Apomorphine

Apomorphine is a rapid-acting dopamine agonist given subcutaneously to treat OFF episodes in advanced Parkinson disease, either as intermittent rescue injections or as a continuous infusion. It is specialist-initiated because of severe nausea, hypotension and cardiac risks.

Mechanism. Non-ergot agonist at dopamine D1 and D2 receptors, acting within minutes.

Pharmacokinetics. Subcutaneous absorption is rapid, with onset in 5 to 15 minutes and duration of 45 to 90 minutes. Oral bioavailability is negligible. Half-life is about 30 to 60 minutes. Hepatic metabolism is extensive.

Specialist use. Refractory motor fluctuations in Parkinson disease not controlled by oral therapy.

• Before starting: give an antiemetic such as domperidone 20 mg three times daily for at least 2 days (where available), and obtain a baseline ECG. Avoid 5-HT3 antagonists such as ondansetron, because of profound hypotension.

• Test dose under supervision: 1.5 to 2 mg subcutaneously. If there is no response after 30 to 40 minutes, repeat with increments of 1 mg until a clear response, up to a maximum single dose of 10 mg.

• Intermittent injection: the effective single dose, up to 10 mg, given as needed at the start of OFF periods. Usual total 3 to 30 mg daily, with a maximum of 100 mg daily.

• Continuous infusion: start 1 mg/hour while awake (usually 12 to 16 hours), increase by 0.5 mg/hour at intervals of at least 4 hours. Usual 1 to 4 mg/hour. Maximum total 100 mg daily.

Kidney, liver, weight and age.

• Kidney: start with a lower test dose (for example 1 mg) in mild to moderate impairment; use caution in severe impairment.

• Liver: caution; avoid in significant impairment.

• Older adults: increased risk of hypotension, confusion and hallucinations.

Contraindications. Respiratory depression, dementia, psychotic disease, hepatic insufficiency, severe on-phase dyskinesia, concurrent 5-HT3 antagonists, and hypersensitivity (including to sulphites).

Serious adverse effects. Severe nausea and vomiting, orthostatic hypotension, hallucinations and psychosis, QT prolongation, haemolytic anaemia with a positive Coombs test, impulse control disorders, injection site nodules and fibrosis, priapism and sudden sleep onset.

Common adverse effects. Nausea, vomiting, injection site reactions, somnolence, dyskinesia and yawning.

Interactions. Ondansetron and other 5-HT3 antagonists are contraindicated. QT-prolonging drugs (domperidone, macrolides, antipsychotics) add risk. Antihypertensives add hypotension. Antipsychotics antagonise the effect.

Common prescribing errors. Giving it intravenously. Starting without an antiemetic or ECG. Not rotating injection sites. Using ondansetron for nausea.

Special groups.

• Pregnancy: avoid unless essential.

• Breastfeeding: avoid.

• Regional: costly and often unavailable, and needs specialist nursing support.

Formulations. Ampoules 10 mg/mL, prefilled pens 30 mg in 3 mL, and prefilled syringes for infusion 50 mg in 10 mL. Give subcutaneously only, in the abdomen or thigh, rotating sites. Protect from light and discard any discoloured solution.

Monitoring.

• Baseline and periodic ECG, especially after dose or interacting drug changes.

• Full blood count and Coombs test periodically, lying and standing blood pressure, injection sites, mental state and impulse control.

Stopping. Reduce under specialist supervision, with levodopa cover maintained.

Referral and escalation. Initiate in a specialist Parkinson disease service. Refer urgently for syncope, arrhythmia or severe psychiatric effects.