeks) oral amiodarone administration impairs metabolism of dextromethorphan can lead to increased serum concentrations.

Dabigatran etexilate when taken concomitantly with oral amiodarone can result in elevated serum concentration of dabigatran.

Cyclophosphamide is a prodrug, metabolized by CYP450 including CYP3A to an active metabolite. The metabolism of cyclophosphamide may be inhibited by amiodarone.

Clopidogrel, an inactive thienopyridine prodrug, is metabolized in the liver by CYP3A to an active metabolite. A potential interaction between clopidogrel and amiodarone resulting in ineffective inhibition of platelet aggregation has been reported.

No carcinogenicity studies were conducted with intravenous administration of amiodarone. However, oral amiodarone caused a statistically significant, dose-related increase in the incidence of thyroid tumors (follicular adenoma and carcinoma) in rats. The incidence of thyroid tumors in rats was greater than the incidence in controls even at the lowest dose level tested, i.e., 5 mg/kg/day (much less, on a body surface area basis, than the maximum recommended human maintenance dose of 600 mg/day).

Mutagenicity studies conducted with amiodarone HCl (Ames, micronucleus, and lysogenic induction tests) were negative.

No fertility studies were conducted with intravenous administration of amiodarone. However, in a study in which amiodarone HCl was orally administered to male and female rats, beginning 9 weeks prior to mating, reduced fertility was observed at a dose level of 90 mg/kg/day (approximately 1.4 times the maximum recommended human maintenance dose of 600 mg/day). 

Apart from studies in patients with VT or VF, described below, there are two other studies of amiodarone showing an antiarrhythmic effect before significant levels of DEA could have accumulated. A placebo-controlled study of intravenous amiodarone (300 mg over 2 hours followed by 1200 mg/day) in post-coronary artery bypass graft patients with supraventricular and 2- to 3-consecutive-beat ventricular arrhythmias showed a reduction in arrhythmias from 12 hours on. A baseline-controlled study using a similar IV regimen in patients with recurrent, refractory VT/VF also showed rapid onset of antiarrhythmic activity; amiodarone therapy reduced episodes of VT by 85% compared to baseline.

{ "type": "p", "children": [], "text": "\nApart from studies in patients with VT or VF, described below, there are two other studies of amiodarone showing an antiarrhythmic effect before significant levels of DEA could have accumulated. A placebo-controlled study of intravenous amiodarone (300 mg over 2 hours followed by 1200 mg/day) in post-coronary artery bypass graft patients with supraventricular and 2- to 3-consecutive-beat ventricular arrhythmias showed a reduction in arrhythmias from 12 hours on. A baseline-controlled study using a similar IV regimen in patients with recurrent, refractory VT/VF also showed rapid onset of antiarrhythmic activity; amiodarone therapy reduced episodes of VT by 85% compared to baseline." }

The acute effectiveness of intravenous amiodarone in suppressing recurrent VF or hemodynamically unstable VT is supported by two randomized, parallel, dose-response studies of approximately 300 patients each. In these studies, patients with at least two episodes of VF or hemodynamically unstable VT in the preceding 24 hours were randomly assigned to receive doses of approximately 125 or 1000 mg over the first 24 hours, an 8-fold difference. In one study, a middle dose of approximately 500 mg was evaluated. The dose regimen consisted of an initial rapid loading infusion, followed by a slower 6-hour loading infusion, and then an 18-hour maintenance infusion. The maintenance infusion was continued up to hour 48. Additional 10-minute infusions of 150 mg intravenous amiodarone were given for "breakthrough" VT/VF more frequently to the 125 mg dose group, thereby considerably reducing the planned 8-fold differences in total dose to 1.8- and 2.6-fold, respectively, in the two studies.

{ "type": "p", "children": [], "text": "The acute effectiveness of intravenous amiodarone in suppressing recurrent VF or hemodynamically unstable VT is supported by two randomized, parallel, dose-response studies of approximately 300 patients each. In these studies, patients with at least two episodes of VF or hemodynamically unstable VT in the preceding 24 hours were randomly assigned to receive doses of approximately 125 or 1000 mg over the first 24 hours, an 8-fold difference. In one study, a middle dose of approximately 500 mg was evaluated. The dose regimen consisted of an initial rapid loading infusion, followed by a slower 6-hour loading infusion, and then an 18-hour maintenance infusion. The maintenance infusion was continued up to hour 48. Additional 10-minute infusions of 150 mg intravenous amiodarone were given for \"breakthrough\" VT/VF more frequently to the 125 mg dose group, thereby considerably reducing the planned 8-fold differences in total dose to 1.8- and 2.6-fold, respectively, in the two studies." }

The prospectively defined primary efficacy end point was the rate of VT/VF episodes per hour. For both studies, the median rate was 0.02 episodes per hour in patients receiving the high dose and 0.07 episodes per hour in patients receiving the low dose, or approximately 0.5 versus 1.7 episodes per day (p=0.07, 2-sided, in both studies). In one study, the time to first episode of VT/VF was significantly prolonged (approximately 10 hours in patients receiving the low dose and 14 hours in patients receiving the high dose). In both studies, significantly fewer supplemental infusions were given to patients in the high-dose group. At the end of double-blind therapy or after 48 hours, all patients were given open access to whatever treatment (including intravenous amiodarone) was deemed necessary. Mortality was not affected in these studies.

{ "type": "p", "children": [], "text": "The prospectively defined primary efficacy end point was the rate of VT/VF episodes per hour. For both studies, the median rate was 0.02 episodes per hour in patients receiving the high dose and 0.07 episodes per hour in patients receiving the low dose, or approximately 0.5 versus 1.7 episodes per day (p=0.07, 2-sided, in both studies). In one study, the time to first episode of VT/VF was significantly prolonged (approximately 10 hours in patients receiving the low dose and 14 hours in patients receiving the high dose). In both studies, significantly fewer supplemental infusions were given to patients in the high-dose group. At the end of double-blind therapy or after 48 hours, all patients were given open access to whatever treatment (including intravenous amiodarone) was deemed necessary. Mortality was not affected in these studies." }

Amiodarone hydrochloride injection is available, as follows:

{ "type": "p", "children": [], "text": "\nAmiodarone hydrochloride injection is available, as follows:" }

NDC 64679-780-01, 50 mg/mL, 900 mg/18 mL, multiple-dose vial, carton of 1 vial.

{ "type": "p", "children": [], "text": "NDC 64679-780-01, 50 mg/mL, 900 mg/18 mL, multiple-dose vial, carton of 1 vial." }

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

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

Protect from light and excessive heat.

{ "type": "p", "children": [], "text": "Protect from light and excessive heat. " }

Use carton to protect contents from light until used.

{ "type": "p", "children": [], "text": "Use carton to protect contents from light until used." }

Amiodarone has the potential to cause serious side effects that limit its use to life-threatening and hemodynamically unstable cardiac arrhythmias.  Advise female patients to discontinue nursing while being treated with amiodarone, as breast-feeding could expose the nursing infant to a significant dose of the drug. Recommend that patients avoid grapefruit juice, over-the-counter cough medicines (which commonly contain dextromethorphan), and St. John's Wort. Inform patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone. Discuss the symptoms of hypo- and hyper-thyroidism, particularly if patients will be transitioned to oral amiodarone.

{ "type": "p", "children": [], "text": "\nAmiodarone has the potential to cause serious side effects that limit its use to life-threatening and hemodynamically unstable cardiac arrhythmias.  Advise female patients to discontinue nursing while being treated with amiodarone, as breast-feeding could expose the nursing infant to a significant dose of the drug. Recommend that patients avoid grapefruit juice, over-the-counter cough medicines (which commonly contain dextromethorphan), and St. John's Wort. Inform patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone. Discuss the symptoms of hypo- and hyper-thyroidism, particularly if patients will be transitioned to oral amiodarone." }

Manufactured by:

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

Wockhardt Limited

{ "type": "p", "children": [], "text": "Wockhardt Limited" }

Mumbai, India.

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

Distributed by:

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

Wockhardt USA LLC.

{ "type": "p", "children": [], "text": "Wockhardt USA LLC." }

20 Waterview Blvd.

{ "type": "p", "children": [], "text": "20 Waterview Blvd." }

Parsippany, NJ 07054

{ "type": "p", "children": [], "text": "Parsippany, NJ 07054" }

USA.

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

Iss.020517

{ "type": "p", "children": [], "text": "Iss.020517" }

DRUG: Amiodarone Hydrochloride

{ "type": "p", "children": [], "text": "\nDRUG: Amiodarone Hydrochloride" }

GENERIC: Amiodarone Hydrochloride

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

DOSAGE: Injection

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

ADMINSTRATION: Intravenous

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

NDC: 64679-780-01

{ "type": "p", "children": [], "text": "NDC: 64679-780-01" }

STRENGTH: 900 mg/18 mL (50 mg/mL)

{ "type": "p", "children": [], "text": "STRENGTH: 900 mg/18 mL (50 mg/mL)" }

QTY: 18 mL Multiple Use Vial Label

{ "type": "p", "children": [], "text": "QTY: 18 mL Multiple Use Vial Label" }

Amiodarone Hydrochloride Injection, USP is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. Amiodarone Hydrochloride Injection, USP also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with Amiodarone Hydrochloride Injection, USP patients may be transferred to oral amiodarone therapy [see Dosage and Administration ( 2)] .

{ "type": "p", "children": [], "text": "Amiodarone Hydrochloride Injection, USP is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. Amiodarone Hydrochloride Injection, USP also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with Amiodarone Hydrochloride Injection, USP patients may be transferred to oral amiodarone therapy\n \n [see Dosage and Administration (\n \n 2)]\n \n .\n\n " }

Use Amiodarone Hydrochloride Injection, USP for acute treatment until the patient's ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but Amiodarone Hydrochloride Injection may be safely administered for longer periods if necessary.

{ "type": "p", "children": [], "text": "Use Amiodarone Hydrochloride Injection, USP for acute treatment until the patient's ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but Amiodarone Hydrochloride Injection may be safely administered for longer periods if necessary." }

Amiodarone shows considerable interindividual variation in response. Although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose is essential. The recommended starting dose of amiodarone is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:

{ "type": "p", "children": [], "text": "Amiodarone shows considerable interindividual variation in response. Although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose is essential. The recommended starting dose of amiodarone is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:" }

<div class="scrollingtable"><table> <caption> <span>Table 1: AMIODARONE DOSE RECOMMENDATIONS: FIRST 24 HOURS</span> </caption> <col width="25%"/> <col width="25%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td valign="top">  <span class="Bold">Loading infusions</span></td><td align="right" valign="top">  <span class="Bold"><span class="Italics">First</span>Rapid: </span></td><td valign="top">  <span class="Bold">150 mg over the FIRST 10 minutes (15 mg/min).</span> <br/> Add 3 mL of amiodarone (150 mg) to 100 mL <br/> D <span class="Sub">5</span>W (concentration = 1.5 mg/mL). Infuse 100 mL over 10 minutes. </td> </tr> <tr> <td valign="top"> </td><td align="right" valign="top">  <span class="Bold"><span class="Italics">Followed by</span>Slow: </span></td><td valign="top">  <span class="Bold">360 mg over the NEXT 6 hours (1 mg/min).</span> <br/> Add 18 mL of amiodarone (900 mg) to 500 mL D <span class="Sub">5</span>W (concentration = 1.8 mg/mL) </td> </tr> <tr class="Last"> <td valign="top">  <span class="Bold">Maintenance infusion</span></td><td align="right" valign="top"> </td><td valign="top">  <span class="Bold">540 mg over the REMAINING 18 hours (0.5 mg/min).</span> <br/> Decrease the rate of the slow loading infusion to 0.5 mg/min. </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 1: AMIODARONE DOSE RECOMMENDATIONS: FIRST 24 HOURS</span>\n</caption>\n<col width=\"25%\"/>\n<col width=\"25%\"/>\n<col width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td valign=\"top\"> \n \n <span class=\"Bold\">Loading infusions</span></td><td align=\"right\" valign=\"top\"> \n \n <span class=\"Bold\"><span class=\"Italics\">First</span>Rapid:\n \n </span></td><td valign=\"top\"> \n \n <span class=\"Bold\">150 mg over the FIRST 10 minutes (15 mg/min).</span>\n<br/> Add 3 mL of amiodarone (150 mg) to 100 mL \n <br/> D\n \n <span class=\"Sub\">5</span>W (concentration = 1.5 mg/mL). Infuse 100 mL over 10 minutes.\n \n </td>\n</tr>\n<tr>\n<td valign=\"top\"> </td><td align=\"right\" valign=\"top\"> \n \n <span class=\"Bold\"><span class=\"Italics\">Followed by</span>Slow:\n \n </span></td><td valign=\"top\"> \n \n <span class=\"Bold\">360 mg over the NEXT 6 hours (1 mg/min).</span>\n<br/> Add 18 mL of amiodarone (900 mg) to 500 mL D\n \n <span class=\"Sub\">5</span>W (concentration = 1.8 mg/mL)\n \n </td>\n</tr>\n<tr class=\"Last\">\n<td valign=\"top\"> \n \n <span class=\"Bold\">Maintenance infusion</span></td><td align=\"right\" valign=\"top\"> </td><td valign=\"top\"> \n \n <span class=\"Bold\">540 mg over the REMAINING 18 hours (0.5 mg/min).</span>\n<br/> Decrease the rate of the slow loading infusion to 0.5 mg/min.\n \n </td>\n</tr>\n</tbody>\n</table></div>" }

After the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) utilizing a concentration of 1 to 6 mg/mL (Use a central venous catheter for amiodarone concentrations greater than 2 mg/mL). The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression.

{ "type": "p", "children": [], "text": "After the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) utilizing a concentration of 1 to 6 mg/mL (Use a central venous catheter for amiodarone concentrations greater than 2 mg/mL). The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression." }

In the event of breakthrough episodes of VF or hemodynamically unstable VT, use 150 mg supplemental infusions of amiodarone (mixed in 100 mL of D 5W and infused over 10 minutes to minimize the potential for hypotension).

{ "type": "p", "children": [], "text": "In the event of breakthrough episodes of VF or hemodynamically unstable VT, use 150 mg supplemental infusions of amiodarone (mixed in 100 mL of D\n \n 5W and infused over 10 minutes to minimize the potential for hypotension).\n\n " }

The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. Do not exceed an initial infusion rate of 30 mg/min.

{ "type": "p", "children": [], "text": "The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. Do not exceed an initial infusion rate of 30 mg/min." }

Based on the experience from clinical studies of intravenous amiodarone, a maintenance infusion of up to 0.5 mg/min can be continued for 2 to 3 weeks regardless of the patient's age, renal function, or left ventricular function. There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks.

{ "type": "p", "children": [], "text": "Based on the experience from clinical studies of intravenous amiodarone, a maintenance infusion of up to 0.5 mg/min can be continued for 2 to 3 weeks regardless of the patient's age, renal function, or left ventricular function. There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks." }

The surface properties of solutions containing injectable amiodarone are altered such that the drop size may be reduced. This reduction may lead to underdosage of the patient by up to 30% if drop counter infusion sets are used. Amiodarone must be delivered by a volumetric infusion pump.

{ "type": "p", "children": [], "text": "The surface properties of solutions containing injectable amiodarone are altered such that the drop size may be reduced. This reduction may lead to underdosage of the patient by up to 30% if drop counter infusion sets are used. Amiodarone must be delivered by a volumetric infusion pump." }

Administer amiodarone, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration.

{ "type": "p", "children": [], "text": "Administer amiodarone, whenever possible, through a central venous catheter dedicated to that purpose. Use an in-line filter during administration." }

Intravenous amiodarone loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death [see Warnings and Precautions ( 5.3)] .

{ "type": "p", "children": [], "text": "Intravenous amiodarone loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death\n \n [see Warnings and Precautions (\n \n 5.3)]\n \n .\n\n " }

Intravenous amiodarone concentrations greater than 3 mg/mL in D 5W have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, do not exceed amiodarone concentrations of 2 mg/mL, unless a central venous catheter is used [see Adverse Reactions ( 6.2)] .

{ "type": "p", "children": [], "text": "Intravenous amiodarone concentrations greater than 3 mg/mL in D\n \n 5W have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, do not exceed amiodarone concentrations of 2 mg/mL, unless a central venous catheter is used\n \n [see Adverse Reactions (\n \n 6.2)]\n \n .\n\n " }

Amiodarone infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D 5W. Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation.

{ "type": "p", "children": [], "text": "Amiodarone infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D\n \n 5W. Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation.\n\n " }

Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, but all of the clinical experience has been with PVC tubing and the concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect dosing in these studies.

{ "type": "p", "children": [], "text": "Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, but all of the clinical experience has been with PVC tubing and the concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect dosing in these studies." }

Amiodarone has been found to leach out plasticizers, including DEHP [di-(2-ethylhexyl)phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing amiodarone at higher concentrations and lower flow rates than provided in DOSAGE AND ADMINISTRATION. Polysorbate 80, a component of amiodarone injection, is also known to leach DEHP from PVC [see Description ( 11)] .

{ "type": "p", "children": [], "text": "Amiodarone has been found to leach out plasticizers, including DEHP [di-(2-ethylhexyl)phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing amiodarone at higher concentrations and lower flow rates than provided in DOSAGE AND ADMINISTRATION. Polysorbate 80, a component of amiodarone injection, is also known to leach DEHP from PVC\n \n [see Description (\n \n 11)]\n \n .\n\n " }

Amiodarone does not need to be protected from light during administration.

