Atropine is indicated for temporary blockade of severe or life threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia.

{ "type": "p", "children": [], "text": "Atropine is indicated for temporary blockade of severe or life threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus, carbamate, or muscarinic mushroom poisoning, and to treat symptomatic bradycardia. \n \n" }

Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless solution is clear and seal is intact.

After initial use, discard unused portion within 24 hours.

Intravenous administration is usually preferred, but subcutaneous, intramuscular, endotracheal, and intraosseous administration are possible.

Table 1: Recommended Dosage in Adult Patients

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="112.55pt"/> <col width="143.4pt"/> <col width="4in"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Use</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Initial Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Continued Treatment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Antisialagogue or</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.5 to 1 mg IV/IM/SC</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Repeat as needed every 4 to 6 hours.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">other antivagal</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">30 to 60 minutes</p> </td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(preanesthesia and</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">preoperatively</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Maximum Total Dose</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">during surgery)</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First">3 mg</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Organophosphorus, carbamate, or muscarinic mushroom poisoning</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 to 6 mg IV/IM/ET depending on severity of symptoms</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Repeat as needed every 3 to 5 minutes</p> <p>Dose may be doubled with each administration until response (reduced bronchospasm, improved oxygenation and drying of pulmonary secretions).</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Maintenance Dose:</span>Administer 10% to 20% of the loading dose required for response as a continuous infusion per hour and titrate. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Maximum Total Dose:</span>No maximum total dose. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Symptomatic</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.5 mg IV/IM or 1 to 2 mg</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">As needed every 3 to 5 minutes</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">bradycardia*</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">ET by diluting in no more than 10 mL sterile water for injection or 0.9% sodium chloride</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Maximum Total Dose</span>3 mg </p> </td> </tr> </tbody> </table></div>

IV=intravenous; IM=intramuscular; SC=subcutaneous; ET=endotracheal

*Do not rely on atropine in type II second-degree or third-degree AV block with wide QRS complexes because these bradyarrhythmias are not likely to be responsive to reversal of cholinergic effects by atropine. Atropine has no effect on bradycardia in patients with transplanted hearts.

Table 2: Recommended Dosage in Pediatric Patients

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="113.4pt"/> <col width="130.7pt"/> <col width="314.95pt"/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold"> </span><span class="Bold">Use</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Initial Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Continued Treatment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Antisialagogue or other antivagal (preanesthesia and during surgery)*</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">0.02 mg/kg IV/IM/SC 30 to 60 minutes preoperatively</p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Repeat as needed every 4 to 6 hours.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Maximum Single Dose</span> </p> <p> <span class="Underline"> </span><span class="Italics">Less than 12 years old:</span>0.5 mg </p> <p> <span class="Italics">12 years and older:</span>1 mg </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Maximum Total Dose</span> </p> <p> <span class="Italics">Less than 12 years old:</span>1 mg </p> <p> <span class="Italics">12 years and older:</span>2 mg </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Organophosphorus,</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.02 to 0.06 mg/kg</p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Repeat as needed every 5 minutes</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">carbamate or</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">IV/IM/IO/ET</p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">muscarinic</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Dose may be doubled with each administration until response</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">mushroom poisoning</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">(reduced bronchospasm, improved oxygenation and drying of pulmonary secretions).</p> <p> <span class="Italics">Maintenance Dose:</span>Administer 10% to 20% of the loading dose required for response as a continuous infusion per hour and titrate as needed. </p> <p> <span class="Underline">Maximum Total Dose:</span>No maximum total dose. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Symptomatic</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.02 mg/kg IV/IO or</p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Repeat as needed every 5 minutes</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">bradycardia due to</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.04 to 0.06 mg/kg via</p> </td><td></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">increased vagal tone</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">endotracheal tube</p> </td><td> <p class="First"> <span class="Underline">Maximum Single Dose</span> </p> </td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">or primary AV</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">followed by 1 to 5 mL</p> </td><td> <p class="First"> <span class="Italics">Less than 12 years old:</span>0.5 mg </p> </td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">conduction block</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">flush of normal saline</p> </td><td> <p class="First"> <span class="Italics">12 years and older:</span>1 mg </p> </td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">(not secondary to</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">followed by 5</p> </td><td></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">hypoxia) **</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">ventilations</p> </td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> </tbody> </table></div>

IV=intravenous; IM=intramuscular; SC=subcutaneous; IO=intraosseous; ET=endotracheal;

*Available evidence does not support the routine use of atropine in emergency intubation of critically ill infants and children except in specific emergency intubations when there is higher risk of bradycardia

** Atropine has no effect on bradycardia in patients with transplanted hearts.

Limit the total dose of atropine sulfate to 0.03 to 0.04 mg/kg [see Warnings and Precautions (5.2)].

Atropine Sulfate Injection, USP, 8 mg per 20 mL (0.4 mg per mL), is a non-pyrogenic, isotonic, clear solution and is supplied in a multiple dose glass vial.

{ "type": "p", "children": [], "text": "Atropine Sulfate Injection, USP, 8 mg per 20 mL (0.4 mg per mL), is a non-pyrogenic, isotonic, clear solution and is supplied in a multiple dose glass vial. \n \n" }

None.

{ "type": "p", "children": [], "text": "None. \n \n" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="1pt"/> <tbody class="Headless"> <tr class="First Last"> <td> <p class="First">Atropine may cause anaphylaxis.</p> </td> </tr> </tbody> </table></div>

In patients with ischemic heart disease, the total dose should be restricted to 2 to 3 mg (maximum 0.03 to 0.04 mg/kg) to avoid atropine-induced tachycardia, increased myocardial oxygen demand and the potential for worsening cardiac ischemia or increasing infarction size.

