Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Cartridge, Subcutaneous, as hydrochloride:
Apokyn: 30 mg/3 mL (3 mL) [contains benzyl alcohol, sodium metabisulfite]
Pharmacology
Mechanism of Action
Stimulates postsynaptic D2-type receptors within the caudate putamen in the brain.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: Mean: 218 L
Metabolism
Not established; potential routes of metabolism include sulfation, N-demethylation, glucuronidation, and oxidation; catechol-O methyltransferase and nonenzymatic oxidation
Onset of Action
SubQ: Rapid
Time to Peak
Plasma: 10 to 60 minutes
Half-Life Elimination
Terminal: ~40 minutes
Use in Specific Populations
Special Populations: Renal Function Impairment
Cmax was increased by 50% in patients with moderate renal impairment.
Special Populations: Hepatic Function Impairment
Cmax was increased by 25% in patients with moderate hepatic impairment.
Use: Labeled Indications
Parkinson disease: Treatment of hypomobility “off” episodes with advanced Parkinson disease
Contraindications
Hypersensitivity to apomorphine, any component of the formulation, or to a sulfite; concomitant use with 5-HT3 antagonists
Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with antihypertensives or vasodilators; severe hepatic or renal impairment
Dosage and Administration
Dosing: Adult
Begin antiemetic therapy (eg, trimethobenzamide) 3 days prior to initiation and continue only as long as necessary, and generally no longer than 2 months, due to increased risk of adverse events; apomorphine is intended to be used as adjunctive therapy with other anti-Parkinson agents.
Parkinson disease, “off” episode: SubQ: Initial test dose 0.2 mL (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: 0.2 mL (2 mg) as needed; may increase dose in 0.1 mL (1 mg) increments every few days; maximum dose: 0.6 mL (6 mg)
If patient tolerates but does not respond to 0.2 mL (2 mg) test dose: Second test dose: 0.4 mL (4 mg)
If patient tolerates and responds to 0.4 mL (4 mg) test dose: Starting dose: 0.3 mL (3 mg), as needed for “off” episodes; may increase dose in 0.1 mL (1 mg) increments every few days; maximum dose: 0.6 mL (6 mg)
If patient does not tolerate 0.4 mL (4 mg) test dose: Third test dose: 0.3 mL (3 mg)
If patient tolerates 0.3 mL (3 mg) test dose: Starting dose: 0.2 mL (2 mg) as needed for “off” episodes; after a few days, may increase dose up to 0.3 mL (3 mg). Medically supervise for any subsequent dose increases >0.3 mL (3 mg).
If therapy is interrupted for >1 week, restart at 0.2 mL (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 (and after 60 minutes, if there is significant hypotension at 60 minutes). 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, single doses >0.6 mL (6 mg), and with total daily doses >2 mL (20 mg).
Dosing: Geriatric
Refer to adult dosing.
Administration
SubQ: For subcutaneous administration only; do not administer IV (thrombus formation or pulmonary embolism may occur due to IV crystallization). Administer in abdomen, upper arm, or upper leg; change site with each injection. Three mL cartridges are used with a manual, reusable, multidose injector pen. Injector pen can deliver up to 1 mL (10 mg) in 0.02 mL (0.2 mg) increments.
Storage
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Drug Interactions
Alcohol (Ethyl): May enhance the hypotensive effect of Apomorphine. Avoid combination
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alizapride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amisulpride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride. Avoid combination
Antiemetics (5HT3 Antagonists): May enhance the hypotensive effect of Apomorphine. Avoid combination
Antipsychotic Agents (First Generation [Typical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of anti-Parkinson agents. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bromopride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy
Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination
BuPROPion: Anti-Parkinson Agents (Dopamine Agonist) may enhance the adverse/toxic effect of BuPROPion. Monitor therapy
COMT Inhibitors: May decrease the metabolism of COMT Substrates. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Methylphenidate: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy
Metoclopramide: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroglycerin: May enhance the hypotensive effect of Apomorphine. Management: Patients taking apomorphine should lie down before and after taking sublingual nitroglycerin. Monitor blood pressure for hypotension and orthostatic hypotension when these agents are combined. Consider therapy modification
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Solriamfetol: Anti-Parkinson Agents (Dopamine Agonist) may enhance the hypertensive effect of Solriamfetol. Monitor therapy
Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination
Adverse Reactions
Note: Frequency not always defined.
>10%:
Cardiovascular: Angina pectoris (15%), chest pain (15%), chest pressure (15%)
Central nervous system: Drowsiness (35%), dizziness (20%), orthostatic hypotension (20%)
Gastrointestinal: Nausea (30%), vomiting (30%)
Neuromuscular & skeletal: Dyskinesia (24% to 35%), falling (30%)
Respiratory: Yawning (40%), rhinorrhea (20%)
1% to 10%:
Cardiovascular: Edema (10%), vasodilation (3%), hypotension (2%), syncope (2%), cardiac failure
Central nervous system: Confusion (10%), hallucinations (10%), anxiety, depression, fatigue, headache, insomnia, pain
Dermatologic: Bruise
Endocrine & metabolic: Dehydration
Gastrointestinal: Constipation, diarrhea
Local: Injection site reaction
Neuromuscular & skeletal: Arthralgia, weakness
Miscellaneous: Diaphoresis
<1%, postmarketing, and/or case reports: Aggressive behavior, agitation, cardiac arrest, confusion, hemolytic anemia (combination therapy, Colosimo 1994; Frankel 1990), impulse control disorder, impulsivity, increased libido, myocardial infarction, panniculitis (focal), paranoia, priapism, psychosis (acute)
Warnings/Precautions
Concerns related to adverse effects:
- GI effects: Severe nausea and vomiting may occur. Pretreatment with antiemetic (eg, trimethobenzamide) is necessary and should be started 3 days prior to initiation of therapy and continued only as long as necessary to control nausea/vomiting, and generally no longer than 2 months. Trimethobenzamide increases the risk of somnolence, dizziness, and falls. Avoid use of antidopaminergic antiemetic agents (eg, promethazine, prochlorperazine, chlorpromazine, metoclopramide, haloperidol).
