Glycopyrrolate

1 INDICATIONS AND USAGE Glycopyrrolate Injection is an anticholinergic indicated: in anesthesia (adult and pediatric patients) for reduction of salivary, tracheobronchial, and pharyngeal secretions, reduction of volume and acidity of gastric secretions, and blockade of cardiac inhibitory reflexes during induction of anesthesia and intubation. intraoperatively to counteract surgically or drug-induced or vagal reflex-associated arrhythmias. for protection against peripheral muscarinic effects of cholinergic agents. ( 1 ) in peptic ulcer (adults) To reduce symptoms of a peptic ulcer as an adjunct to treatment of peptic ulcer when rapid anticholinergic effect is desired or oral medication is not tolerated. Limitations of Use Glycopyrrolate Injection is not indicated as monotherapy for the treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established. ( 1 ) 1.1 Preanesthetic Glycopyrrolate Injection is indicated in adults and pediatric patients for reduction of salivary, tracheobronchial, and pharyngeal secretions, reduction of volume and acidity of gastric secretions, and blockade of cardiac inhibitory reflexes during induction of anesthesia and intubation. 1.2 Intraoperative Glycopyrrolate Injection is indicated in adults and pediatric patients to counteract surgically or drug-induced or vagal reflex-associated arrhythmias. 1.3 Reversal of Neuromuscular Blockade Glycopyrrolate Injection is indicated in adults and pediatric patients for protection against peripheral muscarinic effects of cholinergic agents such as neostigmine and pyridostigmine given to reverse the neuromuscular blockade due to non-depolarizing agents. 1.4 Peptic Ulcer Glycopyrrolate Injection is indicated in adults to reduce symptoms of a peptic ulcer as an adjunct to treatment of peptic ulcer when rapid anticholinergic effect is desired or when oral medication is not tolerated. Limitations of Use Glycopyrrolate Injection is not indicated as monotherapy for the treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established.

