Usage
Glycopyrronium, also known as glycopyrrolate, is prescribed for the symptomatic treatment of severe sialorrhea (chronic pathological drooling) in children and adolescents aged 3 years and older with chronic neurological disorders. It is also used preoperatively to reduce salivary, tracheobronchial, and pharyngeal secretions; to reduce the volume and free acidity of gastric secretions; and to block cardiac vagal inhibitory reflexes during induction of anesthesia and intubation. It is also useful intraoperatively to counteract drug-induced or vagal traction reflexes with associated arrhythmias. Additionally, it can be used as adjunctive therapy in adults for the treatment of peptic ulcer when rapid anticholinergic effect is desired or when oral medication is not tolerated.
It can also be used to treat hyperhidrosis (topically) and chronic obstructive pulmonary disease (inhalation). Its pharmacological classification is anticholinergic.
Glycopyrronium works by competitively blocking the action of acetylcholine at peripheral muscarinic receptors. This inhibition reduces secretions from exocrine glands like salivary, bronchial, and gastric glands. It also increases heart rate by blocking vagal effects on the sinoatrial node.
Alternate Names
Glycopyrrolate, Glycopyrronium bromide
Some brand names include: Robinul, Cuvposa, Seebri, Robinul Forte
How It Works
Pharmacodynamics: Glycopyrronium acts as a competitive antagonist at peripheral muscarinic (M1, M2, and M3) receptors, inhibiting the effects of acetylcholine. This leads to decreased secretions from exocrine glands (salivary, bronchial, gastric), increased heart rate, bronchodilation, mydriasis, and decreased gastrointestinal motility.
Pharmacokinetics:
- Absorption: Absorption from the gastrointestinal tract is incomplete and variable. The presence of high-fat food reduces the oral bioavailability.
- Distribution: Glycopyrronium is a quaternary ammonium compound that does not readily cross the blood-brain barrier.
- Metabolism: Limited information suggests minimal hepatic metabolism.
- Elimination: Primarily excreted unchanged in the urine, with some biliary excretion. Dose adjustments may be necessary in patients with renal impairment.
Mode of Action: Binds competitively to muscarinic receptors, preventing acetylcholine from binding and exerting its effects.
Receptor binding: Muscarinic (M1, M2, M3) receptor antagonist.
Elimination pathways: Primarily renal excretion of unchanged drug, some biliary excretion.
Dosage
Standard Dosage
Adults:
- Oral: For peptic ulcer: 1-2 mg three times a day. Maximum: 8 mg/day.
- Intravenous/Intramuscular: Pre-anesthesia: 0.2-0.4 mg or 0.004-0.005 mg/kg (up to 0.4 mg). Intraoperative: 0.1 mg every 2-3 minutes as needed. For COPD: 50 mcg once daily via inhaler.
- Topical: For hyperhidrosis: 0.05% solution applied to affected area before iontophoretic treatment.
Children:
- Oral (Sialorrhea): For children ≥3 years: Initial dose of 0.02 mg/kg three times a day. Titrate in increments of 0.02 mg/kg every 5-7 days, up to a maximum of 0.1 mg/kg three times a day, not to exceed 1.5-3 mg per dose.
- Intravenous/Intramuscular: 0.004-0.008 mg/kg (up to 0.2 mg) before induction of anesthesia.
Special Cases:
- Elderly Patients: Caution is advised; start at the lower end of the dosing range and titrate cautiously.
- Patients with Renal Impairment: Dose adjustment may be necessary. Contraindicated in severe renal impairment (eGFR <30 ml/min/1.73m²).
- Patients with Hepatic Dysfunction: No specific dosage adjustments provided, but caution is recommended.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease (acute myocardial infarction, hypertension, hyperthyroidism, cardiac insufficiency, coronary artery disease, cardiac arrhythmias), gastrointestinal disorders (gastro-oesophageal reflux disease, ulcerative colitis, pre-existing constipation, or diarrhea), and respiratory conditions.
Clinical Use Cases
- Intubation: 0.2-0.4 mg IV/IM before induction.
- Surgical Procedures: 0.2-0.4 mg IV/IM preoperatively. Intraoperatively as needed (0.1 mg every 2-3 minutes)
- Mechanical Ventilation: Can be used to reduce secretions.
- Intensive Care Unit (ICU) Use: As indicated for management of secretions or bradycardia.
- Emergency Situations: Can be used for bradycardia associated with vagal reflexes.
Dosage Adjustments: Adjust based on patient response and tolerability, renal function, and comorbid conditions.
