GLYCOPYRROLATE: 4,625 Adverse Event Reports & Safety Profile
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Drug Class: Anticholinergic [EPC] · Route: INTRAMUSCULAR · Manufacturer: Henry Schein, Inc. · FDA Application: 012827 · HUMAN PRESCRIPTION DRUG · FDA Label: Available
Patent Expires: Sep 14, 2035 · First Report: 1995 · Latest Report: 20250624
What Are the Most Common GLYCOPYRROLATE Side Effects?
All GLYCOPYRROLATE Side Effects by Frequency
| Side Effect | Reports | % of Total | Deaths | Hosp. |
|---|---|---|---|---|
| Dyspnoea | 1,499 | 32.4% | 51 | 593 |
| Asthma | 1,033 | 22.3% | 3 | 533 |
| Cough | 950 | 20.5% | 11 | 255 |
| Wheezing | 782 | 16.9% | 22 | 438 |
| Pneumonia | 454 | 9.8% | 38 | 322 |
| Malaise | 452 | 9.8% | 31 | 165 |
| Drug ineffective | 448 | 9.7% | 8 | 188 |
| Chronic obstructive pulmonary disease | 407 | 8.8% | 30 | 272 |
| Productive cough | 384 | 8.3% | 21 | 178 |
| Chest discomfort | 362 | 7.8% | 4 | 173 |
| Therapeutic product effect incomplete | 341 | 7.4% | 0 | 228 |
| Obstructive airways disorder | 321 | 6.9% | 2 | 179 |
| Condition aggravated | 271 | 5.9% | 7 | 169 |
| Nasal congestion | 267 | 5.8% | 1 | 106 |
| Loss of personal independence in daily activities | 264 | 5.7% | 0 | 164 |
| Product use in unapproved indication | 262 | 5.7% | 30 | 121 |
| Gastrooesophageal reflux disease | 255 | 5.5% | 1 | 144 |
| Sleep disorder due to a general medical condition | 248 | 5.4% | 0 | 145 |
| Nasopharyngitis | 243 | 5.3% | 1 | 82 |
| Dyspnoea exertional | 240 | 5.2% | 19 | 111 |
Who Reports GLYCOPYRROLATE Side Effects? Age & Gender Data
Gender: 58.2% female, 41.8% male. Average age: 61.4 years. Most reports from: US. View detailed demographics →
Is GLYCOPYRROLATE Getting Safer? Reports by Year
| Year | Reports | Deaths | Hosp. |
|---|---|---|---|
| 2001 | 8 | 1 | 7 |
| 2002 | 1 | 0 | 1 |
| 2003 | 1 | 0 | 1 |
| 2006 | 1 | 0 | 1 |
| 2007 | 2 | 0 | 0 |
| 2008 | 2 | 0 | 1 |
| 2010 | 4 | 0 | 1 |
| 2011 | 5 | 0 | 2 |
| 2013 | 31 | 7 | 18 |
| 2014 | 102 | 12 | 43 |
| 2015 | 141 | 13 | 68 |
| 2016 | 155 | 27 | 58 |
| 2017 | 114 | 20 | 42 |
| 2018 | 219 | 11 | 39 |
| 2019 | 197 | 22 | 36 |
| 2020 | 71 | 12 | 19 |
| 2021 | 73 | 8 | 33 |
| 2022 | 18 | 1 | 7 |
| 2023 | 21 | 1 | 3 |
| 2024 | 25 | 0 | 18 |
| 2025 | 20 | 1 | 14 |
What Is GLYCOPYRROLATE Used For?
| Indication | Reports |
|---|---|
| Product used for unknown indication | 1,724 |
| Chronic obstructive pulmonary disease | 861 |
| Asthma | 404 |
| Emphysema | 87 |
| Bradycardia | 68 |
| Neuromuscular blockade reversal | 53 |
| Hyperhidrosis | 52 |
| Lung disorder | 37 |
| Salivary hypersecretion | 33 |
| Dyspnoea | 26 |
GLYCOPYRROLATE vs Alternatives: Which Is Safer?
Other Drugs in Same Class: Anticholinergic [EPC]
Official FDA Label for GLYCOPYRROLATE
Official prescribing information from the FDA-approved drug label.
