Product Monograph - Glycopyrrolate Injection USP (Sandoz Canada)
Recent Major Label Changes
| 2025-11 |
|---|---|
| 2025-11 |
Table of Contents
Certain sections or subsections that are not applicable at the time of the preparation of the most recent authorized product monograph are not listed.
Recent Major Label Changes ................................................................................................................ 2
Table of Contents ................................................................................................................................. 2
Part 1: Healthcare Professional Information ......................................................................................... 4
- 1. Indications ............................................................................................................................... 4
1.1. Pediatrics ................................................................................................................................. 4
1.2. Geriatrics ................................................................................................................................. 4
- 2. Contraindications .................................................................................................................... 4
- 4. Dosage and Administration ..................................................................................................... 5
4.1. Dosing Considerations ..................................................................................................................... 5
4.2. Recommended Dose and Dosage Adjustment ................................................................................ 5
4.4. Administration ................................................................................................................................. 6
- 5. Overdose ................................................................................................................................. 6
- 6. Dosage Forms, Strengths, Composition and Packaging ............................................................. 7
- 7. Warnings and Precautions ....................................................................................................... 7
Cardiovascular ...................................................................................................................................... 7
Driving and Operating Machinery .......................................................................................................... 7
Gastrointestinal .................................................................................................................................... 7
Musculoskeletal ................................................................................................................................... 8
Perioperative Considerations ................................................................................................................ 8
7.1. Special Populations .................................................................................................................. 8
7.1.1. Pregnancy ................................................................................................................................ 8
7.1.2. Breastfeeding ........................................................................................................................... 8
7.1.3. Pediatrics ................................................................................................................................. 8
7.1.4. Geriatrics ................................................................................................................................. 8
- 8. Adverse Reactions ................................................................................................................... 9
8.1. Adverse Reaction Overview ...................................................................................................... 9
8.2. Clinical trial adverse reactions .................................................................................................. 9
- 9. Drug Interactions ..................................................................................................................... 9
9.2. Drug Interaction Overview ........................................................................................................ 9
9.3. Drug-Behaviour Interactions ..................................................................................................... 9
9.4. Drug-Drug Interactions ............................................................................................................. 9
9.5. Drug-Food Interactions ............................................................................................................. 9
9.6. Drug-Herb Interactions ............................................................................................................. 9
9.7. Drug-Laboratory Test Interactions .......................................................................................... 10
- 10. Clinical Pharmacology ............................................................................................................ 10
10.1. Mechanism of Action ..................................................................................................................... 10
10.2. Pharmacodynamics ........................................................................................................................ 10
10.3. Pharmacokinetics ........................................................................................................................... 11
- 11. Storage, Stability and Disposal ............................................................................................... 11
Part 2: Scientific Information ............................................................................................................. 12
- 13. Pharmaceutical Information .................................................................................................. 12
- 14. Clinical Trials ......................................................................................................................... 12
- 16. Non-Clinical Toxicology .......................................................................................................... 12
Patient Medication Information ......................................................................................................... 14
Part 1: Healthcare Professional Information
1. Indications
GLYCOPYRROLATE INJECTION USP is indicated for:
- Gastrointestinal Disorders: GLYCOPYRROLATE INJECTION USP may be used in the management of gastrointestinal disorders amenable to anticholinergic therapy when oral medication is not tolerated or a rapid anticholinergic effect is desired.
- Anesthesia: GLYCOPYRROLATE INJECTION USP is of value as a preanesthetic antimuscarinic agent. Due to its benzyl alcohol content, GLYCOPYRROLATE INJECTION USP when packaged in multidose vials should not be used in children less than 3 years of age or in newborns. See 2 Contraindications.
Reversal of Neuromuscular Blockade: During reversal of neuromuscular blockade induced by nondepolarizing muscle relaxants, it protects against the peripheral muscarinic effects (e.g. bradycardia and excessive secretions) of cholinergic agents such as neostigmine and pyridostigmine.