{ "type": "p", "children": [], "text": "Amiodarone does not need to be protected from light during administration." }

NOTE: Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.

{ "type": "p", "children": [], "text": "NOTE: Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit." }

<div class="scrollingtable"><table> <caption> <span>Table 2: AMIODARONE HYDROCHLORIDE SOLUTION STABILITY</span> </caption> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <thead> <tr class="First Last"> <th align="center" class="Botrule">Solution</th><th align="center" class="Botrule">Concentration <br/> (mg/mL) </th><th align="center" class="Botrule">Container</th><th align="center" class="Botrule">Comments</th> </tr> </thead> <tbody> <tr class="First"> <td align="center">5% Dextrose in Water (D <span class="Sub">5</span>W) </td><td align="center">1 to 6</td><td align="center">PVC</td><td align="center">Physically compatible, with amiodarone loss &lt;10% at 2 hours at room temperature.</td> </tr> <tr class="Last"> <td align="center">5% Dextrose in Water (D <span class="Sub">5</span>W) </td><td align="center">1 to 6</td><td align="center">Polyolefin, Glass</td><td align="center">Physically compatible, with no amiodarone loss at 24 hours at room temperature.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 2: AMIODARONE HYDROCHLORIDE SOLUTION STABILITY</span>\n</caption>\n<col width=\"1px\"/>\n<col width=\"1px\"/>\n<col width=\"1px\"/>\n<col width=\"1px\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Botrule\">Solution</th><th align=\"center\" class=\"Botrule\">Concentration \n <br/> (mg/mL)\n </th><th align=\"center\" class=\"Botrule\">Container</th><th align=\"center\" class=\"Botrule\">Comments</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"center\">5% Dextrose in Water (D\n \n <span class=\"Sub\">5</span>W)\n \n </td><td align=\"center\">1 to 6</td><td align=\"center\">PVC</td><td align=\"center\">Physically compatible, with amiodarone loss &lt;10% at 2 hours at room temperature.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\">5% Dextrose in Water (D\n \n <span class=\"Sub\">5</span>W)\n \n </td><td align=\"center\">1 to 6</td><td align=\"center\">Polyolefin, Glass</td><td align=\"center\">Physically compatible, with no amiodarone loss at 24 hours at room temperature.</td>\n</tr>\n</tbody>\n</table></div>" }

Admixture Incompatibility

{ "type": "p", "children": [], "text": "\nAdmixture Incompatibility\n" }

Amiodarone in D 5W is incompatible with the drugs shown in Table 3.

{ "type": "p", "children": [], "text": "Amiodarone in D\n \n 5W is incompatible with the drugs shown in Table 3.\n\n " }

<div class="scrollingtable"><table> <caption> <span>Table 3: Y-SITE INJECTION INCOMPATIBILITY</span> </caption> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <thead> <tr class="First Last"> <th align="center" class="Botrule">Drug</th><th align="center" class="Botrule">Vehicle</th><th align="center" class="Botrule">Amiodarone Concentration</th><th align="center" class="Botrule">Comments</th> </tr> </thead> <tbody> <tr class="First"> <td align="center">Aminophylline</td><td align="center">D <span class="Sub">5</span>W </td><td align="center">4 mg/mL</td><td align="center">Precipitate</td> </tr> <tr> <td align="center">Cefamandole Nafate</td><td align="center">D <span class="Sub">5</span>W </td><td align="center">4 mg/mL</td><td align="center">Precipitate</td> </tr> <tr> <td align="center">Cefazolin Sodium</td><td align="center">D <span class="Sub">5</span>W </td><td align="center">4 mg/mL</td><td align="center">Precipitate</td> </tr> <tr> <td align="center">Mezlocillin Sodium</td><td align="center">D <span class="Sub">5</span>W </td><td align="center">4 mg/mL</td><td align="center">Precipitate</td> </tr> <tr> <td align="center">Heparin Sodium</td><td align="center">D <span class="Sub">5</span>W </td><td align="center">--</td><td align="center">Precipitate</td> </tr> <tr class="Last"> <td align="center">Sodium Bicarbonate</td><td align="center">D <span class="Sub">5</span>W </td><td align="center">3 mg/mL</td><td align="center">Precipitate</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 3: Y-SITE INJECTION INCOMPATIBILITY</span>\n</caption>\n<col width=\"1px\"/>\n<col width=\"1px\"/>\n<col width=\"1px\"/>\n<col width=\"1px\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Botrule\">Drug</th><th align=\"center\" class=\"Botrule\">Vehicle</th><th align=\"center\" class=\"Botrule\">Amiodarone Concentration</th><th align=\"center\" class=\"Botrule\">Comments</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"center\">Aminophylline</td><td align=\"center\">D\n \n <span class=\"Sub\">5</span>W\n \n </td><td align=\"center\">4 mg/mL</td><td align=\"center\">Precipitate</td>\n</tr>\n<tr>\n<td align=\"center\">Cefamandole Nafate</td><td align=\"center\">D\n \n <span class=\"Sub\">5</span>W\n \n </td><td align=\"center\">4 mg/mL</td><td align=\"center\">Precipitate</td>\n</tr>\n<tr>\n<td align=\"center\">Cefazolin Sodium</td><td align=\"center\">D\n \n <span class=\"Sub\">5</span>W\n \n </td><td align=\"center\">4 mg/mL</td><td align=\"center\">Precipitate</td>\n</tr>\n<tr>\n<td align=\"center\">Mezlocillin Sodium</td><td align=\"center\">D\n \n <span class=\"Sub\">5</span>W\n \n </td><td align=\"center\">4 mg/mL</td><td align=\"center\">Precipitate</td>\n</tr>\n<tr>\n<td align=\"center\">Heparin Sodium</td><td align=\"center\">D\n \n <span class=\"Sub\">5</span>W\n \n </td><td align=\"center\">--</td><td align=\"center\">Precipitate</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\">Sodium Bicarbonate</td><td align=\"center\">D\n \n <span class=\"Sub\">5</span>W\n \n </td><td align=\"center\">3 mg/mL</td><td align=\"center\">Precipitate</td>\n</tr>\n</tbody>\n</table></div>" }

Intravenous to Oral Transition 

{ "type": "p", "children": [], "text": "\nIntravenous to Oral Transition \n" }

Patients whose arrhythmias have been suppressed by amiodarone may be switched to oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients. See package insert for oral amiodarone.

{ "type": "p", "children": [], "text": "Patients whose arrhythmias have been suppressed by amiodarone may be switched to oral amiodarone. When changing to oral amiodarone therapy, clinical monitoring is recommended, particularly for elderly patients. See package insert for oral amiodarone." }

Since grapefruit juice is known to inhibit CYP3A-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, do not drink grapefruit juice during treatment with oral amiodarone [see Drug Interactions ( 7)] .

{ "type": "p", "children": [], "text": "Since grapefruit juice is known to inhibit CYP3A-mediated metabolism of oral amiodarone in the intestinal mucosa, resulting in increased plasma levels of amiodarone, do not drink grapefruit juice during treatment with oral amiodarone\n \n [see Drug Interactions (\n \n 7)]\n \n .\n\n " }

Table 4 provides suggested doses of oral amiodarone to be initiated after varying durations of amiodarone administration. These recommendations are made on the basis of a similar total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone.

{ "type": "p", "children": [], "text": "Table 4 provides suggested doses of oral amiodarone to be initiated after varying durations of amiodarone administration. These recommendations are made on the basis of a similar total body amount of amiodarone delivered by the intravenous and oral routes, based on 50% bioavailability of oral amiodarone." }

<div class="scrollingtable"><table> <caption> <span>Table 4: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS INFUSION</span> </caption> <col/> <col/> <thead> <tr class="First Last"> <th align="center">Duration of Amiodarone Infusion <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th><th align="center">Initial Daily Dose of Oral Amiodarone</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Assuming a 720 mg/day infusion (0.5 mg/min).</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>Intravenous amiodarone is not intended for maintenance treatment.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="center">&lt; 1 week</td><td align="center">800 to 1600 mg</td> </tr> <tr> <td align="center">1-3 weeks</td><td align="center">600 to 800 mg</td> </tr> <tr class="Last"> <td align="center">&gt; 3 weeks <a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a></td><td align="center">400 mg</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 4: RECOMMENDATIONS FOR ORAL DOSAGE AFTER INTRAVENOUS INFUSION</span>\n</caption>\n<col/>\n<col/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\">Duration of Amiodarone Infusion\n \n <a class=\"Sup\" href=\"#footnote-1\" name=\"footnote-reference-1\">*</a></th><th align=\"center\">Initial Daily Dose of Oral Amiodarone</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"2\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-1\" name=\"footnote-1\">*</a>\n</dt>\n<dd>Assuming a 720 mg/day infusion (0.5 mg/min).</dd>\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">†</a>\n</dt>\n<dd>Intravenous amiodarone is not intended for maintenance treatment.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"center\">&lt; 1 week</td><td align=\"center\">800 to 1600 mg</td>\n</tr>\n<tr>\n<td align=\"center\">1-3 weeks</td><td align=\"center\">600 to 800 mg</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\">&gt; 3 weeks\n \n <a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">†</a></td><td align=\"center\">400 mg</td>\n</tr>\n</tbody>\n</table></div>" }

Injection, 50 mg/mL

{ "type": "p", "children": [], "text": "Injection, 50 mg/mL" }

Amiodarone is contraindicated in patients with:

{ "type": "p", "children": [], "text": "Amiodarone is contraindicated in patients with:" }

{ "type": "ul", "children": [ "Known hypersensitivity to any of the components of amiodarone, including iodine. Hypersensitivity reactions may involve rash, angioedema, cutaneous/mucosal hemorrhage (bleeding), fever, arthralgias (joint pains), eosinophilia (abnormal blood counts), urticaria (hives), thrombotic thrombocytopenic purpura, or severe periarteritis (inflammation around blood vessels).", "Cardiogenic shock.", "Marked sinus bradycardia.", "Second- or third-degree atrio-ventricular (AV) block unless a functioning pacemaker is available." ], "text": "" }

Hypotension is the most common adverse reaction seen with intravenous amiodarone. In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with intravenous amiodarone. Clinically significant hypotension during infusions was seen most often in the first several hours of treatment and was not dose related, but appeared to be related to the rate of infusion. Hypotension necessitating alterations in intravenous amiodarone therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients.

Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion. Monitor the initial rate of infusion closely and do not exceed the recommended rate [see Dosage and Administration ( 2)] .

In some cases, hypotension may be refractory and result in a fatal outcome [see Adverse Reactions ( 6.2)] .

In 90 (4.9%) of 1836 patients in clinical trials, drug-related bradycardia that was not dose-related occurred while they were receiving intravenous amiodarone for life-threatening VT/VF. Treat bradycardia by slowing the infusion rate or discontinuing amiodarone. In some patients, a pacemaker is required. Despite such measures, bradycardia was progressive and terminal in 1 patient during the controlled trials. Treat patients with a known predisposition to bradycardia or AV block with amiodarone in a setting where a temporary pacemaker is available.

Elevations of blood hepatic enzyme values [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)] are commonly seen in patients with immediately life-threatening VT/VF. Interpreting elevated AST activity can be difficult because the values may be elevated in patients who have had recent myocardial infarction, congestive heart failure, or multiple electrical defibrillations. Approximately 54% of patients receiving intravenous amiodarone in clinical studies had baseline liver enzyme elevations, and 13% had clinically significant elevations. In 81% of patients with both baseline and on-therapy data available, the liver enzyme elevations either improved during therapy or remained at baseline levels. Baseline abnormalities in hepatic enzymes are not a contraindication to treatment.

Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of intravenous amiodarone at a much higher loading dose concentration and much faster rate of infusion than recommended (see Dosage and Administration ( 2)) .

In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential benefit of amiodarone therapy. Carefully monitor patients receiving amiodarone for evidence of progressive hepatic injury. In such cases, consider reducing the rate of administration or withdrawing amiodarone.

Amiodarone may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation, by intravenous amiodarone, of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving intravenous amiodarone, TdP or new-onset VF occurred infrequently (less than 2%). Monitor patients for QTc prolongation during infusion with amiodarone. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent.

Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly [see Drug Interactions ( 7)] .

Amiodarone causes thyroid dysfunction in some patients, which may lead to potentially fatal breakthrough or exacerbated arrhythmias.

There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings have included pulmonary infiltrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure or death.

Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy.

Only 1 of more than 1000 patients treated with intravenous amiodarone in clinical studies developed pulmonary fibrosis. In that patient, the condition was diagnosed 3 months after treatment with intravenous amiodarone, during which time the patient received oral amiodarone. Pulmonary toxicity is a well-recognized complication of long-term amiodarone use (see package insert for oral amiodarone).

Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment, have been reported in patients treated with oral amiodarone. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. Perform an ophthalmic examination if symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision. Re-evaluate the necessity of amiodarone therapy if optic neuropathy or neuritis is suspected. Perform regular ophthalmic examination, including fundoscopy and slit-lamp examination, during administration of amiodarone.

There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks. See package insert for oral amiodarone.

Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Amiodarone is also a potential source of large amounts of inorganic iodine and can cause either hypothyroidism or hyperthyroidism. Evaluate thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid-function tests may persist for months following amiodarone withdrawal.

There have been postmarketing reports of thyroid nodules/thyroid cancer in patients treated with amiodarone. In some instances hyperthyroidism was also present [see Adverse Reactions ( 6.2)] .

Hyperthyroidism occurs in about 2% of patients receiving amiodarone, but the incidence may be higher among patients with prior inadequate dietary iodine intake. Amiodarone-induced hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism because of the possibility of thyrotoxicosis and arrhythmia breakthrough or aggravation, all of which may result in death. There have been reports of death associated with amiodarone-induced thyrotoxicosis. Consider the possibility of hyperthyroidism if any new signs of arrhythmia appear.

Identify hyperthyroidism by relevant clinical signs and symptoms, subnormal serum levels of thyroid stimulating hormone (TSH), abnormally elevated serum free T4, and elevated or normal serum T3. Since arrhythmia breakthroughs may accompany amiodarone-induced hyperthyroidism, aggressive medical treatment is indicated, including, if possible, dose reduction or withdrawal of amiodarone. Amiodarone hyperthyroidism may be followed by a transient period of hypothyroidism.

The institution of antithyroid drugs, β-adrenergic blockers or temporary corticosteroid therapy may be necessary. The action of antithyroid drugs may be especially delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. Radioactive iodine therapy is contraindicated because of the low radioiodine uptake associated with amiodarone-induced hyperthyroidism.

When aggressive treatment of amiodarone-induced thyrotoxicosis has failed or amiodarone cannot be discontinued because it is the only drug effective against the resistant arrhythmia, surgical management may be an option. Experience with thyroidectomy as a treatment for amiodarone-induced thyrotoxicosis is limited, and this form of therapy could induce thyroid storm. Therefore, surgical and anesthetic management require careful planning.

Amiodarone can cause fetal harm when administered to a pregnant woman. Although amiodarone use during pregnancy is uncommon, there have been a small number of published reports of congenital goiter/hypothyroidism and hyperthyroidism associated with oral administration. Inform the patient of the potential hazard to the fetus if amiodarone is administered during pregnancy or if the patient becomes pregnant while taking amiodarone.

Hypothyroidism has been reported in 2 to 4% of patients in most series, but in 8 to 10% in some series. This condition may be identified by relevant clinical symptoms and particularly by elevated serum TSH levels. In some clinically hypothyroid amiodarone-treated patients, free thyroxine index values may be normal. Manage hypothyroidism by reducing the amiodarone dose and considering the need for thyroid hormone supplement. However, therapy must be individualized, and it may be necessary to discontinue amiodarone in some patients.

Perform close perioperative monitoring in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction defects of halogenated inhalational anesthetics.

Advise patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone.

Correct hypokalemia or hypomagnesemia whenever possible before initiating treatment with amiodarone, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics.

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 a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received intravenous amiodarone for at least one week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks, without an increased incidence of severe adverse reactions. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days.

The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse reactions. The most common adverse reactions leading to discontinuation of intravenous amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%).

Table 5 lists the most common (incidence ≥2%) adverse reactions during intravenous amiodarone therapy considered at least possibly drug-related. These data were collected in clinical trials involving 1836 patients with life-threatening VT/VF. Data from all assigned treatment groups are pooled because none of the adverse reactions appeared to be dose-related.

