FDA

Glycopyrrolate

Approved 7 Oct 2024OralSolution

The FDA lists this product in 60 strengths and forms.

Indications

Glycopyrrolate oral solution is indicated to reduce chronic severe drooling in patients aged 3 years to 16 years with neurologic conditions associated with problem drooling (e.g., cerebral palsy). Glycopyrrolate oral solution is an anticholinergic indicated to reduce chronic severe drooling in patients aged 3 years to 16 years with neurologic conditions associated with problem drooling (e.g., cerebral palsy). ( 1 )

Contraindications

Glycopyrrolate oral solution is contraindicated in: Patients with medical conditions that preclude anticholinergic therapy (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis). Patients taking solid oral dosage forms of potassium chloride. The passage of potassium chloride tablets through the gastrointestinal (GI) tract may be arrested or delayed with co‑administration of glycopyrrolate oral solution.

Medical conditions that preclude anticholinergic therapy. ( 4 ) Concomitant use of solid oral dosage forms of potassium chloride. ( 4 )

Warnings and precautions

Constipation or intestinal pseudo-obstruction: May present as abdominal distention, pain, nausea, or vomiting. Assess patients for constipation, particularly within 4 days to 5 days of initial dosing or after a dose increase. ( 5.1 ) Incomplete mechanical intestinal obstruction: May present as diarrhea. If obstruction is suspected, discontinue glycopyrrolate oral solution and evaluate. ( 5.2 ) High ambient temperature: To reduce the risk of heat prostration, avoid high temperatures.

( 5.3 )

5.1Constipation or Intestinal Pseudo-obstruction

Constipation is a common dose-limiting adverse reaction which sometimes leads to glycopyrrolate discontinuation [see Adverse Reactions (6.1) ]. Assess patients for constipation, particularly within 4 days to 5 days of initial dosing or after a dose increase. Intestinal pseudo-obstruction has been reported and may present as abdominal distention, pain, nausea or vomiting.

5.2Incomplete Mechanical Intestinal Obstruction

Diarrhea may be an early symptom of incomplete mechanical intestinal obstruction, especially in patients with ileostomy or colostomy. If incomplete mechanical intestinal obstruction is suspected, discontinue treatment with glycopyrrolate oral solution and evaluate for intestinal obstruction.

At a glance

Brand name: Glycopyrrolate
Route: Oral
Dosage form: Solution
Applicant: Sciegen Pharms
Status: Prescription
FDA approval: 7 Oct 2024
Application: ANDA216297-001

Indications

Contraindications

Medical conditions that preclude anticholinergic therapy. ( 4 ) Concomitant use of solid oral dosage forms of potassium chloride. ( 4 )

Warnings and precautions

( 5.3 )

5.1Constipation or Intestinal Pseudo-obstruction

5.2Incomplete Mechanical Intestinal Obstruction

Interactions

Digoxin tablets: Use with glycopyrrolate can increase digoxin serum levels. Monitor patients and consider use of alternative dosage forms of digoxin. ( 7 ) Amantadine: Effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing the dose of glycopyrrolate during concomitant use. ( 7 ) Atenolol or metformin: Glycopyrrolate may increase serum levels of atenolol or metformin.

Consider dose reduction when used with glycopyrrolate. ( 7 ) Haloperidol or levodopa: Glycopyrrolate may decrease serum levels of haloperidol or levodopa. Consider a dose increase when used with glycopyrrolate. ( 7 ) Drugs Affected by Reduced GI Transit Time Glycopyrrolate reduces GI transit time, which may result in altered release of certain drugs when formulated in delayed- or controlled-release dosage forms. The passage of potassium chloride tablets through the GI tract may be arrested or delayed with co-administration of glycopyrrolate.