1.1. Pediatrics
Pediatrics (<18 years of age): No data are available to Health Canda on the use of GLYCOPYRROLATE INJECTION USP in the management of gastrointestinal disorders in children; therefore Health Canada has not authorized this indication for pediatric use.
1.2. Geriatrics
Geriatrics (≥65 years of age): Evidence suggests that use in the geriatric population may be associated with differences in safety or effectiveness, use with caution in this population.
2. Contraindications
GLYCOPYRROLATE INJECTION USP is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6. Dosage Forms, Strengths, Composition, and Packaging.
Due to its benzyl alcohol content, GLYCOPYRROLATE INJECTION USP when packaged in multidose vials should not be used in children less than 3 years of age or in newborns.
In the treatment of gastrointestinal disorders, glycopyrrolate injection is contraindicated in the presence of:
- glaucoma
- obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy)
- obstructive disease of the gastrointestinal tract (for example, pyloroduodenal stenosis)
- paralytic ileus
- intestinal atony or chronic lung disease of the elderly or debilitated patient
- unstable cardiovascular status in acute hemorrhage
- severe ulcerative colitis
- toxic megacolon complicating ulcerative colitis
- myasthenia gravis
4. Dosage and Administration
4.1. Dosing Considerations
Children with disorders such as Down’s syndrome should not be given anticholinergics, or if they are necessary, the usual dose should be reduced by half.
Investigate any tachycardia before giving anticholinergic (atropine-like) drugs since they may increase the heart rate.
4.2. Recommended Dose and Dosage Adjustment
Gastroenterology: The usual recommended dose of GLYCOPYRROLATE INJECTION USP is 0.1 mg administered at 4 hour intervals, three or four times a day. Where a more profound effect is required, 0.2 mg may be given.
Frequency of administration depends upon individual patient response, but a 4 hour interval between injections is recommended. Some patients may need only a single dose; others may require administration two, three or four times a day.
Data on the use of GLYCOPYRROLATE INJECTION USP in the management of gastrointestinal disorders in children is not available. Therefore, Health Canada has not granted an indication for use in this population. See 1.1. Pediatrics.
Anesthesia - Preanesthetic Medication: Adults and Children:
0.005 mg/kg of body weight by intramuscular injection, given 30 minutes to one hour prior to the anticipated time of induction of anesthesia, or at the time the preanesthetic narcotic and/or sedative are administered.
Children (up to 12 years of age) may require a dose up to 0.01 mg/kg of body weight. See 2. Contraindications.
The timing of administration of GLYCOPYRROLATE INJECTION USP with relation to the time of anesthetic induction is not as critical, since GLYCOPYRROLATE INJECTION USP has a prolonged duration of action, providing protection two to three times as long as that provided by atropine or scopolamine.
Preanesthetic Dosage 0.005 mg/kg Intramuscularly | ||
|---|---|---|
Preanesthetic Dosage 0.005 mg/kg Intramuscularly | ||
| Weight | Glycopyrrolate | mL of 0.2 mg/mL strength |
| Weight | Glycopyrrolate | mL of 0.2 mg/mL strength |
| 10 kg | 0.05 mg | 0.25 mL |
| 20 kg | 0.1 mg | 0.5 mL |
| 30 kg | 0.15 mg | 0.75 mL |
| 40 kg | 0.2 mg | 1 mL |
| 50 kg | 0.25 mg | 1.25 mL |
| 60 kg | 0.3 mg | 1.5 mL |
| 70 kg | 0.35 mg | 1.75 mL |
| 80 kg | 0.4 mg | 2 mL |
| 90 kg | 0.45 mg | 2.25 mL |
| 100 kg | 0.5 mg | 2.5 mL |
Intraoperative Medication: GLYCOPYRROLATE INJECTION USP may be used during surgery to counteract drug-induced or vagal traction reflexes with the associated arrhythmias (e.g. bradycardia). The usual attempts should be made to determine the etiology of the arrhythmia, and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed. See 7. Warnings and Precautions, Cardiovascular.
