Atropine Sulfate

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

Injection: 0.05 mg/mL and 0.1 mg/mL in Ansyr ® Plastic Syringe. Injection: 0.1 mg/mL in LifeShield ® Abboject ® Glass Syringe.

• 0.05 mg/mL injection in Ansyr ® Plastic Syringe ( 3 )
• 0.1 mg/mL injection in Ansyr ® Plastic Syringe ( 3 )
• 0.1 mg/mL injection in LifeShield ® Abboject ® Glass Syringe ( 3 )

None. None. ( 4 )

• Tachycardia ( 5.1 )
• Glaucoma ( 5.2 )
• Pyloric obstruction ( 5.3 )
• Worsening urinary retention ( 5.4 )
• Viscid bronchial plugs ( 5.5 )

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

5.2 Acute Glaucoma Atropine may precipitate acute glaucoma.

5.3 Pyloric Obstruction Atropine may convert partial organic pyloric stenosis into complete obstruction.

5.4 Complete Urinary Retention Atropine may lead to complete urinary retention in patients with prostatic hypertrophy.

5.5 Viscid Plugs 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. 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. 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 Pfizer Inc. at 1-800-438-1985 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.

8.1 Pregnancy Risk Summary There are risks to the mother and fetus associated with untreated severe or life-threatening muscarinic events (see Clinical Considerations ) . Available data from published observational studies on atropine sulfate use in pregnant women are insufficient to evaluate for a drug‑associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ) . Animal developmental and reproductive toxicity studies have not been conducted with atropine. 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 because of concerns regarding the effects of atropine on the fetus. Data Human Data Atropine crosses the placenta [see Clinical Pharmacology (12.3) ] . 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 malformations. 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 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.

8.2 Lactation Risk Summary Trace amounts of atropine have been reported in human milk. 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. 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.

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

8.5 Geriatric Use 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.

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.