Solid dosage forms of potassium chloride are contraindicated [see Contraindications (4) ]. Digoxin administered as slow dissolution oral tablets may have increased serum levels and enhanced action when administered with glycopyrrolate. Monitor patients receiving slow dissolution digoxin for increased action if glycopyrrolate is co-administered regularly. Consider the use of other oral dosage forms of digoxin (e.g., elixir or capsules).

Amantadine The anticholinergic effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing the dose of glycopyrrolate during co-administration of amantadine. Drugs Whose Plasma Levels May be Increased by Glycopyrrolate Co-administration of glycopyrrolate may result in increased levels of certain drugs. Atenolol’s bioavailability may be increased with co-administration of glycopyrrolate.

A reduction in the atenolol dose may be needed. Metformin plasma levels may be elevated with co-administration of glycopyrrolate, increasing metformin’s pharmacologic and toxic effects. Monitor clinical response to metformin with concomitant glycopyrrolate administration; consider a dose reduction of metformin if warranted. Drugs Whose Plasma Levels May be Decreased by Glycopyrrolate Co-administration of glycopyrrolate may result in decreased levels of certain drugs.

Haloperidol’s serum level may be decreased when co-administered with glycopyrrolate, resulting in worsening of schizophrenic symptoms, and development of tardive dyskinesia. Closely monitor patients if co-administration cannot be avoided. Levodopa’s therapeutic effect may be reduced with glycopyrrolate administration. Consider increasing the dose of levodopa.

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are no available data in pregnant women for glycopyrrolate oral solution to inform decisions concerning any drug-associated risks. In pregnant rats, daily oral administration of glycopyrrolate during organogenesis at dose exposures 2.5 times to 113 times the exposure at the maximum recommended human dose (MRHD) did not result in an increased incidence of gross external or visceral defects [see Data]. When glycopyrrolate was administered intravenously to pregnant rabbits during organogenesis at dose exposures equivalent to up to approximately 7.8 times the exposure at the MRHD, no adverse effects on embryo-fetal development were seen.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. Animal Data Glycopyrrolate was orally administered to pregnant rats at dosages of 50 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day during the period of organogenesis.

These dosages resulted in systemic exposures (estimated AUC 0-inf values) approximately 2.5 times, 23 times, and 113 times, respectively, the estimated systemic exposure in humans at the MRHD (9 mg per day, administered in three divided doses). Glycopyrrolate had no effect on maternal survival, but significantly reduced mean maternal body weight gain over the period of dosing at all dosages evaluated. Mean fetal weight was significantly reduced in the 200 mg/kg/day and 400 mg/kg/day dose groups.

There were two litters with all resorbed fetuses in the 400 mg/kg/day dose group. There were no effects of treatment on the incidence of gross external or visceral defects. Minor treatment-related skeletal effects included reduced ossification of various bones in the 200 mg/kg/day and 400 mg/kg/day dose groups; these skeletal effects were likely secondary to maternal toxicity. Glycopyrrolate was intravenously administered to pregnant rabbits at dosages of 0.1 mg/kg/day, 0.5 mg/kg/day, and 1 mg/kg/day during the period of organogenesis.

These dosages resulted in systemic exposures (estimated AUC 0-inf values) approximately 0.8 times, 4.6 times, and 7.8 times, respectively, the estimated systemic exposure in humans at the MRHD. Glycopyrrolate did not affect maternal survival under the conditions of this study. Mean maternal body weight gain and mean food consumption over the period of dosing were lower than the corresponding control value in the 0.5 mg/kg/day and 1 mg/kg/day treatment groups.

There were no effects of treatment on fetal parameters, including fetal survival, mean fetal weight, and the incidence of external, visceral, or skeletal defects. Female rats that were pregnant or nursing were orally dosed with glycopyrrolate daily at dosages of 0 mg/kg/day, 50 mg/kg/day, 200 mg/kg/day, or 400 mg/kg/day, beginning on day 7 of gestation, and continuing until day 20 of lactation. These dosages resulted in systemic exposures (estimated AUC 0-inf values) approximately 2.5 times, 23 times, and 113 times, respectively, the estimated systemic exposure in humans at the MRHD (9 mg per day, administered in three divided doses).