Dosage: Administer intravenously and repeat as needed at intervals of two to three minutes. Adults: 0.1 mg. Children: 0.005 mg/kg of body weight, not to exceed 0.1 mg in a single dose.
Reversal of Neuromuscular Blockade: Dosage - Adults and Children (not less than 3 years of age or newborns): 0.2 mg of GLYCOPYRROLATE INJECTION USP for each 1 mg of neostigmine or 5 mg of pyridostigmine. See 2. Contraindications.
4.4. Administration
GLYCOPYRROLATE INJECTION USP may be administered intramuscularly or intravenously, without dilution. Gastroenterology administration can be either intramuscularly or intravenously, preoperative administration is intramuscularly, and intraoperative and postoperative (reversal of neuromuscular blockade) administration is intravenously.
In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by intravenous injection and may be mixed in the same syringe. Mixtures containing more than 5 mg of neostigmine or 25 mg of pyridostigmine plus 1 mg of glycopyrrolate are not recommended.
5. Overdose
Symptoms: Widespread paralysis of organs innervated by parasympathetic nerves may be due to poisoning by antimuscarinic agents. Dry mucous membranes, widely dilated and unresponsive pupils, tachycardia, cutaneous flush and fever are significant. A curariform neuromuscular block may occur and lead to respiratory paralysis.
Treatment: To combat peripheral anticholinergic effects, a quaternary ammonium anticholinesterase such as neostigmine methylsulfate may be given in a dose of 1 mg for each mg of glycopyrrolate injection known to have been administered.
To combat hypotension, pressor amines may be tried. To combat respiratory depression, administer oxygen and respiratory stimulant or artificial respiration. Catheterization is sometimes necessary.
For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764-7669).
6. Dosage Forms, Strengths, Composition and Packaging
Single use vial: Each mL contains glycopyrrolate 0.2 mg, sodium chloride 8.5 mg, hydrochloric acid and/or sodium hydroxide to adjust pH (pH 2-3), and water for injection. Discard unused portion.
Multidose vial: Each mL contains glycopyrrolate 0.2 mg, sodium chloride 7.47 mg, benzyl alcohol (as preservative) 0.9%, hydrochloric acid and/or sodium hydroxide to adjust pH (pH 2-3), and water for injection.
GLYCOPYRROLATE INJECTION USP 0.2 mg/mL is available in 2 mL single use vials, boxes of 10, and in 20 mL multidose vials, boxes of 1.
The chlorobutyl rubber stopper is not made with natural rubber latex.
7. Warnings and Precautions
Cardiovascular
The intravenous administration of any anticholinergic in the presence of cyclopropane anesthesia can result in ventricular arrhythmias therefore, caution should be observed if glycopyrrolate injection must be used during cyclopropane anesthesia. If the drug is given in small incremental doses of 0.1 mg or less, the likelihood of producing ventricular arrhythmias is reduced. See 4.2. Recommended Dose and Dosage Adjustment.
Investigate any tachycardia before giving anticholinergic (atropine-like) drugs since they may increase the heart rate.
Driving and Operating Machinery
Glycopyrrolate injection may produce drowsiness or blurred vision. In this event, patients should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, and not to perform hazardous work while taking this drug.
Gastrointestinal
Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance, treatment with this drug would be inappropriate and possibly harmful.
The use of anticholinergic drugs in the treatment of gastric ulcer may produce a delay in gastric emptying time and may complicate such therapy (antral stasis). The use of an indwelling nasogastric tube should be considered whenever more than two doses in succession are to be administered.
Do not use in the presence of complications of biliary tract disease. See 2. Contraindications.
Musculoskeletal
With overdosage, a curare-like action may occur, i.e. neuromuscular blockade leading to muscular weakness and possible paralysis. However, it has not yet been reported.
Perioperative Considerations
In the presence of a high environmental temperature, heat prostration can occur (fever, heat stroke due to decreased sweating) with all anticholinergic agents.
7.1. Special Populations
7.1.1. Pregnancy
Use of the drug in pregnancy and women of childbearing potential requires that the potential benefits of the drug be weighed against the possible risks to mother and child. See 16. Non-Clinical Toxicology.