<div class="scrollingtable"><table> <caption> <span>Table 5: ADVERSE REACTIONS IN PATIENTS RECEIVING INTRAVENOUS AMIODARONE IN CONTROLLED AND OPEN-LABEL STUDIES (≥ 2% INCIDENCE)</span> </caption> <col/> <col/> <col/> <col/> <thead> <tr class="First Last"> <th valign="top">Study Event</th><th align="center" valign="top">Controlled Studies <br/> (n = 814) </th><th align="center" valign="top">Open-Label Studies <br/> (n = 1022) </th><th align="center" valign="top">Total <br/> (n = 1836) </th> </tr> </thead> <tbody> <tr class="First"> <td valign="top">  <span class="Bold">Body as a whole</span></td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td> </tr> <tr> <td valign="top">   Fever</td><td align="center" valign="top"> 24 (2.9%)</td><td align="center" valign="top"> 13 (1.2%)</td><td align="center" valign="top"> 37 (2.0%)</td> </tr> <tr> <td valign="top">  <span class="Bold">Cardiovascular System</span></td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td> </tr> <tr> <td valign="top">   Bradycardia</td><td align="center" valign="top"> 49 (6.0%)</td><td align="center" valign="top"> 41 (4.0%)</td><td align="center" valign="top"> 90 (4.9%)</td> </tr> <tr> <td valign="top">   Congestive heart failure</td><td align="center" valign="top"> 18 (2.2%)</td><td align="center" valign="top"> 21 (2.0%)</td><td align="center" valign="top"> 39 (2.1%)</td> </tr> <tr> <td valign="top">   Heart arrest</td><td align="center" valign="top"> 29 (3.5%)</td><td align="center" valign="top"> 26 (2.5%)</td><td align="center" valign="top"> 55 (2.9%)</td> </tr> <tr> <td valign="top">   Hypotension</td><td align="center" valign="top"> 165 (20.2%)</td><td align="center" valign="top"> 123 (12.0%)</td><td align="center" valign="top"> 288 (15.6%)</td> </tr> <tr> <td valign="top">   Ventricular tachycardia</td><td align="center" valign="top"> 15 (1.8%)</td><td align="center" valign="top"> 30 (2.9%)</td><td align="center" valign="top"> 45 (2.4%)</td> </tr> <tr> <td valign="top">  <span class="Bold">Digestive System</span></td><td align="center" valign="top"> </td><td align="center" valign="top"> </td><td align="center" valign="top"> </td> </tr> <tr> <td valign="top">   Liver function tests abnormal</td><td align="center" valign="top"> 35 (4.2%)</td><td align="center" valign="top"> 29 (2.8%)</td><td align="center" valign="top"> 64 (3.4%)</td> </tr> <tr class="Last"> <td valign="top">   Nausea</td><td align="center" valign="top"> 29 (3.5%)</td><td align="center" valign="top"> 43 (4.2%)</td><td align="center" valign="top"> 72 (3.9%)</td> </tr> </tbody> </table></div>

Other adverse reactions reported in less than 2% of patients receiving intravenous amiodarone in controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.

The following adverse reactions have been identified during post-approval use of amiodarone. 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.

Body as a Whole:anaphylactic/anaphylactoid reaction (including shock), fever

Cardiovascular:hypotension (sometimes fatal), sinus arrest

Dermatologic:toxic epidermal necrolysis (sometimes fatal), exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, skin cancer, pruritus, angioedema

Endocrine:syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Hematologic:pancytopenia, neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia, agranulocytosis, granuloma

Hepatic:hepatitis, cholestatic hepatitis, cirrhosis

Injection Site Reactions:pain, erythema, edema, pigment changes, venous thombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing

Musculoskeletal:myopathy, muscle weakness, rhabdomyolysis

Nervous System:hallucination, confusional state, disorientation, and delirium, pseudotumor cerebri

Pancreatic:pancreatitis

Renal:renal impairment, renal insufficiency, acute renal failure

Respiratory:bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates, and /or mass, pleuritis

Thyroid:thyroid nodules/thyroid cancer

Vascular:vasculitis

Amiodarone is metabolized to the active metabolite desethylamiodarone by the cytochrome P450 (CYP450) enzyme group, specifically cytochromes P4503A4 (CYP3A) and CYP2C8. The CYP3A isoenzyme is present in both the liver and intestines.

{ "type": "p", "children": [], "text": "Amiodarone is metabolized to the active metabolite desethylamiodarone by the cytochrome P450 (CYP450) enzyme group, specifically cytochromes P4503A4 (CYP3A) and CYP2C8. The CYP3A isoenzyme is present in both the liver and intestines." }

Amiodarone is an inhibitor of CYP3A. Therefore, amiodarone has the potential for interactions with drugs or substances that may be substrates, inhibitors or inducers of CYP3A. While only a limited number of in vivodrug-drug interactions with amiodarone have been reported, chiefly with the oral formulation, the potential for other interactions should be anticipated. This is especially important for drugs associated with serious toxicity, such as other antiarrhythmics. If such drugs are needed, reassess their dose and, where appropriate, measure plasma concentrations. In view of the long and variable half-life of amiodarone, potential for drug interactions exists not only with concomitant medication but also with drugs administered after discontinuation of amiodarone.

{ "type": "p", "children": [], "text": "Amiodarone is an inhibitor of CYP3A. Therefore, amiodarone has the potential for interactions with drugs or substances that may be substrates, inhibitors or inducers of CYP3A. While only a limited number of\n \n in vivodrug-drug interactions with amiodarone have been reported, chiefly with the oral formulation, the potential for other interactions should be anticipated. This is especially important for drugs associated with serious toxicity, such as other antiarrhythmics. If such drugs are needed, reassess their dose and, where appropriate, measure plasma concentrations. In view of the long and variable half-life of amiodarone, potential for drug interactions exists not only with concomitant medication but also with drugs administered after discontinuation of amiodarone.\n\n " }

Since amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone.  Reported examples include the following:

{ "type": "p", "children": [], "text": "\nSince amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone.  Reported examples include the following:\n" }

Protease inhibitors: Protease inhibitors are known to inhibit CYP3A to varying degrees. A case report of one patient taking amiodarone 200 mg and indinavir 800 mg three times a day resulted in increases in amiodarone concentrations from 0.9 mg/L to 1.3 mg/L. DEA concentrations were not affected. There was no evidence of toxicity. Consider monitoring for amiodarone toxicity and serial measurement of amiodarone serum concentration during concomitant protease inhibitor therapy.

{ "type": "p", "children": [], "text": "\nProtease inhibitors: \n \nProtease inhibitors are known to inhibit CYP3A to varying degrees. A case report of one patient taking amiodarone 200 mg and indinavir 800 mg three times a day resulted in increases in amiodarone concentrations from 0.9 mg/L to 1.3 mg/L. DEA concentrations were not affected. There was no evidence of toxicity. Consider monitoring for amiodarone toxicity and serial measurement of amiodarone serum concentration during concomitant protease inhibitor therapy.\n\n " }

Histamine H 1antagonists: Loratadine, a non-sedating antihistaminic, is metabolized primarily by CYP3A. QT interval prolongation and TdP have been reported with the coadministration of loratadine and amiodarone.

{ "type": "p", "children": [], "text": "\nHistamine H\n \n 1antagonists: \n \nLoratadine, a non-sedating antihistaminic, is metabolized primarily by CYP3A. QT interval prolongation and TdP have been reported with the coadministration of loratadine and amiodarone.\n\n " }

Histamine H 2antagonists: Cimetidineinhibits CYP3A and can increase serum amiodarone levels.

{ "type": "p", "children": [], "text": "\nHistamine H\n \n 2antagonists: \n \nCimetidineinhibits CYP3A and can increase serum amiodarone levels.\n\n " }

Antidepressants: Trazodone, an antidepressant, is metabolized primarily by CYP3A. QT interval prolongation and TdP have been reported with the coadministration of trazodone and amiodarone.

{ "type": "p", "children": [], "text": "\nAntidepressants: \n \nTrazodone, an antidepressant, is metabolized primarily by CYP3A. QT interval prolongation and TdP have been reported with the coadministration of trazodone and amiodarone.\n\n " }

Other substances: Grapefruit juicegiven to healthy volunteers increased amiodarone AUC by 50% and C maxby 84%, resulting in increased plasma levels of amiodarone. Do not take grapefruit juice during treatment with amiodarone.

{ "type": "p", "children": [], "text": "\nOther substances: \n \nGrapefruit juicegiven to healthy volunteers increased amiodarone AUC by 50% and C\n \n maxby 84%, resulting in increased plasma levels of amiodarone. Do not take grapefruit juice during treatment with amiodarone.\n\n " }

Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates for p-glycoprotein. Reported examples of this interaction include the following:

{ "type": "p", "children": [], "text": "\nAmiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates for p-glycoprotein. Reported examples of this interaction include the following:\n" }

Immunosuppressives: Cyclosporine(CYP3A substrate) administered in combination with oral amiodarone has been reported to produce persistently elevated plasma concentrations of cyclosporine resulting in elevated creatinine, despite reduction in dose of cyclosporine.

{ "type": "p", "children": [], "text": "\nImmunosuppressives: \n \nCyclosporine(CYP3A substrate) administered in combination with oral amiodarone has been reported to produce persistently elevated plasma concentrations of cyclosporine resulting in elevated creatinine, despite reduction in dose of cyclosporine.\n\n " }

HMG-CoA Reductase Inhibitors: Simvastatin(CYP3A substrate) in combination with amiodarone has been associated with reports of myopathy/rhabdomyolysis.

{ "type": "p", "children": [], "text": "\nHMG-CoA Reductase Inhibitors: \n \nSimvastatin(CYP3A substrate) in combination with amiodarone has been associated with reports of myopathy/rhabdomyolysis.\n\n " }

Cardiovasculars: Cardiac glycosides: In patients receiving digoxintherapy, administration of oral amiodarone regularly results in an increase in serum digoxin concentration that may reach toxic levels with resultant clinical toxicity. Amiodarone taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day. On administration of oral amiodarone, review the need for digitalis therapy and reduce the dose of digitalis by approximately 50% or discontinue digitalis. If digitalis treatment is continued, monitor serum levels closely and observe patients for clinical evidence of toxicity.

{ "type": "p", "children": [], "text": "\nCardiovasculars: \n \nCardiac glycosides: In patients receiving\n \n digoxintherapy, administration of oral amiodarone regularly results in an increase in serum digoxin concentration that may reach toxic levels with resultant clinical toxicity. Amiodarone taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day. On administration of oral amiodarone, review the need for digitalis therapy and reduce the dose of digitalis by approximately 50% or discontinue digitalis. If digitalis treatment is continued, monitor serum levels closely and observe patients for clinical evidence of toxicity.\n\n " }

Antiarrhythmics: Other antiarrhythmic drugs, such as quinidine, procainamide, disopyramide, and phenytoin,have been used concurrently with amiodarone. There have been case reports of increased steady-state levels of quinidine, procainamide, and phenytoin during concomitant therapy with amiodarone. Phenytoin decreases serum amiodarone levels. Amiodarone taken concomitantly with quinidine increases quinidine serum concentration by 33% after two days. Amiodarone taken concomitantly with procainamide for less than seven days increases plasma concentrations of procainamide and n-acetyl procainamide by 55% and 33%, respectively. Reduce quinidine and procainamide doses by one-third when either is administered with amiodarone.

{ "type": "p", "children": [], "text": "\nAntiarrhythmics:\n Other antiarrhythmic drugs, such as\n \n quinidine, procainamide, disopyramide, and phenytoin,have been used concurrently with amiodarone. There have been case reports of increased steady-state levels of quinidine, procainamide, and phenytoin during concomitant therapy with amiodarone. Phenytoin decreases serum amiodarone levels. Amiodarone taken concomitantly with quinidine increases quinidine serum concentration by 33% after two days. Amiodarone taken concomitantly with procainamide for less than seven days increases plasma concentrations of procainamide and n-acetyl procainamide by 55% and 33%, respectively. Reduce quinidine and procainamide doses by one-third when either is administered with amiodarone.\n\n " }

Plasma levels of flecainidehave been reported to increase in the presence of oral amiodarone; adjust the dose of flecainide when these drugs are administered concomitantly. In general, initiate any added antiarrhythmic drug at a lower than usual dose and monitor the patient carefully.

{ "type": "p", "children": [], "text": "Plasma levels of\n \n flecainidehave been reported to increase in the presence of oral amiodarone; adjust the dose of flecainide when these drugs are administered concomitantly. In general, initiate any added antiarrhythmic drug at a lower than usual dose and monitor the patient carefully.\n\n " }

Reserve the combination of amiodarone with other antiarrhythmic therapy to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent or incompletely responsive to amiodarone. During transfer to oral amiodarone, reduce the dose levels of previously administered agents by 30 to 50% several days after the addition of oral amiodarone. Review the continued need for the other antiarrhythmic agent after the effects of amiodarone have been established, and attempt discontinuation. If the treatment is continued, carefully monitor these patients for adverse effects, especially for conduction disturbances and exacerbation of tachyarrhythmias. In amiodarone-treated patients who require additional antiarrhythmic therapy, the initial dose of such agents should be approximately half of the usual recommended dose.

{ "type": "p", "children": [], "text": "Reserve the combination of amiodarone with other antiarrhythmic therapy to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent or incompletely responsive to amiodarone. During transfer to oral amiodarone, reduce the dose levels of previously administered agents by 30 to 50% several days after the addition of oral amiodarone. Review the continued need for the other antiarrhythmic agent after the effects of amiodarone have been established, and attempt discontinuation. If the treatment is continued, carefully monitor these patients for adverse effects, especially for conduction disturbances and exacerbation of tachyarrhythmias. In amiodarone-treated patients who require additional antiarrhythmic therapy, the initial dose of such agents should be approximately half of the usual recommended dose." }

Antihypertensives: Use amiodarone with caution in patients receiving ß-receptor blocking agents (e.g., propranolol, a CYP3A inhibitor) or calcium channel antagonists (e.g., verapamil, a CYP3A substrate, and diltiazem, a CYP3A inhibitor) because of the possible potentiation of bradycardia, sinus arrest, and AV block; if necessary, amiodarone can continue to be used after insertion of a pacemaker in patients with severe bradycardia or sinus arrest.

{ "type": "p", "children": [], "text": "\nAntihypertensives: \n \nUse amiodarone with caution in patients receiving ß-receptor blocking agents (e.g.,\n \n propranolol, a CYP3A inhibitor) or calcium channel antagonists (e.g.,\n \n verapamil, a CYP3A substrate, and\n \n diltiazem, a CYP3A inhibitor) because of the possible potentiation of bradycardia, sinus arrest, and AV block; if necessary, amiodarone can continue to be used after insertion of a pacemaker in patients with severe bradycardia or sinus arrest.\n\n " }

Anticoagulants: Potentiation of warfarin-type (CYP2C9 and CYP3A substrate) anticoagulant response is almost always seen in patients receiving amiodarone and can result in serious or fatal bleeding. Since the concomitant administration of warfarin with amiodarone increases the prothrombin time by 100% after 3 to 4 days, reduce the dose of the anticoagulant by one-third to one-half, and monitor prothrombin times closely.

{ "type": "p", "children": [], "text": "\nAnticoagulants: \n \nPotentiation of\n \n warfarin-type (CYP2C9 and CYP3A substrate) anticoagulant response is almost always seen in patients receiving amiodarone and can result in serious or fatal bleeding. Since the concomitant administration of warfarin with amiodarone increases the prothrombin time by 100% after 3 to 4 days, reduce the dose of the anticoagulant by one-third to one-half, and monitor prothrombin times closely.\n\n " }

Clopidogrel, an inactive thienopyridine prodrug, is metabolized in the liver by CYP3A to an active metabolite. A potential interaction between clopidogrel and amiodarone resulting in ineffective inhibition of platelet aggregation has been reported.

{ "type": "p", "children": [], "text": "\nClopidogrel, an inactive thienopyridine prodrug, is metabolized in the liver by CYP3A to an active metabolite. A potential interaction between clopidogrel and amiodarone resulting in ineffective inhibition of platelet aggregation has been reported.\n\n " }

Some drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the synthesis of CYP3A (enzyme induction). This may lead to low amiodarone serum levels and potential decrease in efficacy. Reported examples of this interaction include the following:

{ "type": "p", "children": [], "text": "\nSome drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the synthesis of CYP3A (enzyme induction). This may lead to low amiodarone serum levels and potential decrease in efficacy. Reported examples of this interaction include the following:\n" }

Antibiotics: Rifampinis a potent inducer of CYP3A. Administration of rifampin concomitantly with oral amiodarone has been shown to result in decreases in serum concentrations of amiodarone and desethylamiodarone.

{ "type": "p", "children": [], "text": "\nAntibiotics: \n \nRifampinis a potent inducer of CYP3A. Administration of rifampin concomitantly with oral amiodarone has been shown to result in decreases in serum concentrations of amiodarone and desethylamiodarone.\n\n " }

Other substances, including herbal preparations: St. John's Wort( Hypericum perforatum) induces CYP3A. Since amiodarone is a substrate for CYP3A, St. John's Wort likely reduces amiodarone levels.

{ "type": "p", "children": [], "text": "\nOther substances, including herbal preparations: \n \nSt. John's Wort(\n \n Hypericum perforatum) induces CYP3A. Since amiodarone is a substrate for CYP3A, St. John's Wort likely reduces amiodarone levels.\n\n " }

Other reported interactions with amiodarone: Fentanyl(CYP3A substrate) in combination with amiodarone may cause hypotension, bradycardia, and decreased cardiac output.

{ "type": "p", "children": [], "text": "\nOther reported interactions with amiodarone: \n \nFentanyl(CYP3A substrate) in combination with amiodarone may cause hypotension, bradycardia, and decreased cardiac output.\n\n " }

Sinus bradycardia has been reported with oral amiodarone in combination with lidocaine(CYP3A substrate) given for local anesthesia. Seizure, associated with increased lidocaine concentrations, has been reported with concomitant administration of intravenous amiodarone.

{ "type": "p", "children": [], "text": "Sinus bradycardia has been reported with oral amiodarone in combination with\n \n lidocaine(CYP3A substrate) given for local anesthesia. Seizure, associated with increased lidocaine concentrations, has been reported with concomitant administration of intravenous amiodarone.\n\n " }

Dextromethorphanis a substrate for both CYP2D6 and CYP3A. Amiodarone inhibits CYP2D6.

{ "type": "p", "children": [], "text": "\nDextromethorphanis a substrate for both CYP2D6 and CYP3A. Amiodarone inhibits CYP2D6.\n\n " }

Cholestyramineincreases enterohepatic elimination of amiodarone and may reduce its serum levels and t ½.

