Atropine Sulfate

5 WARNINGS AND PRECAUTIONS 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) 5.1 Hypersensitivity Atropine may cause anaphylaxis. 5.2 Worsening of Ischemic Heart Disease 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. 5.3 Acute Glaucoma Atropine may precipitate acute glaucoma. 5.4 Pyloric Obstruction Atropine may convert partial organic pyloric stenosis into complete obstruction. 5.5 Complete Urinary Retention Atropine may lead to complete urinary retention in patients with prostatic hypertrophy. 5.6 Viscid Plugs Atropine may cause thickening of bronchial secretions and formation of viscid plugs in patients with chronic lung disease. 5.7 Benzyl Alcohol 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.

6 ADVERSE REACTIONS 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 Somerset Therapeutics, LLC at 1- 800-417-9175 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch