Usage
Apomorphine is primarily prescribed for the acute, intermittent treatment of hypomobility, “off” episodes (end-of-dose wearing “off” and unpredictable “on-off” episodes) associated with advanced Parkinson’s disease. It belongs to the pharmacological class of dopamine agonists, specifically non-ergoline dopamine agonists. Apomorphine’s mechanism of action involves stimulating dopamine receptors in the brain, mimicking the effects of dopamine, a neurotransmitter essential for movement control.
Alternate Names
Generic Name: Apomorphine hydrochloride
Brand Names: Apokyn, Apokyn NXT, Kynmobi, Onapgo
How It Works
Pharmacodynamics: Apomorphine is a potent dopamine receptor agonist, primarily stimulating D1 and D2 receptors. This stimulation leads to improved motor symptoms in Parkinson’s disease patients by restoring dopaminergic activity in the basal ganglia.
Pharmacokinetics:
- Absorption: Subcutaneous (SC) injection provides rapid absorption with peak plasma concentrations within 5-20 minutes. Sublingual administration results in slower absorption.
- Metabolism: Primarily metabolized in the liver via glucuronidation and sulfation.
- Elimination: Excreted mainly through the kidneys. The terminal elimination half-life is approximately 30-60 minutes after intravenous administration and 1.7 hours after sublingual administration.
Mode of Action: Apomorphine directly activates postsynaptic dopamine receptors, bypassing the presynaptic dopamine neurons that are dysfunctional in Parkinson’s disease.
Receptor Binding/Neurotransmitter Modulation: Agonist at D1 and D2 dopamine receptors in the brain.
Elimination Pathways: Primarily renal excretion with some hepatic metabolism.
Dosage
Standard Dosage
Adults (Subcutaneous Injection - Apokyn):
- Initial: 1-2 mg (0.1-0.2 mL) SC as needed.
- Titration: Increase by 1 mg increments every 2 hours as needed, based on response and tolerance.
- Maximum Dose: 6 mg (0.6 mL) per injection; no more than 5 injections per day; total daily dose should not exceed 20 mg.
Adults (Sublingual Film - Kynmobi):
- Initial: 10 mg sublingually as needed.
- Titration: Increase by 5 mg increments if needed and tolerated, with at least 2 hours between doses.
- Maximum Dose: 30 mg per dose; no more than 5 doses per day.
Children: Use and dose must be determined by the physician as safety and efficacy have not been established in children.
Special Cases:
- Elderly Patients: Initiate with caution due to the risk of postural hypotension. Start at the low end of the dosing range and titrate slowly.
- Patients with Renal Impairment: Reduce the initial dose and titrate cautiously, especially in severe renal disease. Avoid use in end-stage renal disease.
- Patients with Hepatic Dysfunction: Use with caution as pharmacokinetic data is limited. Monitor closely.
- Patients with Comorbid Conditions: Careful consideration is required for patients with cardiovascular disease, respiratory disease, or neuropsychiatric disorders.
Clinical Use Cases
Apomorphine is not typically used in settings like intubation, surgical procedures, mechanical ventilation, or ICU use. It is specifically for intermittent treatment of “off” episodes in advanced Parkinson’s disease patients.
Dosage Adjustments
Dosage adjustments are based on individual patient response, tolerance, and renal function. Close monitoring of blood pressure, pulse, and motor symptoms is essential during dose titration.
Side Effects
Common Side Effects:
Nausea, vomiting, yawning, dizziness, drowsiness, hallucinations, dyskinesias, orthostatic hypotension, injection site reactions (nodules, bruising).
Rare but Serious Side Effects:
Severe hypotension, syncope, hallucinations, psychosis, QT prolongation, blood clots (with intravenous administration), allergic reactions (angioedema, anaphylaxis).
Long-Term Effects:
Long-term side effects can include impulse control disorders (e.g., gambling, compulsive shopping).
