Opicapone

Opicapone is a long-acting peripheral catechol-O-methyltransferase inhibitor given once daily at bedtime as an adjunct to levodopa in Parkinson disease with end-of-dose fluctuations. Its long duration of enzyme inhibition allows a single daily dose, without diarrhoea being as prominent as with older drugs of the class.

Mechanism. Binds catechol-O-methyltransferase tightly and reduces peripheral breakdown of levodopa, extending its action.

Pharmacokinetics. Bioavailability about 20% and protein binding over 99%. Plasma half-life is short (about 1 to 3 hours) but enzyme inhibition lasts over 24 hours. It is mainly sulphated and excreted in faeces.

Alternative use. Adjunct to levodopa with a decarboxylase inhibitor in adults with end-of-dose motor fluctuations.

• Oral opicapone: 50 mg once daily at bedtime, at least 1 hour before or after levodopa. Maximum 50 mg daily.

• If dyskinesia appears, reduce the levodopa dose, usually by 10 to 30%.

Kidney, liver, weight and age.

• Kidney: no adjustment in mild to moderate impairment; use caution in severe impairment.

• Liver: moderate impairment (Child-Pugh B), 25 mg daily. Severe impairment, avoid.

• Older adults: no adjustment.

Contraindications. Phaeochromocytoma, paraganglioma or other catecholamine-secreting tumours, history of neuroleptic malignant syndrome or non-traumatic rhabdomyolysis, concurrent non-selective monoamine oxidase inhibitors, and hypersensitivity.

Serious adverse effects. Worsened dyskinesia, hallucinations and psychosis, impulse control disorders, orthostatic hypotension, syncope and sudden sleep onset.

Common adverse effects. Dyskinesia, constipation, dry mouth, insomnia, raised creatine kinase and dizziness.

Interactions. Catecholamine drugs (adrenaline, noradrenaline, dopamine, dobutamine, isoprenaline, methyldopa, apomorphine) can cause tachycardia or hypertension. Avoid non-selective monoamine oxidase inhibitors. Use caution with drugs cleared by cytochrome P450 2C8.

Common prescribing errors. Taking it with a levodopa dose rather than separately. Not reducing levodopa when dyskinesia increases. Using it without levodopa.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: avoid.

• Regional: costly and seldom available.

Formulations. Capsules 25 and 50 mg. Swallow whole at bedtime, at least 1 hour before or after levodopa and food where possible.

Monitoring.

• Motor diary, dyskinesia, blood pressure, mood, impulse control and sleepiness.

• Creatine kinase if muscle symptoms occur.

Stopping. Stop gradually where possible, as levodopa doses may need to rise.

Referral and escalation. Refer for severe dyskinesia, psychosis or impulse control disorders.