Side Effects
Common Side Effects
Dry mouth, blurred vision, constipation, urinary hesitancy, drowsiness, headache, dizziness, nausea, vomiting.
Rare but Serious Side Effects
Allergic reactions (rash, itching, swelling, difficulty breathing), acute angle-closure glaucoma, urinary retention, paralytic ileus, confusion, hallucinations, tachycardia, arrhythmias.
Long-Term Effects
Chronic dry mouth can lead to dental problems. Long-term use can potentially cause tolerance.
Adverse Drug Reactions (ADR)
Anaphylaxis, angioedema, severe cardiovascular events.
Contraindications
Hypersensitivity to glycopyrronium, angle-closure glaucoma, urinary retention, gastrointestinal obstruction, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon, myasthenia gravis, concomitant use with solid oral potassium chloride.
Drug Interactions
Other anticholinergic drugs (additive effects), potassium chloride (increased risk of gastrointestinal lesions), antacids (decreased absorption of glycopyrronium), antihistamines, antidepressants, antipsychotics (increased anticholinergic effects), ketoconazole (decreased absorption of ketoconazole), metoclopramide, domperidone (antagonistic effects), nitrates (decreased efficacy of sublingual nitrates). See source [2] and [18] for a more detailed list of drug interactions.
Pregnancy and Breastfeeding
Pregnancy Safety Category: B (Australian classification)
Limited human data available. Animal studies inadequate to assess reproductive toxicity. Use only if clearly needed.
Glycopyrronium is excreted in breast milk in small amounts. Consider the benefits of breastfeeding versus potential risks to the infant. Discontinue breastfeeding or drug, taking into account risks and benefits.
Drug Profile Summary
- Mechanism of Action: Muscarinic receptor antagonist.
- Side Effects: Dry mouth, blurred vision, constipation, urinary retention, drowsiness, dizziness. Serious side effects include allergic reactions, angle-closure glaucoma, paralytic ileus.
- Contraindications: Hypersensitivity, glaucoma, urinary retention, GI obstruction, myasthenia gravis.
- Drug Interactions: Other anticholinergics, potassium chloride, antacids, antihistamines.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Adults: 1-2 mg PO TID. Children: 0.02 mg/kg PO TID initially, titrate as needed. IV/IM as indicated for various clinical situations.
- Monitoring Parameters: Heart rate, blood pressure, bowel sounds, urinary output, mental status.
Popular Combinations
Neostigmine/pyridostigmine for reversal of neuromuscular blockade.
Precautions
- General Precautions: Use with caution in patients with cardiovascular, gastrointestinal, or respiratory disease. Monitor for anticholinergic side effects.
- Specific Populations:
- Pregnant Women: Limited human data; use with caution if benefits outweigh risks.
- Breastfeeding Mothers: Excreted in breast milk; weigh risks/benefits.
- Children & Elderly: Start at lower doses and titrate carefully.
- Lifestyle Considerations: May cause drowsiness or blurred vision; avoid driving or operating machinery if affected.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Glycopyrronium?
A: It varies depending on the indication and patient population. Adults: 1-2 mg PO three times a day for peptic ulcer; 0.2-0.4 mg IV/IM pre-anesthesia. Children: 0.02 mg/kg PO three times a day initially for sialorrhea, titrate as needed.
Q2: How does Glycopyrronium work?
A: It is an anticholinergic that blocks acetylcholine’s action at muscarinic receptors, reducing secretions and increasing heart rate.
Q3: What are the common side effects?
A: Dry mouth, blurred vision, constipation, urinary hesitancy, drowsiness.
Q4: What are the serious side effects?
A: Allergic reactions, angle-closure glaucoma, urinary retention, paralytic ileus.
Q5: Is Glycopyrronium safe during pregnancy?
A: Limited human data. Use with caution only if benefits outweigh potential risks.
Q6: Can I take Glycopyrronium while breastfeeding?
A: It is excreted in breast milk. Consider risks/benefits for both mother and infant.
Q7: What drugs interact with Glycopyrronium?
A: Other anticholinergics, potassium chloride, antacids, antihistamines, antidepressants, antipsychotics, ketoconazole.
Q8: What precautions should I take while using Glycopyrronium?
A: Use cautiously in patients with cardiovascular, gastrointestinal, or respiratory disease. Monitor for anticholinergic side effects. Adjust dosage for renal impairment.
Q9: How should Glycopyrronium be administered for sialorrhea?
A: Orally, starting at 0.02 mg/kg three times daily and titrating up as needed based on response and tolerance.
Q10: Can Glycopyrronium be used in children younger than 3 years old?
A: Safety and efficacy in children younger than 3 years old have not been established.
