Section 03 · Monograph

Apomorphine

Reviewed Nov 2026FDA label

Apokyn / OnapgoDopamine agonist · injectable

Indications

Acute, intermittent treatment of hypomobility 'OFF' episodes (end-of-dose wearing-off and unpredictable on/off fluctuations) in advanced Parkinson's disease — Apokyn (intermittent subcutaneous injection)FDA-labeled
Treatment of motor fluctuations (OFF episodes) in adults with advanced Parkinson's disease — Onapgo (continuous subcutaneous infusion via pump)FDA-labeled

Non-ergoline dopamine agonist with highest binding affinity for D4 receptors and moderate affinity for D2, D3, D5, and alpha-adrenergic receptors
Clinical benefit in Parkinson's disease OFF episodes is believed to result from stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen
Not a derivative of morphine and has no significant affinity for opioid receptors despite the name

Antiemetic pretreatment: trimethobenzamide 300 mg three times daily is recommended, started 3 days before the first apomorphine dose, to reduce nausea/vomiting; discontinue as soon as clinically feasible (generally within ~2 months) as prolonged use increases somnolence/fall risk; 5-HT3 antagonist antiemetics (e.g., ondansetron) must never be substituted
Apokyn (intermittent injection): administer an initial in-office test dose (0.2 mL/2 mg) with supine/standing BP and pulse monitored at baseline and 20, 40, 60 minutes; do not continue if clinically significant orthostatic hypotension occurs
Apokyn titration: increase in 0.1 mL (1 mg) increments at separate OFF episodes as tolerated; usual effective dose range 0.2–0.6 mL (2–6 mg); maximum single dose 0.6 mL (6 mg); minimum 2 hours between doses; average up to 3 times daily
Apokyn restart after >1 week off therapy: resume at 0.2 mL (2 mg) with gradual retitration
Onapgo (continuous SC infusion): initiate continuous infusion at 1 mg/hour during waking hours (~16 hr/day); titrate in 0.1–1 mg/hour increments; maximum 6 mg/hour
Onapgo supplemental 'extra doses': initial 0.5 mg, titrate in 0.1–1 mg increments, maximum single extra dose 2 mg, up to 3 extra doses/day, minimum 3 hours apart
Onapgo maximum total daily dose (continuous + extra doses): 98 mg/day

Apokyn renal impairment (mild-moderate): reduce test and starting doses to 0.1 mL (1 mg)

Concomitant use with 5-HT3 (serotonin) receptor antagonists — including ondansetron, granisetron, dolasetron, palonosetron, and alosetron — is CONTRAINDICATED due to reports of profound hypotension and loss of consciousness with this combination
Known hypersensitivity to apomorphine or product components, including sodium metabisulfite (sulfite sensitivity may cause anaphylaxis or severe asthma exacerbation)
Intravenous administration is contraindicated (subcutaneous use only) due to risk of thrombus formation and pulmonary embolism from crystallization

5-HT3 antagonists (ondansetron, granisetron, dolasetron, palonosetron, alosetron): CONTRAINDICATED — risk of profound hypotension and loss of consciousness
Antihypertensives and vasodilators: additive hypotension; increased risk of falls, myocardial infarction, pneumonia, and injury
Sublingual nitroglycerin: additive blood pressure reduction — advise patient to lie down before and after dosing
Alcohol: potentiates hypotensive effects and increases apomorphine exposure
Dopamine antagonists (antipsychotics, metoclopramide): may reduce apomorphine efficacy and worsen parkinsonian symptoms
QT-prolonging drugs: use caution due to dose-dependent QTc prolongation with apomorphine

Nausea/vomiting, yawning, rhinorrhea
Somnolence/drowsiness and sudden onset of sleep during daily activities, including driving
Dyskinesias, including exacerbation of pre-existing dyskinesia
Orthostatic hypotension and syncope; dose-related blood pressure decreases roughly 20–40 minutes post-dose
Falls, sometimes serious, related to hypotension and altered mobility
Hallucinations, confusion, and new or worsening psychotic behavior
Injection/infusion site reactions: bruising, erythema, nodules, induration, pruritus; cellulitis reported with continuous infusion
Impulse control disorders (pathological gambling, hypersexuality, compulsive spending, binge eating)
QTc interval prolongation (dose-related); potential for torsades de pointes/sudden death (not observed in trials)
Cardiac events (angina, myocardial infarction, palpitations, sudden death) reported, some within 2 hours of dosing
Rare immune-mediated hemolytic anemia (postmarketing) requiring hospitalization/transfusion
Priapism (rare)
Withdrawal-emergent hyperpyrexia and confusion resembling neuroleptic malignant syndrome with abrupt discontinuation/rapid dose reduction

Supine and standing blood pressure and pulse at initiation, with each dose titration, and periodically thereafter
Assess for daytime somnolence and sudden sleep episodes; counsel on driving/hazardous activity restrictions
Monitor for falls, particularly in elderly patients
Screen for hallucinations, new/worsening psychosis, and impulse control symptoms
Baseline and periodic ECG/QTc assessment, particularly with risk factors or concomitant QT-prolonging drugs
CBC/signs of hemolytic anemia (fatigue, pallor, jaundice, dark urine) if suspected
Inspect infusion/injection sites daily for nodules, erythema, or infection; rotate sites (Onapgo)
Medication reconciliation at every encounter to exclude contraindicated 5-HT3 antagonist antiemetics

Pregnancy: No adequate human data; animal studies showed increased neonatal mortality (rats) and cardiac/great vessel malformations (rabbits) at clinically relevant exposures — based on animal data, apomorphine may cause fetal harm; use only if benefit justifies risk
Lactation: No data on presence of apomorphine in human milk; advise patients not to breastfeed during treatment given the potential for serious adverse reactions in a breastfed infant