2 DOSAGE AND ADMINISTRATION Glycopyrrolate injection may be administered intramuscularly (IM), or intravenously (IV) without dilution, in the following indications. Adults ( 2.2 , 2.3 , 2.4 , 2.5 ) Preanesthetic Medication: 0.004 mg/kg IM, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia Intraoperative Medication: single doses of 0.1 mg IV and repeated, as needed, at intervals of 2 to 3 minutes Reversal of Neuromuscular Blockade: 0.2 mg for each 1 mg of neostigmine or 5 mg of pyridostigmine Peptic Ulcer: 0.1 mg IV or IM at 4-hour intervals, 3 or 4 times daily Pediatric patients ( 2.2 , 2.3 , 2.4 ) Preanesthetic Medication: 0.004 mg/kg IM, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia. Patients under 2 years of age may require up to 0.009 mg/kg Intraoperative Medication: 0.004 mg/kg IV, not to exceed 0.1 mg in a single dose and repeated, as needed, at intervals of 2 to 3 minutes Reversal of Neuromuscular Blockade: 0.2 mg IV for each 1 mg of neostigmine or 5 mg of pyridostigmine Peptic Ulcer: Glycopyrrolate injection is not indicated for the treatment of peptic ulcer in pediatric patients 2.2 Recommended Dosage of Preanesthetic Medication in Adults and Pediatric Patients The recommended dose of Glycopyrrolate injection is 0.004 mg/kg by intramuscular injection, given 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered. Patients less than 2 years of age may require up to 0.009 mg/kg. 2.3 Recommended Dosage as Intraoperative Medication to Counteract Drug-induced or Vagal Reflexes and Their Associated Arrhythmias (e.g., bradycardia) in Adults and Pediatric Patients The recommended adult dose of Glycopyrrolate injection is 0.1 mg intravenously. Repeat this dose, as needed, at intervals of 2 to 3 minutes. The recommended pediatric dosage is 0.004 mg/kg intravenously, not to exceed 0.1 mg in a single dose, repeated every 2 to 3 minutes. Attempt to determine the etiology of the arrhythmia, and perform the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance. Because of the long duration of action of Glycopyrrolate injection if used as preanesthetic medication, additional glycopyrrolate injection for anticholinergic effect intraoperatively is rarely needed. 2.4 Recommended Dosage for Reversal of Neuromuscular Blockade in Adults and Pediatric Patients The recommended dose of Glycopyrrolate injection is 0.2 mg IV for each 1 mg of neostigmine or 5 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection. 2.5 Recommended Dosage for Peptic Ulcer in Adults The recommended dosage of Glycopyrrolate injection is 0.1 mg administered at 4-hour intervals, 3 or 4 times daily, intravenously or intramuscularly. Where more profound effect is required, 0.2 mg may be given. Some patients may need only a single dose. Frequency of administration should be dictated by patient response up to a maximum of four times daily. 2.6 Preparation and Handling Diluent Compatibilities Dextrose 5% and 10% in water, or saline, dextrose 5% in sodium chloride 0.45%, sodium chloride 0.9%, and Ringer's Injection. Diluent Incompatibilities Lactated Ringer's solution. Admixture Compatibilities Physical Compatibility This list does not constitute an endorsement of the clinical utility or safety of co-administration of Glycopyrrolate injection with these drugs. Glycopyrrolate injection is compatible for mixing and injection with the following injectable dosage forms: atropine sulfate, USP; physostigmine salicylate; diphenhydramine HCl; codeine phosphate, USP; benz-quinamide HCl; hydromorphone HCl, USP; droperidol; levorphanol tartrate; lidocaine, USP; meperidine HCl, USP; pyridostigmine bromide; morphine sulfate, USP; nalbuphine HCl; oxymorphone HCl; procaine HCl, USP; promethazine HCl, USP; neostigmine methylsulfate, USP; scopolamine HBr, USP; butorphanol tartrate; fentanyl citrate; trimethobenzamide HCl; and hydroxyzine HCl. Glycopyrrolate injection may be administered via the tubing of a running infusion of normal saline. Admixture Incompatibilities Physical Incompatibility Because the stability of glycopyrrolate is questionable above a pH of 6.0 do not combine Glycopyrrolate injection in the same syringe with methohexital Na; chloramphenicol Na succinate; dimenhydrinate; pentobarbital Na; thiopental Na; secobarbital Na; sodium bicarbonate; diazepam; dexamethasone Na phosphate; or pentazocine lactate. These mixtures will result in a pH higher than 6.0 and may result in gas production or precipitation.

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. To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc. at 1-888-808-5529, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For Product Inquiry call 1-844-824-8426.

7 DRUG INTERACTIONS The concurrent use of glycopyrrolate injection with other anticholinergics or medications with anticholinergic activity, such as phenothiazines, antiparkinson drugs, or tricyclic antidepressants, may intensify the antimuscarinic effects and result in an increase in anticholinergic side effects. Concomitant administration of glycopyrrolate injection and potassium chloride in a wax matrix may increase the severity of potassium chloride-induced gastrointestinal lesions as a result of a slower gastrointestinal transit time. Other anticholinergics or drugs with anticholinergic activity : May intensify the antimuscarinic effects and result in an increase in anticholinergic side effects. Potassium Chloride in a Wax Matrix : May increase severity of potassium chloride-induced gastrointestinal lesions.

16 HOW SUPPLIED/STORAGE AND HANDLING Glycopyrrolate Injection, USP is a clear, colorless solution and is supplied as follows: NDC Glycopyrrolate Injection, USP (0.2 mg per mL) Package Factor 71288- 414 -03 0.2 mg per 1 mL Single-Dose Vial 25 vials per carton 71288- 414 -04 0.4 mg per 2 mL Single-Dose Vial 25 vials per carton 71288- 415 -06 1 mg per 5 mL Multi-Dose Vial 25 vials per carton 71288- 415 -21 4 mg per 20 mL Multi-Dose Vial 10 vials per carton Storage Conditions Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. For single-dose vials only, discard unused portion. Sterile. The container closure is not made with natural rubber latex.