{ "type": "p", "children": [], "text": "\nCholestyramineincreases enterohepatic elimination of amiodarone and may reduce its serum levels and t\n \n ½.\n\n " }

Disopyramidecauses QT prolongation which could induce arrhythmia.

{ "type": "p", "children": [], "text": "\nDisopyramidecauses QT prolongation which could induce arrhythmia.\n\n " }

Fluoroquinolones, macrolide antibiotics, and azolesare known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly [see Warnings and Precautions ( 5.4)] .

{ "type": "p", "children": [], "text": "\nFluoroquinolones, macrolide antibiotics, and azolesare known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly\n \n [see Warnings and Precautions (\n \n 5.4)]\n \n .\n\n " }

Hemodynamic and electrophysiologic interactions have also been observed after concomitant administration with propranolol, diltiazem, and verapamil.

{ "type": "p", "children": [], "text": "Hemodynamic and electrophysiologic interactions have also been observed after concomitant administration with\n \n propranolol, diltiazem, and verapamil.\n\n " }

Volatile Anesthetic Agents: Patients who are on amiodarone therapy may be more sensitive to the myocardial depressant and conduction defects of halogenated inhalational anesthetics [see Warnings and Precautions ( 5.9)] .

{ "type": "p", "children": [], "text": "\nVolatile Anesthetic Agents: Patients who are on amiodarone therapy may be more sensitive to the myocardial depressant and conduction defects of halogenated inhalational anesthetics\n \n [see Warnings and Precautions (\n \n 5.9)]\n \n .\n\n " }

In addition to the interactions noted above, chronic (> 2 weeks) oralamiodarone administration impairs metabolism of phenytoin, dextromethorphan, and methotrexate.

{ "type": "p", "children": [], "text": "In addition to the interactions noted above, chronic (> 2 weeks)\n \n oralamiodarone administration impairs metabolism of phenytoin, dextromethorphan, and methotrexate.\n\n " }

Pregnancy Category D [see Warnings and Precautions ( 5.8)] .

In addition to causing infrequent congenital goiter/hypothyroidism and hyperthyroidism, amiodarone has caused a variety of adverse effects in animals.

In a reproductive study in which amiodarone was given intravenously to rabbits at dosages of 5, 10, or 25 mg/kg per day (about 0.1, 0.3, and 0.7 times the maximum recommended human dose [MRHD] on a body surface area basis), maternal deaths occurred in all groups, including controls. Embryotoxicity (as manifested by fewer full-term fetuses and increased resorptions with concomitantly lower litter weights) occurred at dosages of 10 mg/kg and above. No evidence of embryotoxicity was observed at 5 mg/kg and no teratogenicity was observed at any dosages.

In a teratology study in which amiodarone was administered by continuous IV infusion to rats at dosages of 25, 50, or 100 mg/kg per day (about 0.4, 0.7, and 1.4 times the MRHD when compared on a body surface area basis), maternal toxicity (as evidenced by reduced weight gain and food consumption) and embryotoxicity (as evidenced by increased resorptions, decreased live litter size, reduced body weights, and retarded sternum and metacarpal ossification) were observed in the 100 mg/kg group.

Use amiodarone during pregnancy only if the potential benefit to the mother justifies the risk to the fetus.

It is not known whether the use of amiodarone during labor or delivery has any immediate or delayed adverse effects. Preclinical studies in rodents have not shown any effect on the duration of gestation or on parturition.

Amiodarone and one of its major metabolites, desethylamiodarone (DEA), are excreted in human milk, suggesting that breastfeeding could expose the nursing infant to a significant dose of the drug. Nursing offspring of lactating rats administered amiodarone have demonstrated reduced viability and reduced body weight gains. The risk of exposing the infant to amiodarone must be weighed against the potential benefit of arrhythmia suppression in the mother. Advise the mother to discontinue nursing.

The safety and effectiveness of amiodarone in pediatric patients have not been established; therefore, the use of amiodarone in pediatric patients is not recommended. In a pediatric trial of 61 patients, aged 30 days to 15 years, hypotension (36%), bradycardia (20%), and AV block (15%) were common dose-related adverse reactions and were severe or life-threatening in some cases. Injection site reactions were seen in 5 (25%) of the 20 patients receiving intravenous amiodarone through a peripheral vein irrespective of dose regimen.

Amiodarone injection contains the preservative benzyl alcohol [see Description ( 11)] . There have been reports of fatal "gasping syndrome" in neonates (children less than one month of age) following the administration of intravenous solutions containing the preservative benzyl alcohol. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse.

Clinical studies of amiodarone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Carefully consider dose selection in an elderly patient. In general, start at the low end of the dosing range in the elderly to reflect the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

There have been cases, some fatal, of amiodarone overdose. Effects of an inadvertent overdose of intravenous amiodarone include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity. Treat hypotension and cardiogenic shock by slowing the infusion rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion. Bradycardia and AV block may require temporary pacing. Monitor hepatic enzyme concentrations closely. Amiodarone is not dialyzable.

{ "type": "p", "children": [], "text": "There have been cases, some fatal, of amiodarone overdose. Effects of an inadvertent overdose of intravenous amiodarone include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity. Treat hypotension and cardiogenic shock by slowing the infusion rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion. Bradycardia and AV block may require temporary pacing. Monitor hepatic enzyme concentrations closely. Amiodarone is not dialyzable." }

Amiodarone Hydrochloride Injection contains Amiodarone Hydrochloride (C 25H 29I 2NO 3•HCl), a class III antiarrhythmic drug. Amiodarone Hydrochloride is (2-butyl-3-benzo-furanyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone hydrochloride.

{ "type": "p", "children": [], "text": "Amiodarone Hydrochloride Injection contains Amiodarone Hydrochloride (C\n \n 25H\n \n 29I\n \n 2NO\n \n 3•HCl), a class III antiarrhythmic drug. Amiodarone Hydrochloride is (2-butyl-3-benzo-furanyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone hydrochloride.\n\n " }

Amiodarone Hydrochloride has the following structural formula:

{ "type": "p", "children": [], "text": "Amiodarone Hydrochloride has the following structural formula:" }

Amiodarone Hydrochloride is a white to slightly yellow crystalline powder, and is very slightly soluble in water. It has a molecular weight of 681.78 and contains 37.3% iodine by weight. Amiodarone Hydrochloride Injection is a sterile clear, pale-yellow micellar solution visually free from particulates. Each milliliter of the amiodarone formulation contains 50 mg of amiodarone hydrochloride, 20.2 mg of benzyl alcohol, 100 mg of polysorbate 80, and water for injection.

{ "type": "p", "children": [], "text": "Amiodarone Hydrochloride is a white to slightly yellow crystalline powder, and is very slightly soluble in water. It has a molecular weight of 681.78 and contains 37.3% iodine by weight. Amiodarone Hydrochloride Injection is a sterile clear, pale-yellow micellar solution visually free from particulates. Each milliliter of the amiodarone formulation contains 50 mg of amiodarone hydrochloride, 20.2 mg of benzyl alcohol, 100 mg of polysorbate 80, and water for injection." }

Amiodarone Hydrochloride Injection contains polysorbate 80, which is known to leach di-(2-ethylhexyl)phthalate (DEHP) from polyvinylchloride (PVC) [(see Dosage and Administration ( 2)] .

{ "type": "p", "children": [], "text": "Amiodarone Hydrochloride Injection contains polysorbate 80, which is known to leach di-(2-ethylhexyl)phthalate (DEHP) from polyvinylchloride (PVC)\n \n [(see Dosage and Administration (\n \n 2)]\n \n .\n\n " }

Amiodarone is generally considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, amiodarone exerts a noncompetitive antisympathetic action. One of its main effects, with prolonged administration, is to lengthen the cardiac action potential, a class III effect. The negative chronotropic effect of amiodarone in nodal tissues is similar to the effect of class IV drugs. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness. The antisympathetic action and the block of calcium and potassium channels are responsible for the negative dromotropic effects on the sinus node and for the slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node. Its vasodilatory action can decrease cardiac workload and consequently myocardial oxygen consumption.

Intravenous amiodarone administration prolongs intranodal conduction (Atrial-His, AH) and refractoriness of the atrioventricular node (ERP AVN), but has little or no effect on sinus cycle length (SCL), refractoriness of the right atrium and right ventricle (ERP RA and ERP RV), repolarization (QTc), intraventricular conduction (QRS), and infra-nodal conduction (His-ventricular, HV). A comparison of the electrophysiologic effects of intravenous amiodarone and oral amiodarone is shown in the table below.

<div class="scrollingtable"><table> <caption> <span>Table 6: EFFECTS OF INTRAVENOUS AND ORAL AMIODARONE ON ELECTROPHYSIOLOGIC PARAMETERS</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <thead> <tr class="First Last"> <th valign="top">Formulation</th><th align="center" valign="top">SCL</th><th align="center" valign="top">QRS</th><th align="center" valign="top">QTc</th><th align="center" valign="top">AH</th><th align="center" valign="top">HV</th><th align="center" valign="top">ERP <br/> RA </th><th align="center" valign="top">ERP <br/> RV </th><th align="center" valign="top">ERP <br/> AVN </th> </tr> </thead> <tfoot> <tr class="First Last"> <td colspan="9" valign="top">  <span class="Bold">↔ No change</span></td> </tr> </tfoot> <tbody> <tr class="First"> <td valign="top"> Intravenous</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↑</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↑</td> </tr> <tr class="Last"> <td valign="top"> Oral</td><td align="center" valign="top"> ↑</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↑</td><td align="center" valign="top"> ↑</td><td align="center" valign="top"> ↔</td><td align="center" valign="top"> ↑</td><td align="center" valign="top"> ↑</td><td align="center" valign="top"> ↑</td> </tr> </tbody> </table></div>

At higher doses (>10 mg/kg) of intravenous amiodarone, prolongation of the ERP RV and modest prolongation of the QRS have been seen. These differences between oral and IV administration suggest that the initial acute effects of intravenous amiodarone may be predominately focused on the AV node, causing an intranodal conduction delay and increased nodal refractoriness due to slow channel blockade (class IV activity) and noncompetitive adrenergic antagonism (class II activity).

Intravenous amiodarone has been reported to produce negative inotropic and vasodilatory effects in animals and humans. In clinical studies of patients with refractory VF or hemodynamically unstable VT, treatment-emergent, drug-related hypotension occurred in 288 of 1836 patients (16%) treated with intravenous amiodarone. No correlations were seen between the baseline ejection fraction and the occurrence of clinically significant hypotension during infusion of intravenous amiodarone.

No data are available on the activity of DEA in humans, but in animals, it has significant electrophysiologic and antiarrhythmic effects generally similar to amiodarone itself. DEA's precise role and contribution to the antiarrhythmic activity of oral amiodarone are not certain. The development of maximal ventricular class III effects after oral amiodarone administration in humans correlates more closely with DEA accumulation over time than with amiodarone accumulation. On the other hand, after intravenous amiodarone administration, there is evidence of activity well before significant concentrations of DEA are attained [see Clinical Trials( 14)] .

Amiodarone exhibits complex disposition characteristics after intravenous administration. Peak serum concentrations after single 5 mg/kg 15-minute intravenous infusions in healthy subjects range between 5 and 41 mg/L. Peak concentrations after 10-minute infusions of 150 mg intravenous amiodarone in patients with ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT) range between 7 and 26 mg/L. Due to rapid distribution, serum concentrations decline to 10% of peak values within 30 to 45 minutes after the end of the infusion. In clinical trials, after 48 hours of continued infusions (125, 500 or 1000 mg/day) plus supplemental (150 mg) infusions (for recurrent arrhythmias), amiodarone mean serum concentrations between 0.7 to 1.4 mg/L were observed (n=260).

N-desethylamiodarone (DEA) is the major active metabolite of amiodarone in humans. DEA serum concentrations above 0.05 mg/L are not usually seen until after several days of continuous infusion but with prolonged therapy reach approximately the same concentration as amiodarone. Amiodarone is metabolized to DEA by the cytochrome P450 enzyme group, specifically cytochromes CYP3A and CYP2C8. The CYP3A isoenzyme is present in both the liver and intestines. The highly variable systemic availability of oral amiodarone may be attributed to large interindividual variability in CYP3A activity.

From in vitrostudies, the protein binding of amiodarone is >96%. Amiodarone and DEA cross the placenta and both appear in breast milk. Neither amiodarone nor DEA is dialyzable.

Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine. In studies in healthy subjects following single intravenous administration (5 mg/kg of amiodarone over 15 min), the plasma concentration vs. time profile could be characterized by linear sum of four exponential terms with terminal elimination half-lives (t½) of 9 - 36 days for amiodarone and 9 - 30 days for DEA. The clearance of amiodarone and DEA ranged between 63 - 231 mL/hr/kg and 140 - 400 mL/hr/kg, respectively. In clinical studies of 2 to 7 days, clearance of amiodarone after intravenous administration in patients with VT and VF ranged between 220 and 440 mL/hr/kg.

Effect of Age:The pharmacokinetics of amiodarone and DEA are affected by age. Normal subjects over 65 years of age show lower clearances (about 100 mL/hr/kg) than younger subjects (about 150 mL/hr/kg) and an increase in t ½from about 20 to 47 days.

Effect of Gender:Pharmacokinetics of amiodarone and DEA are similar in males and females.

Renal Impairment:Renal disease does not influence the pharmacokinetics of amiodarone or DEA.

Hepatic Impairment:After a single dose of intravenous amiodarone to cirrhotic patients, significantly lower C maxand average concentration values are seen for DEA, but mean amiodarone levels are unchanged.

Cardiac Disease:In patients with severe left ventricular dysfunction, the pharmacokinetics of amiodarone are not significantly altered but the terminal elimination t ½of DEA is prolonged.

Although no dosage adjustment for patients with renal, hepatic, or cardiac abnormalities has been defined during chronic treatment with oral amiodarone, close clinical monitoring is prudent for elderly patients and those with severe left ventricular dysfunction.

There is no established relationship between drug concentration and therapeutic response for short-term intravenous use.

No carcinogenicity studies were conducted with intravenous administration of amiodarone. However, oral amiodarone caused a statistically significant, dose-related increase in the incidence of thyroid tumors (follicular adenoma and carcinoma) in rats. The incidence of thyroid tumors in rats was greater than the incidence in controls even at the lowest dose level tested, i.e., 5 mg/kg/day (much less, on a body surface area basis, than the maximum recommended human maintenance dose of 600 mg/day).

Mutagenicity studies conducted with amiodarone hydrochloride (Ames, micronucleus, and lysogenic induction tests) were negative.

No fertility studies were conducted with intravenous administration of amiodarone. However, in a study in which amiodarone hydrochloride was orally administered to male and female rats, beginning 9 weeks prior to mating, reduced fertility was observed at a dose level of 90 mg/kg/day (approximately 1.4 times the maximum recommended human maintenance dose of 600 mg/day).

Apart from studies in patients with VT or VF, described below, there are two other studies of amiodarone showing an antiarrhythmic effect before significant levels of DEA could have accumulated. A placebo-controlled study of intravenous amiodarone (300 mg over 2 hours followed by 1200 mg/day) in post-coronary artery bypass graft patients with supraventricular and 2- to 3-consecutive-beat ventricular arrhythmias showed a reduction in arrhythmias from 12 hours on. A baseline-controlled study using a similar IV regimen in patients with recurrent, refractory VT/VF also showed rapid onset of antiarrhythmic activity; amiodarone therapy reduced episodes of VT by 85% compared to baseline.

{ "type": "p", "children": [], "text": "Apart from studies in patients with VT or VF, described below, there are two other studies of amiodarone showing an antiarrhythmic effect before significant levels of DEA could have accumulated. A placebo-controlled study of intravenous amiodarone (300 mg over 2 hours followed by 1200 mg/day) in post-coronary artery bypass graft patients with supraventricular and 2- to 3-consecutive-beat ventricular arrhythmias showed a reduction in arrhythmias from 12 hours on. A baseline-controlled study using a similar IV regimen in patients with recurrent, refractory VT/VF also showed rapid onset of antiarrhythmic activity; amiodarone therapy reduced episodes of VT by 85% compared to baseline." }

The acute effectiveness of intravenous amiodarone in suppressing recurrent VF or hemodynamically unstable VT is supported by two randomized, parallel, dose-response studies of approximately 300 patients each. In these studies, patients with at least two episodes of VF or hemodynamically unstable VT in the preceding 24 hours were randomly assigned to receive doses of approximately 125 or 1000 mg over the first 24 hours, an 8-fold difference. In one study, a middle dose of approximately 500 mg was evaluated. The dose regimen consisted of an initial rapid loading infusion, followed by a slower 6-hour loading infusion, and then an 18-hour maintenance infusion. The maintenance infusion was continued up to hour 48. Additional 10-minute infusions of 150 mg intravenous amiodarone were given for "breakthrough" VT/VF more frequently to the 125 mg dose group, thereby considerably reducing the planned 8-fold differences in total dose to 1.8- and 2.6-fold, respectively, in the two studies.

