Apomorphine Side Effects

Medically reviewed by Philip Thornton, DipPharm. Last updated on Jan 6, 2025.

Applies to apomorphine: sublingual film.

Other dosage forms:

• subcutaneous solution

Precautions

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Do not take this medicine together with alosetron (‎Lotronex®), dolasetron (Anzemet®), granisetron (Kytril®, Sancuso®), ondansetron (Ondisolv®, Zofran®), or palonosetron (Aloxi®).

Do not change your dose or stop using this medicine without first checking with your doctor. Stopping this medicine suddenly may cause fever, confusion, or severe muscle stiffness.

Call your doctor if your symptoms do not improve or if they get worse.

This medicine may make you dizzy or drowsy, or cause trouble with controlling body movements, which may lead to falls. It may also cause you to fall asleep without warning. This could happen while you are driving, eating, or talking. Tell your doctor right away if this happens. Do not drive or do anything else that could be dangerous until you know how this medicine affects you. Standing up slowly from a sitting or lying position can help prevent getting dizzy.

This medicine may cause serious allergic reactions, which an be life-threatening and require immediate medical attention. Tell your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after using this medicine.

This medicine can cause swelling or inflammation of the mouth. Talk to your doctor if you have any concerns.

Some people who have used this medicine had unusual changes in their mood or behavior. Talk with your doctor right away if you start seeing, hearing, or feeling things that are not there, or start having unusual urges, such as gambling urges, binge or compulsive eating, compulsive shopping, or sexual urges while using this medicine.

Check with your doctor right away if you have back, leg, or stomach pains, bleeding gums, chills, dark urine, difficulty breathing, fever, general body swelling, headache, loss of appetite, nausea or vomiting, nosebleeds, pale skin, sore throat, unusual tiredness or weakness, or yellowing of the eyes or skin. These may be symptoms of a blood problem called hemolytic anemia.

This medicine may also increase your risk of having serious heart and blood vessel problems such as chest pain or heart attack. Check with your doctor right away if you start having chest pain or discomfort, pain or discomfort in the arms, jaw, back or neck, trouble breathing, nausea, sweating, or vomiting.

Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you had a heart rhythm problem, such as QT prolongation.

This medicine may increase your risk for fibrotic complications (tissue changes in the pelvis, lungs, and heart valves). Check with your doctor right away if you have fever, general feeling of illness, loss of appetite, lower stomach or back pain, cough, or trouble breathing.

If you experience a prolonged or painful erection of the penis for more than 4 hours, check with your doctor right away.

Check with your doctor before using this medicine with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with apomorphine may worsen the side effects of this medicine, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Serious side effects of apomorphine

Along with its needed effects, apomorphine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking apomorphine:

Other side effects of apomorphine

Some side effects of apomorphine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

For healthcare professionals

Applies to apomorphine: compounding powder, subcutaneous solution, sublingual film.

General adverse events

The most common adverse reactions reported with the intermittent injection formulation were yawning, drowsiness/somnolence, dyskinesias, dizziness/postural hypotension, rhinorrhea, nausea and/or vomiting, hallucination/confusion, and edema/swelling of extremities. The most common adverse reactions reported with the continuous infusion formulation were infusion-site nodule, nausea, somnolence, infusion-site erythema, dyskinesia, headache, and insomnia. The most common adverse reactions reported with the sublingual formulation were nausea, somnolence, dizziness, and oropharyngeal adverse events (swelling, edema, pain, irritation, ulceration).^[Ref]

Cardiovascular

• Very common (10% or more): Orthostatic/postural hypotension (up to 44.4%), chest pain/pressure/angina (up to 15%)
• Common (1% to 10%): Hypotension, hot flush, hypertension, flushing, congestive heart failure, orthostatic intolerance, cardiac disorder, left bundle branch block, myocardial infarction, palpitations, tachycardia, prolonged QTc interval
• Uncommon (0.1% to 1%): Cardiac arrest, atrial fibrillation, pallor, decreased heart rate, prolonged QT on ECG
• Frequency not reported: Thrombus formation

Patients undergoing titration of the intermittent injection formulation showed an increased incidence (from 4% predose to 18% postdose) of systolic orthostatic hypotension (at least 20 mmHg decrease) when evaluated at various times after in-office dosing. A small number of patients developed severe systolic orthostatic hypotension (at least 30 mmHg decrease and systolic blood pressure up to 90 mmHg) after subcutaneous injection of this drug. In clinical trials of the intermittent injection formulation in patients with advanced Parkinson's disease, 11% of patients had orthostatic hypotension, hypotension, and/or syncope; these events occurred both with initial dosing and during long-term therapy.

