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Apomorphine

Medically reviewed by Drugs.com. Last updated on Sep 5, 2020.

Pronunciation

(a poe MOR feen)

Index Terms

  • Apomorphine Hydrochloride
  • Apomorphine Hydrochloride Hemihydrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Film, Sublingual, as hydrochloride:

Kynmobi: 10 mg (30 ea); 15 mg (30 ea); 20 mg (30 ea); 25 mg (30 ea); 30 mg (30 ea) [contains brilliant blue fcf (fd&c blue #1), edetate (edta) disodium dihydrate, levomenthol, sodium metabisulfite]

Kit, Sublingual, as hydrochloride:

Kynmobi Titration Kit: 10 mg (2s), 15 mg (2s), 20 mg (2s), 25 mg (2s), 30 mg (2s) [contains brilliant blue fcf (fd&c blue #1), edetate (edta) disodium dihydrate, levomenthol, sodium metabisulfite]

Solution Cartridge, Subcutaneous, as hydrochloride:

Apokyn: 30 mg/3 mL (3 mL) [contains benzyl alcohol, sodium metabisulfite]

Brand Names: U.S.

  • Apokyn
  • Kynmobi
  • Kynmobi Titration Kit

Pharmacologic Category

  • Anti-Parkinson Agent, Dopamine Agonist

Pharmacology

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

Distribution

Vd: Sublingual: 3,630 L; SubQ: 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: Sublingual: 0.5 to 1 hour; SubQ: 10 to 60 minutes.

Half-Life Elimination

Terminal: Sublingual: ~1.7 hours (range: 0.8 to 3 hours); SubQ: ~40 minutes.

Special Populations: Renal Function Impairment

SubQ: Cmax was increased by 50% in patients with moderate renal impairment.

Special Populations: Hepatic Function Impairment

SubQ: Cmax was increased by 25% in patients with moderate hepatic impairment.

Use: Labeled Indications

Parkinson disease:

Sublingual film: Treatment of acute, intermittent "off" episodes in patients with Parkinson disease.

SubQ: Treatment of hypomobility "off" episodes in patients 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.

Dosing: Adult

Note: 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:

Sublingual film: Note: Determine starting dose when patient is in an "off" state and in a setting where a health care provider can monitor blood pressure and pulse. In clinical trials, to achieve an "off" state, the morning dose of carbidopa/levodopa (or any adjunctive Parkinson disease medications) was withheld and any Parkinson disease medications were avoided after midnight the night before. If response insufficient but dose tolerated, patient should resume usual Parkinson medications and return to health care provider in an "off" state to reinitiate at the next dose increment.

Initial: 10 mg as needed at intervals ≥2 hours for "off episodes" up to a maximum of 5 doses per day; may increase dose in 5 mg increments every 3 days based on response and tolerability up to a maximum single dose of 30 mg at intervals ≥2 hours and a maximum of 5 doses per day.

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).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Use with caution; adverse effects (confusion and hallucinations), some serious, are reported more frequently in patients ≥65 years of age. Refer to adult dosing.

Administration

Sublingual film: Do not remove from pouch until immediately before use. Drink water to moisten mouth, then place film under the tongue and allow to dissolve (~3 minutes). Do not talk or swallow saliva while dissolving because this can impact absorption. Administer whole; do not cut, chew, or swallow.

SubQ: For SubQ 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 20°C to 25°C (68°F to 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 used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Consider therapy modification

Amisulpride (Injection): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Amisulpride (Oral): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Amisulpride (Oral). 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. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). 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

Brivudine [INT]: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Specifically, the risk of chorea may be increased. 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 increase the serum concentration 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

Methotrimeprazine: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Methotrimeprazine. Avoid combination

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). Avoid combination

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: May enhance the adverse/toxic effect of Anti-Parkinson Agents (Dopamine Agonist). Monitor therapy

Sulpiride: May diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Angina pectoris (≤15%), chest pain (≤15%), chest pressure (≤15%), hypotension (≤11%), orthostatic hypotension (diastolic or systolic: ≤43%; can be severe), syncope (≤11%)