7.1.2. Breastfeeding
It is unknown if GLYCOPYRROLATE INJECTION USP is excreted in human milk. Precaution should be exercised because many drugs can be excreted in human milk. See 16. Non-Clinical Toxicology.
7.1.3. Pediatrics
Data on the use of GLYCOPYRROLATE INJECTION USP in the management of gastrointestinal disorders in children is not available.
Due to its benzyl alcohol content, GLYCOPYRROLATE INJECTION USP when packaged in multidose vials should not be used in children less than 3 years of age or in newborns. See 2. Contraindications.
7.1.4. Geriatrics
Use GLYCOPYRROLATE INJECTION USP with caution in the elderly and in all patients with:
- Autonomic neuropathy;
- Hepatic or renal disease;
- Ulcerative colitis – large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason precipitate or aggravate the serious complication of toxic megacolon;
- Hyperthyroidism, coronary heart disease, congestive heart failure, cardiac arrhythmias, hypertension and prostatic hypertrophy;
- Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition;
- Incipient glaucoma (acute glaucoma can be precipitated in susceptible individuals).
8. Adverse Reactions
8.1. Adverse Reaction Overview
Adverse reactions to anticholinergics may include: xerostomia; urinary hesitancy and retention; blurred vision due to mydriasis and cycloplegia; photophobia; increased ocular tension including acute glaucoma; tachycardia; palpitation; decreased sweating and heat prostration; loss of taste; headache; nervousness; drowsiness, weakness; dizziness, insomnia, nausea; vomiting; impotence; suppression of lactation; constipation; bloated feeling; severe allergic reaction or drug idiosyncrasies including anaphylaxis, urticaria and other dermal manifestations; some degree of mental confusion and/or excitement, especially in elderly persons.
8.2. Clinical trial adverse reactions
No clinical trial data is available for GLYCOPYRROLATE INJECTION USP. Therefore, there are no clinical adverse event tables or data available.
9. Drug Interactions
No clinical drug interactions studies have been conducted with GLYCOPYRROLATE INJECTION USP.
9.2. Drug Interaction Overview
No clinical drug interactions studies have been conducted with GLYCOPYRROLATE INJECTION USP.
9.3. Drug-Behaviour Interactions
The interaction of GLYCOPYRROLATE INJECTION USP with individual behavioural risks (e.g. cigarette smoking, cannabis use, and/or alcohol consumption) has not been studied.
9.4. Drug-Drug Interactions
Interactions with other drugs have not been established.
9.5. Drug-Food Interactions
Interactions with food have not been established.
9.6. Drug-Herb Interactions
Interactions with herbal products have not been established.
9.7. Drug-Laboratory Test Interactions
Interactions with laboratory tests have not been established.
10. Clinical Pharmacology
10.1. Mechanism of Action
Glycopyrrolate, like other anticholinergic (antimuscarinic) agents, competitively antagonizes the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation.
Glycopyrrolate antagonizes muscarinic symptoms (e.g. bronchorrhea, bronchospasm, bradycardia and intestinal hypermotility) induced by cholinergic drugs such as anticholinesterases.
As a premedicant, glycopyrrolate injection reduces excessive pharyngeal, tracheal and bronchial secretions and, during anesthesia, it appears to protect the heart against excessive vagal stimulation.
The polar ammonium moiety of glycopyrrolate limits its passage across lipid membranes such as the blood-brain barrier, in contrast to the belladonna alkaloids (such as atropine), which are nonpolar tertiary amines. Consequently, glycopyrrolate injection does not cause the central nervous system effects seen with the belladonna alkaloids.
10.2. Pharmacodynamics
Pharmacological studies in animals have demonstrated that glycopyrrolate antagonizes parasympathetically-mediated effects. In dogs, it inhibited basal and histamine-stimulated gastric secretion, and was effective in blocking the enhanced secretion resulting from insulin-induced hypoglycemia. Intestinal tone was reduced at dosages which produced little or no effect on peristaltic movements.