Atropine may precipitate acute glaucoma.

Atropine may convert partial organic pyloric stenosis into complete obstruction.

Atropine may lead to complete urinary retention in patients with prostatic hypertrophy.

Atropine may cause thickening of bronchial secretions and formation of viscid plugs in patients with chronic lung disease.

The preservative benzyl alcohol has been associated with serious adverse events and death in neonates. The “gasping syndrome” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth weight infants. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.

Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth weight infants may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="1pt"/> <tbody class="Headless"> <tr class="First"> <td> <p class="First">The following adverse reactions are described elsewhere in labeling:</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li> <span class="Italics">Hypersensitivity ( <a href="#LINK_78eb58e7-b629-459f-8d93-d789dff4a74a">5.1</a>) </span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li> <span class="Italics">Worsening of Ischemic Heart Disease ( <a href="#LINK_243d826c-0114-4620-9dde-2af1c612e7bc">5.2</a>) </span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li> <span class="Italics">Acute Glaucoma ( <a href="#LINK_3d209236-46c9-48db-94af-35063840b846">5.3</a>) </span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li> <span class="Italics">Pyloric Obstruction ( <a href="#LINK_5c004d6b-12d3-44cc-ab66-3b04c99579c0">5.4</a>) </span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li> <span class="Italics">Complete Urinary Retention ( <a href="#LINK_f3f9b1ec-344c-4928-8b3b-b315dded30fb">5.5</a>) </span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <ul class="Disc"> <li> <span class="Italics">Viscid Plugs ( <a href="#LINK_f79e9315-fa4b-45dc-8f66-f9188dec8226">5.6</a>) </span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">The following adverse reactions have been identified during post-approval use of atropine sulfate.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Because these reactions are reported voluntarily from a population of uncertain size, it is not always</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">possible to reliably estimate their frequency or establish a causal relationship to drug exposure.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Most of the side effects of atropine are directly related to its antimuscarinic action. Dryness of the</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">mouth, blurred vision, photophobia and tachycardia commonly occur. Anhidrosis can produce heat</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">intolerance. Constipation and difficulty in micturition may occur. Occasional hypersensitivity</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">reactions have been observed, including serious skin rashes. Paralytic ileus may occur. Exacerbation</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">of reflux has been reported. Larger or toxic doses may produce such central effects as restlessness,</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">tremor, fatigue, locomotor difficulties, delirium, followed by hallucinations, depression, and</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">ultimately, medullary paralysis and death. Large doses can also lead to circulatory collapse. In such</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">coma.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n<col width=\"1pt\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">The following adverse reactions are described elsewhere in labeling:</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Italics\">Hypersensitivity (\n \n <a href=\"#LINK_78eb58e7-b629-459f-8d93-d789dff4a74a\">5.1</a>)\n \n </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Italics\">Worsening of Ischemic Heart Disease (\n \n <a href=\"#LINK_243d826c-0114-4620-9dde-2af1c612e7bc\">5.2</a>)\n \n </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Italics\">Acute Glaucoma (\n \n <a href=\"#LINK_3d209236-46c9-48db-94af-35063840b846\">5.3</a>)\n \n </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Italics\">Pyloric Obstruction (\n \n <a href=\"#LINK_5c004d6b-12d3-44cc-ab66-3b04c99579c0\">5.4</a>)\n \n </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Italics\">Complete Urinary Retention (\n \n <a href=\"#LINK_f3f9b1ec-344c-4928-8b3b-b315dded30fb\">5.5</a>)\n \n </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Italics\">Viscid Plugs (\n \n <a href=\"#LINK_f79e9315-fa4b-45dc-8f66-f9188dec8226\">5.6</a>)\n \n </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">The following adverse reactions have been identified during post-approval use of atropine sulfate.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Because these reactions are reported voluntarily from a population of uncertain size, it is not always</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">possible to reliably estimate their frequency or establish a causal relationship to drug exposure.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Most of the side effects of atropine are directly related to its antimuscarinic action. Dryness of the</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">mouth, blurred vision, photophobia and tachycardia commonly occur. Anhidrosis can produce heat</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">intolerance. Constipation and difficulty in micturition may occur. Occasional hypersensitivity</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">reactions have been observed, including serious skin rashes. Paralytic ileus may occur. Exacerbation</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">of reflux has been reported. Larger or toxic doses may produce such central effects as restlessness,</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">tremor, fatigue, locomotor difficulties, delirium, followed by hallucinations, depression, and</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">ultimately, medullary paralysis and death. Large doses can also lead to circulatory collapse. In such</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">coma.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="1pt"/> <tbody class="Headless"> <tr class="First"> <td> <p class="First">Atropine Sulfate Injection decreased the rate of mexiletine absorption without altering the relative oral</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">bioavailability; this delay in mexiletine absorption was reversed by the combination of atropine and</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">intravenous metoclopramide during pretreatment for anesthesia.</p> </td> </tr> </tbody> </table></div>

Risk Summary

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="1pt"/> <tbody class="Headless"> <tr class="First"> <td> <p class="First">Limited available data with Atropine Sulfate Injection use in pregnant women are insufficient to</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">inform a drug associated risk of adverse developmental outcomes <span class="Italics">(see Data)</span>. There are risks to the </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">mother and fetus associated with untreated severe or life-threatening muscarinic events <span class="Italics">(see Clinical</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Considerations)</span>. Animal reproduction studies have not been conducted with Atropine Sulfate </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Injection.</p> </td> </tr> </tbody> </table></div>

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

Severe or life-threatening muscarinic events such as acute organophosphate poisoning and symptomatic bradycardia are medical emergencies in pregnancy which can be fatal if left untreated. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of atropine on the fetus.