Adverse Drug Reactions (ADR):
Significant ADRs requiring immediate attention include anaphylaxis, angioedema, and severe hypotension.
Contraindications
- Concomitant use with 5-HT3 antagonists (e.g., ondansetron).
- Hypersensitivity to apomorphine or its components, including sodium metabisulfite.
- Severe respiratory or CNS depression.
- Severe cardiovascular disease.
- Neuropsychiatric disorders, including psychosis and dementia.
- Severe hepatic impairment.
Drug Interactions
- 5-HT3 antagonists: Contraindicated due to the risk of severe hypotension.
- Antihypertensives: Additive hypotensive effects.
- Alcohol: Increased risk of CNS depression and orthostatic hypotension.
- Dopamine antagonists: Reduced efficacy of apomorphine.
- QT prolonging drugs: Increased risk of QT prolongation and torsades de pointes.
Pregnancy and Breastfeeding
- Pregnancy: Limited human data. Animal studies show potential for adverse effects. Use only if clearly needed.
- Breastfeeding: It is not known if apomorphine is excreted in breast milk. A decision should be made whether to discontinue breastfeeding or discontinue the drug, considering the benefits and risks for both mother and infant.
Drug Profile Summary
- Mechanism of Action: Dopamine receptor agonist.
- Side Effects: Nausea, vomiting, yawning, dizziness, hallucinations, dyskinesias, orthostatic hypotension.
- Contraindications: Concomitant use with 5-HT3 antagonists, hypersensitivity, severe respiratory/CNS depression, severe cardiovascular disease.
- Drug Interactions: 5-HT3 antagonists, antihypertensives, alcohol, dopamine antagonists.
- Pregnancy & Breastfeeding: Limited human data; use with caution.
- Dosage: Refer to dosage section above.
- Monitoring Parameters: Blood pressure, pulse, motor symptoms, ECG (for QT interval), signs of dyskinesias, neuropsychiatric symptoms.
Popular Combinations
Apomorphine is often used in combination with domperidone (an antiemetic) to manage nausea and vomiting associated with apomorphine therapy.
Precautions
- Pre-screening for cardiovascular disease, respiratory problems, neuropsychiatric disorders, and hepatic/renal impairment is crucial.
- Monitor blood pressure and pulse regularly, especially during dose titration.
- Educate patients about the risk of orthostatic hypotension and syncope.
- Advise patients not to drive or operate machinery if experiencing drowsiness or sudden sleep episodes.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Apomorphine?
A: The dosage depends on the formulation and individual patient response. See the detailed dosage section above.
Q2: How should Apomorphine be administered?
A: Apokyn is administered via subcutaneous injection, while Kynmobi is administered as a sublingual film.
Q3: What are the common side effects of Apomorphine?
A: Common side effects include nausea, vomiting, yawning, dizziness, drowsiness, and hallucinations.
Q4: What are the serious side effects of Apomorphine?
A: Serious side effects can include severe hypotension, syncope, psychosis, QT prolongation, and allergic reactions.
Q5: What are the contraindications for Apomorphine?
A: Contraindications include concomitant use with 5-HT3 antagonists, hypersensitivity to the drug, severe respiratory/CNS depression, and severe cardiovascular disease.
Q6: Can Apomorphine be used during pregnancy?
A: Apomorphine should be used during pregnancy only if clearly needed, after careful consideration of the potential risks and benefits.
Q7: Can Apomorphine be used during breastfeeding?
A: It’s unknown if apomorphine is excreted in breast milk. A decision should be made to discontinue breastfeeding or the drug.
Q8: What are the potential drug interactions with Apomorphine?
A: Apomorphine can interact with several drugs, including 5-HT3 antagonists, antihypertensives, alcohol, and dopamine antagonists.
Q9: How does Apomorphine work in Parkinson’s Disease?
A: It stimulates dopamine receptors in the brain, mimicking the effects of dopamine, a neurotransmitter deficient in Parkinson’s disease.
