Glycopyrrolate

Pronunciation

Pronunciation: GLYE-koe-PIR-oh-late
Class: Antispasmodic, Quaternary

Trade Names

Cuvposa
- Solution, oral 1 mg per 5 mL

Robinul
- Tablets, oral 1 mg
- Injection, solution 0.2 mg/mL

Robinul Forte
- Tablets , oral 2 mg

Pharmacology

Exerts anticholinergic effects, resulting in GI smooth muscle relaxation, diminished volume and acidity of GI secretions, and reduced pharyngeal, tracheal, and bronchial secretions.

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Pharmacokinetics

Absorption

Absorption is poor (bioavailability approximately 3%) and unreliable. C max and AUC of oral solution (fasting) were 23% and 28% lower compared with the tablet. For oral solution (fasting), C max , AUC, and T max were 0.318 ng/mL, 1.74 ng•h/mL, and 3.1 h, respectively. C max and AUC under high-fat fed conditions were 74% and 78% lower compared with fasting.

Distribution

Highly polar ammonium group of glycopyrrolate limits its passage across blood-brain barrier and other lipid membranes. Vd in children is 1.3 to 1.8 L/kg following IV injection and lower in adults 60 to 75 y of age (0.42 L/kg).

Metabolism

Up to 80% of the drug remains unchanged. Only a small amount is metabolized.

Elimination

Up to 80% is eliminated unchanged in urine. Cl of IV form ranged from 1.01 to 1.41 L/kg/h in pediatric patients and 0.54 L/kg/h in adults. Oral solution Cl ranged from 8.07 to 25.65 L/h/kg in patients with cerebral palsy. Half-life (oral solution-fasting) was 3 h.

Onset

Within 1 min after IV injection.

Peak

30 to 45 min after IM administration.

Duration

Vagal blocking effects persist for 2 to 3 h. Antisialagogue effects persist up to 7 h.

Special Populations

Renal Function Impairment

AUC of IV is 10.6 mcg•h/L in renally impaired patients. Elimination is severely impaired in patients with renal failure with plasma Cl of IV lowering to 0.43 L/h/kg.

Indications and Usage

Oral solution

Reduction of chronic severe drooling in patients 3 to 16 y of age with neurologic conditions associated with problem drooling (eg, cerebral palsy).

Oral tablet

Adjunctive treatment of peptic ulcer.

Parenteral

Preoperative administration for reduction of salivary, tracheobronchial, and pharyngeal secretions, reduction of volume and acidity of gastric secretions, and blockade of cardiac vagal inhibitory reflexes before and during induction of anesthesia and intubation; intraoperatively for counteraction of drug-induced or vagal reflex–associated arrhythmias; adjunctive therapy for treatment of peptic ulcer when rapid anticholinergic effect is desired or oral medication is not tolerated.

Contraindications

Glaucoma; obstructive uropathy; obstructive disease of GI tract; paralytic ileus; intestinal atony of elderly or debilitated patients; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; unstable CV status in acute hemorrhage; myasthenia gravis; hypersensitivity to glycopyrrolate; patients taking solid oral dosage forms of potassium chloride (oral solution only).

Dosage and Administration

Drooling
Children 3 to 16 y of age

PO (oral solution) Initial dosage: 0.02 mg/kg 3 times daily. Titrate in 0.02 mg/kg increments every 5 to 7 days based on response and adverse reactions (max, 0.1 mg/kg 3 times daily not to exceed 1.5 to 3 mg per dose based on weight).

Peptic Ulcer
Adults and children 12 y and older

PO (tablets) 1 to 2 mg 2 or 3 times daily.

Adults

IM/IV 0.1 to 0.2 mg 3 or 4 times daily (max dose, 0.8 mg/day).

Preanesthetic Medication
Adults and children older than 2 y

IM 0.004 mg/kg 30 min to 1 h prior to anesthesia or at the time of preanesthetic narcotic and/or sedative administration.

Infants (1 month to 2 y of age)

IM May require up to 0.009 mg/kg.

