APOKYN Injection for Advanced Parkinson’s Disease 'Off' Episodes | Apomorphine Hydrochloride

APOKYN is a subcutaneous injection containing apomorphine hydrochloride, a dopamine agonist used for the rapid relief of 'off' episodes in advanced Parkinson's disease. It provides an acute, intermittent treatment option for periods of hypomobility where usual medications are less effective.

APOKYN is prescribed for adults with advanced Parkinson's disease to acutely treat hypomobility or "off" episodes, including "end-of-dose wearing off" and unpredictable "on/off" fluctuations. It is intended as an adjunct to patients' existing Parkinson's therapy to manage these acute motor symptoms.

Apomorphine hydrochloride

Apomorphine hydrochloride is a non-ergoline dopamine agonist that works by stimulating dopamine receptors in the brain. This action helps to alleviate motor symptoms related to dopamine deficiency in Parkinson's disease, providing rapid relief during 'off' episodes when patients experience decreased movement.

Administration

APOKYN is for subcutaneous use only and is administered via the multiple-dose APOKYN Pen with supplied cartridges. The dose must always be expressed in milliliters (mL) to avoid confusion due to pen markings.

Initial Dosing and Titration

• Start with a test dose of 0.1 mL (1 mg) to 0.2 mL (2 mg) under medical supervision monitoring blood pressure and pulse in both supine and standing positions at baseline and multiple intervals up to 60 minutes post-dose.
• Patients developing significant orthostatic hypotension after the test dose should not continue treatment.
• If tolerated and effective, the starting maintenance dose is the same as the test dose, used as needed for recurring off episodes.
• Dose can be increased in 0.1 mL (1 mg) increments every few days under outpatient supervision, not to exceed 0.6 mL (6 mg) per dose.

Test Dose Adjustments

• If a 0.1 mL test dose is tolerated but ineffective, a 0.2 mL test dose may be tried at least 2 hours later.
• If a 0.2 mL dose is tolerated but ineffective, a 0.4 mL (4 mg) test dose can be tried similarly.
• If 0.4 mL dose is not tolerated, a 0.3 mL (3 mg) dose trial is recommended.

Renal Impairment

For mild to moderate renal impairment, reduce the test and starting doses to 0.1 mL (1 mg).

Dosing Frequency and Limits

• Doses must be separated by at least 2 hours.
• Do not exceed 5 doses per day or total daily dose of 2 mL (20 mg).
• If a dose is ineffective for an off period, do not administer a second dose for the same episode.
• After interruption of therapy longer than one week, restart at 0.2 mL (2 mg) and titrate as needed.

Nausea Prevention

Initiate trimethobenzamide 300 mg three times daily at least 3 days prior to first APOKYN dose to reduce nausea and vomiting. Continue trimethobenzamide only as long as necessary and generally no longer than two months.

• Use with 5HT3 antagonist class drugs (e.g., ondansetron, granisetron, dolasetron, palonosetron, alosetron) due to risk of profound hypotension and loss of consciousness.
• Hypersensitivity to apomorphine or any of its excipients, especially sodium metabisulfite, which can cause allergic reactions including angioedema or anaphylaxis.

Serious Risks and Monitoring

• Administration route: APOKYN must be given subcutaneously. Intravenous use is contraindicated due to risk of thrombus formation and pulmonary embolism from crystallization.
• Hypotension and Syncope: APOKYN can cause orthostatic hypotension and syncope. Monitor blood pressure before and after dosing, especially during titration.
• Somnolence and Falling Asleep: Sudden onset of sleep during activities occurs; patients should be assessed for daytime sleepiness. Discontinue if significant somnolence occurs; patients should avoid driving or hazardous tasks.
• Falls: Increased risk of falls due to postural instability and blood pressure effects.
• Hallucinations and Psychosis: May cause or worsen hallucinations or psychotic symptoms, especially in patients with pre-existing psychiatric disorders.
• Dyskinesia: Can cause or worsen involuntary movements; reported in about 24% of patients.
• Hemolytic Anemia: Immune-mediated hemolytic anemia has been reported. Monitor for anemia and consider discontinuation if it occurs.
• Impulse Control Disorders: Patients may develop intense uncontrolled urges (gambling, sexual, spending). Clinicians should monitor and consider dose adjustment or stopping medication if these occur.
• Cardiovascular Events: Coronary events including angina, myocardial infarction, cardiac arrest, and sudden death have been reported; close monitoring advised especially in those with cardiovascular disease.
• QTc Prolongation: Dose-related QTc interval prolongation occurs; doses above 6 mg are not recommended due to lack of additional benefit and increased risk.
• Drug Interactions: Concomitant use with 5HT3 antagonists (e.g., ondansetron) is contraindicated due to risk of profound hypotension and loss of consciousness.

Common Adverse Reactions

• Nausea (31%)
• Vomiting (11%)
• Somnolence (35%)
• Dyskinesia (24%)
• Hallucinations (14%)
• Dizziness (increased with trimethobenzamide co-treatment)
• Falls (increased with trimethobenzamide co-treatment)

Serious Adverse Reactions

• Hemolytic anemia requiring hospitalization
• Orthostatic hypotension leading to syncope
• Coronary events including myocardial infarction and sudden death

• 5HT3 Antagonists: Concomitant use with drugs like ondansetron, granisetron, dolasetron, palonosetron, and alosetron is contraindicated due to reported severe hypotension and loss of consciousness.
• Antihypertensives and Vasodilators: May enhance blood pressure lowering, increasing hypotension risk; monitor blood pressure closely.
• Alcohol: Potentiates hypotensive effects; patients should avoid alcohol while using APOKYN.
• Antiemetics with anti-dopaminergic activity: Avoid drugs such as haloperidol, chlorpromazine, promethazine, prochlorperazine, and metoclopramide as they may worsen Parkinson's symptoms.

Manifestations of overdose may include profound hypotension, sedation, nausea, vomiting, and worsening of Parkinsonian symptoms. Management is supportive; monitor cardiovascular and respiratory function and provide symptomatic treatment as needed.

Store APOKYN cartridges according to specific product instructions. Visually inspect solution before use; do not use if cloudy, discolored, or containing particulates. Rotate injection site to avoid local complications and maintain aseptic technique.