Rotigotine

Rotigotine is a non-ergot dopamine agonist given as a once daily transdermal patch for Parkinson disease and restless legs syndrome. The patch gives continuous delivery, which suits people with swallowing problems, erratic absorption or nil-by-mouth status.

Mechanism. Agonist at dopamine D1, D2 and D3 receptors, with some serotonergic and adrenergic activity.

Pharmacokinetics. About 45% of the drug in the patch is absorbed over 24 hours. Protein binding is about 92%, and half-life after patch removal is 5 to 7 hours. Metabolism is by multiple cytochrome P450 enzymes and conjugation, with little renal clearance of active drug.

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

• Early Parkinson disease, transdermal rotigotine: 2 mg/24 hours once daily, increased weekly by 2 mg/24 hours to an effective dose. Usual 6 mg/24 hours, maximum 8 mg/24 hours.

• Advanced Parkinson disease with levodopa: start 4 mg/24 hours, increase weekly by 2 mg/24 hours. Usual 8 to 16 mg/24 hours. Maximum 16 mg/24 hours.

• Restless legs syndrome: 1 mg/24 hours, increased weekly by 1 mg/24 hours to a usual 2 to 3 mg/24 hours. Maximum 3 mg/24 hours.

• Apply one patch each day at the same time. Rotate sites among the abdomen, thigh, hip, flank, shoulder and upper arm, and avoid reusing the same site for 14 days.

Hospital and perioperative use. The patch is a bridge when oral medicines are not possible, although it does not directly replace levodopa dose for dose. Start under specialist advice, with the aim of preventing a drop in dopaminergic cover.

Kidney, liver, weight and age.

• Kidney: no adjustment.

• Liver: caution in moderate impairment; not studied in severe impairment.

• Older adults: titrate slowly.

Contraindications. Hypersensitivity, including to sulphites in some formulations.

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

Common adverse effects. Application site reactions, nausea, vomiting, somnolence, dizziness and headache.

Interactions. Antipsychotics and metoclopramide antagonise the effect. Sedatives and alcohol add somnolence. Antihypertensives add hypotension.

Common prescribing errors. Applying new patches without removing the old one. Reusing sites. Applying heat to the patch. Abrupt withdrawal.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: suppresses lactation; avoid.

• Older adults: hallucinations and hypotension are more frequent.

Formulations. Transdermal patches releasing 1, 2, 3, 4, 6 and 8 mg/24 hours. Apply to clean, dry, intact skin, press firmly for 30 seconds, and avoid heat sources over the patch. Remove the patch before magnetic resonance imaging and cardioversion where the product contains metal.

Monitoring.

• Skin sites, impulse control, sleepiness, mental state and lying and standing blood pressure at each review.

• Motor diary and weight.

Stopping. Reduce by 2 mg/24 hours on alternate days, or by 1 mg/24 hours for restless legs, to limit withdrawal syndrome.

Referral and escalation. Refer for severe skin reaction, impulse control disorders, psychosis or advanced fluctuations.