Drug Description
PREVDUO @ (neostigmine methylsulfate and glycopyrrolate) injection is a clear colorless solution available as a prefilled syringe that contains a fixed dose combination of neostigmine methylsulfate, a cholinesterase inhibitor and glycopyrrolate, an anticholinergic agent, for intravenous administration. PREVDUO @ is available as a sterile solution in 3 mL Prefilled Syringe. Each mL contains Neostigmine Methylsulfate USP (1 mg), Glycopyrrolate USP (0.2 mg), edetate disodium dihydrate USP (0.5 mg), sodium chloride USP (8 mg) in water for injection. The pH is adjusted, when necessary, with Hydrochloric acid/sodium hydroxide to achieve a value of 3.6.
Neostigmine
Methylsulfate USP Neostigmine methylsulfate, a cholinesterase inhibitor, is (m-hydroxyphenyl) trimethylammonium methylsulfate dimethylcarbamate. The molecular formula is C 13 H 22 N 2 O 6 S, a molecular weight is 334.39 g/mol and the following structural formula is: Glycopyrrolate USP Glycopyrrolate is a quaternary ammonium salt (anticholinergic agent) with a chemical name of 3[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethyl pyrrolidinium bromide. The molecular formula is C 19 H 28 BrNO 3 and the molecular weight is 398.33 and the structural formula is: Neo-structure Glyco-structure
FDA Approved Uses (Indications)
AND USAGE GLYRX ® -PF is indicated: in anesthesia (all ages)
- 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, and
- 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. 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 when oral medication is not tolerated.
- Limitations of Use GLYRX-PF is not indicated as monotherapy for the treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established. GLYRX ® -PF is an anticholinergic indicated: in anesthesia (adult and pediatric patients)
- for reduction of airway or gastric secretions, and 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, and
- 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 when oral medication is not tolerated.
- Limitations of Use GLYRX-PF is not indicated as monotherapy for the treatment of peptic ulcer because effectiveness in peptic ulcer healing has not been established. ( 1 )
Dosage & Administration
AND ADMINISTRATION Glycopyrrolate Injection may be administered intramuscularly, or intravenously, without dilution, in the following indications: Adults ( 2.2 )
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 ( 2.3 )
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 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 Do not use prefilled syringe to administer a dose of less than 0.1 mg (0.5 mL). ( 2.3 )
See Full Prescribing
Information for preparation, handling, and instructions for use of pre-filled syringe ( 2.4 , 2.5 )
2.1 General Dosing and Administration Information Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Glycopyrrolate
Injection may be administered intramuscularly, or intravenously, without dilution. Do not introduce any other fluid into the syringe at any time. Do not dilute for IV push. Do not re-sterilize the syringe. Do not use this product on a sterile field. This product is for single dose only.
2.2 Dosing in Adults Preanesthetic Medication 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.
Intraoperative Medication Glycopyrrolate
Injection may be used during surgery to counteract drug-induced or vagal reflexes and their associated arrhythmias (e.g., bradycardia). It should be administered intravenously as single doses of 0.1 mg and repeated, as needed, at intervals of 2 to 3 minutes. Attempt to determine the etiology of the arrhythmia, and perform the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance. Reversal of Neuromuscular Blockade The recommended dose of Glycopyrrolate Injection is 0.2 mg for each 1 mg of neostigmine or 5 mg of pyridostigmine.
Peptic Ulcer
The usual recommended dose 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.
2.3 Dosing in Pediatric Patients Preanesthetic Medication The recommended dose of Glycopyrrolate Injection in pediatric patients is 0.004 mg/kg intramuscularly, 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 under 2 years of age may require up to 0.009 mg/kg. Do not use this prefilled syringe to administer a dose of less than 0.1 mg (0.5 mL).
Intraoperative Medication
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; in the event it is required the recommended pediatric dose is 0.004 mg/kg intravenously, not to exceed 0.1 mg in a single dose which may be repeated, as needed, at intervals of 2 to 3 minutes. Attempt to determine the etiology of the arrhythmia, and perform the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance. Do not use this prefilled syringe to administer a dose of less than 0.1 mg (0.5 mL). Reversal of Neuromuscular Blockade The recommended pediatric dose of Glycopyrrolate Injection is 0.2 mg 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 and may be mixed in the same syringe. Do not use this prefilled syringe to administer a dose of less than 0.1 mg (0.5 mL).
Peptic Ulcer Glycopyrrolate
Injection is not indicated for the treatment of peptic ulcer in pediatric patients.
2.4 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.
