GLYCOPYRROLATE Drug Interactions: What You Need to Know

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)

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, anti-spasmodics, amantadine) resulting in increased anticholinergic adverse reactions. Co- administration of antipsychotics with glycopyrrolate may lead to worsening of tardive dyskinesia. Glycopyrrolate tablets, USP are not recommended in patients taking other anticholinergic drugs <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3, 5.4, 5.6) ]</span> .

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, USP are not recommended in patients taking other drugs that are affected by altered gastrointestinal motility <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) ]</span> .

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, USP are not recommended in patients taking solid oral dosage forms of potassium chloride.

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, anti-spasmodics, amantadine) resulting in increased anticholinergic adverse reactions. Co- administration of antipsychotics with glycopyrrolate may lead to worsening of tardive dyskinesia. Glycopyrrolate tablets, USP are not recommended in patients taking other anticholinergic drugs <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3, 5.4, 5.6) ]</span> .

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, USP are not recommended in patients taking other drugs that are affected by altered gastrointestinal motility <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) ]</span> .

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, USP are not recommended in patients taking solid oral dosage forms of potassium chloride.

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 ).

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) ].