2.1 Important Dosing Information

• Glycopyrrolate tablet 2 mg is not recommended for patients in whom a lower dosage strength of oral glycopyrrolate (e.g., Glycopyrrolate tablet 1 mg or another 1 mg dosage strength) is appropriate for initial or maintenance treatment because the dosage strength of Glycopyrrolate tablet 2 mg may exceed the recommended initial and maintenance dosage of oral Glycopyrrolate tablets.

2.2 Recommended Dosage

• The recommended initial dosage of Glycopyrrolate tablet for adults is 1 mg three times daily (in the morning, early afternoon, and at bedtime). Some patients may require 2 mg at bedtime to assure overnight control of symptoms. For maintenance, a dosage of 1 mg twice a day is frequently adequate.
• The recommended dosage of Glycopyrrolate tablet 2 mg for adults is 2 mg two or three times daily at equally spaced intervals.
• The maximum recommended daily dosage of glycopyrrolate is 8 mg.
• Use the lowest effective dosage of glycopyrrolate to control symptoms. If patients can be titrated to a lower dose, switch from Glycopyrrolate tablet 2 mg to Glycopyrrolate tablet 1 mg or another 1 mg dosage strength oral tablet of glycopyrrolate.

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)].

7.1 Other Anticholinergic Drugs

There is potential for an additive interaction between glycopyrrolate and concomitantly used anticholinergic drugs (e.g., tricyclic antidepressants, anti-epileptics, class I antiarrhythmics, antispasmodics, amantadine) resulting in increased anticholinergic adverse reactions. Co-administration of antipsychotics with glycopyrrolate may lead to worsening of tardive dyskinesia. Glycopyrrolate tablets are not recommended in patients taking other anticholinergic drugs [see Warnings and Precautions(5.3, 5.4,5.6)].

7.2 Drugs with Altered Absorption due to Decreased Gastrointestinal Motility and Increased Transit Time

Decreased gastrointestinal motility by glycopyrrolate may impact absorption of other drugs leading to increased or decreased drug exposure. Glycopyrrolate tablets are not recommended in patients taking other drugs that are affected by altered gastrointestinal motility [see Warnings and Precautions (5.3)].

7.3 Gastrointestinal Toxicity with Solid Oral Dosage Forms of Potassium Chloride

Oral glycopyrrolate may worsen gastrointestinal mucosal injury reported with solid oral dosage forms of potassium chloride due to decreased gastric motility and increased transit time, leading to prolonged contact with the gastrointestinal mucosa. Glycopyrrolate tablets are not recommended in patients taking solid oral dosage forms of potassium chloride.

8.1 Pregnancy

Risk Summary

Over decades of use, there is an absence of published data on orally administered glycopyrrolate in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animalstudies, at non-maternally toxic doses of oral glycopyrrolate, there were no adverse developmental effects in rats or rabbits. A pre-and post-natal development study of oral glycopyrrolate in rats showed a decrease in pup mean body weight that recovered post nursing, with no other developmental effects observed (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

At non-maternally toxic doses of oral glycopyrrolate, there were no effects on embryo-fetal development or toxicity in rats or rabbits. A pre-and post-natal development study of oral glycopyrrolate in rats showed a decrease in pup mean body weight that recovered post nursing, with no other developmental effects observed.

In a published reproductive and developmental study, male and female rats were administered glycopyrrolate in the diet at 0 mg/kg/day, 32.5 mg/kg/day, 63 mg/kg/day, and 130 mg/kg/day for 3 weeks to 5 weeks and through up to three consecutive litters. There was no indication of abnormalities in the pups of treated dams. There was a decreased rate of conception and in survival rate at weaning for all treated animals in a dose-related manner. Diminished rates of conception may be due to diminished seminal secretion [see Nonclinical Toxicology (13.1)].

8.2 Lactation

Risk Summary

There are no data on the presence of glycopyrrolate in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. As with other anticholinergic drugs, glycopyrrolate may cause suppression of lactation. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Glycopyrrolate tablets and any potential adverse effects on the breastfed infant from Glycopyrrolate tablets.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Geriatric patients 65 years of age and older may be more sensitive to the anticholinergic adverse reactions of glycopyrrolate leading to complications of urinary retention, bowel obstruction, heat prostration, arrhythmias, delirium, and falls or fractures; therefore, Glycopyrrolate tablets are not recommended in geriatric patients and may be contraindicated in some geriatric patients with underlying medical conditions [see Contraindications (4) and Warnings and Precautions (5)].

8.6 Renal Impairment

Glycopyrrolate is substantially excreted by the kidneys [see Clinical Pharmacology (12.3)].

Monitor patients with renal impairment for anticholinergic adverse reactions [see Adverse Reactions (6)]. If anticholinergic adverse reactions occur, discontinue Glycopyrrolate tablets.

12.1 Mechanism of Action

Glycopyrrolate, an anticholinergic (antimuscarinic) agent, inhibits the action of acetylcholine on parietal cells in the stomach and decreases the volume and acidity of gastric secretions.

12.2 Pharmacodynamics

No formal pharmacodynamic studies have been conducted with Glycopyrrolate tablets.

12.3 Pharmacokinetics

Patients with Renal Impairment

In the published literature, glycopyrrolate 4 mcg/kg was administered intravenously (Glycopyrrolate tablets are not recommended for intravenous use) in uremic patients undergoing renal transplantation surgery. The mean AUC (10.6 mcg·h/L) and 24-hour urinary excretion (7%) for glycopyrrolate were significantly different from normal healthy adult subjects undergoing general surgery (3.7 mcg·h/L, and 65%, respectively) [see Use in Specific Populations (8.6)].

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

Reproduction studies in rats resulted in diminished rates of conception in a dose-related manner. Studies in dogs suggest that diminished rates of conception may be due to diminished seminal secretion, which is evident at high doses of glycopyrrolate.