Ropinirole

Ropinirole is a non-ergot dopamine agonist used for Parkinson disease and restless legs syndrome. Compared with pramipexole it is cleared by the liver rather than the kidney, and shares the risks of sleepiness, impulse control disorders and hallucinations.

Mechanism. Agonist at dopamine D2 and D3 receptors.

Pharmacokinetics. Bioavailability is about 55% because of first-pass metabolism by cytochrome P450 1A2. Half-life is about 6 hours for immediate-release, and prolonged-release gives 24-hour coverage. Protein binding is 10 to 40%.

First-line use. Early Parkinson disease as monotherapy, adjunct to levodopa, and restless legs syndrome.

• Parkinson disease, immediate-release tablets, oral ropinirole: 0.25 mg three times daily in week 1, 0.5 mg three times daily in week 2, 0.75 mg three times daily in week 3, 1 mg three times daily in week 4. Then increase by 1.5 to 3 mg daily each week as needed. Usual maintenance 3 to 9 mg daily, often 9 to 16 mg daily with levodopa. Maximum 24 mg daily.

• Prolonged-release tablets: 2 mg once daily for 1 week, 4 mg once daily for the next week, then increase by 2 mg each week or more slowly. Maximum 24 mg daily.

• Restless legs syndrome: 0.25 mg once daily 1 to 3 hours before bedtime, increased to 0.5 mg after 2 days and 1 mg by the end of week 1. Titrate to a usual 2 mg, maximum 4 mg daily.

Kidney, liver, weight and age.

• Kidney: creatinine clearance 30 mL/min or more, no change. Under 30 mL/min not studied except on dialysis, where prolonged-release tablets start at 2 mg daily with a maximum of 18 mg daily.

• Liver: use caution; titrate slowly and avoid in severe impairment.

• Older adults: titrate slowly.

Contraindications. Hypersensitivity, severe hepatic impairment and severe renal impairment without dialysis (in some labels).

Serious adverse effects. Sudden sleep onset, impulse control disorders, hallucinations and psychosis, orthostatic hypotension, dyskinesia, augmentation in restless legs, peripheral oedema, and dopamine agonist withdrawal syndrome.

Common adverse effects. Nausea, somnolence, dizziness, syncope, constipation and oedema.

Interactions. Cytochrome P450 1A2 inhibitors such as ciprofloxacin and fluvoxamine raise levels. Oestrogen-containing therapy raises levels. Smoking induces cytochrome P450 1A2, so stopping smoking can raise levels. Antipsychotics and metoclopramide antagonise the effect.

Common prescribing errors. Fast titration. Not warning about sudden sleep onset and driving. Missing impulse control disorders.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: suppresses lactation; avoid.

• Regional: availability varies; the immediate-release form is more commonly available.

Formulations. Immediate-release tablets 0.25, 0.5, 1, 2 and 5 mg. Prolonged-release tablets 2, 4 and 8 mg. Take with food to reduce nausea. Swallow prolonged-release tablets whole.

Monitoring.

• Impulse control, sleepiness, mental state, lying and standing blood pressure, and oedema at each review.

• Review interacting drugs, smoking changes and hepatic function.

Stopping. Taper over about a week, reducing by 0.5 to 1 mg daily if possible. Stop promptly for severe behavioural or psychiatric effects.

Referral and escalation. Refer for impulse control disorders, psychosis, or advanced motor fluctuations.