{ "type": "p", "children": [], "text": "The acute effectiveness of intravenous amiodarone in suppressing recurrent VF or hemodynamically unstable VT is supported by two randomized, parallel, dose-response studies of approximately 300 patients each. In these studies, patients with at least two episodes of VF or hemodynamically unstable VT in the preceding 24 hours were randomly assigned to receive doses of approximately 125 or 1000 mg over the first 24 hours, an 8-fold difference. In one study, a middle dose of approximately 500 mg was evaluated. The dose regimen consisted of an initial rapid loading infusion, followed by a slower 6-hour loading infusion, and then an 18-hour maintenance infusion. The maintenance infusion was continued up to hour 48. Additional 10-minute infusions of 150 mg intravenous amiodarone were given for \"breakthrough\" VT/VF more frequently to the 125 mg dose group, thereby considerably reducing the planned 8-fold differences in total dose to 1.8- and 2.6-fold, respectively, in the two studies." }

The prospectively defined primary efficacy end point was the rate of VT/VF episodes per hour. For both studies, the median rate was 0.02 episodes per hour in patients receiving the high dose and 0.07 episodes per hour in patients receiving the low dose, or approximately 0.5 versus 1.7 episodes per day (p=0.07, 2-sided, in both studies). In one study, the time to first episode of VT/VF was significantly prolonged (approximately 10 hours in patients receiving the low dose and 14 hours in patients receiving the high dose). In both studies, significantly fewer supplemental infusions were given to patients in the high-dose group. At the end of double-blind therapy or after 48 hours, all patients were given open access to whatever treatment (including intravenous amiodarone) was deemed necessary. Mortality was not affected in these studies.

{ "type": "p", "children": [], "text": "The prospectively defined primary efficacy end point was the rate of VT/VF episodes per hour. For both studies, the median rate was 0.02 episodes per hour in patients receiving the high dose and 0.07 episodes per hour in patients receiving the low dose, or approximately 0.5 versus 1.7 episodes per day (p=0.07, 2-sided, in both studies). In one study, the time to first episode of VT/VF was significantly prolonged (approximately 10 hours in patients receiving the low dose and 14 hours in patients receiving the high dose). In both studies, significantly fewer supplemental infusions were given to patients in the high-dose group. At the end of double-blind therapy or after 48 hours, all patients were given open access to whatever treatment (including intravenous amiodarone) was deemed necessary. Mortality was not affected in these studies." }

Amiodarone Hydrochloride Injection, USP 50 mg/mL, is supplied as follows:

{ "type": "p", "children": [], "text": "Amiodarone Hydrochloride Injection, USP 50 mg/mL, is supplied as follows:" }

NDC: 70518-1231-00

{ "type": "p", "children": [], "text": "NDC: 70518-1231-00" }

NDC: 70518-1231-01

{ "type": "p", "children": [], "text": "NDC: 70518-1231-01" }

PACKAGING: 3 mL in 1 VIAL, TYPE 0

{ "type": "p", "children": [], "text": "PACKAGING: 3 mL in 1 VIAL, TYPE 0" }

PACKAGING: 25 in 1 BOX

{ "type": "p", "children": [], "text": "PACKAGING: 25 in 1 BOX" }

Store at 20º-25ºC (68º-77ºF) [See USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20º-25ºC (68º-77ºF) [See USP Controlled Room Temperature]." }

Protect from light and excessive heat.

{ "type": "p", "children": [], "text": "Protect from light and excessive heat." }

Use carton to protect contents from light until time of use.

{ "type": "p", "children": [], "text": "Use carton to protect contents from light until time of use." }

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" }

Amiodarone has the potential to cause serious side effects that limit its use to life-threatening and hemodynamically unstable cardiac arrhythmias. Advise female patients to discontinue nursing while being treated with amiodarone, as breast-feeding could expose the nursing infant to a significant dose of the drug. Recommend that patients avoid grapefruit juice, over-the-counter cough medicine (which commonly contain dextromethorphan), and St. John's Wort. Inform patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone. Discuss the symptoms of hypo- and hyper-thyroidism, particularly if patients will be transitioned to oral amiodarone.

{ "type": "p", "children": [], "text": "Amiodarone has the potential to cause serious side effects that limit its use to life-threatening and hemodynamically unstable cardiac arrhythmias. Advise female patients to discontinue nursing while being treated with amiodarone, as breast-feeding could expose the nursing infant to a significant dose of the drug. Recommend that patients avoid grapefruit juice, over-the-counter cough medicine (which commonly contain dextromethorphan), and \n St. John's Wort. Inform patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone. Discuss the symptoms of hypo- and hyper-thyroidism, particularly if patients will be transitioned to oral amiodarone.\n " }

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" }

DRUG: Amiodarone Hydrochloride

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

GENERIC: Amiodarone Hydrochloride

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

DOSAGE: INJECTION, SOLUTION

{ "type": "p", "children": [], "text": "DOSAGE: INJECTION, SOLUTION" }

ADMINSTRATION: INTRAVENOUS

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

NDC: 70518-1231-0

{ "type": "p", "children": [], "text": "NDC: 70518-1231-0" }

NDC: 70518-1231-1

{ "type": "p", "children": [], "text": "NDC: 70518-1231-1" }

PACKAGING: 3 mL in 1 VIAL

{ "type": "p", "children": [], "text": "PACKAGING: 3 mL in 1 VIAL" }

OUTER PACKAGING: 25 in 1 BOX

{ "type": "p", "children": [], "text": "OUTER PACKAGING: 25 in 1 BOX" }

ACTIVE INGREDIENT(S):

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

{ "type": "ul", "children": [ "AMIODARONE HYDROCHLORIDE 50mg in 1mL" ], "text": "" }

INACTIVE INGREDIENT(S):

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

{ "type": "ul", "children": [ "WATER", "POLYSORBATE 80", "BENZYL ALCOHOL" ], "text": "" }

Amiodarone hydrochloride tablets are indicated for the treatment of documented, life-threatening recurrent ventricular fibrillation and life-threatening recurrent hemodynamically unstable tachycardia in adults who have not responded to adequate doses of other available antiarrhythmics or when alternative agents cannot be tolerated.

{ "type": "p", "children": [], "text": "Amiodarone hydrochloride tablets are indicated for the treatment of documented, life-threatening recurrent ventricular fibrillation and life-threatening recurrent hemodynamically unstable tachycardia in adults who have not responded to adequate doses of other available antiarrhythmics or when alternative agents cannot be tolerated." }

Recommended Dosage:

Initiate treatment with a loading doses of 800 to 1600 mg/day until initial therapeutic response occurs (usually 1 to 3 weeks). Once adequate arrhythmia control is achieved, or if side effects become prominent, reduce amiodarone hydrochloride tablets dose to 600 to 800 mg/day for one month and then to the maintenance dose, usually 400 mg/day.

Administration:

Administer amiodarone hydrochloride tablets consistently with regard to meals [see Clinical Pharmacology (12.3)] . Administration of amiodarone hydrochloride tablets in divided doses with meals is suggested for total daily doses of 1000 mg or higher, or when gastrointestinal intolerance occurs.

100 mg tablets: round, flat, beveled edge, white tablets; one side plain, the second side engraved with "TARO" at the top and "55" below.

{ "type": "p", "children": [], "text": "100 mg tablets: round, flat, beveled edge, white tablets; one side plain, the second side engraved with \"TARO\" at the top and \"55\" below." }

200 mg tablets: round, flat, beveled edge, light orange tablets; one side plain, the second side scored and engraved with "TARO" above the score and "56" below the score line.

{ "type": "p", "children": [], "text": "200 mg tablets: round, flat, beveled edge, light orange tablets; one side plain, the second side scored and engraved with \"TARO\" above the score and \"56\" below the score line." }

300 mg tablets: round, flat, beveled edge, peach tablets; one side plain, the second side scored and engraved with "TARO" above the score and "58" below the score line.

{ "type": "p", "children": [], "text": "300 mg tablets: round, flat, beveled edge, peach tablets; one side plain, the second side scored and engraved with \"TARO\" above the score and \"58\" below the score line." }

400 mg tablets: round, flat, beveled edge, light yellow tablets; one side plain, the second side scored and engraved with "TARO" above the score and "59" below the score line.

{ "type": "p", "children": [], "text": "400 mg tablets: round, flat, beveled edge, light yellow tablets; one side plain, the second side scored and engraved with \"TARO\" above the score and \"59\" below the score line." }

{ "type": "ul", "children": [ "Cardiogenic shock.", "Sick sinus syndrome, second- or third-degree atrioventricular block, bradycardia leading to syncope without a functioning pacemaker.", "Known hypersensitivity to the drug or to any of its components, including iodine." ], "text": "" }

Because of the long half-life of amiodarone (15 to 142 days) and its active metabolite desethylamiodarone (14 to 75 days), adverse reactions and drug interactions can persist for several weeks following amiodarone discontinuation [see Clinical Pharmacology (12.3)] .

Amiodarone hydrochloride tablets may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium-scan, and pathological data consistent with pulmonary toxicity. Pulmonary toxicity secondary to amiodarone hydrochloride may result from either indirect or direct toxicity as represented by hypersensitivity pneumonitis (including eosinophilic pneumonia) or interstitial/alveolar pneumonitis, respectively. Rates of pulmonary toxicity have been reported to be as high as 17% and is fatal in about 10% of cases. Obtain a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, when amiodarone hydrochloride therapy is initiated. Repeat history, physical exam, and chest X-ray every 3 to 6 months or if symptoms occur. Consider alternative antiarrhythmic therapy if the patient experiences signs or symptoms of pulmonary toxicity. Prednisone 40 to 60 mg/day tapered over several weeks may be helpful in treating pulmonary toxicity.

Adult Respiratory Distress Syndrome (ARDS)

Postoperatively, occurrences of ARDS have been reported in patients receiving amiodarone hydrochloride therapy who have undergone either cardiac or noncardiac surgery. Although patients usually respond well to vigorous respiratory therapy, in rare instances the outcome has been fatal.

Asymptomatic elevations of hepatic enzyme levels are seen frequently, but amiodarone hydrochloride can cause life-threatening hepatic injury. Histology has resembled that of alcoholic hepatitis or cirrhosis. Obtain baseline and periodic liver transaminases. If transaminases exceed three times normal, or doubles in a patient with an elevated baseline, discontinue or reduce dose of amiodarone hydrochloride tablets, obtain follow-up tests and treat appropriately.

Amiodarone hydrochloride tablets can exacerbate the presenting arrhythmia in about 2 to 5% of patients or cause new ventricular fibrillation, incessant ventricular tachycardia, increased resistance to cardioversion, and polymorphic ventricular tachycardia associated with QTc prolongation (Torsade de Pointes [TdP]).

Correct hypokalemia, hypomagnesemia, and hypocalcemia before initiating treatment with amiodarone hydrochloride tablets, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or receiving drugs affecting electrolyte levels, such as diuretics, laxatives, systemic corticosteroids, or amphotericin B.

Optic Neuropathy and Optic Neuritis

Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment and sometimes permanent blindness, have been reported in patients treated with amiodarone and may occur at any time during therapy. If symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision, consider discontinuing amiodarone hydrochloride tablets and promptly refer for ophthalmic examination. Regular ophthalmic examination, including funduscopy and slit-lamp examination, is recommended during administration of amiodarone hydrochloride tablets [see Adverse Reactions (6.1)] .

Corneal Microdeposits

Corneal microdeposits appear in the majority of adults treated with amiodarone hydrochloride tablets. They are usually discernible only by slit-lamp examination, but give rise to symptoms such as visual halos or blurred vision in as many as 10% of patients. Corneal microdeposits are reversible upon reduction of dose or termination of treatment. Asymptomatic microdeposits alone are not a reason to reduce dose or discontinue treatment [see Adverse Reactions (6.1)] .

Amiodarone hydrochloride inhibits peripheral conversion of thyroxine (T 4) to triiodothyronine (T 3) and may cause increased thyroxine levels, decreased T 3levels, and increased levels of inactive reverse T 3(rT 3) in clinically euthyroid patients. Amiodarone hydrochloride tablets can cause either hypothyroidism (reported in up to 10% of patients) or hyperthyroidism (occurring in about 2% of patients). Monitor thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction.

Hyperthyroidism mayinduce arrhythmia breakthrough. If any new signs of arrhythmia appear, the possibility of hyperthyroidism should be considered. Antithyroid drugs, β-adrenergic blockers, temporary corticosteroid therapy may be necessary to treat the symptoms of hyperthyroidism. The action of antithyroid drugs may be delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. Radioactive iodine therapy is contraindicated because of the low radioiodine uptake associated with amiodarone-induced hyperthyroidism. Amiodarone hydrochloride-induced hyperthyroidism may be followed by a transient period of hypothyroidism.

Hypothyrodism may be primary or subsequent to resolution of preceding amiodarone hydrochloride-induced hyperthyroidism. Severe hypothyroidism and myxedema coma, sometimes fatal, have been reported in association with amiodarone therapy. In some clinically hypothyroid amiodarone-treated patients, free thyroxine index values may be normal. Manage hypothyroidism by reducing the dose of or discontinuing amiodarone hydrochloride tablets and thyroid hormone supplementation.

Amiodarone hydrochloride causes symptomatic bradycardia or sinus arrest with suppression of escape foci in 2 to 4% of patients. The risk is increased by electrolytic disorders or use of concomitant antiarrhythmics or negative chronotropes [see Drug Interactions (7)] . Bradycardia may require a pacemaker for rate control.

Postmarketing cases of symptomatic bradycardia, some requiring pacemaker insertion and at least one fatal, have been reported when ledipasvir/sofosbuvir or sofosbuvir with simeprevir were initiated in patients on amiodarone. Bradycardia generally occurred within hours to days, but in some cases presented up to 2 weeks after initiating antiviral treatment. Bradycardia generally resolved after discontinuation of antiviral treatment. The mechanism for this effect is unknown. Monitor heart rate in patients taking or recently discontinuing amiodarone hydrochloride tablets when starting antiviral treatment [see Drug Interactions (7)] .

In patients with implanted defibrillators or pacemakers, chronic administration of antiarrhythmic drugs may affect pacing or defibrillation thresholds. Therefore, at the inception of and during amiodarone treatment, pacing and defibrillation thresholds should be assessed.

Amiodarone hydrochloride tablets may cause fetal harm when administered to a pregnant woman. Fetal exposure may increase the potential for cardiac, thyroid, neurodevelopmental, neurological, and growth effects in neonate [see Use in Specific Populations (8.1)] .

Chronic administration of amiodarone hydrochloride tablets may lead to peripheral neuropathy, which may not resolve when amiodarone is discontinued.

Amiodarone hydrochloride induces photosensitization in about 10% of patients; some protection may be afforded sun-barrier creams or protective clothing. During long-term treatment, a blue-gray discoloration of the exposed skin may occur. The risk may be increased in patients of fair complexion or those with excessive sun exposure. Some reversal of discoloration may occur upon drug discontinuation.

Volatile Anesthetic Agents

Patients on amiodarone hydrochloride tablets therapy may be more sensitive to the myocardial depressant and conduction effects of halogenated inhalational anesthetics.

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.

At the usual maintenance dose (400 mg/day) and above, amiodarone hydrochloride causes adverse reactions in about three-fourths of all patients, resulting in discontinuation in 7 to 18%.

In surveys of almost 5,000 patients treated in open U.S. studies and in published reports of treatment with amiodarone hydrochloride tablets, the adverse reactions most frequently requiring discontinuation of amiodarone hydrochloride included pulmonary infiltrates or fibrosis, paroxysmal ventricular tachycardia, congestive heart failure, and elevation of liver enzymes. Other symptoms causing discontinuations less often included visual disturbances, photosensitivity, blue skin discoloration, hyperthyroidism, and hypothyroidism.

The following side-effect rates are based on a retrospective study of 241 patients treated for 2 to 1,515 days (mean 441.3 days):

Thyroid

Common: Hypothyroidism, hyperthyroidism.

Cardiovascular

Common: Congestive heart failure, cardiac arrhythmias, SA node dysfunction.

Gastrointestinal

Very common: Nausea, vomiting.

Common: Constipation, anorexia, abdominal pain.

Dermatologic

Common: Solar dermatitis/photosensitivity.

Neurologic

Common: Malaise and fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias, decreased libido, insomnia, headache, sleep disturbances.

Ophthalmic

Common: Visual disturbances.

Hepatic

Common: Abnormal liver-function tests, nonspecific hepatic disorders.

Respiratory

Common: Pulmonary inflammation or fibrosis.

Other

Common: Flushing, abnormal taste and smell, edema, abnormal salivation, coagulation abnormalities.

Uncommon: Blue skin discoloration, rash, spontaneous ecchymosis, alopecia, hypotension, and cardiac conduction abnormalities.

The following adverse reactions have been identified during post-approval use of amiodarone hydrochloride. 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.

Hematologic:hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma.

Immune:anaphylactic/anaphylactoid reaction (including shock), angioedema.

Neurologic:pseudotumor cerebri, parkinsonian symptoms such as akinesia and bradykinesia (sometimes reversible with discontinuation of therapy), demyelinating polyneuropathy.

Psychiatric:hallucination, confusional state, disorientation, delirium.

Cardiac:hypotension (sometimes fatal), sinus arrest.

Respiratory:eosinophilic pneumonia, acute respiratory distress syndrome in the post-operative setting, bronchospasm, bronchiolitis obliterans organizing pneumonia, pulmonary alveolar hemorrhage, pleural effusion, pleuritis.

Gastrointestinal:pancreatitis, acute pancreatitis.

Hepatic:hepatitis, cholestatic hepatitis, cirrhosis.

Skin and Subcutaneous Tissue Disorders:urticaria, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS), eczema, pruritus, skin cancer, lupus-like syndrome.

Musculoskeletal:myopathy, muscle weakness, rhabdomyolysis.

Renal:renal impairment, renal insufficiency, acute renal failure.

Reproductive:epididymitis, impotence.

Body as a whole:fever, dry mouth.

Endocrine and metabolic:thyroid nodules/thyroid cancer, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Vascular:vasculitis.

Because of amiodarone's long half-life, expect drug interactions to persist for weeks to months after discontinuation of amiodarone.

