Apomorphine Hydrochloride

Name: Apomorphine Hydrochloride

Cautions for Apomorphine Hydrochloride


  • Concomitant use with selective 5-HT3 receptor antagonists.1 (See Specific Drugs under Interactions.)

  • Known hypersensitivity to apomorphine hydrochloride or any ingredient in the formulation (e.g., sodium metabisulfite).1




Thrombus formation and pulmonary embolism reported following IV administration.1 14 Do not administer IV.1

Nausea and Vomiting

Severe nausea and vomiting expected; concomitant use of an antiemetic recommended.1 Trimethobenzamide was used in clinical studies; other antiemetics are contraindicated (i.e., 5-HT3 receptor antagonists) or not recommended (i.e., dopamine-receptor antagonists).1 (See General under Dosage and Administration and Specific Drugs under Interactions.)

Symptomatic Hypotension

Risk of orthostatic hypotension, hypotension, and/or syncope.1

Whether hypotension contributes to other adverse events (e.g., falls) unknown.1

Prolongation of QT Interval

Possible prolonged QT interval.1 Doses of ≤6 mg are associated with minimal increases in QTc interval.1

Use with caution in patients with congenital or known QT interval prolongation, in those with clinically important bradycardia, in those with uncorrected electrolyte disorders (e.g., hypokalemia, hypomagnesemia), and in those receiving drugs known to prolong the QTc interval.1

Nervous System and Muscular Effects

Risk of falls; may be due to postural and autonomic instability associated with Parkinson’s disease.1 Risk may be increased due to effect of apomorphine on BP and mobility.1

Symptom complex resembling neuroleptic malignant syndrome reported in association with abrupt withdrawal, dosage lowering, or changes in antiparkinsonian therapy.1


Potential for hallucinations.1

Sudden Sleep Episodes

Falling asleep while engaged in activities of daily living has been reported in patients receiving apomorphine.1 While somnolence occurs frequently in patients receiving apomorphine, these patients perceived no warning signs and believed they were alert immediately prior to the event.1 Many experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history.1

Continually reassess patients for drowsiness or sleepiness.1 Patients may not acknowledge drowsiness or sleepiness until directly questioned about such adverse effects during specific activities.1 Ask patients about any factors that may increase the risk of somnolence (e.g., concomitant sedating drugs, the presence of sleep disorders).1

Apomorphine generally should be discontinued if a patient develops clinically important daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating).1 If the drug is continued, the patients should be advised not to drive and to avoid other potentially dangerous activities.1 Insufficient information to establish whether dosage reduction will eliminate episodes of falling asleep while engaged in activities of daily living.1

Cardiovascular Effects

Risk of angina, MI, cardiac arrest, and/or sudden death.1 Angina and MI occurred in some patients within 2 hours of apomorphine dosing; cardiac arrest and sudden death occurred at times unrelated to dosing.1

May exacerbate coronary and cerebral ischemia due to effects of apomorphine on BP.1 Use with caution in patients with cardiovascular and cerebrovascular disease.1

If signs and symptoms of coronary or cerebral ischemia occur, reevaluate continued use of the drug.1

Injection Site Reactions

Injection site reactions (bruising, granuloma, pruritus) reported.1

Abuse and Misuse Potential

Escalation of apomorphine dose beyond the prescribed frequency reported in patients trying to avoid all symptoms of an “off” episode.1 Hypersexuality and increased erections can occur due to abuse of apomorphine.1 11

Monitor patients for excessive use (e.g., use out of proportion to motor signs).1

Sensitivity Reactions

Sulfite Sensitivity

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.1

General Precautions


May cause or exacerbate dyskinesias.1

Cardiorespiratory Fibrosis and 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.1 Possible that nonergot-derived drugs that increase dopaminergic activity (e.g., apomorphine) may induce similar changes.1


Possible prolonged painful erections.1

Ocular Effects

Retinal degeneration reported in albino rats given dopamine agonists for prolonged periods (usually 2-year carcinogenicity studies); similar changes not observed in albino mice, rats, or monkeys.1 Clinical importance in humans not established; however, effect cannot be disregarded because the presumed mechanism of action may apply to all vertebrates.1

Specific Populations


Category C.1


Not known whether apomorphine is distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy for hypermobility episodes not established.1

Geriatric Use

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.1

Hepatic Impairment

Systemic exposure increased in patients with mild to moderate hepatic impairment; use with caution.1 Not studied in patients with severe hepatic impairment.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage adjustment necessary in patients with mild to moderate renal impairment.1 Not studied in patients with severe renal impairment or those undergoing dialysis.1 13 (See Renal Impairment under Dosage and Administration and Special Populations under Pharmacokinetics.)

Common Adverse Effects

Yawning, dyskinesias, nausea and/or vomiting, somnolence, dizziness, rhinorrhea, hallucinations, edema, chest pain, increased sweating, flushing, and pallor.1

Interactions for Apomorphine Hydrochloride

Drugs That Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation).1 (See Prolongation of QT Interval under Cautions.)

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interaction unlikely.1

Specific Drugs




Antihypertensive agents and vasodilators

Potential pharmacologic interaction (additive hypotensive effects)1

Concomitant use associated with increased incidence of hypotension, MI, pneumonia, serious falls, bone and joint injuries1


Catecho-O-methyltransferase (COMT) inhibitors

Pharmacokinetic interaction unlikely1 7

CNS depressants

Alcohol: Potential pharmacologic interaction (additive sedative and hypotensive effects)1

CNS depressants: Potential pharmacologic interaction (additive sedative effects)1

5-HT3 receptor antagonists (dolasetron, granisetron, ondansetron, palonosetron)

Potential pharmacologic interaction (profound hypotension and loss of consciousness)1

Concomitant use contraindicated1

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

Potential pharmacologic interaction (reduced efficacy of apomorphine)1

Phenothiazines, butyrophenones, thioxanthenes: Weigh benefits and risks of therapy with a dopamine agonist in patients receiving one of these dopamine-receptor antagonists for the treatment of major psychosis1


Potential pharmacologic interaction (additive neurologic effect; used to therapeutic effect)1

Pharmacokinetic interaction unlikely1


  • Exhibits a higher affinity for dopamine D4 receptors in vitro than for dopamine D2, D3, or D5 receptors.1

  • Appears to act by stimulating postsynaptic dopamine D2 receptors in the caudate-putamen.1

Advice to Patients

  • Importance of taking apomorphine only as prescribed.1

  • Importance of instructing patient and/or caregiver regarding proper dosage and administration of apomorphine, including detailed instruction in the use of the dosing pen, in patients whose clinician has determined that the drug can safely and effectively be self-administered in the patient’s home by the patient, family member, or other responsible individual.1

  • Advise that hallucinations, hypotension, and other adverse effects (e.g., injection site reactions) may occur.1

  • Risk of orthostatic hypotension with or without dizziness, nausea, syncope, or sweating.1 Advise not to rise rapidly after prolonged sitting or lying down, especially during the first few weeks of therapy.1

  • Risk of somnolence and the possibility of falling asleep during activities of daily living; avoid driving or operating machinery until effects on the individual are known.1

  • Importance of informing clinicians if increased somnolence or new episodes of falling asleep during activities of daily living (e.g., watching television, riding in a car as a passenger) occur at any time during apomorphine therapy.1 Patients should not drive or participate in potentially dangerous activities until their clinician has been notified.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (especially selective 5-HT3 receptor antagonists) and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


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)


Dosage Forms


Brand Names



Injection, for sub-Q use only

10 mg/mL

Apokyn (with sodium metabisulfite; benzyl alcohol 0.5% in cartridges)