Patients undergoing titration of the continuous infusion formulation showed an increased incidence (from 4.5% predose to 44.4% postdose) of systolic orthostatic hypotension (at least 20 mmHg decrease upon standing) when evaluated at various times after dosing. Similarly, increased incidences of diastolic orthostatic hypotension (at least 10 mmHg decrease upon standing) were observed in patients titrated with this product (4.5% predose to 44.4% postdose). Differences in incidence rates for systolic and diastolic orthostatic hypotension remained similar through the 12-week treatment period. Some patients developed severe systolic orthostatic hypotension (at least 40 mmHg decrease) and/or diastolic orthostatic hypotension (at least 20 mmHg decrease). In this study, 13% of patients treated with the continuous infusion formulation reported hypotension/orthostatic hypotension (hypotension: 7%; orthostatic hypotension: 4%; orthostatic intolerance: 2%).

In clinical studies with the intermittent infusion formulation, angina, myocardial infarction, cardiac arrest, and/or sudden death occurred in 4% of patients treated with this drug; some cases of angina and myocardial infarction occurred within 2 hours of dosing, while other cases of cardiac arrest and sudden death were observed at times unrelated to dosing. In a clinical study with the continuous infusion formulation, cardiac disorder (including left bundle branch block [2%], myocardial infarction [2%], palpitations [2%], or tachycardia [2%]) was reported in patients treated with this drug.

Thrombus formation due to IV crystallization of apomorphine has occurred after IV administration of this drug.

Dermatologic

• Common (1% to 10%): Rash, hyperhidrosis, cold sweat, increased sweating, ecchymosis
• Uncommon (0.1% to 1%): Generalized rashes, local rashes
• Frequency not reported: Reduced facial hair growth

Endocrine

• Frequency not reported: Transient increase in serum prolactin

Gastrointestinal

• Very common (10% or more): Nausea/vomiting (up to 59%), nausea (up to 31%), vomiting (up to 11%), oral soft tissue signs/symptoms, stomatitis, ulceration, tongue conditions
• Common (1% to 10%): Oral candidiasis, oral soft tissue swelling, oral soft tissue edema, oral dryness, altered saliva, oral soft tissue disorder, retching, gingival disorder/signs/symptoms, constipation, diarrhea
• Uncommon (0.1% to 1%): Gingivitis, angular cheilitis, dyspepsia, eructation, dysphagia, tooth discoloration, dental caries, tongue polyp
• Frequency not reported: Oropharyngeal adverse events

In clinical trials of the intermittent injection formulation, 98% of patients were premedicated with the antiemetic trimethobenzamide for 3 days before study enrollment and were encouraged to continue trimethobenzamide for at least 6 weeks. While using concomitant trimethobenzamide, 31% and 11% of patients treated with this formulation had nausea and vomiting, respectively. In a 12-week study, trimethobenzamide (compared with placebo) was found to reduce the incidence of nausea and vomiting during the first 4 weeks of treatment with this product (incidence of nausea/vomiting 43% with trimethobenzamide vs 59% with placebo).

In a study of the continuous infusion formulation, 87% of patients were pretreated with an antiemetic. Nausea and vomiting were reported in 22% and 7% of patients treated with this product, respectively.

In clinical trials, paresthesias/dysesthesias of the oral cavity, changes in teeth color, caries, changes in salivary gland secretion, and oropharyngeal adverse events (including irritation, erythema, edema, ulceration, pain) were observed with the sublingual film. Oral soft tissue signs/symptoms commonly observed in patients treated with the sublingual film included oral mucosal erythema, oral hypoesthesia, oral discomfort, oral mucosal blistering, and uncommonly oral contusion, lip exfoliation, oral dysesthesia, oral hyperesthesia, oral mucosal discoloration, and oral mucosal exfoliation. These events were of mild to moderate severity. For most patients, events were tolerated or resolved either spontaneously or soon after discontinuation of therapy.

Genitourinary

• Common (1% to 10%): Urinary tract infection
• Uncommon (0.1% to 1%): Spontaneous penile erection, painful erection

Hematologic

• Uncommon (0.1% to 1%): Hemolytic anemia, thrombocytopenia, positive Coombs test
• Rare (0.01% to 0.1%): Eosinophilia, peripheral blood eosinophilia
• Postmarketing reports: Hemolytic anemia

Hemolytic anemia requiring hospitalization has been reported with this drug during postmarketing experience. Many case reports 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.