Data

Human Data

No adequate and well-controlled studies are available regarding use of atropine in pregnant women. In a cohort study of 401 pregnancies in the first trimester and 797 pregnancies in the second or third trimester, atropine use was not associated with an increased risk of congenital malformation. In a surveillance study, 381 newborns were exposed to atropine during the first trimester; 18 major birth defects were observed when 16 were expected. No specific pattern of major birth defects was identified. In another surveillance study of 50 pregnancies in the first trimester, atropine use was not associated with an increased risk of malformations. Methodological limitations of these observational studies including the inability to control for the dosage and timing of atropine exposure, underlying maternal disease, or concomitant maternal drug use, cannot definitively establish or exclude any drug- associated risk during pregnancy.

Risk Summary

Trace amounts of atropine have been reported in human milk after oral intake. There are no available data on atropine levels in human milk after intravenous injection, the effects on the breastfed infant, or the effects on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of atropine to an infant during lactation.

Clinical Considerations

Minimizing exposure

The elimination half-life of atropine is more than doubled in children less than 2 years of age [see Clinical Pharmacology (12.3)]. To minimize potential infant exposure to Atropine Sulfate Injection, a woman may pump and discard her milk for 24 hours after use before resuming to breastfeed her infant .

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. 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.

Excessive dosing may cause palpitation, dilated pupils, difficulty in swallowing, hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia. Toxic doses lead to restlessness and excitement, hallucinations, delirium and coma. Depression and circulatory collapse occur only with severe intoxication. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma.

{ "type": "p", "children": [], "text": "Excessive dosing may cause palpitation, dilated pupils, difficulty in swallowing, hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia. Toxic doses lead to restlessness and excitement, hallucinations, delirium and coma. Depression and circulatory collapse occur only with severe intoxication. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma." }

The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be fatal.

{ "type": "p", "children": [], "text": "The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be fatal." }

In the event of toxic overdosage, a short acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning.

{ "type": "p", "children": [], "text": "In the event of toxic overdosage, a short acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning." }

Central stimulants are not recommended.

{ "type": "p", "children": [], "text": "Central stimulants are not recommended." }

Physostigmine, given as an atropine antidote by slow intravenous injection of 1 to 4 mg (0.5 to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required.

{ "type": "p", "children": [], "text": "Physostigmine, given as an atropine antidote by slow intravenous injection of 1 to 4 mg (0.5 to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required." }

Artificial respiration with oxygen may be necessary. Ice bags and alcohol sponges help to reduce fever, especially in pediatric populations.

{ "type": "p", "children": [], "text": "Artificial respiration with oxygen may be necessary. Ice bags and alcohol sponges help to reduce fever, especially in pediatric populations." }

Atropine is not removed by dialysis.

{ "type": "p", "children": [], "text": "Atropine is not removed by dialysis." }

Atropine Sulfate Injection, USP is a sterile, nonpyrogenic, isotonic, clear solution of atropine sulfate in water for injection with sodium chloride sufficient to render the solution isotonic. It is administered parenterally by subcutaneous, intramuscular or intravenous injection.

{ "type": "p", "children": [], "text": "Atropine Sulfate Injection, USP is a sterile, nonpyrogenic, isotonic, clear solution of atropine sulfate in water for injection with sodium chloride sufficient to render the solution isotonic. It is administered parenterally by subcutaneous, intramuscular or intravenous injection." }

Each mL contains atropine sulfate, 0.4 mg; benzyl alcohol, 9 mg; sodium chloride 9 mg. May contain sulfuric acid for pH adjustment. pH 3.5 (3.0 to 3.8).

{ "type": "p", "children": [], "text": "Each mL contains atropine sulfate, 0.4 mg; benzyl alcohol, 9 mg; sodium chloride 9 mg. May contain sulfuric acid for pH adjustment. pH 3.5 (3.0 to 3.8)." }

Sodium chloride added to render the solution isotonic for injection of the active ingredient is present in amounts insufficient to affect serum electrolyte balance of sodium (Na+) and chloride (Cl-) ions.

{ "type": "p", "children": [], "text": "Sodium chloride added to render the solution isotonic for injection of the active ingredient is present in amounts insufficient to affect serum electrolyte balance of sodium (Na+) and chloride (Cl-) ions." }

Atropine Sulfate, USP is chemically designated lα H, 5α H-Tropan-3-α-ol (±)-tropate (ester), sulfate (2:1) (salt) monohydrate, (C 17H 23NO 3) 2· H 2SO 4· H 2O, colorless crystals or white crystalline powder very soluble in water. It has the following structural formula:

{ "type": "p", "children": [], "text": "\n Atropine Sulfate, USP is chemically designated lα H, 5α H-Tropan-3-α-ol (±)-tropate (ester), sulfate (2:1) (salt) monohydrate, (C\n \n 17H\n \n 23NO\n \n 3)\n \n 2· H\n \n 2SO\n \n 4· H\n \n 2O, colorless crystals or white crystalline powder very soluble in water. It has the following structural formula:\n\n " }

Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and 1-hyocyamine, whose activity is due almost entirely to the levo isomer of the drug.

{ "type": "p", "children": [], "text": "Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and 1-hyocyamine, whose activity is due almost entirely to the levo isomer of the drug." }

Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water.

{ "type": "p", "children": [], "text": "Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water." }

Atropine is an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters.

Atropine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves, and on smooth muscles which respond to endogenous acetylcholine but are not so innervated. As with other antimuscarinic agents, the major action of atropine is a competitive or surmountable antagonism which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents which inhibit the enzymatic destruction of acetylcholine). The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine (i.e., exocrine glands and smooth and cardiac muscle). Responses to postganglionic cholinergic nerve stimulation also may be inhibited by atropine but this occurs less readily than with responses to injected (exogenous) choline esters.

Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control. Atropine exerts a more potent and prolonged effect on heart, intestine and bronchial muscle than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of scopolamine. Unlike the latter, atropine in clinical doses does not depress the central nervous system but may stimulate the medulla and higher cerebral centers. Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) increased depth of respiration produced by atropine are more probably the result of bronchiolar dilatation. Accordingly, atropine is an unreliable respiratory stimulant and large or repeated doses may depress respiration.

Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Atropine also may lessen the degree of partial heart block when vagal activity is an etiologic factor. In some patients with complete heart block, the idioventricular rate may be accelerated by atropine; in others, the rate is stabilized. Occasionally a large dose may cause atrioventricular (A-V) block and nodal rhythm.

Atropine in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure. Systemic doses slightly raise systolic and lower diastolic pressures and can produce significant postural hypotension. Such doses also slightly increase cardiac output and decrease central venous pressure. Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the “blush” area (atropine flush), and may cause atropine “fever” due to suppression of sweat gland activity in infants and small children.

The effects of intravenous atropine on heart rate (maximum heart rate) and saliva flow (minimum flow) after I.V. administration (rapid, constant infusion over 3 min.) are delayed by 7 to 8 minutes after drug administration and both effects are non-linearly related to the amount of drug in the peripheral compartment. Changes in plasma atropine levels following intramuscular administration (0.5 to 4 mg doses) and heart rate are closely overlapped but the time course of the changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limiting mechanism for the central nervous system effect of atropine.

Absorption

After intramuscular administration, atropine is absorbed with peak concentration occurring at 30 min following injection.

Effects of exercise:

Exercise following intramuscular administration of atropine significantly increases the absorption of atropine due to increased perfusion in the muscle, with an increase in AUC by approximately 20% and C maxby approximately 80%.

Distribution

Atropine is distributed throughout the body. Atropine’s plasma protein binding is about 44% and saturable in the 2 to 20 mcg/mL concentration range.

Elimination

The pharmacokinetics of atropine is nonlinear after intravenous administration of 0.5 to 4 mg. Atropine disappears from the blood following injection with a plasma half-life of about 2 to 4 hours. Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver, with 13 to 50% is excreted unchanged in the urine.

Metabolism

The major metabolites of atropine are noratropine, atropin-n-oxide, tropine, and tropic acid. The metabolism of atropine is inhibited by organophosphate pesticides.

Specific Populations

Pregnant Women

Atropine readily crosses the placental barrier and enters the fetal circulation, but is not found in amniotic fluid.

Nursing Mother

Traces are found in various secretions, including milk.

Pediatric and Geriatric Patients

The elimination half-life of atropine is more than doubled in children under two years, and the elderly (> 65 years old) compared to other age groups.

Studies have not been performed to evaluate the carcinogenic or mutagenic potential of atropine or its potential to affect fertility adversely.

Atropine Sulfate Injection, USP is a non-pyrogenic, isotonic, clear solution and is supplied as follows:

{ "type": "p", "children": [], "text": "Atropine Sulfate Injection, USP is a non-pyrogenic, isotonic, clear solution and is supplied as follows:" }

20 mL multiple-dose vial, packaged in a carton containing 10 vials.

{ "type": "p", "children": [], "text": "20 mL multiple-dose vial, packaged in a carton containing 10 vials." }

NDC: 70518-4329-00

{ "type": "p", "children": [], "text": "NDC: 70518-4329-00" }

NDC: 70518-4329-01

{ "type": "p", "children": [], "text": "NDC: 70518-4329-01" }

OUTER PACKAGING: 10 in 1 CARTON

{ "type": "p", "children": [], "text": "OUTER PACKAGING: 10 in 1 CARTON" }

PACKAGING: 20 mL in 1 VIAL TYPE 0

{ "type": "p", "children": [], "text": "PACKAGING: 20 mL in 1 VIAL TYPE 0" }

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. After initial use, store between 20° to 25°C (68° to 77°F) and discard within 24 hours.

{ "type": "p", "children": [], "text": "Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. After initial use, store between 20° to 25°C (68° to 77°F) and discard within 24 hours." }

Repackaged and Distributed By:

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

Remedy Repack, Inc.

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

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

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

DRUG: Atropine Sulfate

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

GENERIC: Atropine Sulfate

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

DOSAGE: INJECTION

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

ADMINSTRATION: ENDOTRACHEAL

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

NDC: 70518-4329-0

{ "type": "p", "children": [], "text": "NDC: 70518-4329-0" }

NDC: 70518-4329-1

{ "type": "p", "children": [], "text": "NDC: 70518-4329-1" }

PACKAGING: 20 mL in 1 VIAL

{ "type": "p", "children": [], "text": "PACKAGING: 20 mL in 1 VIAL" }

OUTER PACKAGING: 10 in 1 CARTON

{ "type": "p", "children": [], "text": "OUTER PACKAGING: 10 in 1 CARTON" }

ACTIVE INGREDIENT(S):

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

{ "type": "ul", "children": [ "ATROPINE SULFATE 0.4mg in 1mL" ], "text": "" }

INACTIVE INGREDIENT(S):

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

{ "type": "ul", "children": [ "SULFURIC ACID", "SODIUM CHLORIDE", "BENZYL ALCOHOL" ], "text": "" }

These highlights do not include all the information needed to use ATROPINE SULFATE INJECTION safely and effectively. See full prescribing information for ATROPINE SULFATE INJECTION.

