Dopamine Agonist; Impotency Agent

Investigational: Treatment of erectile dysfunction

C

Studies in pregnant animals have not been conducted. The effects on the fetus of a drug-exposed male are unknown.

Known hypersensitivity to morphine or other opiates, or any component of the tablet; men in whom sexual activity is inadvisable due to cardiovascular status

May cause a brief, self-limiting decrease in blood pressure leading to dizziness, lightheadedness, and/or fainting. Most cases occur within 2 hours of administering the first dose or following a dosage increase, and are preceded by prodromal symptoms which include moderate to severe nausea, vomiting, pale skin, sweating/hot flashes, and/or dizziness/lightheadedness. Patients should not drive or engage in tasks requiring alertness for 2 hours following administration. Patients with underlying cardiovascular disease taking short and/or long-acting nitrates, in addition to other cardiovascular medications, have experienced vasovagal symptoms and significant decreases in blood pressure when using higher than normal doses of apomorphine. There is a degree of cardiac risk associated with sexual activity, therefore, prescribers should consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction. Agents used for the treatment of erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease), or in patients who have conditions that may predispose them to priapism (sickle cell anemia, multiple myeloma, or leukemia). Use in patients with severe hepatic impairment only if benefits outweigh the risk. The safety and efficacy of apomorphine with other treatments for erectile dysfunction have not been studied and are, therefore, not recommended as combination therapy. Safety and efficacy in females and patients <18 years of age have not been established.

>10%: Gastrointestinal: Nausea (12.7%)

2% to 10%:

Central nervous system: Dizziness (8.5%), headache (8.4%), somnolence (6.2%)

Cardiovascular: Vasodilation (2.6%), hypotension (2.1%)

Gastrointestinal: Taste perversion (3.9%)

Neuromuscular & skeletal: Weakness (2.6%)

Respiratory: Yawn (6.2%), pharyngitis (2.7%)

Miscellaneous: Sweating (5.7%)

<2%: Abdominal pain, abnormal ejaculation, abnormal vision, accidental injury, acne, agitation, allergic reaction, amblyopia, amnesia, anxiety, apnea, arthralgia, asthma, ataxia, back pain, bradycardia, bronchitis, bruising, bursitis, cardiovascular disorder, cerebrovascular accident, chest pain, chills, circumoral paresthesia, confusion, conjunctivitis, constipation, coronary artery disorder, cough (increased), cyst, deafness, depression, diarrhea, dry mouth, dry skin, dyspnea, dyspepsia, dysuria, ear disorder, ear pain, edema, epididymitis, epistaxis, eructation, euphoria, eye disorder, fever, flu-like syndrome, gastritis, hair disorder, hepatitis, hernia, herpes simplex, hostility, hypertension, hypertonia, hypothermia, increased appetite, infection, insomnia, fungal infection, laryngismus, leg cramps, libido (decreased), lichenoid dermatitis, lung disorder, malaise, melena, mouth ulceration, myalgia, neck pain, nervousness, neoplasm, neuropathy, oral moniliasis, pain, pallor, palpitation, paresthesia, pelvic pain, penis disorder, periodontal abscess, peripheral edema, prostatic disorder, pneumonia, psoriasis, rash, rhinitis, sialadenitis, sinusitis, skin carcinoma, skin disorder, skin hypertrophy, skin ulcer, sleep disorder, stomatitis, syncope, tachycardia, testis disorder, thinking abnormality, tinnitus, tremor, tongue edema, tooth disorder, ulcerative stomatitis, urinary frequency, urinary incontinence, urinary tract infection, vertigo, vesiculobullous rash, vomiting

No overdoses have been reported. Treatment should be supportive and symptomatic. High doses may cause vomiting.

CYP1A2, 3A, 2C19 substrate (minor)

Alcohol: Moderate alcohol ingestion (0.3 g/kg) had little effect on the bioavailability of apomorphine or the blood pressure of patients using higher than normal doses of apomorphine. Larger amounts of alcohol (0.6 g/kg) lead to increased dizziness, hypotension, nausea and pallor. The bioavailability of ethanol is decreased by apomorphine.

Nitrates: Patients with cardiovascular disease, taking nitrates in addition to other cardiovascular medications, have experienced vasovagal symptoms and significant decreases in blood pressure when using higher than normal doses of apomorphine.

Store at 25°C (77°F); protect from light and moisture

Centrally acting dopaminergic agonist (D1 and D2 receptors); initiates erection and enhances pro-erectile stimuli; improves central neural signaling to initiate penile vascular response

Absorption: Rapid following sublingual administration

Protein binding: 90%

Metabolism: Extensive; metabolized by conjugation to apomorphine sulfate and apomorphine glucuronide and metabolized by N-demethylation to norapomorphine

Bioavailability: 17% to 18%

Half-life: 2-3 hours

Time to peak: 40-60 minutes

Elimination: 93% urine (59% as apomorphine sulfate, 12% apomorphine glucuronides, 18% norapomorphine); 16% feces

Adult: Sublingual: Initial dose: 2 mg; subsequent doses may be adjusted to a maximum of 4 mg; onset of erection usually occurs within 15-25 minutes; allow at least 8 hours between doses

Dosage adjustment in hepatic impairment: Half-life and plasma levels are increased with hepatic impairment; use in patients with severe hepatic impairment only if benefits outweigh the risk. Begin with 2 mg/dose; any dosage increases should be made with caution

Elderly: No dosage adjustment necessary

Avoid excessive alcohol consumption; alcohol affects sexual performance and may increase side effects

Moisten mouth with water or another nonalcoholic beverage. Place tablet under tongue 15-25 minutes prior to anticipated intercourse and allow the tablet to dissolve under the tongue. If any part of the tablet is still remaining after 20 minutes, it can then be swallowed. Proceed with intercourse when ready.

May cause a brief, self-limiting decrease in blood pressure leading to dizziness, lightheadedness, and/or fainting. Most cases occur within 2 hours of administering the first dose or following a dosage increase, and are preceded by prodromal symptoms. These symptoms include moderate to severe nausea, vomiting, pale skin, sweating/hot flashes, and/or dizziness/lightheadedness. If any of these symptoms occur, do not stand up. Lie down and elevate legs until symptoms have resolved. Call physician before taking another dose. Because of this potential reaction, do not drive or engage in tasks requiring alertness for 2 hours following administration. The use of apomorphine offers no protection against sexually transmitted diseases, including the human immunodeficiency virus. In addition, the appropriate use of contraceptives should be considered when using apomorphine with a partner of childbearing potential or who is breast-feeding. Allow at least 8 hours between doses.

Tablet, sublingual: 2 mg, 3 mg, 4 mg

Apomorphine has little structural similarity to opiates and no narcotic activity.