Intraoperative Medication
Adults

IV 0.1 mg. May repeat at 2- to 3-min intervals.

Children

IV 0.004 mg/kg (max, 0.1 mg in single dose); may repeat at 2- to 3-min intervals.

Reversal of Neuromuscular Blockade
Adults and children

IV 0.2 mg for each 1 mg of neostigmine or 5 mg of pyridostigmine. Administer simultaneously.

General Advice

  • IV
  • Give drug undiluted or mixed with dextrose 5% or 10% in water, dextrose 5% in saline, dextrose 10% in saline, dextrose 5% in sodium chloride 0.45%, sodium chloride 0.9%, or Ringer's injection.
  • Compatibilities: Atropine, physostigmine, diphenhydramine, codeine, benz-quinamide, hydromorphone, droperidol, levorphanol, lidocaine, meperidine, pyridostigmine, morphine, nalbuphine, oxymorphone, procaine, promethazine, neostigmine, scopolamine, butorphanol, fentanyl, trimethobenzamide, hydroxyzine.
  • Incompatibilities: Because stability of glycopyrrolate is questionable above pH of 6, do not combine in same syringe with methohexital, chloramphenicol, dimenhydrinate, pentobarbital, thiopental, secobarbital, sodium bicarbonate, diazepam, dexamethasone, pentazocine, or lactated Ringer's solution.
  • Do not administer parenteral solution if cloudy.
  • Oral Solution
  • Administer at least 1 h before or 2 h after meals.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Anticholinergic agents (eg, atropine), antiparkinson drugs (eg, amantadine), phenothiazines (eg, chlorpromazine), tricyclic antidepressants (eg, amitriptyline)

Coadministration of glycopyrrolate with other drugs that have anticholinergic activity may increase the frequency and/or severity of anticholinergic adverse effects (eg, blurred vision, constipation, dry mouth, somnolence). Monitor for adverse reactions and adjust therapy as needed.

Beta-blockers (ie, atenolol)

Beta-blocker bioavailability may be increased, increasing the pharmacologic effects and risk of adverse reactions. A reduction in the beta-blocker dose may be needed.

Digoxin

Glycopyrrolate may reduce GI transit time of slow dissolution digoxin tablets. Digoxin serum concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity. Consider use of other oral dosage forms (eg, digoxin oral solution).

Food

High-fat meals may increase the glycopyrrolate C max and AUC compared with fasting conditions. Therefore, glycopyrrolate oral solution should be dosed at least 1 h before or 2 h after meals.

Haloperidol

May cause decreased serum haloperidol levels, worsened schizophrenic symptoms, and tardive dyskinesia.

Levodopa

Levodopa serum concentrations may be reduced, decreasing the pharmacologic effects. An increased levodopa dose may be needed.

Metformin

Metformin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity. Monitor the clinical response. A reduction in the metformin dose may be needed.

Potassium chloride

All solid dosage forms of potassium chloride are contraindicated in patients receiving anticholinergic agents. Arrest or delay in tablet passage through the GI tract may occur. Administration of potassium chloride as a liquid preparation is a suitable alternative.

Adverse Reactions

Cardiovascular

Pallor, tachycardia (less than 2%); palpitations; orthostatic hypotension; cardiac arrhythmias (including bradycardia, ventricular tachycardia, ventricular fibrillation), cardiac arrest, heart block and QTc interval prolongation (when combined with an anticholinesterase), hypertension, hypotension (postmarketing).

CNS

Flushing (30%); headache (15%); abnormal behavior, aggression, agitation, convulsion, crying, impulse control disorder, moaning, mood altered, restlessness (less than 2%); CNS stimulation (eg, tremor, hallucinations); dizziness; drowsiness; fever (especially in children); insomnia; mental confusion or excitement (especially in elderly, even with small doses); nervousness; weakness.

Dermatologic

Dry skin, pruritus, rash (less than 2%).

EENT

Nasal congestion (30%); nasal dryness, nystagmus (less than 2%); blurred vision; cycloplegia; increased IOP; mydriasis; photophobia.