{ "type": "p", "children": [], "text": "Because of amiodarone's long half-life, expect drug interactions to persist for weeks to months after discontinuation of amiodarone." }

Drug interactions with amiodarone are described in Table 1 below.

{ "type": "p", "children": [], "text": "Drug interactions with amiodarone are described in Table 1 below." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Amiodarone Drug Interactions</span> </caption> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Concomitant Drug Class/Name</th><th align="left" class="Rrule">Examples</th><th align="left" class="Rrule">Clinical Comment</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="3"><span class="Italics">Pharmacodynamic Interactions</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">QT Prolonging Drugs</td><td align="left" class="Rrule">class I and III antiarrhythmics, lithium, certain phenothiazines, tricyclic antidepressants, certain fluoroquinolone and macrolide antibiotics, azole antifungals, halogenated inhalation anesthetic agents</td><td align="left" class="Rrule">Increased risk of Torsade de Pointes. Avoid concomitant use.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Negative Chronotropes</td><td align="left" class="Rrule">digoxin, beta blockers, verapamil, diltiazem, clonidine, ivabradine</td><td align="left" class="Rrule">Potentiates the electrophysiologic and hemodynamic effects of amiodarone, resulting in bradycardia, sinus arrest, and AV block. Monitor heart rate.</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" colspan="3"><span class="Italics">Pharmacokinetic Interactions</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">CYP450 Inhibitors</td><td align="left" class="Rrule">grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors</td><td align="left" class="Rrule">Increased exposure of amiodarone. Avoid concomitant use.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">CYP450 Inducers</td><td align="left" class="Rrule">St. John's Wort</td><td align="left" class="Rrule">Reduced amiodarone serum levels.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Cyclosporine</td><td align="left" class="Rrule"></td><td align="left" class="Rrule">Increased plasma levels of cyclosporine have been reported resulting in elevated creatinine, despite reduction of cyclosporine dose. Monitor cyclosporine drug levels and renal function with concomitant use.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Cholestyramine</td><td align="left" class="Rrule"></td><td align="left" class="Rrule">Reduced amiodarone serum levels.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Antiarrhythmics</td><td align="left" class="Rrule">quinidine, procainamide, flecainide</td><td align="left" class="Rrule">Reserve concomitant use for patients who are unresponsive to a single agent. Antiarrhythmic metabolism inhibited by amiodarone. Initiate antiarrhythmic at a lower than usual dose and monitor patient carefully. Reduce dose levels of previously administered antiarrhythmic by 30 to 50% for several days after transitioning to oral amiodarone. Evaluate continued need for antiarrhythmic.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Digoxin</td><td align="left" class="Rrule"></td><td align="left" class="Rrule">Increased digoxin concentration. <br/> Reduce digoxin by half or discontinue. If continued, monitor for evidence of toxicity. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">HMG-CoA Reductase Inhibitors</td><td align="left" class="Rrule">simvastatin, lovastatin, atorvastatin</td><td align="left" class="Rrule">Increased plasma concentration of HMG-CoA reductase inhibitor. <br/> Limit the dose of lovastatin to 40 mg. <br/> Limit the coadministered dose of simvastatin to 20 mg. <br/> Lower starting dose of other CYP3A4 substrates may be required. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Warfarin</td><td align="left" class="Rrule"></td><td align="left" class="Rrule">Potentiates anticoagulant response and can result in serious or fatal bleeding. Coadministration increases prothrombin time by 100% after 3 to 4 days. Reduce warfarin dose by one-third to one-half and monitor prothrombin times.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Phenytoin</td><td align="left" class="Rrule"></td><td align="left" class="Rrule">Increased steady-state levels of phenytoin. Monitor phenytoin levels.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Hepatitis C Direct Acting Antiviral</td><td align="left" class="Rrule">sofosbuvir</td><td align="left" class="Rrule">Cases of symptomatic bradyarrhythmia requiring pacemaker insertion have been reported in patients on oral maintenance amiodarone who initiated therapy with sofosbuvir.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">CYP3A Substrate</td><td align="left" class="Rrule">lidocaine</td><td align="left" class="Rrule">Sinus bradycardia has been reported with oral amiodarone in combination with lidocaine given for local anesthesia. Monitor heart rate. A lower starting dose of lidocaine may be required.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">CYP3A Substrate</td><td align="left" class="Rrule">fentanyl</td><td align="left" class="Rrule">Fentanyl in combination with amiodarone may cause hypotension, bradycardia, and decreased cardiac output.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 1: Amiodarone Drug Interactions</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" class=\"Lrule Rrule\">Concomitant Drug Class/Name</th><th align=\"left\" class=\"Rrule\">Examples</th><th align=\"left\" class=\"Rrule\">Clinical Comment</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Italics\">Pharmacodynamic Interactions</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">QT Prolonging Drugs</td><td align=\"left\" class=\"Rrule\">class I and III antiarrhythmics, lithium, certain phenothiazines, tricyclic antidepressants, certain fluoroquinolone and macrolide antibiotics, azole antifungals, halogenated inhalation anesthetic agents</td><td align=\"left\" class=\"Rrule\">Increased risk of Torsade de Pointes. Avoid concomitant use.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Negative Chronotropes</td><td align=\"left\" class=\"Rrule\">digoxin, beta blockers, verapamil, diltiazem, clonidine, ivabradine</td><td align=\"left\" class=\"Rrule\">Potentiates the electrophysiologic and hemodynamic effects of amiodarone, resulting in bradycardia, sinus arrest, and AV block. Monitor heart rate.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Italics\">Pharmacokinetic Interactions</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">CYP450 Inhibitors</td><td align=\"left\" class=\"Rrule\">grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors</td><td align=\"left\" class=\"Rrule\">Increased exposure of amiodarone. Avoid concomitant use.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">CYP450 Inducers</td><td align=\"left\" class=\"Rrule\">St. John's Wort</td><td align=\"left\" class=\"Rrule\">Reduced amiodarone serum levels.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Cyclosporine</td><td align=\"left\" class=\"Rrule\"></td><td align=\"left\" class=\"Rrule\">Increased plasma levels of cyclosporine have been reported resulting in elevated creatinine, despite reduction of cyclosporine dose. Monitor cyclosporine drug levels and renal function with concomitant use.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Cholestyramine</td><td align=\"left\" class=\"Rrule\"></td><td align=\"left\" class=\"Rrule\">Reduced amiodarone serum levels.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Antiarrhythmics</td><td align=\"left\" class=\"Rrule\">quinidine, procainamide, flecainide</td><td align=\"left\" class=\"Rrule\">Reserve concomitant use for patients who are unresponsive to a single agent. Antiarrhythmic metabolism inhibited by amiodarone. Initiate antiarrhythmic at a lower than usual dose and monitor patient carefully. Reduce dose levels of previously administered antiarrhythmic by 30 to 50% for several days after transitioning to oral amiodarone. Evaluate continued need for antiarrhythmic.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Digoxin</td><td align=\"left\" class=\"Rrule\"></td><td align=\"left\" class=\"Rrule\">Increased digoxin concentration. \n <br/> Reduce digoxin by half or discontinue. If continued, monitor for evidence of toxicity.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">HMG-CoA Reductase Inhibitors</td><td align=\"left\" class=\"Rrule\">simvastatin, lovastatin, atorvastatin</td><td align=\"left\" class=\"Rrule\">Increased plasma concentration of HMG-CoA reductase inhibitor. \n <br/> Limit the dose of lovastatin to 40 mg. \n <br/> Limit the coadministered dose of simvastatin to 20 mg. \n <br/> Lower starting dose of other CYP3A4 substrates may be required.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Warfarin</td><td align=\"left\" class=\"Rrule\"></td><td align=\"left\" class=\"Rrule\">Potentiates anticoagulant response and can result in serious or fatal bleeding. Coadministration increases prothrombin time by 100% after 3 to 4 days. Reduce warfarin dose by one-third to one-half and monitor prothrombin times.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Phenytoin</td><td align=\"left\" class=\"Rrule\"></td><td align=\"left\" class=\"Rrule\">Increased steady-state levels of phenytoin. Monitor phenytoin levels.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Hepatitis C Direct Acting Antiviral</td><td align=\"left\" class=\"Rrule\">sofosbuvir</td><td align=\"left\" class=\"Rrule\">Cases of symptomatic bradyarrhythmia requiring pacemaker insertion have been reported in patients on oral maintenance amiodarone who initiated therapy with sofosbuvir.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">CYP3A Substrate</td><td align=\"left\" class=\"Rrule\">lidocaine</td><td align=\"left\" class=\"Rrule\">Sinus bradycardia has been reported with oral amiodarone in combination with lidocaine given for local anesthesia. Monitor heart rate. A lower starting dose of lidocaine may be required.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">CYP3A Substrate</td><td align=\"left\" class=\"Rrule\">fentanyl</td><td align=\"left\" class=\"Rrule\">Fentanyl in combination with amiodarone may cause hypotension, bradycardia, and decreased cardiac output.</td>\n</tr>\n</tbody>\n</table></div>" }

Risk Summary

Available data from postmarketing reports and published case series indicate that amiodarone use in pregnant women may increase the risk for fetal adverse effects including neonatal hypo- and hyperthyroidism, neonatal bradycardia, neurodevelopmental abnormalities, preterm birth and fetal growth restriction. Amiodarone and its metabolite, desethylamiodarone (DEA), cross the placenta. Untreated underlying arrhythmias, including ventricular arrhythmias, during pregnancy pose a risk to the mother and fetus (see Clinical Considerations) . In animal studies, administration of amiodarone to rabbits, rats, and mice during organogenesis resulted in embryo-fetal toxicity at doses less than the maximum recommended human maintenance dose (see Data) . Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population 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.

Clinical Considerations

Disease-associated maternal and or embryo/fetal Risk

The incidence of ventricular tachycardia is increased and may be more symptomatic during pregnancy. Ventricular arrhythmias most often occur in pregnant women with underlying cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse. Most tachycardia episodes are initiated by ectopic beats and the occurrence of arrhythmia episodes may therefore, increase during pregnancy due to the increased propensity to ectopic activity. Breakthrough arrhythmias may also occur during pregnancy, as therapeutic treatment levels may be difficult to maintain due to the increased volume of distribution and increased drug metabolism inherent in the pregnant state.

Fetal/Neonatal adverse reactions

Amiodarone and its metabolite have been shown to cross the placenta. Adverse fetal effects associated with maternal amiodarone use during pregnancy may include neonatal bradycardia, QT prolongation, and periodic ventricular extrasystoles, neonatal hypothyroidism (with or without goiter) detected antenatally or in the newborn and reported even after a few days of exposure, neonatal hyperthyroxinemia, neurodevelopmental abnormalities independent of thyroid function, including speech delay and difficulties with written language and arithmetic, delayed motor development, and ataxia, jerk nystagmus with synchronous head titubation, fetal growth restriction, and premature birth. Monitor the newborn for signs and symptoms of thyroid disorder and cardiac arrhythmias.

Labor and Delivery

Risk of arrhythmias may increase during labor and delivery. Patients treated with amiodarone hydrochloride tablets should be monitored continuously during labor and delivery [see Warnings and Precautions (5.4)] .

Data

Animal Data

In pregnant rats and rabbits during the period of organogenesis, amiodarone hydrochloride in doses of 25 mg/kg/day (approximately 0.4 and 0.9 times, respectively, the maximum recommended human maintenance dose 1) had no adverse effects on the fetus. In the rabbit, 75 mg/kg/day (approximately 2.7 times the maximum recommended human maintenance dose 1) caused abortions in greater than 90% of the animals. In the rat, doses of 50 mg/kg/day or more were associated with slight displacement of the testes and an increased incidence of incomplete ossification of some skull and digital bones; at 100 mg/kg/day or more, fetal body weights were reduced; at 200 mg/kg/day, there was an increased incidence of fetal resorption. (These doses in the rat are approximately 0.8, 1.6 and 3.2 times the maximum recommended human maintenance dose 1) Adverse effects on fetal growth and survival also were noted in one of two strains of mice at a dose of 5 mg/kg/day (approximately 0.04 times the maximum recommended human maintenance dose 1).

Risk Summary

Amiodarone and one of its major metabolites, DEA, are present in breastmilk at between 3.5% and 45% of the maternal weight-adjusted dosage of amiodarone. There are cases of hypothyroidism and bradycardia in breastfed infants, although it is unclear if these effects are due to amiodarone exposure in breastmilk. Breastfeeding is not recommended during treatment with amiodarone hydrochloride tablets [see Warnings and Precautions (5.6, 5.7)] .

Infertility

Based on animal fertility studies, amiodarone hydrochloride tablets may reduce female and male fertility. It is not known if this effect is reversible [see Nonclinical Toxicology (13.1)] .

The safety and effectiveness of amiodarone hydrochloride tablets in pediatric patients have not been established.

Normal subjects over 65 years of age show lower clearances and increased drug half-life than younger subjects [see Clinical Pharmacology (12.3)] . In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

There have been cases, some fatal, of amiodarone hydrochloride overdose.

{ "type": "p", "children": [], "text": "There have been cases, some fatal, of amiodarone hydrochloride overdose." }

Monitor the patient's cardiac rhythm and blood pressure, and, if bradycardia ensues, a β-adrenergic agonist or a pacemaker may be used. Treat hypotension with inadequate tissue perfusion with positive inotropic and vasopressor agents. Neither amiodarone hydrochloride nor its metabolite is dialyzable.

{ "type": "p", "children": [], "text": "Monitor the patient's cardiac rhythm and blood pressure, and, if bradycardia ensues, a β-adrenergic agonist or a pacemaker may be used. Treat hypotension with inadequate tissue perfusion with positive inotropic and vasopressor agents. Neither amiodarone hydrochloride nor its metabolite is dialyzable." }

Amiodarone Hydrochloride Tablets, USP is an antiarrhythmic drug, available for oral administration as white tablets containing 100 mg of amiodarone hydrochloride, light orange, scored tablets containing 200 mg of amiodarone hydrochloride, peach, scored tablets containing 300 mg of amiodarone hydrochloride, and light yellow, scored tablets containing 400 mg of amiodarone hydrochloride. The inactive ingredients present are colloidal silicon dioxide, corn starch, D&C yellow No. 10 lake (200 and 400 mg only), FD&C yellow No. 6 lake (200 and 300 mg only), lactose anhydrous, magnesium stearate and povidone. Amiodarone is a benzofuran derivative: 2-butyl-3-benzofuranyl 4-[2-(diethylamino)-ethoxy]-3,5-diiodophenyl ketone hydrochloride.

{ "type": "p", "children": [], "text": "Amiodarone Hydrochloride Tablets, USP is an antiarrhythmic drug, available for oral administration as white tablets containing 100 mg of amiodarone hydrochloride, light orange, scored tablets containing 200 mg of amiodarone hydrochloride, peach, scored tablets containing 300 mg of amiodarone hydrochloride, and light yellow, scored tablets containing 400 mg of amiodarone hydrochloride. The inactive ingredients present are colloidal silicon dioxide, corn starch, D&C yellow No. 10 lake (200 and 400 mg only), FD&C yellow No. 6 lake (200 and 300 mg only), lactose anhydrous, magnesium stearate and povidone. Amiodarone is a benzofuran derivative: 2-butyl-3-benzofuranyl 4-[2-(diethylamino)-ethoxy]-3,5-diiodophenyl ketone hydrochloride." }

The structural formula is as follows:

{ "type": "p", "children": [], "text": "The structural formula is as follows:" }

Amiodarone hydrochloride is a white to cream-colored crystalline powder. It is slightly soluble in water, soluble in alcohol, and freely soluble in chloroform. It contains 37.3% iodine by weight. Amiodarone Hydrochloride Tablets USP, 100 mg and 200 mg meet USP Dissolution Test 3. Amiodarone Hydrochloride Tablets USP, 300 mg and 400 mg meet USP Dissolution Test 4.

{ "type": "p", "children": [], "text": "Amiodarone hydrochloride is a white to cream-colored crystalline powder. It is slightly soluble in water, soluble in alcohol, and freely soluble in chloroform. It contains 37.3% iodine by weight. Amiodarone Hydrochloride Tablets USP, 100 mg and 200 mg meet USP Dissolution Test 3. Amiodarone Hydrochloride Tablets USP, 300 mg and 400 mg meet USP Dissolution Test 4." }

Amiodarone is considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, amiodarone exerts a noncompetitive antisympathetic action. One of its main effects, with prolonged administration, is to lengthen the cardiac action potential, a class III effect. The negative chronotropic effect of amiodarone in nodal tissues is similar to the effect of class IV drugs. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness. The antisympathetic action and the block of calcium and potassium channels are responsible for the negative dromotropic effects on the sinus node and for the slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node. Its vasodilatory action can decrease cardiac workload and consequently myocardial oxygen consumption.

Amiodarone hydrochloride prolongs the duration of the action potential of all cardiac fibers while causing minimal reduction of dV/dt (maximal upstroke velocity of the action potential). The refractory period is prolonged in all cardiac tissues. Amiodarone hydrochloride increases the cardiac refractory period without influencing resting membrane potential, except in automatic cells where the slope of the prepotential is reduced, generally reducing automaticity. These electrophysiologic effects are reflected in a decreased sinus rate of 15 to 20%, increased PR and QT intervals of about 10%, the development of U-waves, and changes in T-wave contour. These changes should not require discontinuation of amiodarone hydrochloride tablets as they are evidence of its pharmacological action, although amiodarone hydrochloride tablets can cause marked sinus bradycardia or sinus arrest and heart block [see Warnings and Precautions (5.4)] .

