FDA label e12378fa-bc6b-54c5-e27d-058d7470d494

5 WARNINGS AND PRECAUTIONS Precipitation of Acute Glaucoma: May cause mydriasis and increase intraocular pressure in patients with glaucoma. Advise patients with glaucoma to promptly seek medical care if they experience symptoms of acute angle closure glaucoma. ( 5.1 ) Drowsiness or Blurred Vision: May cause drowsiness or blurred vision. Advise patients not to drive or perform hazardous work until resolved. ( 5.2 ) Heat Prostration: Advise patients to avoid exertion and high environmental temperatures after receiving glycopyrrolate injection. ( 5.3 ) Intestinal Obstruction: Diarrhea may be an early symptom of incomplete intestinal obstruction. Avoid use in patients with diarrhea and ileostomy or colostomy. ( 5.4 ) Tachycardia: Increase in heart rate may occur. Use with caution in patients with coronary artery disease, congestive heart failure, cardiac arrhythmias, hypertension, or hyperthyroidism. ( 5.5 ) 5.1 Precipitation of Acute Glaucoma Glycopyrrolate injection may cause mydriasis and increase intraocular pressure in patients with glaucoma. Advise patients with glaucoma to promptly seek medical care in the event that they experience symptoms of acute angle closure glaucoma (pain and reddening of the eyes, accompanied by dilated pupils). Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources. 5.2 Drowsiness or Blurred Vision Glycopyrrolate injection may cause drowsiness or blurred vision. Warn patients not to participate in activities requiring mental alertness, such as operating a motor vehicle or other machinery or performing hazardous work, until these issues resolve. 5.3 Heat Prostration In the presence of fever, high environmental temperature, and/or during physical exercise, heat prostration can occur with use of anticholinergic agents including glycopyrrolate injection (due to decreased sweating), particularly in children and the elderly. Advise patients to avoid exertion and high environmental temperature after receiving glycopyrrolate injection. 5.4 Intestinal Obstruction Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance treatment with glycopyrrolate injection is inappropriate and possibly harmful. Glycopyrrolate is contraindicated in patients with these conditions. 5.5 Tachycardia Investigate any tachycardia before giving glycopyrrolate injection because an increase in the heart rate may occur. Use with caution in patients with coronary artery disease, congestive heart failure, cardiac arrhythmias, hypertension, or hyperthyroidism. 5.6 Risk of Use in Patients with Renal Impairment Renal elimination of glycopyrrolate may be significantly reduced in patients with renal failure. Dosage adjustments may be necessary in this population [see Clinical Pharmacology ( 12.3 )]. 5.7 Autonomic Neuropathy, Hepatic Disease, Ulcerative Colitis, Prostatic Hypertrophy, or Hiatal Hernia Use glycopyrrolate injection with caution in the elderly and in all patients with autonomic neuropathy, hepatic disease, ulcerative colitis, prostatic hypertrophy, or hiatal hernia, because anticholinergic drugs may aggravate these conditions. Consider dose reduction and closely monitor the elderly and patients with autonomic neuropathy, hepatic disease, ulcerative colitis, prostatic hypertrophy, or hiatal hernia. 5.8 Delayed Gastric Emptying/Gastric Stasis The use of anticholinergic drugs, including glycopyrrolate injection, in the treatment of peptic ulcer may produce a delay in gastric emptying due to antral stasis. Monitor patients for symptoms such as vomiting, dyspepsia, early satiety, abdominal distention, and increased abdominal pain. Discontinue glycopyrrolate injection treatment if these symptoms develop or worsen on treatment. 5.9 Light Sensitivity Patients may experience sensitivity of the eyes to light. Advise patients to protect their eyes from light after receiving glycopyrrolate injection.

6 ADVERSE REACTIONS The following adverse reactions were identified in clinical studies or postmarketing reports. Because some of these reactions were 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. Adverse reactions to anticholinergics include xerostomia (dry mouth); urinary hesitancy and retention; blurred vision and photophobia due to mydriasis (dilation of the pupil); cycloplegia; increased ocular tension; tachycardia; palpitation; decreased sweating; loss of taste; headache; nervousness; drowsiness; weakness; dizziness; insomnia; nausea; vomiting; impotence; suppression of lactation; constipation; bloated feeling; severe allergic reactions including anaphylactic/anaphylactoid reactions; hypersensitivity; urticaria, pruritus, dry skin, and other dermal manifestations; some degree of mental confusion and/or excitement, especially in elderly persons. The following adverse events have been reported from post-marketing experience with glycopyrrolate: malignant hyperthermia; cardiac arrhythmias (including bradycardia, ventricular tachycardia, ventricular fibrillation); cardiac arrest; hypertension; hypotension; seizures; and respiratory arrest. Post-marketing reports have included cases of heart block and QTc interval prolongation associated with the combined use of glycopyrrolate and an anticholinesterase. Injection site reactions including pruritus, edema, erythema, and pain have also been reported. Most common adverse reactions are related to anticholinergic pharmacology and may include xerostomia (dry mouth); urinary hesitancy and retention; blurred vision and photophobia due to mydriasis (dilation of the pupil); cycloplegia; increased ocular tension; tachycardia; bradycardia; palpitation; and decreased sweating. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 , or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.