{ "type": "p", "children": [], "text": "\nThese highlights do not include all the information needed to use ATROPINE SULFATE INJECTION safely and effectively. See full prescribing information for ATROPINE SULFATE INJECTION.\n" }

ATROPINE SULFATE injection, for intravenous use Initial U.S. Approval: 1960

{ "type": "p", "children": [], "text": "\nATROPINE SULFATE injection, for intravenous use\n\nInitial U.S. Approval: 1960\n" }

Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus or muscarinic mushroom poisoning and to treat bradyasystolic cardiac arrest.

{ "type": "p", "children": [], "text": "Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus or muscarinic mushroom poisoning and to treat bradyasystolic cardiac arrest." }

2.1 General Administration

{ "type": "p", "children": [], "text": "\n2.1 General Administration\n" }

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless solution is clear and seal is intact. Each syringe is intended for single-dose only. Discard unused portion.

{ "type": "p", "children": [], "text": "Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless solution is clear and seal is intact. Each syringe is intended for single-dose only. Discard unused portion." }

For intravenous administration.

{ "type": "p", "children": [], "text": "For intravenous administration." }

Titrate based on heart rate, PR interval, blood pressure and symptoms.

{ "type": "p", "children": [], "text": "Titrate based on heart rate, PR interval, blood pressure and symptoms." }

2.2 Adult Dosage

{ "type": "p", "children": [], "text": "\n2.2 Adult Dosage\n" }

Table 1: Recommended Dosage

{ "type": "p", "children": [], "text": "\nTable 1: Recommended Dosage\n" }

2.3 Pediatric Dosage

{ "type": "p", "children": [], "text": "\n2.3 Pediatric Dosage\n" }

Dosing in pediatric populations has not been well studied. Usual initial dose is 0.01 mg/kg to 0.03 mg/kg.

{ "type": "p", "children": [], "text": "Dosing in pediatric populations has not been well studied. Usual initial dose is 0.01 mg/kg to 0.03 mg/kg." }

2.4 Dosing in Patients with Coronary Artery Disease

{ "type": "p", "children": [], "text": "\n2.4 Dosing in Patients with Coronary Artery Disease\n" }

Limit the total dose of atropine sulfate to 0.03 mg/kg to 0.04 mg/kg [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Limit the total dose of atropine sulfate to 0.03 mg/kg to 0.04 mg/kg [see Warnings and Precautions (5.1)].\n" }

Atropine Sulfate Injection USP, 0.5 mg/5 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution supplied in 5 mL single-dose glass syringe for intravenous administration.

{ "type": "p", "children": [], "text": "Atropine Sulfate Injection USP, 0.5 mg/5 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution supplied in 5 mL single-dose glass syringe for intravenous administration." }

Atropine Sulfate Injection USP, 1 mg/10 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution supplied in 10 mL single-dose glass syringe for intravenous administration.

{ "type": "p", "children": [], "text": "Atropine Sulfate Injection USP, 1 mg/10 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution supplied in 10 mL single-dose glass syringe for intravenous administration." }

None. (4)

{ "type": "p", "children": [], "text": "None. (4)" }

5.1 Tachycardia

{ "type": "p", "children": [], "text": "\n5.1 Tachycardia\n" }

When the recurrent use of atropine is essential in patients with coronary artery disease, the total dose should be restricted to 2 mg to 3 mg (maximum 0.03 mg/kg to 0.04 mg/kg) to avoid the detrimental effects of atropine-induced tachycardia on myocardial oxygen demand.

{ "type": "p", "children": [], "text": "When the recurrent use of atropine is essential in patients with coronary artery disease, the total dose should be restricted to 2 mg to 3 mg (maximum 0.03 mg/kg to 0.04 mg/kg) to avoid the detrimental effects of atropine-induced tachycardia on myocardial oxygen demand." }

5.2 Acute Glaucoma

{ "type": "p", "children": [], "text": "\n5.2 Acute Glaucoma\n" }

Atropine may precipitate acute glaucoma.

{ "type": "p", "children": [], "text": "Atropine may precipitate acute glaucoma." }

5.3 Pyloric Obstruction

{ "type": "p", "children": [], "text": "\n5.3 Pyloric Obstruction\n" }

Atropine may convert partial organic pyloric stenosis into complete obstruction.

{ "type": "p", "children": [], "text": "Atropine may convert partial organic pyloric stenosis into complete obstruction." }

5.4 Complete Urinary Retention

{ "type": "p", "children": [], "text": "\n5.4 Complete Urinary Retention\n" }

Atropine may lead to complete urinary retention in patients with prostatic hypertrophy.

{ "type": "p", "children": [], "text": "Atropine may lead to complete urinary retention in patients with prostatic hypertrophy." }

5.5 Viscid Plugs

{ "type": "p", "children": [], "text": "\n5.5 Viscid Plugs\n" }

Atropine may cause inspissation of bronchial secretions and formation of viscid plugs in patients with chronic lung disease.

{ "type": "p", "children": [], "text": "Atropine may cause inspissation of bronchial secretions and formation of viscid plugs in patients with chronic lung disease." }

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

{ "type": "p", "children": [], "text": "The following adverse reactions have been identified during post-approval use of atropine sulfate. 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." }

Most of the side effects of atropine are directly related to its antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur. Anhidrosis can produce heat intolerance. Constipation and difficulty in micturition may occur in elderly patients. Occasional hypersensitivity reactions have been observed, especially skin rashes which in some instances progressed to exfoliation.

