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Apomorphine (Monograph)

Brand names: Apokyn [Web] ;, Onapgo [Web]
Drug class: Nonergot-derivative Dopamine Receptor Agonists

Medically reviewed by Drugs.com on Jul 10, 2025. Written by ASHP.

Introduction

Nonergot-derivative dopamine receptor agonist.

Uses for Apomorphine

Parkinson Disease

Used subcutaneously for treatment of episodes of hypomobility (i.e., “off” episodes, including end-of-dose “wearing off” and unpredictable “on-off” episodes) associated with advanced Parkinson disease; designated an orphan drug by FDA for treatment of on-off fluctuations associated with late-stage Parkinson disease.

Guidelines from international experts generally recommend oral agents (i.e., levodopa, dopamine agonists, monoamine oxidase B inhibitors) first-line for early treatment of motor symptoms in patients with Parkinson disease; parenteral options (such as apomorphine) are generally reserved for treatment of bothersome motor fluctuations in suitable patients with advanced disease.

Apomorphine Dosage and Administration

General

Patient Monitoring

Premedication and Prophylaxis

Dispensing and Administration Precautions

Other General Considerations

Administration

Administer by intermittent sub-Q injection (Apokyn) or continuous sub-Q infusion (Onapgo). Do not administer IV; possibility of serious adverse effects (e.g., thrombosis, pulmonary embolism).

Intermittent Sub-Q Injection (Apokyn)

Administer by sub-Q injection using the dosing pen (with supplied cartridges) or with the disposable prefilled pen on an as-needed basis.

Administer sub-Q injections in the stomach area (≥2 inches from the naval), upper thigh, or upper arm; rotate injection sites.

Separate administration of doses by at least 2 hours.

Continuous Sub-Q Infusion (Onapgo)

Administer by sub-Q infusion via portable pump. Refer to prescribing information for detailed instructions for use.

Administer sub-Q into the abdomen (≥2 inches from the naval), top of thigh, or lower back; healthcare provider or caregiver may also administer into the upper back. Change infusion site daily; avoid infusion into areas that are bruised, have bumps or nodules, or are irritated. Use a new single-dose cartridge and cartridge holder every day and discard any unused portion.

Dosage

Available as apomorphine hydrochloride; dosage expressed in terms of the salt.

Titrate dose according to patient response and tolerance.

Adults

Parkinson Disease
Intermittent Sub–Q Injection (Apokyn)

Initial test dose is 0.1–0.2 mL (1–2 mg). Consider 0.1 mL (1 mg) starting dose to mitigate risk of nausea and vomiting. If the test dose is effective and tolerated, this dose may be used on an as-needed, outpatient basis. If necessary, the dose may be increased in 0.1 mL (1 mg) increments every few days.

Patient is not a candidate for apomorphine therapy if clinically significant orthostatic hypotension occurs in response to initial test dose.

For patients who tolerate, but do not respond to an initial 0.1 mL (1 mg) test dose, administer a second test dose of 0.2 mL (2 mg) at the next observed “off” period, no sooner than 2 hours after the initial test dose. For patients who tolerate, but do not respond to the initial 0.2 mL (2 mg) test dose, administer a second test dose of 0.4 mL (4 mg) at the next observed “off” period, no sooner than 2 hours after the initial test dose. Patients unable to tolerate a 0.2 mL (2 mg) dose may require slow titration. If the 0.4 mL (4 mg) dose is effective and tolerated, a 0.3 mL (3 mg) dose may be used on an as-needed, outpatient basis. If necessary, the dose may be increased in 0.1 mL (1 mg) increments every few days.

For patients who respond, but do not tolerate the 0.4 mL (4 mg) test dose, administer a third test dose of 0.3 mL (3 mg) at the next observed “off” period, but no sooner than 2 hours after the 0.4 mL (4 mg) test dose. If the 0.3 mL (3 mg) dose is effective and tolerated, a 0.2 mL (2-mg) dose may be used on an as-needed, outpatient basis. If the 0.2 mL (2 mg) dose is tolerated, the dose may be increased, if needed, to 0.3 mL (3 mg) after a few days. The dose should not usually be increased to 0.4 mL (4 mg) on an outpatient basis in these patients.

If therapy has been interrupted for >1 week, reinitiate at a dose of 0.2 mL (2 mg) and gradually titrate to effect.

No more than one dose of apomorphine should be administered for treatment of a single “off” episode. Safety and efficacy of a second dose during the same “off” episode in patients not responding to the initial dose have not been established. A repeat dose should not be administered sooner than 2 hours after the last dose.

Doses >0.6 mL (6 mg) not associated with additional therapeutic effect and are not recommended.

Limited experience with >5 doses per day or daily dosages >2 mL (20 mg).

