Rasagiline

Rasagiline is an irreversible selective monoamine oxidase B inhibitor used for Parkinson disease as monotherapy or as an adjunct to levodopa. It is dosed once daily without titration and, unlike selegiline, does not produce amphetamine-like metabolites.

Mechanism. Irreversibly inhibits monoamine oxidase B, which slows breakdown of dopamine in the brain.

Pharmacokinetics. Bioavailability about 36% and protein binding 60 to 70%. Half-life is about 3 hours, but enzyme inhibition lasts days. It is metabolised by cytochrome P450 1A2 to an inactive aminoindan.

First-line and alternative use. Early Parkinson disease as monotherapy, and as adjunct to levodopa for end-of-dose fluctuations.

• Oral rasagiline: 1 mg once daily with or without food. No titration is needed. Maximum 1 mg daily.

• With ciprofloxacin or other cytochrome P450 1A2 inhibitors: 0.5 mg once daily.

• With levodopa: reduce the levodopa dose if dyskinesia worsens.

Kidney, liver, weight and age.

• Kidney: no adjustment.

• Liver: mild impairment, 0.5 mg daily. Moderate to severe impairment, avoid.

• Older adults: no adjustment; monitor hypotension and hallucinations.

Contraindications. Hypersensitivity, severe hepatic impairment, and concurrent monoamine oxidase inhibitors, pethidine, tramadol and methadone.

Serious adverse effects. Serotonin syndrome with serotonergic drugs, hypertensive reactions with sympathomimetics, hallucinations, impulse control disorders, worsened dyskinesia, orthostatic hypotension, sudden sleep onset and a possible melanoma association.

Common adverse effects. Headache, arthralgia, dyspepsia, depression, weight loss and dyskinesia when used with levodopa.

Interactions. Ciprofloxacin roughly doubles exposure. Pethidine, tramadol, methadone and dextromethorphan are contraindicated. Wait at least 14 days between stopping rasagiline and starting an antidepressant, and at least 5 weeks after stopping fluoxetine before starting rasagiline. Sympathomimetic decongestants risk hypertensive crisis.

Common prescribing errors. Co-prescribing antidepressants or opioids such as tramadol. Not halving the dose with ciprofloxacin. Failing to reduce levodopa when dyskinesia increases.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: avoid; it may suppress lactation.

• Regional: over-the-counter cough and cold products may contain interacting drugs, so counsel carefully.

Formulations. Tablets 1 mg. Take with or without food, at the same time each day.

Monitoring.

• Motor function, dyskinesia, blood pressure, mood, impulse control and sleepiness at each review.

• Periodic skin examination for melanoma. Review the medicines list for serotonergic and sympathomimetic drugs at each change.

Stopping. Benefit fades within days of stopping. Stop gradually where possible, and allow 14 days before starting antidepressants.

Referral and escalation. Refer for hallucinations, impulse control disorders, serotonin syndrome features or worsening motor fluctuations.