2.5 Instructions for Use of Pre-filled Syringe: Figure 1: Outer Packaging and Prefilled Syringe Inspect the outer packaging (blister pack) to confirm the integrity of the packaging. Do not use if the blister pack or the prefilled syringe has been damaged. Remove the syringe from the outer packaging. (See Figure 2 )
Figure
2 Visually inspect the syringe. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Twist off the syringe tip cap. Do not remove the label around the luer lock collar. (See Figure 3 )
Figure
3 Expel air bubble(s). Adjust the dose (if applicable). Administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration. Discard the used syringe into an appropriate receptacle.
Figure
1 Figure 2 Figure 3
Contraindications
PREVDUO ® is contraindicated in patients with:
- known hypersensitivity to neostigmine methylsulfate (known hypersensitivity reactions have included urticaria, angioedema, erythema multiforme, generalized rash, facial swelling, peripheral edema, pyrexia, flushing, hypotension, bronchospasm, bradycardia and anaphylaxis) and glycopyrrolate or any inactive ingredients [ see Warnings and Precautions ( 5.3 ) ].
- peritonitis or mechanical obstruction of the intestinal or urinary tract.
- Glaucoma; obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis, etc.); paralytic ileus, intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis.
- Hypersensitivity to neostigmine, glycopyrrolate, or nonactive ingredients ( 4 )
- Peritonitis or mechanical obstruction of the intestinal or urinary tract ( 4 )
- Patients with glaucoma; obstructive uropathy; obstructive disease of the gastrointestinal tract; paralytic ileus, intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis ( 4 ).
Known Adverse Reactions
REACTIONS
- Most common adverse reactions to neostigmine during treatment: bradycardia, nausea, vomiting, blurred vision and photophobia. ( 6 )
- Most common adverse reactions to glycopyrrolate 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 Endo at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Neostigmine Methylsulfate Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions to neostigmine methylsulfate are most often attributable to exaggerated pharmacological effects, in particular, at muscarinic receptor sites. The addition of glycopyrrolate to the neostigmine-glycopyrrolate prefilled syringe may prevent or mitigate these reactions. Quantitative adverse event data are available from trials of neostigmine methylsulfate in which 200 adult patients were exposed to the product. The following table lists the adverse reactions that occurred with an overall frequency of 1% or greater. S y s t e m Organ Class Adverse Reaction Cardiovascular Disorders bradycardia, hypotension, tachycardia/heart rate increase Gastrointestinal Disorders dry mouth, nausea, post-procedural nausea, vomiting General Disorders and Administration Site Conditions incision site complication, pharyngolaryngeal pain, procedural complication, procedural pain Nervous System Disorders dizziness, headache, postoperative shivering, prolonged neuromuscular blockade Psychiatric Disorders Insomnia Respiratory, Thoracic and Mediastinal Disorders dyspnea, oxygen desaturation < 90% Skin and Subcutaneous Tissue Disorders Pruritus Glycopyrrolate Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Anticholinergics, including glycopyrrolate, can produce certain effects, most of which are extensions of their pharmacologic actions. Adverse reactions 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; 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.
6.2 Post Marketing Experience Neostigmine Methylsulfate The following adverse reactions have been identified during post-approval parenteral use of neostigmine methylsulfate. 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. S y s t e m Organ Class Adverse Reaction Allergic Disorders allergic reactions, anaphylaxis Nervous System Disorders convulsions, drowsiness, dysarthria, fasciculation, loss of consciousness, miosis, visual changes Cardiovascular Disorders cardiac arrest, cardiac arrhythmias (A-V block, nodal rhythm), hypotension, nonspecific EKG changes, syncope Respiratory, Thoracic and Mediastinal Disorders bronchospasm; increased oral, pharyngeal and bronchial secretions; respiratory arrest; respiratory depression Skin and Sub-cutaneous Tissue Disorders rash, urticaria Gastrointestinal Disorders bowel cramps, diarrhea, flatulence, increased peristalsis Renal and Urinary Disorders urinary frequency Musculoskeletal and Connective Tissue Disorders arthralgia, muscle cramps, spasms, weakness Miscellaneous diaphoresis, flushing Glycopyrrolate The following adverse events have been identified during post-approval use of glycopyrrolate. 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: S y s t e m Organ Class Adverse Reaction Cardiovascular Disorders cardiac arrhythmias (including bradycardia, ventricular tachycardia, ventricular fibrillation), cardiac arrest, hypertension, hypotension, heart block and QTc interval prolongation Respiratory, Thoracic and Mediastinal Disorders respiratory arrest Injection site reactions pruritus, edema, erythema, and pain at injection site Miscellaneous malignant hyperthermia Glycopyrrolate is chemically a quaternary ammonium compound; hence, its passage across lipid membranes, such as the blood-brain barrier is limited. For this reason, the occurrence of CNS-related side effects is lower, in comparison to their incidence following administration of anticholinergics which are chemically tertiary amines that can cross this barrier readily.