{ "type": "p", "children": [], "text": "Most of the side effects of atropine are directly related to its antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur. Anhidrosis can produce heat intolerance. Constipation and difficulty in micturition may occur in elderly patients. Occasional hypersensitivity reactions have been observed, especially skin rashes which in some instances progressed to exfoliation." }

7.1 Mexiletine

{ "type": "p", "children": [], "text": "\n7.1 Mexiletine\n" }

Atropine sulfate injection decreased the rate of mexiletine absorption without altering the relative oral bioavailability; this delay in mexiletine absorption was reversed by the combination of atropine and intravenous metoclopramide during pretreatment for anesthesia.

{ "type": "p", "children": [], "text": "Atropine sulfate injection decreased the rate of mexiletine absorption without altering the relative oral bioavailability; this delay in mexiletine absorption was reversed by the combination of atropine and intravenous metoclopramide during pretreatment for anesthesia." }

8.1 Pregnancy

{ "type": "p", "children": [], "text": "\n8.1 Pregnancy\n" }

Animal reproduction studies have not been conducted with atropine. It also is not known whether atropine can cause fetal harm when given to a pregnant woman or can affect reproduction capacity.

{ "type": "p", "children": [], "text": "Animal reproduction studies have not been conducted with atropine. It also is not known whether atropine can cause fetal harm when given to a pregnant woman or can affect reproduction capacity." }

8.3 Nursing Mothers

{ "type": "p", "children": [], "text": "\n8.3 Nursing Mothers\n" }

Trace amounts of atropine was found in breast milk. The clinical impact of this is not known.

{ "type": "p", "children": [], "text": "Trace amounts of atropine was found in breast milk. The clinical impact of this is not known." }

8.4 Pediatric Use

{ "type": "p", "children": [], "text": "\n8.4 Pediatric Use\n" }

Recommendations for use in pediatric patients are not based on clinical trials.

{ "type": "p", "children": [], "text": "Recommendations for use in pediatric patients are not based on clinical trials." }

8.5 Geriatric Use

{ "type": "p", "children": [], "text": "\n8.5 Geriatric Use\n" }

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. 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.

{ "type": "p", "children": [], "text": "An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. 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." }

Excessive dosing may cause palpitation, dilated pupils, difficulty in swallowing, hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia. Toxic doses lead to restlessness and excitement, hallucinations, delirium and coma. Depression and circulatory collapse occur only with severe intoxication. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma.

{ "type": "p", "children": [], "text": "Excessive dosing may cause palpitation, dilated pupils, difficulty in swallowing, hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia. Toxic doses lead to restlessness and excitement, hallucinations, delirium and coma. Depression and circulatory collapse occur only with severe intoxication. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma." }

The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be fatal.

{ "type": "p", "children": [], "text": "The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be fatal." }

In the event of toxic overdosage, a short acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning. Central stimulants are not recommended.

{ "type": "p", "children": [], "text": "In the event of toxic overdosage, a short acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning. Central stimulants are not recommended." }

Physostigmine, given as an atropine antidote by slow intravenous injection of 1 mg to 4 mg (0.5 mg to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required.

{ "type": "p", "children": [], "text": "Physostigmine, given as an atropine antidote by slow intravenous injection of 1 mg to 4 mg (0.5 mg to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required." }

Artificial respiration with oxygen may be necessary. Ice bags and alcohol sponges help to reduce fever, especially in pediatric populations.

{ "type": "p", "children": [], "text": "Artificial respiration with oxygen may be necessary. Ice bags and alcohol sponges help to reduce fever, especially in pediatric populations." }

Atropine is not removed by dialysis.

{ "type": "p", "children": [], "text": "Atropine is not removed by dialysis." }

Atropine sulfate injection, USP is a sterile, nonpyrogenic isotonic solution of atropine sulfate monohydrate in water for injection with sodium chloride sufficient to render the solution isotonic. It is administered parenterally by intravenous injection.

{ "type": "p", "children": [], "text": "Atropine sulfate injection, USP is a sterile, nonpyrogenic isotonic solution of atropine sulfate monohydrate in water for injection with sodium chloride sufficient to render the solution isotonic. It is administered parenterally by intravenous injection." }

Each milliliter (mL) contains 0.1 mg (adult strength) of atropine sulfate monohydrate equivalent to 0.083 mg (adult strength) of atropine, and sodium chloride, 9 mg. May contain sodium hydroxide and/or sulfuric acid for pH adjustment.

{ "type": "p", "children": [], "text": "Each milliliter (mL) contains 0.1 mg (adult strength) of atropine sulfate monohydrate equivalent to 0.083 mg (adult strength) of atropine, and sodium chloride, 9 mg. May contain sodium hydroxide and/or sulfuric acid for pH adjustment." }

0.308 mOsmol/mL (calc.). pH 3.0 to 6.5.

{ "type": "p", "children": [], "text": "0.308 mOsmol/mL (calc.). pH 3.0 to 6.5." }

Sodium chloride added to render the solution isotonic for injection of the active ingredient is present in amounts insufficient to affect serum electrolyte balance of sodium (Na+) and chloride (Cl-) ions.

{ "type": "p", "children": [], "text": "Sodium chloride added to render the solution isotonic for injection of the active ingredient is present in amounts insufficient to affect serum electrolyte balance of sodium (Na+) and chloride (Cl-) ions." }

The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended for use only as a single-dose injection. When smaller doses are required the unused portion should be discarded.