Continuous Sub-Q Infusion (Onapgo)

Daily dosage composed of a continuous dosage and additional dose(s) administered as needed. Initial continuous dosage (continuous infusion) of 1 mg/hr is recommended; titrate up in increments of 0.5–1 mg/hr as needed.

Dosage adjustments can be made daily, or at longer intervals as needed. In clinical trials, average continuous dosage was 4 mg/hr. Maximum dosage is 6 mg/hr administered over the waking day (e.g., 16 hours).

Extra doses may be administered in addition to continuous dosage: 1) upon starting in the morning; 2) upon restart of continuous dosage following break in use or ≥1 hour; or 3) as a supplement to manage uncontrolled “off” symptoms. A maximum of 3 extra doses may be administered per day over 16 hours; allow at least 3 hours between extra doses. Titrate extra dose in increments of 0.5–1 mg based on clinical response and tolerability. Subsequent extra doses may be between 0.5–2 mg.

If 3 extra doses per day are routinely required, consider adjusting continuous dosage. Maximum recommended daily dosage (including continuous and extra doses) is 98 mg during the waking day (e.g., 16 hours).

Sudden discontinuation or rapid dose reduction can increase severity of motor symptoms; taper dosage before discontinuing if possible.

Special Populations

Hepatic Impairment

No specific dosage recommendations. Exercise caution and closely monitor if administered in patients with mild or moderate hepatic impairment. Has not been studied in severe hepatic impairment.

Renal Impairment

In patients with mild or moderate renal impairment receiving intermittent sub-Q infusion (Apokyn), reduce initial test dose and subsequent starting dose to 0.1 mL (1 mg). In patients with mild or moderate renal impairment receiving continuous sub-Q infusion (Onapgo), initial extra dose between 0.5–1 mg (not exceeding 1 mg) recommended. No dosage adjustment needed for continuous dose, maximum recommended daily dose, or subsequent extra doses.

Apomorphine has not been studied in severe renal impairment.

Geriatric Patients

No specific dosage recommendations. Cautious dosage selection, starting at the low end of the dosing range recommended due to increased incidence of decreased hepatic, renal, or cardiac function and comorbid disease or other drug therapy.

Cautions for Apomorphine

Contraindications

Warnings/Precautions

Serious Reactions After IV Administration

Thrombus formation and pulmonary embolism due to IV crystallization of apomorphine reported following IV administration. Do not administer IV.

Nausea and Vomiting

Severe nausea and vomiting expected; concomitant use of an antiemetic recommended. Trimethobenzamide was used in clinical studies; other antiemetics are contraindicated (i.e., 5-HT3 receptor antagonists) or not recommended (i.e., dopamine-receptor antagonists). Trimethobenzamide has been shown to reduce nausea and vomiting during first 4 weeks of apomorphine treatment, but can increase risk of somnolence, dizziness, and falls. Therefore, balance risks versus benefits. Limit duration of trimethobenzamide therapy to shortest amount of time necessary to control nausea and vomiting (generally no longer than 2 months).

Falling Asleep During Activities of Daily Living and Somnolence

Falling asleep while engaged in activities of daily living reported. While somnolence occurs frequently in patients receiving apomorphine, these patients perceived no warning signs and believed they were alert immediately prior to the event. Falling asleep while engaged in activities of daily living is thought to always occur in a setting of preexisting somnolence, although patients may not give such a history.

Continually reassess patients for drowsiness or sleepiness. Patients may not acknowledge drowsiness or sleepiness until directly questioned about such adverse effects during specific activities. Ask patients about any factors that may increase the risk of somnolence (e.g., concomitant sedating drugs, the presence of sleep disorders).

In general, discontinue therapy if a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating). If the drug is continued, advise patients to not drive and to avoid other potentially dangerous activities. Insufficient information to establish whether dosage reduction will eliminate this adverse effect.

Syncope/Hypotension/Orthostatic Hypotension

Dopamine agonists appear to impair systemic regulation of BP, resulting in postural/orthostatic hypotension, especially during dosage escalation. Patients with Parkinson disease may also have impaired capacity to respond to an orthostatic challenge. Apomorphine causes dose-related decreases in systolic and diastolic BP. Orthostatic hypotension, hypotension, and/ or syncope reported in clinical studies with apomorphine. Orthostatic hypotension can also be a manifestation of Parkinson disease.

Monitor patients for signs and symptoms of orthostatic hypotension, particularly during dosage escalation, and inform patients of this potential risk. Concomitant use of alcohol not recommended due to additive hypotensive effects. Patients taking apomorphine should lie down before and after taking sublingual nitroglycerin. Monitor patients taking other vasodilators or antihypertensive agents closely for hypotension and orthostatic hypotension.