Hypersensitivity

• Very common (10% or more): Hypersensitivity (up to 11%)
• Rare (0.01% to 0.1%): Allergic reactions

In 1 study, hypersensitivity (including rash [4%], infusion-site pruritus [4%], infusion-site rash [2%], hypersensitivity [2%], or infusion-site hypersensitivity [2%]) occurred in 11% of patients treated with the continuous infusion formulation.

Allergic reactions (including anaphylaxis and bronchospasm) have occurred due to the presence of sodium metabisulfite (most products) or sodium bisulfite (APO-go Pen).

Local

• Very common (10% or more): Infusion-site reactions (up to 63%), infusion-site nodule (up to 44%), injection-site reactions (up to 26%), infusion-site erythema (up to 17%), injection-site bruising (up to 16%), local reactions
• Common (1% to 10%): Injection-site granuloma, injection-site pruritus, infusion-site infections, infusion-site pruritus, infusion-site rash, infusion-site hypersensitivity
• Uncommon (0.1% to 1%): Injection-site necrosis, injection-site ulceration
• Frequency not reported: Itchy nodular lesions at the injection site

In 1 study, at least 1 infusion-site reaction was reported in 63% of patients treated with the continuous infusion formulation. Various types of reactions at the infusion site have been reported including nodules, erythema, hematomas, inflammation, pruritus, swelling, discoloration, hemorrhage, hypersensitivity, induration, edema, pain, rash, or bruising. Infusion-site reactions were most commonly reported as nodule formation (44%) or erythema (17%).

Injection-/infusion-site reactions included subcutaneous nodules, induration, erythema, tenderness, and panniculitis.

Local reactions included irritation, itching, bruising, fibrosis, and pain.

Infusion-site infections occurred in 4% of patients treated with the continuous infusion formulation. The most common infusion-site infection was cellulitis.

Metabolic

• Common (1% to 10%): Dehydration
• Uncommon (0.1% to 1%): Decreased appetite, increased vitamin B6

Musculoskeletal

• Common (1% to 10%): Arthralgia, limb pain, back pain

Nervous system

• Very common (10% or more): Somnolence/drowsiness (up to 35%), dyskinesias (up to 35%), headache (up to 13%)
• Common (1% to 10%): Dizziness/lightheadedness, syncope, transient sedation, Parkinson's disease aggravated, sedation
• Uncommon (0.1% to 1%): Drooling, sudden onset of sleep
• Frequency not reported: Neuroleptic malignant syndrome, transient metallic taste

This drug has induced dyskinesias during "on" periods; some cases were severe. In clinical trials, dyskinesia or worsening of dyskinesia was reported in 15% and 24% of patients treated with the continuous infusion formulation and intermittent injection formulation, respectively.

Ocular

• Common (1% to 10%): Blurred vision
• Uncommon (0.1% to 1%): Increased lacrimation

Other

• Very common (10% or more): Falls (up to 30%), edema/swelling of extremities (up to 10%)
• Common (1% to 10%): Fatigue, asthenia, feeling abnormal, feeling cold, chills, weakness
• Uncommon (0.1% to 1%): Malaise, feeling drunk, peripheral edema
• Frequency not reported: Gait disturbance, dopamine agonist withdrawal syndrome, sudden death

In clinical trials, 30% of patients had events that could reasonably be considered falls; about 5% of patients had falls that were considered serious.

Psychiatric

• Very common (10% or more): Hallucinations (up to 14%), insomnia (up to 11%)
• Common (1% to 10%): Neuropsychiatric disturbances, depression, anxiety, confusional state/confusion, psychotic disorder
• Uncommon (0.1% to 1%): Obsessive-compulsive disorder, dopamine dysregulation syndrome, agitation
• Frequency not reported: Impulse control disorders, visual hallucination, gambling disorder/pathological gambling, increased libido, hypersexuality, compulsive shopping/spending/buying, binge/compulsive eating, aggression, loss of libido
• Postmarketing reports: New/worsening mental status/behavioral changes

Neuropsychiatric disturbances included transient mild confusion and visual hallucinations.

Postmarketing reports showed new/worsening mental status and behavioral changes (which were sometimes severe and included psychotic-like behavior) after starting or increasing the dose of the intermittent injection formulation.

Respiratory

• Very common (10% or more): Yawning (up to 40%), rhinorrhea (up to 20%)
• Common (1% to 10%): Dyspnea/breathing difficulties, pneumonia
• Uncommon (0.1% to 1%): Nasal congestion
• Frequency not reported: Pulmonary embolism

Pulmonary embolism due to IV crystallization of apomorphine has occurred after IV administration of this drug.

See also:

Further information

Apomorphine side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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