Apomorphine

Apomorphine is a prescription medication used to treat the symptoms of Parkinson’s Disease. 

• Apomorphine is available under the following different brand names: Apokyn, Kynmobi

Common side effects of Apomorphine include:

• Swelling,
• Confusion,
• Yawning,
• Runny nose, and
• Itching, bruising or swelling where the medicine was injected

Serious side effects of Apomorphine include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Ongoing nausea,
• Vomiting,
• Twitching,
• Uncontrollable movements of the eyes, lips, tongue, face, arms, or legs,
• Worsening of Parkinson’s symptoms,
• Chest pain,
• Fast or slow heartbeats,
• Shortness of breath,
• Lightheadedness,
• Daytime sleepiness,
• Drowsiness,
• Confusion,
• Hallucinations,
• Unusual thoughts or behavior,
• New or worsening cough,
• Fever,
• Pain while breathing,
• Shortness of breath while lying down,
• Unexplained pain in the stomach, back, or legs,
• Swelling in your lower legs,
• Penis erection that is painful or lasts 4 hours or longer,
• Increased sexual urges,
• Unusual urges to gamble, and
• Other intense urges

Rare side effects of Apomorphine include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Solution for SC injection

• 10 mg/mL (30mg/3mL pen injector) (Apokyn, generic)

SL film (Kynmobi)

• 10 mg
• 15 mg
• 20 mg
• 25 mg
• 30 mg

Parkinson Disease

Adult dosage

Subcutaneous (Apokyn)

• Initial: 2 mg (0.2 mL) Subcutaneous as needed
• Also see Administration for details regarding test dose
• Titrate based on effectiveness and tolerance; not to exceed 6 mg (0.6 mL)/dose
• Average frequency of dosing in clinical trials was Three times a day
• Limited experience with single doses above 6 mg, dosing above 5 times per day, or with total daily doses above 20 mg

Sublingual (Kynmobi)

• Initial: 10 mg SL as needed; not to exceed 5 doses/day
• Separate doses by at least 2 hours; if a single dose is ineffective for a particular “off” episode, a second dose should not be given for that “off” episode
• Maximum single dose: 30 mg
• Premedication
  • High incidence of nausea and vomiting with treatment; initiate an antiemetic (.g, trimethobenzamide 300 mg Three times a day) 3 days before the initial apomorphine dose
  • Treatment with trimethobenzamide should only be continued if necessary to control nausea and vomiting, and generally no longer than 2 months after initiation of treatment
  • Trimethobenzamide increases the incidence of somnolence, dizziness, and falls
  • Contraindicated with 5HT3 antagonist antiemetics (. g, ondansetron, granisetron, dolasetron, palonosetron) owing to profound hypotension and loss of consciousness when coadministered

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Apomorphine has severe interactions with the following drugs
  • aldosterone
  • cisapride
  • dolasetron
  • dronedarone
  • granisetron
  • netupitant/palonosetron
  • ondansetron
  • palonosetron
  • thioridazine
• Apomorphine has serious interactions with at least 92 other drugs.
• Apomorphine has moderate interactions with at least 200 other drugs.
• Apomorphine has minor interactions with the following drugs
  • eucalyptus
  • flecainide
  • ruxolitinib topical
  • sage
  • trimethobenzamide

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity, including angioedema or anaphylaxis
• Sulfite/sulfur allergies (Apokyn contains sodium metabisulfite)
• Do not use 5-HT3 antagonists, including antiemetics (. g, granisetron, dolasetron, ondansetron, palonosetron) – the risk of profound hypotension and loss of consciousness

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Apomorphine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Apomorphine?”

