Applies to apomorphine: subcutaneous solution. Other dosage forms:

• sublingual film

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:

More common

• Anxiety
• bladder pain
• bloody or cloudy urine
• chest pain, pressure, or tightness
• chills
• confusion
• cough
• decreased urination
• difficult, burning, or painful urination
• dilated neck veins
• discouragement
• dizziness
• dry mouth extreme
• fainting
• falls
• feeling sad or empty
• fever
• frequent urge to urinate
• increase in heart rate
• irregular breathing or heartbeat
• irritability
• lack of appetite
• lightheadedness
• loss of interest or pleasure
• lower back or side pain
• nausea
• rapid breathing
• seeing, hearing, or feeling things that are not there
• sleepiness or unusual drowsiness
• sneezing
• sore throat
• sunken eyes
• swelling of face, fingers, feet, or lower legs
• thirst
• trouble breathing
• trouble concentrating
• trouble sleeping
• twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• unusual tiredness or weakness
• vomiting
• weight gain
• wrinkled skin

Incidence not known

• Back, leg, or stomach pains
• bleeding gums
• dark urine
• general body swelling
• nosebleeds
• pale skin
• yellowing of the eyes or skin

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:

More common

• Arm pain
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• bruising
• constipation
• diarrhea
• difficulty in moving
• headache
• increased sweating
• joint pain
• large, flat, blue or purplish patches in the skin
• muscle pain or stiffness
• runny nose
• yawning

For Healthcare Professionals

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

General

The most commonly reported adverse reactions have included yawning, drowsiness/somnolence, dyskinesias, dizziness/postural hypotension, rhinorrhea, nausea, vomiting, hallucination/confusion, and edema/swelling of extremities.

Gastrointestinal

Very common (10% or more): Nausea and/or vomiting (30%)

Common (1% to 10%): Constipation, diarrhea

Uncommon (0.1% to 1%): Stomatitis, transient metallic taste^[Ref]

This drug is known to cause severe nausea and vomiting when administered at recommended doses; because of this, premedication with antiemetics is recommended. In a clinical trial in which patients received premedication with trimethobenzamide, 31% and 11% of patients had nausea and vomiting, respectively.^[Ref]

Cardiovascular

Very common (10% or more): Orthostatic hypotension (up to 20%), chest pain/pressure/angina (15%)

Common (1% to 10%): Syncope, hypotension, edema/swelling of extremities, congestive heart failure

Rare (0.01% to 0.1%): QTc interval prolongation

Frequency not reported: Profound hypotension and loss of consciousness, thrombus formation, angina, myocardial infarction, cardiac arrest and/or sudden death, QTC prolongation^[Ref]

Concomitant use of ondansetron with apomorphine has resulted in profound hypotension and loss of consciousness. Because of this, US labeling has concomitant use of 5HT3 antagonists and apomorphine as contraindicated.

Thrombus formation due to intravenous crystallization of apomorphine has occurred with IV administration; this drug should not be administered IV.

In clinical studies, 4% of patients receiving this drug experienced angina, myocardial infarction, cardiac arrest and/or sudden death. The specific incidence of each event is unknown; some cases of angina and myocardial infarction occurred in close proximity to apomorphine administration, while other cases of cardiac arrest and sudden death occurred at time not related to dosing.

In a placebo-controlled study, single apomorphine doses from 2 mg to 8 mg resulted in mean differences from placebo in QTc (as measured by Holter monitor) of 0, 1, and 7 milliseconds with 4, 6, and 8 mg does, respectively. In another study, single-doses of apomorphine 2 to 10 mg (mean 5.2 mg) resulted in a mean difference in QTc interval of about 3 milliseconds at 20- and 90-minutes post-dose. For the entire study, 2 patients exhibited larger QTc increases (greater than 60 milliseconds from pre-dose; 1 patient at 2 and 6 mg; 1 patient at 6 mg).^[Ref]

Psychiatric

Very common (10% or more): Hallucinations (up to 14%)

Common (1% to 10%): Confusion, insomnia, depression

Frequency not reported: Impulse control/compulsive behaviors

Postmarketing reports: New or worsening mental status and behavioral changes including psychotic-like behavior, paranoid ideation, delusions, disorientation, aggressive behavior, agitation, and delirium^[Ref]

For patients taking medications that increase central dopaminergic tone including this drug, there have been case reports of intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, and the inability to control these urges.^[Ref]

Other

Very common (10% or more): Falls (up to 30%)

Common (1% to 10%): Fatigue^[Ref]

Local

Very common (10% or more): Injection site reactions (26%)

Frequency not reported: Panniculitis^[Ref]

Nervous system

Very common (10% or more): Drowsiness or somnolence (up to 35%), dyskinesia (up to 35%)

Common (1% to 10%): Headache, aggravated Parkinson's disease, weakness

Frequency not reported: Falling asleep during activities of daily living

Local

Injection site reactions including bruising, granuloma, and pruritus have occurred with subcutaneous injections. Local induration and nodules (usually asymptomatic) often develop with continuous use. At higher doses, erythema, tenderness and induration at site of subcutaneous injection may occur. Panniculitis has been reported when a skin biopsy has been performed.^[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection

Uncommon (0.1% to 1%): Spontaneous penile erection

Rare (0.01% to 0.1%): Painful erection

Very rare (less than 0.01%): Priapism^[Ref]

Hematologic

Common (1% to 10%): Ecchymosis

Uncommon (0.1% to 1%): Thrombocytopenia

Rare (0.01% to 0.1%): Coombs' positive hemolytic anemia, eosinophilia

Hypersensitivity

Frequency not reported: Angioedema, anaphylaxis, bronchospasm

Sodium metabisulfite is an excipient in many apomorphine solutions. Angioedema and anaphylaxis and bronchospasm have been reported with this excipient in sulfite sensitive individuals.

Musculoskeletal

Common (1% to 10%): Limb pain, arthralgia, back pain

Ocular

Uncommon (0.1% to 1%): Increased lacrimation

Metabolic

Common (1% to 10%): Dehydration

Respiratory

Pulmonary embolism due to intravenous crystallization of apomorphine has occurred with IV administration; this drug should not be administered IV.

Very common (10% or more): Yawning (40%), rhinorrhea (20%)

Common (1% to 10%): Pneumonia, dyspnea

Uncommon (0.1% to 1%): Breathing difficulties

Frequency not reported: Pulmonary embolism

Dermatologic

Uncommon (0.1% to 1%): Reduced facial hair growth, local and generalized rashes

Endocrine

Uncommon (0.1% to 1%): Transient rise in serum prolactin, loss of libido