{ "type": "p", "children": [], "text": "The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended for use only as a single-dose injection. When smaller doses are required the unused portion should be discarded." }

Atropine sulfate, USP is chemically designated 1α H, 5α H-tropan-3-α-ol (±)-tropate (ester), sulfate (2:1) (salt) monohydrate, (C17H23NO3)2 H2SO4 H2O, colorless, almost white to white solid. It is very soluble in water and glacial acetic acid, freely soluble in ethanol (96%) and practically insoluble in diethyl ether. It has the following structural formula:

{ "type": "p", "children": [], "text": "Atropine sulfate, USP is chemically designated 1α H, 5α H-tropan-3-α-ol (±)-tropate (ester), sulfate (2:1) (salt) monohydrate, (C17H23NO3)2 H2SO4 H2O, colorless, almost white to white solid. It is very soluble in water and glacial acetic acid, freely soluble in ethanol (96%) and practically insoluble in diethyl ether. It has the following structural formula:" }

Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and 1-hyocyamine, whose activity is due almost entirely to the levo isomer of the drug.

{ "type": "p", "children": [], "text": "\nAtropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and 1-hyocyamine, whose activity is due almost entirely to the levo isomer of the drug.\n" }

Sodium chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water.

{ "type": "p", "children": [], "text": "Sodium chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water." }

12.1 Mechanism of Action

{ "type": "p", "children": [], "text": "\n12.1 Mechanism of Action\n" }

Atropine is an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters.

{ "type": "p", "children": [], "text": "Atropine is an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters." }

Atropine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves, and on smooth muscles which respond to endogenous acetylcholine but are not so innervated. As with other antimuscarinic agents, the major action of atropine is a competitive or surmountable antagonism which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents which inhibit the enzymatic destruction of acetylcholine). The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine (i.e. exocrine glands and smooth and cardiac muscle). Responses to postganglionic cholinergic nerve stimulation also may be inhibited by atropine but this occurs less readily than with responses to injected (exogenous) choline esters.

{ "type": "p", "children": [], "text": "Atropine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves, and on smooth muscles which respond to endogenous acetylcholine but are not so innervated. As with other antimuscarinic agents, the major action of atropine is a competitive or surmountable antagonism which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents which inhibit the enzymatic destruction of acetylcholine). The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine (i.e. exocrine glands and smooth and cardiac muscle). Responses to postganglionic cholinergic nerve stimulation also may be inhibited by atropine but this occurs less readily than with responses to injected (exogenous) choline esters." }

12.2 Pharmacodynamics

{ "type": "p", "children": [], "text": "\n12.2 Pharmacodynamics\n" }

Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control. Atropine exerts a more potent and prolonged effect on heart, intestine and bronchial muscle than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of scopolamine. Unlike the latter, atropine in clinical doses does not depress the central nervous system but may stimulate the medulla and higher cerebral centers. Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) increased depth of respiration produced by atropine are more probably the result of bronchiolar dilatation. Accordingly, atropine is an unreliable respiratory stimulant and large or repeated doses may depress respiration.

{ "type": "p", "children": [], "text": "Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control. Atropine exerts a more potent and prolonged effect on heart, intestine and bronchial muscle than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of scopolamine. Unlike the latter, atropine in clinical doses does not depress the central nervous system but may stimulate the medulla and higher cerebral centers. Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) increased depth of respiration produced by atropine are more probably the result of bronchiolar dilatation. Accordingly, atropine is an unreliable respiratory stimulant and large or repeated doses may depress respiration." }

Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Atropine also may lessen the degree of partial heart block when vagal activity is an etiologic factor. In some patients with complete heart block, the idioventricular rate may be accelerated by atropine; in others, the rate is stabilized. Occasionally a large dose may cause atrioventricular (A-V) block and nodal rhythm.

{ "type": "p", "children": [], "text": "Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Atropine also may lessen the degree of partial heart block when vagal activity is an etiologic factor. In some patients with complete heart block, the idioventricular rate may be accelerated by atropine; in others, the rate is stabilized. Occasionally a large dose may cause atrioventricular (A-V) block and nodal rhythm." }

Atropine sulfate injection in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure. Systemic doses slightly raise systolic and lower diastolic pressures and can produce significant postural hypotension. Such doses also slightly increase cardiac output and decrease central venous pressure. Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the “blush” area (atropine flush) and may cause atropine “fever” due to suppression of sweat gland activity in infants and small children.

{ "type": "p", "children": [], "text": "Atropine sulfate injection in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure. Systemic doses slightly raise systolic and lower diastolic pressures and can produce significant postural hypotension. Such doses also slightly increase cardiac output and decrease central venous pressure. Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the “blush” area (atropine flush) and may cause atropine “fever” due to suppression of sweat gland activity in infants and small children." }

The effects of intravenous atropine on heart rate (maximum heart rate) and saliva flow (minimum flow) after intravenous administration (rapid, constant infusion over 3 minutes) are delayed by 7 to 8 minutes after drug administration and both effects are non-linearly related to the amount of drug in the peripheral compartment. Changes in plasma atropine levels following intramuscular administration (0.5 mg to 4 mg doses) and heart rate are closely overlapped but the time course of the changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limiting mechanism for the central nervous system effect of atropine.