Gastrointestinal: Nausea (≤30%; can be severe nausea; can occur with antiemetic pretreatment), oral paresthesia (sublingual film: ≤13%), vomiting (≤30%; can be severe vomiting; can occur with antiemetic pretreatment)

Local: Injection site reaction (5% to 26%; bruising at injection site [16%], injection site granuloma [4%], injection site pruritus [2%])

Nervous system: Dizziness (≤20%), drowsiness (11% to 35%), falling (4% to 30%), hallucination (≤14%), yawning (40%)

Neuromuscular & skeletal: Dyskinesia (24% to 35%)

Respiratory: Oropharyngeal edema (sublingual film: 1% to 15%), oropharyngeal pain (sublingual film: ≤13%), rhinorrhea (6% to 20%)

1% to 10%:

Cardiovascular: Acute myocardial infarction (≤4%), cardiac failure (≥5%), edema (≤10%), presyncope (≤4%)

Dermatologic: Diaphoresis (≥5%), ecchymoses (≥5%), facial swelling (≤6%), hyperhidrosis (6%), urticaria (≤6%)

Endocrine & metabolic: Dehydration (≥5%)

Gastrointestinal: Constipation (≥5%), diarrhea (≥5%), oral mucosal erythema (sublingual film: 7%), oral mucosa ulcer (sublingual film: ≤7%), stomatitis (sublingual film: ≤7%), xerostomia (sublingual film: 1% to 6%)

Genitourinary: Urinary tract infection (≥5%)

Hypersensitivity: Hypersensitivity reaction (≤6%)

Nervous system: Anxiety (≥5%), confusion (≤10%), delusion (≤6%), depression (≥5%), disorientation (≤6%), exacerbation of Parkinson’s disease (≥5%), fatigue (3% to 7%), headache (5% to 8%), insomnia (≥5%)

Neuromuscular & skeletal: Arthralgia (≥5%), asthenia (≥5%), back pain (≥5%), limb pain (≥5%), swelling of extremities (≤10%)

Respiratory: Dyspnea (≥5%), pneumonia (≥5%)

Miscellaneous: Laceration (sublingual film: 1% to 6%)

<1%: Genitourinary: Priapism

Postmarketing:

Cardiovascular: Prolonged QT interval on ECG (dose related)

Hematologic & oncologic: Hemolytic anemia (combination therapy) (Colosimo 1994; Frankel 1990)

Nervous system: Aggressive behavior, agitation, behavioral changes, impulse control disorder (including pathological gambling, increased libido), mental status changes, paranoid ideation, psychosis (acute), sudden onset of sleep

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; avoid use in severe hepatic impairment (sublingual film).

• Renal impairment: Use with caution in patients with renal impairment; avoid use in severe renal impairment (sublingual film).

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).

• Sublingual film: Mild to moderate oral mucosal irritation (ulceration, stomatitis, pain, paresthesia) has occurred; usually resolved after discontinuation (rechallenge is not recommended).

Other warnings/precautions:

• Abuse: Rare cases of abuse have been reported.

• Appropriate administration: Do not give SubQ formulation IV; 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 BP and pulse (for SubQ, monitor predose and 20, 40, and 60 minutes post dose with each test dose); signs and symptoms of orthostatic hypotension; drowsiness or sleepiness; mental status and behavioral changes.

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.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Headache

• Runny nose

• Loss of strength and energy

• Yawning

• Injection site irritation

• Joint pain

• Trouble sleeping

• Back pain

• Constipation

• Diarrhea

• Painful extremities

• Mouth irritation

• Mouth sores

• Numbness or tingling

• Dry mouth

• Fatigue

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• 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

• Change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes

• Neuroleptic malignant syndrome like fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot

• Flushing

• 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

• Vision changes

• Chest pain

• Bruising

• Skin discoloration

• Narcolepsy

• Fast heartbeat

• Erection that lasts more than 4 hours

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.