Prolongation of QT Interval and Potential for Proarrhythmic Effects

Risk of dose-related QT-interval prolongation with exposure similar to that achieved with therapeutic doses of the drug. Although torsades de pointes has not been observed in clinical studies, an increased risk cannot be ruled out. Doses of Apokyn >6 mg do not provide additional clinical benefit and should not be used.

Consider risks versus benefits in patients with risk factors for QT-interval prolongation (e.g., congenital or known QT-interval prolongation, clinically important bradycardia, hypokalemia, hypomagnesemia, concomitant use of drugs known to prolong the QTc interval).

Falls

Risk of falls; may be due to postural and autonomic instability associated with Parkinson disease. Risk may be increased due to effect of apomorphine on BP and mobility.

Infusion Site Reactions and Infections

Risk of infusion site reactions (e.g., nodules, erythema, hematomas, inflammation, pruritus, swelling, discoloration, hemorrhage, hypersensitivity, induration, edema, pain, rash, and bruising) and infections with the sub-Q infusion formulation (Onapgo).

If infection is suspected at the infusion site, remove the cannula; place new cannula at a new infusion site. If apomorphine therapy is interrupted for a prolonged period, prescribe oral medications to treat Parkinson symptoms.

Hallucinations/Psychotic-like Behavior

Hallucinations or psychotic-like behavior reported in clinical studies.

During postmarketing experience, other new or worsening mental status and behavioral changes (e.g., paranoid ideation, delusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, delirium) reported during therapy or after initiating or increasing dosage. Other antiparkinsonian agents can produce similar effects.

Manufacturer of Apokyn states that use is generally not advised in patients with a major psychotic disorder. Consider risks and benefits prior to initiating therapy in such patients. Also consider that concomitant use with antipsychotic agents may exacerbate parkinsonian symptoms and decrease effectiveness of apomorphine.

Cardiac Events

Angina, MI, cardiac arrest, and/or sudden death reported in patients receiving Apokyn. Angina and MI occurred in some patients within 2 hours of apomorphine dosing; cardiac arrest and sudden death occurred at times unrelated to dosing. Left bundle branch block, MI, palpitations, or tachycardia reported in the clinical study of Onapgo.

May exacerbate coronary and cerebral ischemia due to effects of apomorphine on BP. Use with caution in patients with cardiovascular and cerebrovascular disease.

If signs and symptoms of coronary or cerebral ischemia occur, reevaluate continued use of the drug.

Hypersensitivity

Hypersensitivity/allergic reactions (e.g., urticaria, rash, pruritus, angioedema) caused by apomorphine or the sulfite excipient reported.

The commercially available apomorphine hydrochloride injection contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

Dyskinesia

May cause or exacerbate dyskinesias.

Hemolytic Anemia

Hemolytic anemia requiring hospitalization reported during postmarketing experience. If anemia develops during treatment, consider a workup for hemolytic anemia. If hemolytic anemia occurs, consider discontinuing apomorphine.

Impulse Control/Compulsive Behaviors

Intense urges and compulsive behaviors (e.g., urge to gamble, increased sexual urges, uncontrolled spending, binge eating, other intense urges) and inability to control these urges reported in some patients receiving dopaminergic agents. In some cases, urges stopped when dosage was reduced or drug was discontinued. Because patients may not recognize these behaviors as abnormal, clinicians should ask patients or caregivers about new development of increased gambling urges, sexual urges, uncontrolled spending, or other urges during treatment.

Consider reducing dosage or discontinuing therapy if a patient develops such urges.

Withdrawal-emergent Hyperpyrexia and Confusion

A symptom complex resembling neuroleptic malignant syndrome (NMS; elevated temperature, muscular rigidity, altered consciousness, autonomic instability) has been reported in association with abrupt withdrawal, dosage reduction, or changes in antiparkinsonian therapy.

Fibrotic Complications

Retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, and cardiac valvulopathy reported in patients receiving ergot-derivative dopamine receptor agonists; presumably related to the ergoline structure of these agents. Possible that nonergot-derived drugs that increase dopaminergic activity (e.g., apomorphine) may induce similar changes.

Priapism

Possible prolonged painful erections.

Retinal Pathology in Albino Rats

Retinal degeneration reported in albino rats given dopamine agonists for prolonged periods (usually 2-year carcinogenicity studies); similar changes not observed in albino monkeys. Clinical importance in humans not established; however, effect cannot be disregarded because the presumed mechanism of action may apply to all vertebrates.

Specific Populations

Pregnancy

No adequate data in pregnant women. In animal reproduction studies, increased neonatal deaths and cardiovascular malformations observed at clinically relevant doses associated with maternal toxicity.

Lactation

Not known whether apomorphine is distributed into human milk. Effects on breast-fed infant or on milk production also not known. Consider known benefits of breast-feeding along with mother's clinical need for apomorphine and any potential adverse effects on the breast-fed infant from drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Intermittent sub-Q apomorphine (Apokyn): Increased incidence of confusion, hallucinations, serious adverse events (life-threatening events or events resulting in hospitalization and/or increased disability), falls, cardiovascular events, respiratory disorders, and GI events in geriatric individuals compared with younger adults.

