Galantamine

Galantamine is a reversible cholinesterase inhibitor used for mild to moderate Alzheimer disease. It also modulates nicotinic receptors. Its use has declined because of tolerability and cardiac cautions, and it is not used for mild cognitive impairment.

Mechanism. Competitive reversible inhibitor of acetylcholinesterase, with allosteric potentiation of nicotinic acetylcholine receptors.

Pharmacokinetics. Bioavailability about 90%, protein binding about 18%, and half-life 7 to 8 hours. It is metabolised by cytochrome P450 2D6 and 3A4, and about 20% is excreted unchanged in urine.

Alternative use. Mild to moderate Alzheimer disease.

• Oral immediate-release galantamine: 4 mg twice daily for 4 weeks, then 8 mg twice daily for at least 4 weeks, then 12 mg twice daily if needed. Usual maintenance 16 to 24 mg daily. Maximum 24 mg daily.

• Prolonged-release capsules: 8 mg once daily for 4 weeks, 16 mg once daily for at least 4 weeks, then 24 mg once daily if needed.

• If interrupted for more than 3 days, restart at the lowest dose.

Kidney, liver, weight and age.

• Kidney: creatinine clearance 9 to 60 mL/min, maximum 16 mg daily. Under 9 mL/min, avoid.

• Liver: moderate impairment (Child-Pugh 7 to 9), maximum 16 mg daily. Severe impairment, avoid.

• Older adults: titrate slowly.

Contraindications. Severe hepatic or renal impairment and hypersensitivity.

Serious adverse effects. Bradycardia, heart block, syncope, QT prolongation, severe skin reactions (Stevens-Johnson syndrome, acute generalised exanthematous pustulosis), gastrointestinal bleeding, seizures and urinary obstruction.

Common adverse effects. Nausea, vomiting, diarrhoea, anorexia, weight loss, dizziness, headache and fatigue.

Interactions. Paroxetine, fluoxetine, quinidine, ketoconazole and erythromycin raise levels. Anticholinergics oppose its effect. Beta blockers, digoxin and other bradycardic drugs add risk. Succinylcholine-type relaxants are prolonged.

Common prescribing errors. Not adjusting for kidney or liver impairment. Skipping the 4-week titration steps. Missing a skin rash.

Special groups.

• Pregnancy: not indicated.

• Breastfeeding: not indicated.

• Anaesthesia: tell the anaesthetist, because neuromuscular blockade may be prolonged.

Formulations. Tablets 4, 8 and 12 mg. Prolonged-release capsules 8, 16 and 24 mg. Oral solution 4 mg/mL. Take with food and maintain fluid intake.

Monitoring.

• Weight, pulse, gastrointestinal symptoms, skin and cognition. ECG if cardiac disease or interacting drugs.

• Review benefit at 3 months, then about every 6 months.

Stopping. Reduce gradually. Stop at once for rash.

Referral and escalation. Refer for syncope, bradycardia, rash, rapid decline or behavioural symptoms.