Rivastigmine

Rivastigmine is a cholinesterase inhibitor used for mild to moderate Alzheimer disease and for Parkinson disease dementia. It inhibits both acetylcholinesterase and butyrylcholinesterase, and has transdermal and oral forms, with the patch being better tolerated.

Mechanism. Pseudo-irreversible inhibitor of acetylcholinesterase and butyrylcholinesterase, increasing brain acetylcholine.

Pharmacokinetics. Oral bioavailability about 36% at 3 mg, half-life about 1.5 hours, with enzyme inhibition lasting about 10 hours. It is hydrolysed by esterases, not by cytochrome P450, so interactions are few. The patch gives steady delivery over 24 hours.

First-line use. Mild to moderate Alzheimer disease and mild to moderate Parkinson disease dementia.

• Oral rivastigmine: 1.5 mg twice daily with meals. Increase by 1.5 mg twice daily after at least 2 weeks to 3 mg, 4.5 mg and 6 mg twice daily as tolerated. Usual maintenance 3 to 6 mg twice daily. Maximum 12 mg daily.

• Transdermal rivastigmine: 4.6 mg/24 hours once daily. After at least 4 weeks, increase to 9.5 mg/24 hours, the usual effective dose. A 13.3 mg/24 hours patch may be used after at least 6 months of benefit at 9.5 mg/24 hours where a larger dose is considered.

• Switching from oral to patch: oral daily dose under 6 mg, start 4.6 mg/24 hours patch; 6 to 12 mg daily, start 9.5 mg/24 hours patch. Apply the first patch the day after the last oral dose.

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

Kidney, liver, weight and age.

• Kidney and liver: mild to moderate impairment, titrate to tolerance. Severe liver impairment, use caution.

• Body weight under 50 kg: higher risk of adverse effects, so titrate slowly.

Contraindications. Hypersensitivity to rivastigmine, other carbamates or excipients. History of generalised skin reaction to the patch.

Serious adverse effects. Severe vomiting with dehydration, bradycardia, heart block, syncope, gastrointestinal bleeding, seizures, urinary obstruction, worsening of asthma or chronic obstructive lung disease, and worsened tremor in Parkinson disease.

Common adverse effects. Nausea, vomiting, diarrhoea, anorexia, weight loss, dizziness, headache and, with the patch, local skin reactions.

Interactions. Anticholinergics oppose its effect. Beta blockers and other bradycardic drugs add risk. Metoclopramide adds extrapyramidal effects. Succinylcholine-type relaxants are prolonged. Other cholinomimetics add toxicity.

Common prescribing errors. Restarting at a high dose after missing treatment. Applying more than one patch. Reusing the same skin site within 14 days. Using it in someone with a patch allergy.

Special groups.

• Pregnancy: not indicated.

• Breastfeeding: not indicated.

• Parkinson disease dementia: tremor can worsen, so monitor motor function.

Formulations. Capsules 1.5, 3, 4.5 and 6 mg. Oral solution 2 mg/mL. Transdermal patches 4.6, 9.5 and 13.3 mg/24 hours.

Preparation. Apply one patch daily to clean, dry, hairless, intact skin on the upper or lower back, upper arm or chest, and remove the old patch first. Rotate sites and avoid reusing a site for 14 days. Avoid heat sources over the patch. Capsules are taken with food.

Monitoring.

• Weight, pulse, gastrointestinal symptoms and skin sites.

• Cognition and function at 3 months, then about every 6 months. Stop if no benefit.

Stopping. Reduce gradually. Stop for severe adverse effects or generalised skin reaction.

Referral and escalation. Refer for behavioural symptoms, syncope, weight loss, rapid decline, or patch allergy.