Apomorphine continuous sub-Q infusion (Onapgo): clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger adults.

Hepatic Impairment

Systemic exposure increased in patients with mild to moderate hepatic impairment; use with caution. Not studied in patients with severe hepatic impairment.

Renal Impairment

Dosage adjustment necessary in patients with mild to moderate renal impairment; peak plasma concentrations and AUC increased in such patients. Not studied in patients with severe renal impairment.

Common Adverse Effects

Apokyn (incidence ≥10% versus placebo): yawning, drowsiness/somnolence, dyskinesias, dizziness/postural hypotension, rhinorrhea, nausea and/or vomiting, hallucination/confusion, and edema/swelling of extremities.

Onapgo (incidence ≥10% and at least twice the rate of placebo): infusion site nodule, nausea, somnolence, infusion site erythema, dyskinesia, headache, and insomnia.

Does Apomorphine interact with my other drugs?

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Drug Interactions

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT-interval prolongation); exercise caution if used concomitantly.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.

Specific Drugs

Drug

Interaction

Comments

Alcohol

Additive hypotensive effects demonstrated; potential for additive sedative effects

Avoid concomitant use

Antihypertensive agents and vasodilators

Potential pharmacologic interaction (additive hypotensive effects)

Concomitant use associated with increased incidence of hypotension, MI, pneumonia, serious falls, bone and joint injuries

Monitor BP

CNS depressants

Potential for additive sedative effects

5-HT3 receptor antagonists (e.g., granisetron, ondansetron, palonosetron)

Profound hypotension with loss of consciousness may occur

Concomitant use contraindicated

Dopamine-receptor antagonists (e.g., phenothiazines, butyrophenones, thioxanthenes, metoclopramide)

May reduce efficacy of apomorphine

Phenothiazines, butyrophenones, thioxanthenes: Weigh benefits and risks of concomitant therapy with these dopamine-receptor antagonists for the treatment of major psychosis

Levodopa/carbidopa

Potential additive neurologic effect; used to therapeutic effect

Pharmacokinetic interaction unlikely

Nitroglycerin

Additive hypotensive effects demonstrated

Monitor BP; patients should lie down before and after taking sublingual nitroglycerin

Apomorphine Pharmacokinetics

Absorption

Bioavailability

Bioavailability following sub-Q administration is 100%. Peak plasma concentrations achieved in 10–60 minutes.

Onset

Following sub-Q injection, peak concentrations usually reached in 10–60 minutes (peak CSF concentrations occur within 10–20 minutes).

Following initiation of continuous infusion, steady-state concentrations reached within approximately 2 hours; can be reduced by administering an extra dose.

Special Populations

In individuals with moderate hepatic impairment receiving a single sub-Q dose of apomorphine, peak plasma concentrations and AUC were increased 25 and 10%, respectively, compared with healthy individuals.

In patients with moderate renal impairment receiving a single sub-Q dose of apomorphine, peak plasma concentrations and AUC were increased 50 and 16%, respectively, compared with healthy individuals. Time to peak plasma concentrations was not affected by renal status.

Distribution

Extent

Maximum CSF concentrations are <10% of peak plasma concentrations.

Plasma Protein Binding

89%.

Elimination

Metabolism

Primarily via conjugation.

Within 30 minutes of administration of a sub-Q dose, only 8.3% of plasma radioactivity was apomorphine; 83% was apomorphine sulfate, 3.5% was apomorphine glucuronide, and 1% was nor-apomorphine glucuronide.

Elimination Route

Following a sub-Q dose, 86% recovered in urine within 48 hours (as apomorphine sulfate, apomorphine glucuronide, and nor-apomorphine glucuronide) and 4.6% in feces over 144 hours (as apomorphine sulfate, apomorphine glucuronide, and apomorphine).

Half-life

40 minutes.

Special Populations

No pharmacokinetic differences observed based on age, gender, weight, duration of Parkinson disease, levodopa dose, or duration of therapy.

Stability

Storage

Parenteral

Sub-Q Injection (Apokyn)

25°C (excursions permitted between 15–30°C).

Injection, for Sub-Q Infusion (Onapgo)

20–25°C (excursions permitted between 15–30°C).

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Apomorphine Hydrochloride (Hemihydrate)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for sub-Q infusion

4.9 mg/mL

Onapgo (available as cartridges)

Injection, for sub-Q injection

10 mg/mL

Apokyn (available as cartridges for use with a reusable pen injector device)

MDD US Operations

Apokyn NXT (available as disposable prefilled injection pens)

AHFS DI Essentials™. © Copyright 2025, Selected Revisions July 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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