Hemodynamics

In animal studies and after intravenous administration in man, amiodarone hydrochloride relaxes vascular smooth muscle, reduces peripheral vascular resistance (afterload), and slightly increases cardiac index. After oral dosing, however, amiodarone hydrochloride produces no significant change in left ventricular ejection fraction (LVEF), even in patients with depressed LVEF. After acute intravenous dosing in man, amiodarone hydrochloride tablets may have a mild negative inotropic effect.

There is no well-established relationship between plasma concentration and effectiveness, but it does appear that concentrations much below 1 mg/L are often ineffective and that levels above 2.5 mg/L are generally not needed. Plasma-concentration measurements can be used to identify patients whose levels are unusually low, and who might benefit from a dose increase, or unusually high, and who might have dosage reduction in the hope of minimizing side effects.

Effects on abnormal rhythms are not seen before 2 to 3 days and usually require 1 to 3 weeks, even when a loading dose is used. There may be a continued increase in effect for longer periods still. There is evidence that the time to effect is shorter when a loading-dose regimen is used.

Consistent with the slow rate of elimination, antiarrhythmic effects persist for weeks or months after amiodarone hydrochloride is discontinued, but the time of recurrence is variable and unpredictable. In general, when the drug is resumed after recurrence of the arrhythmia, control is established relatively rapidly compared to the initial response, presumably because tissue stores were not wholly depleted.

Absorption

Following oral administration in humans, amiodarone hydrochloride is slowly and variably absorbed. The bioavailability of amiodarone hydrochloride is approximately 50%. Maximum plasma concentrations are attained 3 to 7 hours after a single dose. Plasma concentrations with chronic dosing at 100 to 600 mg/day are approximately dose proportional, with a mean 0.5 mg/L increase for each 100 mg/day. These means, however, include considerable individual variability.

Food increases the rate and extent of absorption of amiodarone hydrochloride. The effects of food upon the bioavailability of amiodarone hydrochloride have been studied in 30 healthy subjects who received a single 600-mg dose immediately after consuming a high-fat meal and following an overnight fast. The area under the plasma concentration-time curve (AUC) and the peak plasma concentration (C max) of amiodarone hydrochloride increased by 2.3 (range 1.7 to 3.6) and 3.8 (range 2.7 to 4.4) times, respectively, in the presence of food. Food also increased the rate of absorption of amiodarone hydrochloride, decreasing the time to peak plasma concentration (T max) by 37%. The mean AUC and mean C maxof the major metabolite of amiodarone, DEA increased by 55% (range 58 to 101%) and 32% (range 4 to 84%), respectively, but there was no change in the T maxin the presence of food.

Distribution

Amiodarone hydrochloride is highly protein-bound (approximately 96%). Amiodarone hydrochloride has a very large but variable volume of distribution, averaging about 60 L/kg, because of extensive accumulation in various sites, especially adipose tissue and highly perfused organs, such as the liver, lung, and spleen.

One major metabolite of amiodarone hydrochloride, DEA, has been identified in man; it accumulates to an even greater extent in almost all tissues. No data are available on the activity of DEA in humans, but in animals, it has significant electrophysiologic and antiarrhythmic effects generally similar to amiodarone itself. DEA's precise role and contribution to the antiarrhythmic activity of oral amiodarone are not certain. The development of maximal ventricular class III effects after oral amiodarone hydrochloride administration in humans correlates more closely with DEA accumulation over time than with amiodarone accumulation.

Elimination

Following single dose administration in 12 healthy subjects, amiodarone hydrochloride exhibited multi-compartmental pharmacokinetics with a mean apparent plasma terminal elimination half-life of 58 days (range 15 to 142 days) for amiodarone and 36 days (range 14 to 75 days) for the active metabolite (DEA). In patients, following discontinuation of chronic oral therapy, amiodarone hydrochloride has been shown to have a biphasic elimination with an initial 50% reduction of plasma levels after 2.5 to 10 days. A much slower terminal plasma-elimination phase shows a half-life of the parent compound ranging from 26 to 107 days, with a mean of approximately 53 days and most patients in the 40- to 55-day range. In the absence of a loading-dose period, steady-state plasma concentrations, at constant oral dosing, would therefore be reached between 130 and 535 days, with an average of 265 days. For the metabolite, the mean plasma-elimination half-life was approximately 61 days. These data probably reflect an initial elimination of drug from well-perfused tissue (the 2.5- to 10-day half-life phase), followed by a terminal phase representing extremely slow elimination from poorly perfused tissue compartments such as fat.

The considerable inter-subject variation in both phases of elimination, as well as uncertainty as to what compartment is critical to drug effect, requires attention to individual responses once arrhythmia control is achieved with loading doses because the correct maintenance dose is determined, in part, by the elimination rates. Individualize maintenance doses of amiodarone hydrochloride [see Dosage and Administration (2)] .

Metabolism

Amiodarone is metabolized to DEA by the cytochrome P450 (CYP) enzyme group, specifically CYP3A and CYP2C8. The CYP3A isoenzyme is present in both the liver and intestines. In vitro, amiodarone and DEA exhibit a potential to inhibit CYP2C9, CYP2C19, CYP2D6, CYP3A, CYP2A6, CYP2B6 and CYP2C8. Amiodarone and DEA have also a potential to inhibit some transporters such as P-glycoprotein and organic cation transporter (OCT2).

Excretion

Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine. Neither amiodarone nor DEA is dialyzable.

Specific Populations

Effect of Age:Normal subjects over 65 years of age show lower clearances (about 100 mL/hr/kg) than younger subjects (about 150 mL/hr/kg) and an increase in t ½from about 20 to 47 days.

Renal Impairment:Renal impairment does not influence the pharmacokinetics of amiodarone or DEA.

Hepatic Impairment:After a single dose of intravenous amiodarone to cirrhotic patients, significantly lower C maxand average concentration values are seen for DEA, but mean amiodarone levels are unchanged.

Cardiac Disease:In patients with severe left ventricular dysfunction, the pharmacokinetics of amiodarone are not significantly altered but the terminal elimination t ½of DEA is prolonged.

Although no dosage adjustment for patients with renal, hepatic, or cardiac abnormalities has been defined during chronic treatment with oral amiodarone, close clinical monitoring is prudent for elderly patients and those with severe left ventricular dysfunction.

Drug Interactions:

Effects of other agents on amiodarone

Grapefruit juice: Grapefruit juice given to healthy volunteers increased amiodarone AUC by 50% and C maxby 84%, and decreased DEA to unquantifiable concentrations.

Cimetidineinhibits CYP3A and can increase serum amiodarone levels.

Cholestyraminereduces enterohepatic circulation of amiodarone thereby increasing its elimination. This results in reduced amiodarone serum levels and half-life.

Effects of amiodarone on agents:

CYP3A substrates:

Amiodarone taken concomitantly with quinidineincreases the quinidine serum concentration by 33% after two days. Amiodarone taken concomitantly with procainamidefor less than seven days increases plasma concentrations of procainamide and n-acetyl procainamide by 55% and 33%, respectively.

Loratadine, a non-sedating antihistaminic, is metabolized primarily by CYP3A and its metabolism can be inhibited by amiodarone.

Metabolism of lidocainecan be inhibited by amiodarone.

Cyclophosphamideis a prodrug, metabolized by CYP450 including CYP3A to an active metabolite. The metabolism of cyclophosphamide may be inhibited by amiodarone.

Clopidogrel, an inactive thienopyridine prodrug, is metabolized in the liver by CYP3A to an active metabolite. A potential interaction between clopidogrel and amiodarone resulting in ineffective inhibition of platelet aggregation has been reported.

Macrolide/ketolide antibiotics:

Amiodarone can inhibit the metabolism of macrolide/ketolide antibiotics(except for azithromycin) and systemic azole antifungal drugs.

P-glycoprotein substrates:

Amiodarone taken concomitantly with digoxinincreases the serum digoxin concentration by 70% after one day.

Dabigatran etexilatewhen taken concomitantly with oral amiodarone can result in elevated serum concentration of dabigatran.

Dextromethorphanis a substrate for both CYP2D6 and CYP3A. Amiodarone inhibits CYP2D6. Chronic (> 2 weeks) oral amiodarone administration impairs metabolism of dextromethorphan can lead to increased serum concentrations.

Amiodarone hydrochloride was associated with a statistically significant, dose-related increase in the incidence of thyroid tumors (follicular adenoma and/or carcinoma) in rats. The incidence of thyroid tumors was greater than control at the lowest dose level tested, i.e., 5 mg/kg/day (approximately 0.08 times the maximum recommended human maintenance dose 2).

Mutagenicity studies (Ames, micronucleus, and lysogenic tests) with amiodarone hydrochloride tablets were negative.

In a study in which amiodarone hydrochloride was administered to male and female rats, beginning 9 weeks prior to mating, reduced fertility was observed at a dose level of 90 mg/kg/day (approximately 1.4 times the maximum recommended human maintenance dose 2).

Keep tightly closed.

Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].

Protect from light.

Dispense in a light-resistant, tight container.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide)." }

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy\n \n [see\n \n Use in Specific Populations (8.1)].\n \n \n" }

Advise women that breastfeeding is not recommended during treatment with amiodarone hydrochloride tablets [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise women that breastfeeding is not recommended during treatment with amiodarone hydrochloride tablets\n \n [see\n \n Use in Specific Populations (8.2)].\n \n \n" }

Advise patients to avoid grapefruit juice and St. John's Wort.

{ "type": "p", "children": [], "text": "Advise patients to avoid grapefruit juice and St. John's Wort." }

Advise patients to seek medical attention if they experience the signs and symptoms of pulmonary toxicity, worsening arrhythmia, bradycardia, visual impairment, or hypo- and hyperthyroidism.

{ "type": "p", "children": [], "text": "Advise patients to seek medical attention if they experience the signs and symptoms of pulmonary toxicity, worsening arrhythmia, bradycardia, visual impairment, or hypo- and hyperthyroidism." }

This product's label may have been updated. For full prescribing information, please visit www.taro.com.

{ "type": "p", "children": [], "text": "This product's label may have been updated. For full prescribing information, please visit www.taro.com." }

Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761 Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532 Revised: October 2022 5200381-1022-20 Dispense with Medication Guide available at: https://www.taro.com/usa-medication-guides

{ "type": "p", "children": [], "text": "Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761\n \nDist. by: \n Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532\n \nRevised: October 2022\n \n5200381-1022-20\n \nDispense with Medication Guide available at: \n https://www.taro.com/usa-medication-guides\n" }

Marketed by:

{ "type": "p", "children": [], "text": "Marketed by:" }

GSMS, Inc.