- Hallucinations/psychosis: May cause hallucinations or psychotic-like behavior or thoughts (eg, paranoia, delusions, confusion, disorientation, aggression, agitation, delirium) which may be severe; avoid in patients with major psychotic disorders.
- Hypersensitivity: Hypersensitivity reactions (including angioedema or anaphylaxis) to apomorphine or its sulfite component may occur. If a hypersensitivity reaction to apomorphine occurs, discontinue and do not restart.
- Impulse control disorders: Has been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), binge eating, and/or other intense urges. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
- Orthostatic hypotension/syncope: May cause orthostatic hypotension, especially during dose escalation, and syncope. Parkinson disease patients appear to have an impaired capacity to respond to a postural challenge. The hypotensive effects of apomorphine are exacerbated by concomitant ethanol consumption and sublingual nitroglycerin use. Additional risk factors for hypotension may include concomitant use of other antihypertensive drugs or vasodilators or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Carefully monitor for signs and symptoms of postural hypotension (especially during dose escalation). Avoid ethanol during therapy.
- Pleural/retroperitoneal fibrosis: Ergot-derived dopamine agonists have also been associated with fibrotic complications (eg, retroperitoneal fibrosis, pleural thickening, cardiac valvulopathy, and pulmonary infiltrates); monitor closely for signs and symptoms of fibrosis; effects may or may not be reversible.
- Priapism: Has been reported; severe priapism may require medical attention.
- Somnolence: Somnolence and falling asleep while engaging in activities of daily living, without prior warning signs, has been reported. Monitor for daytime somnolence or preexisting sleep disorder; caution with concomitant sedating medication; discontinue if significant daytime sleepiness or episodes of falling asleep occur. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents. Effects with other sedative drugs or ethanol may be potentiated.
Disease-related concerns:
- Cardiovascular disease: Use with caution in patients with cardiovascular disease; hypotension may cause coronary ischemia.
- Cerebrovascular disease: Use with caution in patients with cerebrovascular disease; hypotension may cause cerebral ischemia.
- Dyskinesias: Use with caution in patients with preexisting dyskinesias; may be exacerbated.
- Hepatic impairment: Use with caution in patients with hepatic impairment.
- Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Adverse effects (confusion and hallucinations), some serious, are reported more frequently in patients ≥65 years; use with caution.
- Patients at risk for torsades de pointes: Use with caution in patients with risk factors for torsades de pointes (hypokalemia, hypomagnesemia, bradycardia, concurrent use of drugs that prolong QTc, or genetic predisposition).
Dosage form specific issues:
- Benzyl alcohol: Injection may contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.
- Metabisulfite: Contains metabisulfite, which may cause hypersensitivity reactions. Sensitivity to sulfites is more common in patients with asthma and may cause hypersensitivity reactions (including anaphylaxis and life-threatening asthma exacerbations).
Other warnings/precautions:
- Abuse: Rare cases of abuse have been reported.
- Appropriate administration: Do not give intravenously; thrombus formation or pulmonary embolism may occur.
- Discontinuation of therapy: Dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome (eg, hyperpyrexia, confusion) on abrupt withdrawal or significant dosage reduction after long-term use.
- Falling: Patients with Parkinson disease are at risk of falling; apomorphine may increase this risk.
Monitoring Parameters
Supine and standing blood pressure and pulse predose and 20, 40, and 60 minutes postdose with each test dose; signs and symptoms of orthostatic hypotension; drowsiness or sleepiness; mental status and behavioral changes; periodic skin examinations.
Pregnancy
Pregnancy Considerations
Adverse events have been observed in animal reproduction studies.
Patient Education
What is this drug used for?
- It is used to treat "off" episodes (when a dose wears off) in people with Parkinson's disease.
Frequently reported side effects of this drug
- Nausea
- Vomiting
- Headache
- Runny nose
- Yawning
- Injection site irritation
- Joint pain
- Trouble sleeping
- Back pain
- Weakness
- Constipation
- Diarrhea
- Painful extremities
- Fatigue
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
- Dehydration like dry skin, dry mouth, dry eyes, increased thirst, fast heartbeat, dizziness, fast breathing, or confusion
- Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes
- Severe dizziness
- Passing out
- Confusion
- Uncontrollable urges
- Mood changes
- Behavioral changes
- Abnormal movements
- Sensing things that seem real but are not
- Sweating a lot
- Abnormal heartbeat
- Shortness of breath
- Excessive weight gain
- Swelling of arms or legs
- Chest pain
- Bruising
- Skin discoloration
- Narcolepsy
- Fast heartbeat
- Erection that lasts more than 4 hours
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