Warnings
AND PRECAUTIONS Precipitation of Acute Glaucoma: May increase intraocular pressure; if symptoms occur, discontinue use and promptly seek medical care. (4 , 5.1) Partial or Complete Mechanical Intestinal Obstruction: Diarrhea may be an early symptom, especially in patients with ileostomy or colostomy. If the obstruction is suspected, discontinue use and evaluate the patient for obstruction. (4, 5.2) GI Adverse Reactions Due to Decreased GI Motility: Delayed gastric emptying, constipation, and intestinal pseudo-obstruction may occur and precipitate or aggravate paralytic ileus and toxic megacolon; not recommended for use with anticholinergics or other medications that decrease GI peristalsis. (4, 5.3, 7.1) Cognitive and Visual Adverse Reactions : May impair mental and/or physical function. Inform patients not to operate motor vehicles or perform other hazardous tasks until reasonably certain they are not adversely affected; discontinue use if signs or symptoms develop. (5.4, 7.1)
Heat
Prostration at High Environmental Temperatures: Heat prostration resulting in fever and heatstroke can occur, especially in geriatric patients. Avoid exposure to hot or very warm environmental temperatures. (5.5, 5.7)
Other Conditions
Exacerbated by Anticholinergic Adverse Reactions: Use is not recommended in patients with autonomic neuropathy, hyperthyroidism, cardiac disease, hiatal hernia, etc. (5.6, 7.1)
Increased
Risk of Anticholinergic Adverse Reactions in Geriatric Patients: Complications include urinary retention, bowel obstruction, heat prostration, arrhythmias, delirium, and falls or fractures. Not recommended in geriatric patients and may be contraindicated in some patients with underlying medical conditions. (4, 5.7, 8.5)
5.1 Precipitation of Acute Glaucoma Glycopyrrolate may cause increased intraocular pressure in patients with glaucoma and reduce the effects of antiglaucoma agents. Instruct patients to discontinue Glycopyrrolate tablets and promptly seek medical care if they experience symptoms of acute angle-closure glaucoma (pain and reddening of the eyes accompanied by dilated pupils) [ see Contraindications (4) ].
5.2 Partial or Complete Mechanical Intestinal Obstruction Glycopyrrolate tablets may worsen intestinal mechanical obstruction, and diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. If partial or complete intestinal obstruction is suspected, discontinue the use of Glycopyrrolate tablets and evaluate for potential intestinal obstruction [ see Contraindications (4) ].
5.3 Gastrointestinal Adverse Reactions Due to Decreased Gastrointestinal Motility Glycopyrrolate reduces gastrointestinal motility and may result in delayed gastric emptying, constipation, and intestinal pseudo-obstruction and may precipitate or aggravate paralytic ileus and toxic megacolon [ see Contraindications (4) ]. The risk of gastrointestinal adverse reactions is further increased with the use of other anticholinergics and other medications that decrease gastrointestinal peristalsis. Monitor patients for symptoms of decreased gastrointestinal motility. Concomitant use of Glycopyrrolate tablets and other anticholinergics or other medications that decrease GI peristalsis is not recommended [ see Drug Interactions (7.2) ].
5.4 Cognitive and Visual Adverse Reactions Glycopyrrolate may produce drowsiness and blurred vision and impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle, operating machinery, or performing other hazardous work [ see Adverse Reactions (6) ]. Concomitant use of other drugs that have anticholinergic properties may increase these effects [ see Drug Interactions (7.1) ]. Inform patients not to operate motor vehicles or other dangerous machinery or perform other hazardous tasks until they are reasonably certain that Glycopyrrolate tablets does not affect them adversely.
Discontinue
Glycopyrrolate tablets if signs or symptoms of cognitive or visual impairment develop.
5.5 Heat Prostration at High Environmental Temperatures In the presence of a high environmental temperature, heat prostration resulting in fever and heatstroke can occur with the use of Glycopyrrolate tablets due to decreased sweating, particularly in geriatric patients [ see Adverse Reactions (6) ]. Advise patients to avoid exposure to hot or very warm environmental temperatures when taking Glycopyrrolate tablets. Glycopyrrolate tablets are not recommended in geriatric patients [ see Warnings and Precautions (5.7) ].