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

Camarillo, CA 93012 USA

{ "type": "p", "children": [], "text": "Camarillo, CA 93012 USA" }

<div class="scrollingtable"><table width="100%"> <colgroup> <col align="left" valign="top" width="6%"/> <col align="left" valign="top" width="47%"/> <col align="left" valign="top" width="47%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule" colspan="3"><span class="Italics">Dispense with Medication Guide available at: <span class="Underline">https://www.taro.com/usa-medication-guides</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" colspan="3"><span class="Bold">MEDICATION GUIDE <br/> Amiodarone Hydrochloride <br/> (A-mee-OH-da-rone HYE-droe-KLOR-ide) Tablets, USP </span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What is the most important information I should know about amiodarone hydrochloride tablets? <br/> Amiodarone hydrochloride tablets can cause serious side effects that can lead to death, including: </span> <ul class="Disc"> <li>lung problems</li> <li>liver problems</li> <li>worsening of heartbeat problems</li> </ul> <span class="Bold">Call your healthcare provider or get medical help right away if you have any of the following symptoms during treatment with amiodarone hydrochloride tablets:</span> <ul class="Disc"> <li>trouble breathing, wheezing, shortness of breath, coughing chest pain, spitting up of blood, or fever</li> <li>nausea or vomiting, brown or dark-colored urine, feel more tired than usual, yellowing of your skin or the whites of your eyes (jaundice), or right upper stomach-area pain</li> <li>heart pounding, skipping a beat, beating fast or slowly, feel light-headed, or if you faint</li> <li>vision problems, including blurred vision, see halos, or your eyes become sensitive to light. You should have regular eye exams before and during treatment with amiodarone hydrochloride tablets.</li> </ul> Amiodarone hydrochloride tablets should be started in a hospital so that your medical condition can be carefully monitored. <br/> Amiodarone hydrochloride tablets should only be used to treat people who have been diagnosed with life-threatening heartbeat problems called ventricular arrhythmias, when other treatments did not work or you cannot tolerate them. <br/> <span class="Bold">Amiodarone hydrochloride tablets can cause other serious side effects. See " <a href="#Effects">What are the possible side effects of amiodarone hydrochloride tablets?</a>" <br/> If you get serious side effects during treatment you may need to stop amiodarone hydrochloride tablets, have your dose changed, or get medical treatment. Talk with your healthcare provider before you stop taking amiodarone hydrochloride tablets. </span> <br/> You may still have side effects after stopping amiodarone hydrochloride tablets because the medicine stays in your body for months after treatment is stopped. <br/> You should have regular check-ups, blood tests, chest x-rays before and during treatment with amiodarone hydrochloride tablets to check for serious side effects. You should also have lung function tests before starting treatment with amiodarone hydrochloride tablets. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are amiodarone hydrochloride tablets?</span> <br/> Amiodarone hydrochloride tablets are a prescription medicine used to treat people who have been diagnosed with life-threatening heartbeat problems called ventricular arrhythmias, when other treatments did not work or you cannot tolerate them. <br/> It is not known if amiodarone hydrochloride tablets are safe and effective in children. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Who should not take amiodarone hydrochloride tablets? <br/> Do not take amiodarone hydrochloride tablets if you: </span> <ul class="Disc"> <li>have a serious heart problem called cardiogenic shock</li> <li>have certain types of the heart condition called heart block, with or without a slow heart rate</li> <li>have a slow heart rate with dizziness or lightheadedness, and you do not have an implanted pacemaker</li> <li>are allergic to amiodarone, iodine, or any of the other ingredients in amiodarone hydrochloride tablets. See the end of this Medication Guide for a complete list of ingredients in amiodarone hydrochloride tablets.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Before taking amiodarone hydrochloride tablets, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have lung or breathing problems</li> <li>have liver problems</li> <li>have or had thyroid problems</li> <li>have a slow heart rate or blood pressure problems</li> <li>have diarrhea or have had diarrhea for a long period of time</li> <li>have been told that you have low levels of potassium, magnesium, or calcium in your blood</li> <li>have an implanted pacemaker or defibrillator</li> <li>if you plan to have surgery with general anesthesia</li> <li>are pregnant or plan to become pregnant. Amiodarone hydrochloride may harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with amiodarone hydrochloride tablets. Amiodarone can stay in your body for months after treatment is stopped.</li> <li>are breastfeeding or plan to breastfeed. Amiodarone can pass into your breast milk and may harm your baby. You should not breast feed while taking amiodarone hydrochloride tablets. Amiodarone can stay in your body for months after treatment is stopped. Talk to your healthcare provider about the best way to feed your baby during this time.</li> </ul> Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. Amiodarone hydrochloride tablets and certain other medicines can affect with each other and cause serious side effects. You can ask your pharmacist for a list of medicines that interact with amiodarone hydrochloride tablets. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">How should I take amiodarone hydrochloride tablets?</span> <ul class="Disc"> <li>When you are discharged from the hospital, take amiodarone hydrochloride tablets <span class="Bold">exactly</span>as your doctor tells you to take it. </li> <li>Your healthcare provider will tell you how much amiodarone hydrochloride tablets to take and when to take it.</li> <li>Your healthcare provider may change your dose of amiodarone hydrochloride tablets as needed if your heart rhythm is controlled, or if you have certain side effects. Your healthcare provider should monitor you carefully when your dose of amiodarone hydrochloride tablets is being changed.</li> <li> <span class="Bold">Take your dose of amiodarone hydrochloride tablets the same way each time, either with or without food.</span> </li> <li>If you take too much amiodarone hydrochloride tablets, call your healthcare provider or go to the nearest hospital emergency room right away. If you miss a dose, wait and take your next dose at your regular time. Do not take two doses at the same. Continue with your next regularly scheduled dose.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What should I avoid while taking amiodarone hydrochloride tablets?</span> <ul class="Disc"> <li>Avoid drinking grapefruit juice during treatment with amiodarone hydrochloride tablets. Drinking grapefruit juice with amiodarone hydrochloride tablets may increase the amount of amiodarone in your blood, and this may lead to side effects.</li> <li>Amiodarone hydrochloride tablets can make your skin sensitive to sunlight. You could get severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin to help protect you if you must be in sunlight. Talk to your healthcare if you get a sunburn. See " <a href="#Skin">Skin problems</a>" in the Medication Guide section <span class="Bold">"What are the possible side effects of amiodarone hydrochloride tablets?"</span>below. </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the possible side effects of amiodarone hydrochloride tablets? <br/> Amiodarone hydrochloride tablets can cause serious side effects, including: </span> <ul class="Disc"> <li>See <span class="Bold">" <a href="#Important">What is the most important information I should know about amiodarone hydrochloride tablets?</a>" </span> </li> <li> <span class="Bold">Nerve problems.</span>Amiodarone hydrochloride tablets can cause nerve problems. Call your healthcare provider if you develop symptoms of nerve problems, including: a feeling of "pins and needles" or numbness in your hands, legs, or feet, muscle weakness, uncontrolled movements, poor coordination, or trouble walking. </li> <li> <span class="Bold">Skin problems.</span>Amiodarone hydrochloride tablets can cause your skin to be more sensitive to the sun or turn a bluish-gray color. People who have fair skin or people who have a lot of sun exposure may be more at risk for these skin problems. Some of the bluish-gray skin color may return to normal after stopping amiodarone hydrochloride tablets. </li> <li> <span class="Bold">Thyroid problems.</span>Amiodarone hydrochloride tablets can cause you to have either decreased thyroid function (hypothyroidism), which can sometimes be severe, or an overactive thyroid (hyperthyroidism), which can be severe. <ul class="Circle"> <li>If you develop decreased thyroid function during treatment with amiodarone, your healthcare provider may need to reduce your dose or stop your treatment with amiodarone hydrochloride tablets, and possibly prescribe medicine to replace your thyroid hormone.</li> <li>An overactive thyroid can cause you to produce too much thyroid hormone. You can have abnormal heartbeats even while you are receiving amiodarone. Your healthcare provider may prescribe certain medicines to treat your overactive thyroid. Call your healthcare provider if you get any abnormal heart beats during treatment with amiodarone hydrochloride tablets. This may mean that you have an overactive thyroid.</li> <li>Your healthcare provider should do tests to check your thyroid function before you start and during treatment with amiodarone hydrochloride tablets.</li> <li>Call your healthcare provider if you develop any of the following symptoms of a thyroid problem during treatment with amiodarone hydrochloride tablets:</li> </ul> </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <ul class="Square"> <li>weakness</li> <li>weight loss or weight gain</li> <li>heat or cold intolerance</li> <li>hair thinning</li> <li>sweating</li> <li>changes in your menstrual periods</li> <li>swelling of your neck (goiter)</li> </ul> </td><td align="left" class="Rrule"> <ul class="Square"> <li>nervousness</li> <li>irritability</li> <li>restlessness</li> <li>decreased concentration</li> <li>feeling depressed (in the elderly)</li> <li>tremor</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3">The most common side effects of amiodarone hydrochloride tablets include: <ul class="Disc"> <li>lung problems</li> <li>heartbeat problems</li> <li>heart problems</li> <li>liver problems</li> </ul> Amiodarone hydrochloride tablets may affect fertility in males and females. It is not known if the effects are reversible. Talk to your healthcare provider if you have concerns about fertility. <br/> These are not all the possible side effects of amiodarone hydrochloride tablets. For more information, ask your healthcare provider or pharmacist. <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">How should I store amiodarone hydrochloride tablets?</span> <ul class="Disc"> <li>Store amiodarone hydrochloride tablets at room temperature between 20° to 25°C (68° to 77°F).</li> <li>Keep amiodarone hydrochloride tablets in a tightly closed container, and keep amiodarone hydrochloride tablets out of the light.</li> </ul> <span class="Bold">Keep amiodarone hydrochloride tablets and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">General information about the safe and effective use of amiodarone hydrochloride tablets</span> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use amiodarone hydrochloride tablets for a condition for which it was not prescribed. Do not give amiodarone hydrochloride tablets to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about amiodarone hydrochloride tablets that is written for health professionals. </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the ingredients in amiodarone hydrochloride tablets? <br/> Active Ingredient: </span>amiodarone hydrochloride <br/> <span class="Bold">Inactive Ingredients:</span>colloidal silicon dioxide, corn starch, D&amp;C yellow No. 10 lake (200 and 400 mg only), FD&amp;C yellow No. 6 lake (200 and 300 mg only), lactose anhydrous, magnesium stearate and povidone. <br/> Manufactured by: Taro Pharmaceutical Industries Ltd. <br/> Haifa Bay, Israel 2624761 <br/> Distributed by: <span class="Bold">Taro Pharmaceuticals U.S.A., Inc.</span> <br/> Hawthorne, NY 10532 <br/> For more information, call 1-866-923-4914 or visit www.taro.com </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<colgroup>\n<col align=\"left\" valign=\"top\" width=\"6%\"/>\n<col align=\"left\" valign=\"top\" width=\"47%\"/>\n<col align=\"left\" valign=\"top\" width=\"47%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Italics\">Dispense with Medication Guide available at: \n <span class=\"Underline\">https://www.taro.com/usa-medication-guides</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">MEDICATION GUIDE\n <br/>\n\t\t\tAmiodarone Hydrochloride\n <br/>\n\t\t\t(A-mee-OH-da-rone HYE-droe-KLOR-ide) Tablets, USP\n </span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What is the most important information I should know about amiodarone hydrochloride tablets?\n <br/>\n\t\t\tAmiodarone hydrochloride tablets can cause serious side effects that can lead to death, including:\n </span>\n<ul class=\"Disc\">\n<li>lung problems</li>\n<li>liver problems</li>\n<li>worsening of heartbeat problems</li>\n</ul>\n<span class=\"Bold\">Call your healthcare provider or get medical help right away if you have any of the following symptoms during treatment with amiodarone hydrochloride tablets:</span>\n<ul class=\"Disc\">\n<li>trouble breathing, wheezing, shortness of breath, coughing chest pain, spitting up of blood, or fever</li>\n<li>nausea or vomiting, brown or dark-colored urine, feel more tired than usual, yellowing of your skin or the whites of your eyes (jaundice), or right upper stomach-area pain</li>\n<li>heart pounding, skipping a beat, beating fast or slowly, feel light-headed, or if you faint</li>\n<li>vision problems, including blurred vision, see halos, or your eyes become sensitive to light. You should have regular eye exams before and during treatment with amiodarone hydrochloride tablets.</li>\n</ul>\n\t\t\tAmiodarone hydrochloride tablets should be started in a hospital so that your medical condition can be carefully monitored.\n <br/>\n\t\t\tAmiodarone hydrochloride tablets should only be used to treat people who have been diagnosed with life-threatening heartbeat problems called ventricular arrhythmias, when other treatments did not work or you cannot tolerate them.\n <br/>\n<span class=\"Bold\">Amiodarone hydrochloride tablets can cause other serious side effects. See \" \n <a href=\"#Effects\">What are the possible side effects of amiodarone hydrochloride tablets?</a>\"\n <br/>\n\t\t\tIf you get serious side effects during treatment you may need to stop amiodarone hydrochloride tablets, have your dose changed, or get medical treatment. Talk with your healthcare provider before you stop taking amiodarone hydrochloride tablets. \n </span>\n<br/>\n\t\t\tYou may still have side effects after stopping amiodarone hydrochloride tablets because the medicine stays in your body for months after treatment is stopped.\n <br/>\n\t\t\tYou should have regular check-ups, blood tests, chest x-rays before and during treatment with amiodarone hydrochloride tablets to check for serious side effects. You should also have lung function tests before starting treatment with amiodarone hydrochloride tablets.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are amiodarone hydrochloride tablets?</span>\n<br/>\n\t\t\tAmiodarone hydrochloride tablets are a prescription medicine used to treat people who have been diagnosed with life-threatening heartbeat problems called ventricular arrhythmias, when other treatments did not work or you cannot tolerate them.\n <br/>\n\t\t\tIt is not known if amiodarone hydrochloride tablets are safe and effective in children.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Who should not take amiodarone hydrochloride tablets?\n <br/>\n\t\t\tDo not take amiodarone hydrochloride tablets if you:\n </span>\n<ul class=\"Disc\">\n<li>have a serious heart problem called cardiogenic shock</li>\n<li>have certain types of the heart condition called heart block, with or without a slow heart rate</li>\n<li>have a slow heart rate with dizziness or lightheadedness, and you do not have an implanted pacemaker</li>\n<li>are allergic to amiodarone, iodine, or any of the other ingredients in amiodarone hydrochloride tablets. See the end of this Medication Guide for a complete list of ingredients in amiodarone hydrochloride tablets.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Before taking amiodarone hydrochloride tablets, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have lung or breathing problems</li>\n<li>have liver problems</li>\n<li>have or had thyroid problems</li>\n<li>have a slow heart rate or blood pressure problems</li>\n<li>have diarrhea or have had diarrhea for a long period of time</li>\n<li>have been told that you have low levels of potassium, magnesium, or calcium in your blood</li>\n<li>have an implanted pacemaker or defibrillator</li>\n<li>if you plan to have surgery with general anesthesia</li>\n<li>are pregnant or plan to become pregnant. Amiodarone hydrochloride may harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with amiodarone hydrochloride tablets. Amiodarone can stay in your body for months after treatment is stopped.</li>\n<li>are breastfeeding or plan to breastfeed. Amiodarone can pass into your breast milk and may harm your baby. You should not breast feed while taking amiodarone hydrochloride tablets. Amiodarone can stay in your body for months after treatment is stopped. Talk to your healthcare provider about the best way to feed your baby during this time.</li>\n</ul>\n\t\t\tTell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. Amiodarone hydrochloride tablets and certain other medicines can affect with each other and cause serious side effects. You can ask your pharmacist for a list of medicines that interact with amiodarone hydrochloride tablets.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">How should I take amiodarone hydrochloride tablets?</span>\n<ul class=\"Disc\">\n<li>When you are discharged from the hospital, take amiodarone hydrochloride tablets \n <span class=\"Bold\">exactly</span>as your doctor tells you to take it.\n </li>\n<li>Your healthcare provider will tell you how much amiodarone hydrochloride tablets to take and when to take it.</li>\n<li>Your healthcare provider may change your dose of amiodarone hydrochloride tablets as needed if your heart rhythm is controlled, or if you have certain side effects. Your healthcare provider should monitor you carefully when your dose of amiodarone hydrochloride tablets is being changed.</li>\n<li>\n<span class=\"Bold\">Take your dose of amiodarone hydrochloride tablets the same way each time, either with or without food.</span>\n</li>\n<li>If you take too much amiodarone hydrochloride tablets, call your healthcare provider or go to the nearest hospital emergency room right away. If you miss a dose, wait and take your next dose at your regular time. Do not take two doses at the same. Continue with your next regularly scheduled dose.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What should I avoid while taking amiodarone hydrochloride tablets?</span>\n<ul class=\"Disc\">\n<li>Avoid drinking grapefruit juice during treatment with amiodarone hydrochloride tablets. Drinking grapefruit juice with amiodarone hydrochloride tablets may increase the amount of amiodarone in your blood, and this may lead to side effects.</li>\n<li>Amiodarone hydrochloride tablets can make your skin sensitive to sunlight. You could get severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin to help protect you if you must be in sunlight. Talk to your healthcare if you get a sunburn. See \" \n <a href=\"#Skin\">Skin problems</a>\" in the Medication Guide section \n <span class=\"Bold\">\"What are the possible side effects of amiodarone hydrochloride tablets?\"</span>below.\n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the possible side effects of amiodarone hydrochloride tablets?\n <br/>\n\t\t\tAmiodarone hydrochloride tablets can cause serious side effects, including:\n </span>\n<ul class=\"Disc\">\n<li>See \n <span class=\"Bold\">\" \n <a href=\"#Important\">What is the most important information I should know about amiodarone hydrochloride tablets?</a>\" \n </span>\n</li>\n<li>\n<span class=\"Bold\">Nerve problems.</span>Amiodarone hydrochloride tablets can cause nerve problems. Call your healthcare provider if you develop symptoms of nerve problems, including: a feeling of \"pins and needles\" or numbness in your hands, legs, or feet, muscle weakness, uncontrolled movements, poor coordination, or trouble walking.\n </li>\n<li>\n<span class=\"Bold\">Skin problems.</span>Amiodarone hydrochloride tablets can cause your skin to be more sensitive to the sun or turn a bluish-gray color. People who have fair skin or people who have a lot of sun exposure may be more at risk for these skin problems. Some of the bluish-gray skin color may return to normal after stopping amiodarone hydrochloride tablets.\n </li>\n<li>\n<span class=\"Bold\">Thyroid problems.</span>Amiodarone hydrochloride tablets can cause you to have either decreased thyroid function (hypothyroidism), which can sometimes be severe, or an overactive thyroid (hyperthyroidism), which can be severe.\n\t\t\t\t\n <ul class=\"Circle\">\n<li>If you develop decreased thyroid function during treatment with amiodarone, your healthcare provider may need to reduce your dose or stop your treatment with amiodarone hydrochloride tablets, and possibly prescribe medicine to replace your thyroid hormone.</li>\n<li>An overactive thyroid can cause you to produce too much thyroid hormone. You can have abnormal heartbeats even while you are receiving amiodarone. Your healthcare provider may prescribe certain medicines to treat your overactive thyroid. Call your healthcare provider if you get any abnormal heart beats during treatment with amiodarone hydrochloride tablets. This may mean that you have an overactive thyroid.</li>\n<li>Your healthcare provider should do tests to check your thyroid function before you start and during treatment with amiodarone hydrochloride tablets.</li>\n<li>Call your healthcare provider if you develop any of the following symptoms of a thyroid problem during treatment with amiodarone hydrochloride tablets:</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<ul class=\"Square\">\n<li>weakness</li>\n<li>weight loss or weight gain</li>\n<li>heat or cold intolerance</li>\n<li>hair thinning</li>\n<li>sweating</li>\n<li>changes in your menstrual periods</li>\n<li>swelling of your neck (goiter)</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Square\">\n<li>nervousness</li>\n<li>irritability</li>\n<li>restlessness</li>\n<li>decreased concentration</li>\n<li>feeling depressed (in the elderly)</li>\n<li>tremor</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">The most common side effects of amiodarone hydrochloride tablets include:\n\t\t\t\n <ul class=\"Disc\">\n<li>lung problems</li>\n<li>heartbeat problems</li>\n<li>heart problems</li>\n<li>liver problems</li>\n</ul>\n\t\t\tAmiodarone hydrochloride tablets may affect fertility in males and females. It is not known if the effects are reversible. Talk to your healthcare provider if you have concerns about fertility.\n <br/>\n\t\t\tThese are not all the possible side effects of amiodarone hydrochloride tablets. For more information, ask your healthcare provider or pharmacist.\n <br/>\n\t\t\tCall your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">How should I store amiodarone hydrochloride tablets?</span>\n<ul class=\"Disc\">\n<li>Store amiodarone hydrochloride tablets at room temperature between 20° to 25°C (68° to 77°F).</li>\n<li>Keep amiodarone hydrochloride tablets in a tightly closed container, and keep amiodarone hydrochloride tablets out of the light.</li>\n</ul>\n<span class=\"Bold\">Keep amiodarone hydrochloride tablets and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">General information about the safe and effective use of amiodarone hydrochloride tablets</span>\n<br/>\n\t\t\tMedicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use amiodarone hydrochloride tablets for a condition for which it was not prescribed. Do not give amiodarone hydrochloride tablets to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about amiodarone hydrochloride tablets that is written for health professionals.\n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the ingredients in amiodarone hydrochloride tablets?\n <br/>\n\t\t\tActive Ingredient:\n </span>amiodarone hydrochloride\n <br/>\n<span class=\"Bold\">Inactive Ingredients:</span>colloidal silicon dioxide, corn starch, D&amp;C yellow No. 10 lake (200 and 400 mg only), FD&amp;C yellow No. 6 lake (200 and 300 mg only), lactose anhydrous, magnesium stearate and povidone.\n <br/>\n\t\t\tManufactured by: Taro Pharmaceutical Industries Ltd.\n <br/>\n\t\t\tHaifa Bay, Israel 2624761\n <br/>\n\t\t\tDistributed by: \n <span class=\"Bold\">Taro Pharmaceuticals U.S.A., Inc.</span>\n<br/>\n\t\t\tHawthorne, NY 10532\n <br/>\n\t\t\tFor more information, call 1-866-923-4914 or visit www.taro.com\n </td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration." }

Revised: October 2022 5200381-1022-20

{ "type": "p", "children": [], "text": "Revised: October 2022\n \n5200381-1022-20\n " }

Marketed by:

{ "type": "p", "children": [], "text": "Marketed by:" }

GSMS, Inc.

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

Camarillo, CA 93012 USA

{ "type": "p", "children": [], "text": "Camarillo, CA 93012 USA" }

NDC 51407-873-30 30 Tablets

{ "type": "p", "children": [], "text": "NDC 51407-873-30\n \n30 Tablets\n " }

Amiodarone HCl Tablets USP 100 mg

{ "type": "p", "children": [], "text": "Amiodarone HCl\n \nTablets USP 100 mg\n " }

PHARMACIST: Dispense Medication Guide to each patient. Print Medication Guides at: www.taro.com

{ "type": "p", "children": [], "text": "PHARMACIST: Dispense Medication Guide to each patient.\n \nPrint Medication Guides at: www.taro.com\n " }

Rx only

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

NDC 51407-874-90 90 Tablets

{ "type": "p", "children": [], "text": "NDC 51407-874-90\n \n90 Tablets\n " }

Amiodarone HCl Tablets USP

{ "type": "p", "children": [], "text": "Amiodarone HCl\n \nTablets USP\n " }

200 mg

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

PHARMACIST: Dispense Medication Guide to each patient. Print Medication Guides at: www.taro.com

{ "type": "p", "children": [], "text": "PHARMACIST: Dispense\n \nMedication Guide to each\n \npatient. Print Medication\n \nGuides at: www.taro.com\n " }

Rx only

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

NDC 51407-875-30 30 Tablets

{ "type": "p", "children": [], "text": "NDC 51407-875-30\n \n30 Tablets\n " }

Amiodarone HCl Tablets USP 400 mg

{ "type": "p", "children": [], "text": "Amiodarone HCl\n \nTablets USP 400 mg\n " }

PHARMACIST: Dispense Medication Guide to each patient. Print Medication Guides at: www.taro.com

{ "type": "p", "children": [], "text": "PHARMACIST: Dispense Medication Guide to each patient.\n \nPrint Medication Guides at: www.taro.com\n " }

Rx only

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