{ "type": "p", "children": [], "text": "The effects of intravenous atropine on heart rate (maximum heart rate) and saliva flow (minimum flow) after intravenous administration (rapid, constant infusion over 3 minutes) are delayed by 7 to 8 minutes after drug administration and both effects are non-linearly related to the amount of drug in the peripheral compartment. Changes in plasma atropine levels following intramuscular administration (0.5 mg to 4 mg doses) and heart rate are closely overlapped but the time course of the changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limiting mechanism for the central nervous system effect of atropine." }

12.3 Pharmacokinetics

{ "type": "p", "children": [], "text": "\n12.3 Pharmacokinetics\n" }

Atropine disappears rapidly from the blood following injection and is distributed throughout the body. Exercise, both prior to and immediately following intramuscular administration of atropine, significantly increases the absorption of atropine due to increased perfusion in the muscle and significantly decreases the clearance of atropine. The pharmacokinetics of atropine is nonlinear after intravenous administration of 0.5 mg to 4 mg. Atropine’s plasma protein binding is about 44% and saturable in the 2 mcg/mL to 20 mcg/mL concentration range. Atropine readily crosses the placental barrier and enters the fetal circulation but is not found in amniotic fluid. Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13% to 50% is excreted unchanged in the urine. Traces are found in various secretions, including milk. The major metabolites of atropine are noratropine, atropin-n-oxide, tropine and tropic acid. The metabolism of atropine is inhibited by organophosphate pesticides.

{ "type": "p", "children": [], "text": "Atropine disappears rapidly from the blood following injection and is distributed throughout the body. Exercise, both prior to and immediately following intramuscular administration of atropine, significantly increases the absorption of atropine due to increased perfusion in the muscle and significantly decreases the clearance of atropine. The pharmacokinetics of atropine is nonlinear after intravenous administration of 0.5 mg to 4 mg. Atropine’s plasma protein binding is about 44% and saturable in the 2 mcg/mL to 20 mcg/mL concentration range. Atropine readily crosses the placental barrier and enters the fetal circulation but is not found in amniotic fluid. Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13% to 50% is excreted unchanged in the urine. Traces are found in various secretions, including milk. The major metabolites of atropine are noratropine, atropin-n-oxide, tropine and tropic acid. The metabolism of atropine is inhibited by organophosphate pesticides." }

Specific Populations

{ "type": "p", "children": [], "text": "\nSpecific Populations\n" }

The elimination half-life of atropine is more than doubled in children under two years and the elderly (> 65 years old) compared to other age groups. There is no gender effect on the pharmacokinetics and pharmacodynamics (heart rate changes) of atropine.

{ "type": "p", "children": [], "text": "The elimination half-life of atropine is more than doubled in children under two years and the elderly (> 65 years old) compared to other age groups. There is no gender effect on the pharmacokinetics and pharmacodynamics (heart rate changes) of atropine." }

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

{ "type": "p", "children": [], "text": "\n13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility\n" }

Studies have not been performed to evaluate the carcinogenic or mutagenic potential of atropine or its potential to affect fertility adversely.

{ "type": "p", "children": [], "text": "Studies have not been performed to evaluate the carcinogenic or mutagenic potential of atropine or its potential to affect fertility adversely." }

Atropine Sulfate Injection USP, 0.5 mg/5 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution for intravenous administration and supplied in 5 mL single-dose glass syringe as follows:

{ "type": "p", "children": [], "text": "Atropine Sulfate Injection USP, 0.5 mg/5 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution for intravenous administration and supplied in 5 mL single-dose glass syringe as follows:" }

Atropine Sulfate Injection USP, 1 mg/10 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution for intravenous administration and supplied in 10 mL single-dose glass syringe as follows:

{ "type": "p", "children": [], "text": "Atropine Sulfate Injection USP, 1 mg/10 mL (0.1 mg/mL) is available as a sterile, clear, colorless solution for intravenous administration and supplied in 10 mL single-dose glass syringe as follows:" }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Product repackaged by: Henry Schein, Inc., Bastian, VA 24314 </span> </caption> <tbody class="Headless"> <tr class="First"> <td>From Original Manufacturer/Distributor's NDC and Unit of Sale</td><td>To Henry Schein Repackaged Product NDC and Unit of Sale</td><td>Total Strength/Total Volume (Concentration) per unit </td> </tr> <tr class="Last"> <td>NDC 70121-1705-7<br/>package of 10, 5 mL single-dose glass syringes</td><td>NDC 0404-9784-05<br/>1 syringe in 1 carton in a bag<br/>(Vial bears NDC 70121-1705-1)</td><td>0.5 mg/5 mL<br/>(0.1 mg/mL)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Product repackaged by: Henry Schein, Inc., Bastian, VA 24314 </span>\n</caption>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>From Original Manufacturer/Distributor's NDC and Unit of Sale</td><td>To Henry Schein Repackaged Product NDC and Unit of Sale</td><td>Total Strength/Total Volume (Concentration) per unit </td>\n</tr>\n<tr class=\"Last\">\n<td>NDC 70121-1705-7<br/>package of 10, 5 mL single-dose glass syringes</td><td>NDC 0404-9784-05<br/>1 syringe in 1 carton in a bag<br/>(Vial bears NDC 70121-1705-1)</td><td>0.5 mg/5 mL<br/>(0.1 mg/mL)</td>\n</tr>\n</tbody>\n</table></div>" }

Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Ahmedabad 382213, INDIA

{ "type": "p", "children": [], "text": "Manufactured by:\nAmneal Pharmaceuticals Pvt. Ltd.\nAhmedabad 382213, INDIA" }

Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807

{ "type": "p", "children": [], "text": "Distributed by:\nAmneal Pharmaceuticals LLC\nBridgewater, NJ 08807" }

Rev. 08-2024-02

{ "type": "p", "children": [], "text": "Rev. 08-2024-02" }