5.6 Other Conditions Exacerbated by Anticholinergic Adverse Reactions Glycopyrrolate tablets are not recommended in patients with other conditions exacerbated by anticholinergic adverse reactions (e.g., autonomic neuropathy, hyperthyroidism, cardiac disease, and hiatal hernia associated with reflux esophagitis) and in patients taking other anticholinergic medications [ see Drug Interactions (7.1) ].
5.7 Increased Risk of Anticholinergic Adverse Reactions in Geriatric Patients Geriatric patients 65 years of age and older are at increased risk of anticholinergic adverse reactions that may lead to complications of urinary retention, bowel obstruction, heat prostration, arrhythmias, delirium, and falls or fractures. Glycopyrrolate tablet 1 mg and Glycopyrrolate tablet 2 mg are not recommended in geriatric patients and may be contraindicated in some geriatric patients with underlying medical conditions [ see Contraindications (4) , Warnings and Precautions (5.2, 5.5) , Adverse Reactions (6) and Use in Specific Populations (8.5) ].
5.1 Precipitation of Acute Glaucoma Glycopyrrolate may cause increased intraocular pressure in patients with glaucoma and reduce the effects of antiglaucoma agents. Instruct patients to discontinue Glycopyrrolate tablets and promptly seek medical care if they experience symptoms of acute angle-closure glaucoma (pain and reddening of the eyes accompanied by dilated pupils) [ see Contraindications (4) ].
5.2 Partial or Complete Mechanical Intestinal Obstruction Glycopyrrolate tablets may worsen intestinal mechanical obstruction, and diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. If partial or complete intestinal obstruction is suspected, discontinue the use of Glycopyrrolate tablets and evaluate for potential intestinal obstruction [ see Contraindications (4) ].
5.3 Gastrointestinal Adverse Reactions Due to Decreased Gastrointestinal Motility Glycopyrrolate reduces gastrointestinal motility and may result in delayed gastric emptying, constipation, and intestinal pseudo-obstruction and may precipitate or aggravate paralytic ileus and toxic megacolon [ see Contraindications (4) ]. The risk of gastrointestinal adverse reactions is further increased with the use of other anticholinergics and other medications that decrease gastrointestinal peristalsis. Monitor patients for symptoms of decreased gastrointestinal motility. Concomitant use of Glycopyrrolate tablets and other anticholinergics or other medications that decrease GI peristalsis is not recommended [ see Drug Interactions (7.2) ].
5.4 Cognitive and Visual Adverse Reactions Glycopyrrolate may produce drowsiness and blurred vision and impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle, operating machinery, or performing other hazardous work [ see Adverse Reactions (6) ]. Concomitant use of other drugs that have anticholinergic properties may increase these effects [ see Drug Interactions (7.1) ]. Inform patients not to operate motor vehicles or other dangerous machinery or perform other hazardous tasks until they are reasonably certain that Glycopyrrolate tablets does not affect them adversely.
Discontinue
Glycopyrrolate tablets if signs or symptoms of cognitive or visual impairment develop.
5.5 Heat Prostration at High Environmental Temperatures In the presence of a high environmental temperature, heat prostration resulting in fever and heatstroke can occur with the use of Glycopyrrolate tablets due to decreased sweating, particularly in geriatric patients [ see Adverse Reactions (6) ]. Advise patients to avoid exposure to hot or very warm environmental temperatures when taking Glycopyrrolate tablets. Glycopyrrolate tablets are not recommended in geriatric patients [ see Warnings and Precautions (5.7) ].
5.6 Other Conditions Exacerbated by Anticholinergic Adverse Reactions Glycopyrrolate tablets are not recommended in patients with other conditions exacerbated by anticholinergic adverse reactions (e.g., autonomic neuropathy, hyperthyroidism, cardiac disease, and hiatal hernia associated with reflux esophagitis) and in patients taking other anticholinergic medications [ see Drug Interactions (7.1) ].
5.7 Increased Risk of Anticholinergic Adverse Reactions in Geriatric Patients Geriatric patients 65 years of age and older are at increased risk of anticholinergic adverse reactions that may lead to complications of urinary retention, bowel obstruction, heat prostration, arrhythmias, delirium, and falls or fractures. Glycopyrrolate tablet 1 mg and Glycopyrrolate tablet 2 mg are not recommended in geriatric patients and may be contraindicated in some geriatric patients with underlying medical conditions [ see Contraindications (4) , Warnings and Precautions (5.2, 5.5) , Adverse Reactions (6) and Use in Specific Populations (8.5) ].