Cautions

• Subcutaneous use only; thrombus formation and pulmonary embolism have followed IV administration owing to crystallization of apomorphine
• Severe nausea and vomiting occur at recommended doses; because of this, pretreat or treat with trimethobenzamide; trimethobenzamide reduces the incidence of nausea and vomiting during the first 4 weeks of therapy; patients treated with trimethobenzamide experience a greater incidence of somnolence, dizziness and falls; the benefit of treatment with trimethobenzamide must be balanced with risk for those adverse events, and treatment with trimethobenzamide should only be continued as long as necessary to control nausea and vomiting, which should generally be no longer than 2 months
• Closely monitor patients with mild and moderate hepatic impairment
• Falling asleep during activities of daily living and daytime somnolence may occur
• Oral mucosal irritation reported with SL product
• Syncope and hypotension/orthostatic hypotension may occur
• Falls may occur, or increase owing to underlying postural instability, possible autonomic instability, and syncope caused by low blood pressure
• May cause hallucinations and psychotic-like behavior
• May cause dyskinesia or exacerbate pre-existing dyskinesia (reported with SC administration)
• May cause problems with impulse control and impulsive behaviors; consider dose reduction or discontinuing
• Coronary events (.g, angina, MI, cardiac arrest, and/or sudden death) reported in clinical trials; apomorphine reduces resting systolic and diastolic BP and may have the potential to exacerbate ischemia
• Dose-related QT prolongation observed with therapeutic doses of SC apomorphine; although the extent of systemic exposure and peak plasma concentration of apomorphine are lower following the maximum recommended SL dose (30 mg) than following the maximum recommended dose of SC apomorphine (6 mg), QTc prolongation cannot be excluded with SL administration
• Withdrawal-emergent hyperpyrexia and confusion reported
• Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, and cardiac valvopathy have been reported in some patients treated with ergot-derived dopaminergic agents; these complications are thought to be associated with ergoline structure dopamine-egotists, whether other non-ergot derived dopamine agonists (.g, apomorphine) can cause these reactions is unknown
• Hypersensitivity/allergic reactions characterized by urticaria, rash, pruritus, and/or various manifestations of angioedema may occur with SL or SC dosing; SC has sulfite excipient; sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people
• Rare incidences of priapism reported during clinical trials
• Retinal atrophy was detected at all SC doses in the albino rat; retinal atrophy/degeneration has been observed in albino rats treated with other dopamine agonists for prolonged periods (approximately2 years)
• Hemolytic anemia
  • Hemolytic anemia requiring hospitalization was reported in the postmarketing setting; many of the reported cases included positive direct antiglobulin test (Coombs test), suggesting a potential immune-mediated hemolysis
  • Severe anemia, angina, and dyspnea have occurred with hemolytic anemia; some patients were treated with high-dose glucocorticoids or blood transfusions
  • Hemolytic anemia can appear at any time after apomorphine treatment; if a patient develops anemia while receiving therapy, consider a workup for hemolytic anemia; if hemolytic anemia occurs, consider discontinuing treatment
• Drug interaction overview
  • 5HT3 Antagonists
    • Contraindicated with 5HT3 antagonists (. g, ondansetron, granisetron, dolasetron, palonosetron)
    • Profound hypotension and loss of consciousness were observed when SC apomorphine was administered with ondansetron
  • Antihypertensives and vasodilators
    • Coadministration may decrease blood pressure
    • In a study of SC apomorphine coadministered with SL nitro-glycerine, a greater decrease in blood pressure was observed than apomorphine alone
    • Advise patients to lie down before and after taking SL nitro-glycerine
  • Alcohol
    • Avoid drinking alcohol after taking apomorphine
    • Coadministration may decrease blood pressure
  • Dopamine antagonists
    • Dopamine antagonists such as neuroleptics (.g, phenothiazine, butyrophenones, thioxanthenes) or metoclopramide may diminish the effect of apomorphine (a dopamine agonist)
  • QT-prolonging drugs
    • Caution of coadministered with other drugs that prolong QT interval

Pregnancy and Lactation

• Adequate data on the developmental risk associated with the use of apomorphine is not available in pregnant women
• In animal reproduction studies, apomorphine had adverse developmental effects in rats (increased neonatal deaths) and rabbits (increased incidence of malformation) when administered during pregnancy at clinically relevant doses; these doses were also associated with maternal toxicity
• Lactation
  • Unknown if distributed in human breast milk
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition