Selegiline

Selegiline is an irreversible monoamine oxidase B inhibitor used for early Parkinson disease and as an adjunct to levodopa. It offers modest symptomatic benefit and levodopa-sparing effects, but metabolism to amphetamine-like compounds causes insomnia and confusion, and it has important serotonergic interactions.

Mechanism. Irreversibly inhibits monoamine oxidase B in the brain, which reduces dopamine breakdown. At higher doses it loses selectivity.

Pharmacokinetics. Oral bioavailability is low (about 10%) from first-pass metabolism. The orally disintegrating form is absorbed through the mouth and has higher bioavailability. Plasma half-life is short, but enzyme inhibition lasts days. Metabolites include L-methamphetamine and L-amphetamine.

Alternative use. Early Parkinson disease as monotherapy, and adjunct to levodopa for wearing-off.

• Oral selegiline: 5 mg in the morning, increased to 5 mg at breakfast and 5 mg at lunch (10 mg daily). Avoid evening doses because of insomnia. Maximum 10 mg daily.

• Orally disintegrating tablets: 1.25 mg once daily before breakfast, which may be increased to 2.5 mg after about 6 weeks.

• With levodopa: the levodopa dose may need to be reduced by 10 to 30% after 2 to 3 days if dyskinesia appears.

Kidney, liver, weight and age.

• Kidney and liver: use caution; avoid in severe impairment.

• Older adults: start low and watch for confusion and hallucinations.

Contraindications. Concurrent selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, tricyclic antidepressants, other monoamine oxidase inhibitors, pethidine, tramadol, methadone and dextromethorphan. Also phaeochromocytoma, severe dementia, and severe hepatic or renal impairment.

Serious adverse effects. Serotonin syndrome, hypertensive reactions with sympathomimetics, hallucinations, confusion, orthostatic hypotension and worsened dyskinesia.

Common adverse effects. Insomnia, nausea, dry mouth, dizziness, agitation and vivid dreams.

Interactions. Fatal reactions occur with pethidine and other opioids such as tramadol and methadone. Wait at least 14 days between stopping selegiline and starting an antidepressant, and at least 5 weeks after stopping fluoxetine before starting selegiline. Sympathomimetic decongestants such as pseudoephedrine risk hypertensive crisis. Tyramine restriction is not needed at 10 mg daily or less.

Common prescribing errors. Giving in the evening. Co-prescribing antidepressants. Giving opioid analgesia in hospital without checking the medicines list.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: avoid.

• Regional: decongestants and cough preparations sold over the counter may contain interacting drugs, so counsel carefully.

Formulations. Tablets or capsules 5 and 10 mg. Orally disintegrating tablets 1.25 mg. Take in the morning and at lunch, with food.

Monitoring.

• Blood pressure, sleep, mental state, dyskinesia and motor diary.

• Review the medicines list for serotonergic and opioid drugs at every change.

Stopping. Stop gradually where possible, and allow 14 days before starting antidepressants.

Referral and escalation. Refer for hallucinations, serotonin syndrome features (agitation, fever, clonus) or hypertensive symptoms.