apomorphine hydrochloride

apomorphine hydrochloride

APO-go (UK), Apokyn

Pharmacologic class: Dopaminergic, dopamine-receptor agonist

Therapeutic class: Antiparkinsonian

Pregnancy risk category C

Action

Unclear. May stimulate postsynaptic dopamine D₂-type receptors in caudate-putamen of brain.

Availability

Ampules: 10 mg/ml in 2- and 3-ml cartridges

⊘Indications and dosages

➣ Acute intermittent treatment of hypomobility and "off" ("end-of-dose wearing off" and unpredictable "on/off") episodes associated with Parkinson's disease

Adults: 0.2-ml (2-mg) test dose injected subcutaneously during "off" state in setting where medical personnel can monitor blood pressure. If patient tolerates test dose, give 0.2 ml subcutaneously p.r.n. to treat "off" episodes no sooner than 2 hours after previous dose. Establish dosage based on tolerance and efficacy; increase in 0.1-ml (1 mg) increments, usually to 0.3 to 0.4 ml. Maximum dosage, 0.6 ml up to five times daily.

Patient who tolerates but doesn't respond to test dose may receive 0.4 ml (4 mg) at next observed "off" period, but no sooner than 2 hours after initial 0.2-ml test dose. If patient tolerates 0.4-ml test dose, give starting dosage of 0.3 ml (3 mg) p.r.n. to treat "off" episodes. If needed, increase in increments of 0.1 ml every few days on outpatient basis.

If patient doesn't tolerate 0.4-ml test dose, 0.3-ml test dose may be given during separate "off" period no sooner than 2 hours after 0.4-ml test dose.

If patient tolerates 0.3-ml test dose, starting dosage should be 0.2 ml p.r.n. to treat existing "off" episodes. If needed and if patient tolerates 0.2-ml dose, dosage can be increased to 0.3 ml after several days; in this case, it ordinarily shouldn't be increased to 0.4 ml on outpatient basis.

Dosage adjustment

• Mild or moderate renal impairment

Contraindications

• Hypersensitivity to drug or its components
• Concurrent use of 5-hydroxytryptamine₃ (5-HT₃) antagonists (such as alosetron, dolasetron, granisetron, ondansetron, palonosetron)

Precautions

Use cautiously in:
• renal or hepatic impairment
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• If prescribed, give trimethobenzamide (antiemetic) for 3 days before starting apomorphine and continuing throughout therapy.
• Give only by subcutaneous injection.
☞ Don't give I.V. because this may cause serious adverse events, such as I.V. crystallization of apomorphine, leading to thrombus formation and pulmonary embolism.
• Titrate dosage based on efficacy and patient tolerance.
• Check supine and standing blood pressure before giving test dose and 20, 40, and 60 minutes after. If patient experiences clinically significant orthostatic hypotension in response to test dose, don't give drug.

Route	Onset	Peak	Duration
Subcut.	Unknown	10-60 minutes	Unknown

Adverse reactions

CNS: drowsiness, somnolence, dizziness, hallucinations, confusion, syncope, dyskinesias

CV: orthostatic hypotension, chest pain, chest pressure, angina, cardiac valvulopathy

EENT: rhinorrhea

GI: nausea, vomiting, retroperitoneal fibrosis

GU: priapism

Respiratory: pulmonary infiltrates, pleural effusion, pleural thickening

Other: yawning, edema of extremities, injection site reactions, abuse potential, allergic reactions

Interactions

Drug-drug. Antihypertensive agents, vasodilators: increased incidence of hypotension, myocardial infarction, serious pneumonia, serious falls, bone and joint injuries

Dopamine antagonists: decreased apomorphine efficacy

5-HT₃ antagonists: profound hypotension

Drug-behaviors. Alcohol use: additive drowsiness and somnolence

Patient monitoring

• Monitor for serious cardiovascular and respiratory adverse reactions.
• Monitor for unexpected somnolence, which may interfere with daily activities.

Patient teaching

• Instruct patient to take drug as described in patient instruction leaflet.
• Make sure patient knows that dosages are in milliliters, not milligrams.
• Instruct patient to rotate injection site.
• Inform patient that drug may cause hallucinations and unexpected sleepiness.
• Tell patient drug may cause blood pressure to drop. Caution him to rise slowly from sitting or lying position.
• Urge patient to consult prescriber before taking other drugs.
• Caution patient not to use alcohol during therapy.
• Advise patient to avoid driving and other hazardous activities until drug effects are known.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs mentioned above.