GI

Dry mouth, vomiting (40%); constipation (35%); abdominal distension, abdominal pain, chapped lips, dry tongue, dysgeusia, flatulence, retching, stomach discomfort (less than 2%); dysphagia; heartburn; loss of taste; nausea; paralytic ileus.

Genitourinary

Urinary retention (15%); UTI (less than 2%); impotence; urinary hesitancy.

Local

Injection-site edema, erythema, pain, and pruritus.

Respiratory

Sinusitis, upper respiratory tract infection (15%); increased viscosity of bronchial secretion, pneumonia, tracheostomy infection (less than 2%); respiratory arrest (postmarketing).

Miscellaneous

Dehydration, irritability, pain (less than 2%); decreased sweating; malignant hyperthermia; severe allergic reactions including anaphylaxis, urticaria, and dermal manifestations; suppression of lactation (postmarketing).

Precautions

Monitor

Monitor patients for efficacy of medication on drooling and peptic ulcer, changes in bowel movement, and heart rate.


Pregnancy

Category C (oral); Category B (injection).

Lactation

Undetermined. May suppress lactation.

Children

Injection

Safety and effectiveness in pediatric patients younger than 16 y have not been established. Safety and effectiveness for the treatment of peptic ulcer in children have not been established.

Tablets

Not recommended for treatment of peptic ulcer in children younger than 12 y.

Oral solution

Safety and efficacy in patients younger than 3 y have not been established.

Elderly

May react with excitement, agitation, drowsiness, and other untoward manifestations, even with small doses.

Special Risk Patients

Use with caution in patients with autonomic neuropathy, hepatic or renal disease, ulcerative colitis, hyperthyroidism, coronary heart disease, CHF, cardiac tachyarrhythmias, hypertension, prostatic hypertrophy, or hiatal hernia associated with reflux esophagitis.

Hazardous Tasks

May produce drowsiness or blurred vision, impairing patient's ability to perform hazardous tasks such as operating a motor vehicle or other machinery.

Benzyl alcohol

Because of its benzyl alcohol content, injection should not be used in neonates (younger than 1 mo). Benzyl alcohol has been associated with gasping syndrome, which can be fatal.

Constipation

May lead to medication discontinuation. Assess patients for constipation initially and with dose increases. Intestinal pseudo-obstruction has been reported, presenting as abdominal distention, pain, nausea, or vomiting.

Diarrhea

May be symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. Treatment of diarrhea with drug is inappropriate and possibly harmful.

Gastric ulcer

May delay gastric emptying rate and complicate therapy.

Heat prostration

Can occur in presence of high environmental temperature.

Overdosage

Symptoms

Convulsions, excitement, fever, hypotension, muscular weakness, paralysis, psychotic behavior, respiratory depression.

Patient Information

  • Advise patients to take the oral solution 1 h before or 2 h after meals.
  • Instruct patients that constipation can occur and to institute preventive measures (eg, increase fluids, bulk in diet, and activity).
  • Advise patients to report diarrhea to their health care provider immediately, because diarrhea can be an early symptom of intestinal blockage, especially in patients with ileostomy or colostomy. In these instances, treatment with glycopyrrolate may be inappropriate or harmful.
  • Advise patients that urinary hesitancy or retention may be experienced. Instruct patient to assess urination patterns and to notify their health care provider if urinary retention is experienced.
  • Inform men that impotence is a potential adverse reaction and to report this symptom to their health care provider.
  • Because glycopyrrolate interferes with the body's thermoregulation, instruct patients to avoid exposure to high environmental temperature to prevent heat prostration.
  • Instruct patients to notify their health care provider immediately if eye pain or increased sensitivity to light occurs. Emphasize importance of routine eye examinations throughout therapy.
  • Inform patients that dry mouth is a normal adverse reaction. Instruct patients to take sips of water frequently, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Caution patients to avoid sudden position changes to prevent orthostatic hypotension.
  • Advise patients that glycopyrrolate may cause drowsiness and blurred vision and to use caution while driving or performing other tasks requiring mental alertness.

Copyright © 2009 Wolters Kluwer Health.

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