Glycopyrrolate inhibited salivary secretion induced by methacholine in the anesthetized dog. Methacholine-induced lacrimation in rats was also blocked.
The poor penetration of glycopyrrolate into the CNS was demonstrated in EEG studies in unanesthetized curarized cats. Further confirmation of the lack of a central (CNS) effect was demonstrated in antitremorine studies in mice.
In anesthetized dogs, intravenous doses had essentially no effect on respiration, carotid arterial blood pressure or cardiac rate. Likewise, these doses of glycopyrrolate reduced bradycardia, hypotension and the intestinal hyperactivity resulting from peripheral vagal stimulation. Other than the expected parasympathetic inhibition, no effects on the autonomic nervous system were observed.
10.3. Pharmacokinetics
The onset of action following intramuscular injection of glycopyrrolate injection is 20 to 40 minutes. Peak effects occur approximately 30 to 45 minutes after administration and the duration of action ranges from 4 to 6 hours. With intravenous injection, the onset of action is generally evident within one minute; the duration of action varies. Following intravenous glycopyrrolate, the vagal blocking effects persist for 2 to 3 hours and the antisialagogue effects persist up to 7 hours.
11. Storage, Stability and Disposal
Store between 15 and 30°C.
Part 2: Scientific Information
13. Pharmaceutical Information
Drug Substance
Non-proprietary name of the drug substance(s): Glycopyrrolate
Chemical name: 3-hydroxy-1,1-dimethylpyrrolidiniumbromide α- cyclopentylmandelate.
3-[(cyclopentyl-hydroxyphenylacetyl)oxy]-1,1 dimethyl-,bromide.
Molecular formula and molecular mass: C19H28BrNO3, 398.35
Structure Formula:
Physicochemical properties: White, odourless, crystalline powder, soluble in water and alcohol, with a melting point of 193 to 198°C.
14. Clinical Trials
No clinical trial data is available for GLYCOPYRROLATE INJECTION USP.
16. Non-Clinical Toxicology
General Toxicology
Acute Toxicity:
LD50 values were determined by intravenous, intraperitoneal and oral administration in the mouse, and by intravenous administration in the rat and the rabbit. The following table shows the results.
| Acute Toxicity of Glycopyrrolate | |||
|---|---|---|---|
| Species | Sex | Route | LD50 mg/kg |
| Mouse | M | IV | 15 |
| Mouse | M | IP | 112 |
| Mouse | M | Oral | 550 |
| Rat | F | IV | 15 |
| Rabbit | M,F | IV | 25* |
*Approximate
Higher doses by all routes in mice and rats caused mydriasis, tremors and tonic and clonic convulsions. Death usually followed the convulsions and apparently resulted from respiratory failure. In rabbits, all animals exhibited mydriasis, tachycardia and prostration. All survivors appeared normal at 72 hours. No outstanding gross pathological changes attributable to glycopyrrolate were found in the survivors or the animals that died.
Four-Week Toxicity:
The intravenous administration of glycopyrrolate at 0.2 or 0.4 mg/kg/day five days a week for four weeks caused no signs of toxicity in beagle dogs.
Evaluations included body weight gain, hemograms, gross and microscopic examination of tissues, blood nitrogen, serum alkaline phosphatase, serum glutamic oxalacetic transaminase and qualitative urinalysis.
Irritation Potential:
Repeated intramuscular injection of glycopyrrolate into the hind leg of the rabbit, or topical application of glycopyrrolate solutions to the abraded or intact skin of the rabbit did not induce a reaction sufficient to preclude use of the injectable material. No histological evidence of inflammation was observed following subcutaneous injection of glycopyrrolate in the rabbit.
Reproductive and developmental toxicology
Reproductive studies in rats and rabbits revealed no teratogenic effects from glycopyrrolate. However, diminished rates of conception and of survival at weaning were observed in rats, in a dose-related manner. Studies in dogs suggest that this may be due to diminished seminal secretion which is evident at high doses of glycopyrrolate.