ATROPINE SULFATE

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). 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 17 H 23 NO 3 ) 2 · H 2 SO 4 · H 2 O, colorless crystals or white crystalline powder very soluble in water. 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. Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water. structure

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. Atropine is a muscarinic antagonist indicated for temporary blockade of severe or life threatening muscarinic effects. ( 1 )

• Dosage is individualized by use, refer to the full prescribing information for recommended adult and pediatric dosages ( 2.2 , 2.3 ). • Patients with Ischemic Heart Disease: Do not exceed 0.04 mg/kg. ( 2.4 , 5.2 ) 2.1 General Administration 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. 2.2 Adult Dosage Table 1: Recommended Dosage in Adult Patients Use Initial Dose Continued Treatment Antisialagogue or other antivagal (preanesthesia and during surgery) 0.5 to 1 mg IV/IM/SC 30-60 minutes preoperatively Repeat as needed every 4-6 hours. Maximum Total Dose 3 mg Organophosphorus, carbamate or muscarinic mushroom poisoning 1 to 6 mg IV/IM/ET depending on severity of symptoms Repeat as needed every 3 to 5 minutes Dose may be doubled with each administration until response (reduced bronchospasm, improved oxygenation and drying of pulmonary secretions). Maintenance Dose: Administer 10% to 20% of the loading dose required for response as a continuous infusion per hour and titrate. Maximum Total Dose: No maximum total dose. Symptomatic bradycardia* 0.5 mg IV/IM or 1 to 2 mg ET by diluting in no more than 10 mL sterile water for injection or 0.9% sodium chloride As needed every 3 to 5 minutes Maximum Total Dose 3 mg 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. 2.3 Pediatric Dosage Table 2: Recommended Dosage in Pediatric Patients Use Initial Dose Continued Treatment Antisialagogue or other antivagal (preanesthesia and during surgery)* 0.02 mg/kg IV/IM/SC 30-60 minutes preoperatively Repeat as needed every 4-6 hours. Maximum Single Dose Less than 12 years old:0.5 mg 12 years and older:1 mg Maximum Total Dose Less than 12 years old:1 mg 12 years and older:2 mg Organophosphorus, carbamate, or muscarinic mushroom poisoning 0.02 to 0.06 mg/kg IV/IM/IO/ET Repeat as needed every 5 minutes Dose may be doubled with each administration until response (reduced bronchospasm, improved oxygenation and drying of pulmonary secretions). Maintenance Dose :Administer 10% to 20% of the loading dose required for response as a continuous infusion per hour and titrate as needed. Maximum Total Dose: No maximum total dose. Symptomatic bradycardia due to increased vagal tone or primary AV conduction block (not secondary to hypoxia) * * 0.02 mg/kg IV/IO or 0.04 to 0.06 mg/kg via endotracheal tube followed by 1 to 5 mL flush of normal saline followed by 5 ventilations Repeat as needed every 5 minutes Maximum Single Dose Less than12 years old :0.5 mg 12 years and older: 1 mg 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. 2.4 Dosing in Patients with Ischemic Heart Disease Limit the total dose of atropine sulfate to 0.03 to 0.04 mg/kg [see Warnings and Precautions (5.2)].

None. None. ( 4 )

The following adverse reactions are described elsewhere in labeling: Hypersensitivity (5.1) Worsening of Ischemic Heart Disease (5.2) Acute Glaucoma (5.3) Pyloric Obstruction (5.4) Complete Urinary Retention (5.5) Viscid Plugs (5.6) 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. Occasional hypersensitivity reactions have been observed, including serious skin rashes. Paralytic ileus may occur. Exacerbation of reflux has been reported. Larger or toxic doses may produce such central effects as restlessness, tremor, fatigue, locomotor difficulties, delirium, followed by hallucinations, depression, and ultimately, medullary paralysis and death. Large doses can also lead to circulatory collapse. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma. Most adverse reactions are directly related to atropine’s antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur with chronic administration of therapeutic doses. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Mexiletine : Decreases rate of mexiletine absorption. ( 7.1 ) 7.1 Mexiletine 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.