Pronunciation (a poe MOR feen)

U.S. Brand Names ApokynTM

Synonyms Apomorphine Hydrochloride; Apomorphine Hydrochloride Hemihydrate

Therapeutic Category
Anti-Parkinson's Agent, Dopamine Agonist
Use Treatment of hypomobility, off episodes with Parkinson's disease

Pregnancy Risk Factor C

Pregnancy Implications Reproduction studies have not been conducted; use only if clearly needed.

Contraindications Hypersensitivity to apomorphine or any component of the formulation; concomitant use with 5HT3 antagonists; intravenous administration

Warnings/Precautions May cause orthostatic hypotension especially during dosage escalation; use extreme caution, especially in patients on antihypertensives and/or vasodilators. Orthostasis peaks 20 minutes after dosing and lasts at least 90 minutes. If patient develops clinically-significant orthostatic hypotension with test dose, then apomorphine should not be used. Pretreatment with antiemetic is necessary; avoid pretreatment with antidopaminergic and antiserotonin antiemetic agents. (antiemetic experience is greatest with trimethobenzamide). Monitor patients for drowsiness; patients may not be aware of drowsiness and may fall asleep without warning. Use caution in patients with risk factors for torsade de pointes (hypokalemia, hypomagnesemia, bradycardia, concurrent use of drugs that prolong QTc, or genetic predisposition).
Use caution in cardiovascular and cerebrovascular disease; hypotension may cause coronary and/or cerebral ischemia. Use caution in patients with hepatic or renal dysfunction. Neuroleptic malignant syndrome has been reported with other dopamine agonists. Retinal degeneration has been observed in animal studies when using dopamine agonists for prolonged periods. Rare cases of abuse have been reported. Contains metabisulfite which may cause allergic reactions in some individuals. Safety and efficacy in pediatric patients have not been established.

Adverse Reactions

>10%: Cardiovascular: Chest pain/pressure or angina (15%)
Central nervous system: Drowsiness or somnolence (35%), dizziness or orthostatic hypotension (20%)
Gastrointestinal: Nausea and/or vomiting (30%)
Neuromuscular & skeletal: Falls (30%), dyskinesias (24% to 35%)
Respiratory: Yawning (40%), rhinorrhea (20%)

1% to 10%: Cardiovascular: Edema (10%), vasodilation (3%), hypotension (2%), syncope (2%), congestive heart failure
Central nervous system: Hallucinations or confusion (10%), anxiety, depression, fatigue, headache, insomnia, pain
Dermatologic: Bruising
Endocrine & metabolic: Dehydration
Gastrointestinal: Constipation, diarrhea
Local: Injection site reactions
Neuromuscular & skeletal: Arthralgias, weakness
Miscellaneous: Diaphoresis increased?
<1%: Angina, cardiac arrest, focal panniculitis, libido increased, myocardial infarction, priapism, psychosexual stimulation, skin nodules, sudden death

Overdose/Toxicology An accidental overdose of 25 mg SubQ was reported resulting in nausea, loss of consciousness, bradycardia, and hypotension. Treatment should be supportive and symptomatic.

Drug Interactions Substrate (minor) of CYP1A2, 3A4, 2C19; Inhibits CYP1A2 (weak), 3A (weak), 2C19 (weak)

Antihypertensive medications and vasodilators: Concurrent use increased the risk of hypotension, myocardial infarction, serious falls and bone and joint injuries. May be related to increased hypotension.

Anti-parkinson's agents (dopamine agonist): Antipsychotics (typical) may antagonize the dopaminergic action of dopamine agonist. Avoid concurrent use.

5HT3 antagonists: Use with ondansetron resulted in severe hypotension and loss of consciousness. Concurrent use contraindicated.

Levodopa: Threshold levodopa concentration necessary to improve motor response was significantly reduced, leading to an increased duration of effect.

QTc-prolonging agents: Doses of 6 mg or less are associated with minimal increases in QTc (mean increase of 3 msec at 20 and 90 minutes). A couple of patients exhibited large QTc increments (> 60 msec from predose). Use caution with concurrent use.

Food Interactions

Ethanol: Caution with ethanol consumption; may increase risk of hypotension.

Mechanism of Action Stimulates postsynaptic D2-type receptors within the caudate-putamen in the brain.

Pharmacodynamics/Kinetics

Onset: SubQ: Rapid

Duration: Vd (mean): 218 L

Metabolism: Not established; potential routes of metabolism include sulfation, N-demethylation, glucuronidation, and oxidation; catechol-O methyltranferase and nonenzymatic oxidation. CYP isoenzymes do not appear to play a significant role.

Half-life elimination: Terminal: 40 minutes

Time to peak, plasma: Improved motor scores: 20 minutes

Excretion: Urine 93% (as metabolites); feces 16%

Usual Dosage SubQ: Adults: Begin antiemetic therapy 3 days prior to initiation and continue for 2 months before reassessing need.

Parkinson's disease, off episode: Initial test dose 2 mg, medical supervision required; see Note. Subsequent dosing is based on both tolerance and response to initial test dose. If patient tolerates test dose and responds: Starting dose: 2 mg as needed; may increase dose in 1 mg increments every few days; maximum dose: 6 mg
If patient tolerates but does not respond to 2 mg test dose: Second test dose: 4 mg
If patient tolerates and responds to 4 mg test dose: Starting dose: 2 mg, as needed for off episodes; may increase dose in 1 mg increments every few days; maximum dose 6 mg
If patient does not tolerate 4 mg test dose: Third test dose: 3 mg
If patient tolerates 3 mg test dose: Starting dose: 2 mg as needed for off episodes; may increase dose in 1 mg increments to a maximum of 3 mg

If therapy is interrupted for >1 week, restart at 2 mg and gradually titrate dose.

Note: Medical supervision is required for all test doses with standing and supine blood pressure monitoring predose and 20-, 40-, and 60 minutes postdose. If subsequent test doses are required, wait >2 hours before another test dose is given; next test dose should be timed with another off episode. If a single dose is ineffective for a particular off episode, then a second dose should not be given. The average dosing frequency was 3 times/day in the development program with limited experience in dosing >5 times/day and with total daily doses >20 mg.

Dosage adjustment in renal impairment:Mild-to-moderate impairment: Reduce test dose and starting dose: 1 mg
Severe impairment: Has not been studied

Dosage adjustment in hepatic impairment:Mild-to-moderate: Use caution
Severe impairment: Has not been studied

Dietary Considerations Avoid ethanol consumption.

Administration SubQ: Initiate antiemetic 3 days before test dose of apomorphine and continue for 2 months (if patient to be treated) before reassessment. Injector pen can deliver doses up to 1 mL in 0.02 mL increments. Do not give intravenously; thrombus formation or pulmonary embolism may occur.

Monitoring Parameters Each test dose: Supine and standing blood pressure predose and 20-, 40-, and 60 minutes postdose; drowsiness

Dosage Forms Injection, solution, as hydrochloride: 10 mg/mL (2 mL) [contains sodium metabisulfite]; (3 mL) [multidose cartridge; contains sodium metabisulfite and benzyl alcohol]