Precautions
PRECAUTIONS: General Investigate any tachycardia before giving Glycopyrrolate Injection since an increase in the heart rate may occur. Use with caution in patients with: coronary artery disease; congestive heart failure; cardiac arrhythmias; hypertension; hyperthyroidism. Use with caution in patients with renal disease since the renal elimination of glycopyrrolate may be severely impaired in patients with renal failure. Dosage adjustments may be necessary (see Special Populations , Renal/Hepatic Impairment ).
Use
Glycopyrrolate with caution in the elderly and in all patients with autonomic neuropathy, hepatic disease, ulcerative colitis, prostatic hypertrophy, or hiatal hernia, since anticholinergic drugs may aggravate these conditions. The use of anticholinergetic drugs in the treatment of gastric ulcer may produce a delay in gastric emptying due to antral statis. Information for Patients Because Glycopyrrolate Injection may produce drowsiness or blurred vision, the patient should be cautioned not to engage in activities requiring mental alertness and/or visual acuity such as operating a motor vehicle or other machinery, or performing hazardous work while taking this drug (see WARNINGS ). The patient also should be cautioned about the use of this drug during exercise or hot weather since overheating may result in heat stroke. The patient may experience a possible sensitivity of the eyes to light.
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 may 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. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic potential. Studies to evaluate the mutagenic potential of glycopyrrolate have not been conducted. In reproduction studies in rats, dietary administration of glycopyrrolate resulted in diminished rates of conception in a dose-related manner. Other studies in dogs suggest that this may be due to diminished seminal secretion which is evident at high doses of glycopyrrolate.
Pregnancy Teratogenic Effects Pregnancy
Category B Reproduction studies with glycopyrrolate were performed in rats at a dietary dose of approximately 65 mg/kg/day (exposure was approximately 320 times the maximum recommended daily human dose of 2 mg on a mg/m 2 basis) and rabbits at intramuscular doses of up to 0.5 mg/kg/day (exposure was approximately 5 times the maximum recommended daily human dose on a mg/m 2 basis). These studies produced no teratogenic effects to the fetus. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Single-dose studies in humans found that very small amounts of glycopyrrolate passed the placental barrier.
Nonteratogenic Effects
Published literature suggest the following regarding the use of glycopyrrolate during pregnancy. Unlike atropine, glycopyrrolate in normal doses (0.004 mg/kg) does not appear to affect fetal heart rate or fetal heart rate variability to a significant degree. Concentrations of glycopyrrolate in umbilical venous and aterial blood and in the amniotic fluid are low after intramuscular administration to parturients. Therefore, glycopyrrolate does not appear to penetrate through the placental barrier in significant amounts. In reproduction studies in rats, dietary administration of glycopyrrolate resulted in diminished rats of pup survival in a dose-related manner.
Nursing
Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Glycopyrrolate Injection is administered to a nursing woman. As with other anticholinergics, glycopyrrolate may cause suppression of lactation (see ADVERSE REACTIONS ).
Pediatric Use
Due to its benzyl alcohol content, Glycopyrrolate Injection should not be used in neonates, i.e., patients less than 1 month of age. Safety and effectiveness in pediatric patients below the age of 16 years have not been established. Safety and effectiveness in pediatric patients have not been established for the management of peptic ulcer. Dysrhythmias associated with the use of glycopyrrolate intravenously as a premedicant or during anesthesia have been observed in pediatric patients. Infants, patients with Down’s syndrome, and pediatric patients with spastic paralysis or brain damage may experience an increased response to anticholinergics, thus increasing the potential for side effects. A paradoxical reaction characterized by hyperexcitability may occur in pediatric patients taking large doses of anticholinergics including Glycopyrrolate Injection. Infants and young children are especially susceptible to the toxic effects of anticholinergics. Benzyl alcohol, a component of this drug product, has been associated with serious adverse events and death, particularly in pediatric patients. 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 neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hemotologic 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-birthweight infants, as well as patients receiving high dosages, 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.
Geriatric Use Clinical
Studies of Glycopyrrolate Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the 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 therapy.
Drug Interactions
INTERACTIONS Other Anticholinergic Drugs: Concomitant use is not recommended. (5.3, 5.4, 5.6, 7.1) Drugs with Altered Absorption due to Decreased GI Motility : Concomitant use is not recommended. (7.2) GI Toxicity with Solid Oral Dosage Forms of Potassium Chloride : Concomitant use is not recommended. (7.3)