Mean body weight of pups in all treatment groups was reduced compared to the control group during the period of nursing, but eventually recovered to be comparable to the control group, post-weaning. No other notable delivery or litter parameters were affected by treatment in any group, including no effects on mean duration of gestation or mean numbers of live pups per litter. No treatment-related effects on survival or adverse clinical signs were observed in pups.

There were no effects of maternal treatment on behavior, learning, memory, or reproductive function of pups.

Adverse reactions

The following serious adverse reactions are described elsewhere in the labeling: Constipation or intestinal pseudo-obstruction [see Warnings and Precautions (5.1) ] Incomplete mechanical intestinal obstruction [see Warnings and Precautions (5.2) ] The most common adverse reactions reported with glycopyrrolate oral solution are dry mouth, vomiting, constipation, flushing, and nasal congestion. The most common adverse reactions (incidence ≥ 30%) are dry mouth, vomiting, constipation, flushing, and nasal congestion.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Saptalis Pharmaceuticals, LLC. at 1-833-727-8254 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

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. The data described below reflect exposure to glycopyrrolate oral solution in 151 subjects, including 20 subjects who participated in an 8-week placebo-controlled study (Study 1) and 137 subjects who participated in a 24-week open-label study (six subjects who received glycopyrrolate oral solution in the placebo-controlled study and 131 new subjects).

Table 2 presents adverse reactions reported by ≥ 15% of glycopyrrolate oral solution-treated subjects from the placebo-controlled clinical trial. Table 2: Adverse Reactions Occurring in ≥ 15% of Glycopyrrolate Oral Solution-Treated Subjects and at a Greater Frequency than Placebo in Study 1 Glycopyrrolate Oral Solution (N = 20) n (%) Placebo (N = 18) n (%) Dry Mouth 8 (40%) 2 (11%) Vomiting 8 (40%) 2 (11%) Constipation 7 (35%) 4 (22%) Flushing 6 (30%) 3 (17%) Nasal Congestion 6 (30%) 2 (11%) Headache 3 (15%) 1 (6%) Sinusitis 3 (15%) 1 (6%) Upper Respiratory Tract Infection 3 (15%) 0 Urinary Retention 3 (15%) 0 The following adverse reactions occurred at a rate of < 2% of patients receiving glycopyrrolate oral solution in the open-label study.

Gastrointestinal: Abdominal distention, abdominal pain, stomach discomfort, chapped lips, flatulence, retching, dry tongue General Disorders: Irritability, pain Infections: Pneumonia, sinusitis, tracheostomy infection, upper respiratory tract infection, urinary tract infection Investigations: Heart rate increase Metabolism and Nutrition: Dehydration Nervous System: Headache, convulsion, dysgeusia, nystagmus Psychiatric: Agitation, restlessness, abnormal behavior, aggression, crying, impulse control disorder, moaning, mood altered Respiratory: Increased viscosity of bronchial secretion, nasal congestion, nasal dryness Skin: Dry skin, pruritus, rash Vascular: Pallor

6.2 Post marketing Experience The following adverse reactions have been identified during post approval use of other formulations of glycopyrrolate for other indications. 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. Additional adverse reactions identified during post approval use of glycopyrrolate tablets include: loss of taste and suppression of lactation.

Glycopyrrolate

Indications

Contraindications

Warnings and precautions

5.1Constipation or Intestinal Pseudo-obstruction

5.2Incomplete Mechanical Intestinal Obstruction

At a glance

Two medicines in one question?

Glycopyrrolate

Indications

Contraindications

Warnings and precautions

5.1Constipation or Intestinal Pseudo-obstruction

5.2Incomplete Mechanical Intestinal Obstruction

At a glance

Two medicines in one question?

5.4Operating Machinery or an Automobile

5.5Anticholinergic Drug Effects

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information