Apomorphine Dosage and Administration for 'Off' Episodes in Advanced Parkinson's Disease
The recommended dosage of apomorphine for treating 'off' episodes in advanced Parkinson's disease is initially 1 mg/hour as a continuous subcutaneous infusion, which can be titrated in 0.5-1 mg/hour increments to a maximum of 6 mg/hour, with additional extra doses of 0.5-2 mg as needed (maximum 3 extra doses daily with at least 3 hours between doses). 1
Initial Dosing and Titration
Continuous Infusion
- Start with 1 mg/hour continuous subcutaneous infusion 1
- Titrate as needed in increments of 0.5-1 mg/hour 1
- Dose adjustments may be made daily or at longer intervals during titration
- Maximum continuous dosage: 6 mg/hour (administered over waking day, typically 16 hours)
- Clinical studies showed a mean effective dose of 4 mg/hour 1
Extra Doses for Breakthrough 'Off' Episodes
- Extra doses may be used:
- Upon morning startup
- When restarting after a ≥1-hour break (as loading dose)
- For acute 'off' episodes not controlled by continuous infusion
- Initial extra dose: 0.5-1 mg
- May be titrated in increments of 0.5-1 mg
- Maximum extra dose: 2 mg per administration
- Maximum frequency: 3 extra doses per day with at least 3 hours between doses 1
- Consider increasing continuous dose if 3 extra doses are routinely required
Maximum Daily Dosage
- Maximum total daily dose: 98 mg (including continuous and extra doses) over waking day (typically 16 hours) 1
Premedication and Concomitant Medications
Antiemetic Pretreatment
- Recommended: Trimethobenzamide 300 mg three times daily starting 3 days prior to initial apomorphine dose 1
- Alternative: Start apomorphine at 1 mg/hour without antiemetics and titrate based on effectiveness and tolerance
- Continue trimethobenzamide only as long as necessary to control nausea/vomiting (generally no longer than 2 months) 1
Contraindicated Medications
- 5HT3 antagonist class antiemetics (e.g., ondansetron, granisetron, dolasetron, palonosetron) 1
- Alosetron 1
Administration Considerations
Route of Administration
- Subcutaneous infusion only (not substitutable for intermittent-use apomorphine products) 1
Infusion Sites
- Abdomen (at least 2 inches from navel)
- Top of thigh
- Lower back
- Upper back (only when prepared by caregiver or healthcare provider) 1
- Change infusion site daily
Patient Selection and Training
- Patients must be capable of understanding and using the delivery system (either themselves or with caregiver assistance) 1
- Initiation and dose titration should be done under medical supervision 1
- Patients and caregivers should receive education and training on proper use of apomorphine and the delivery system prior to first use 1
Special Populations
Renal Impairment
- For patients with mild or moderate renal impairment:
- Initial extra dose: 0.5-1 mg (not to exceed 1 mg) 1
- Continuous infusion dosing may need adjustment based on response
Clinical Efficacy and Considerations
- Apomorphine provides consistent rescue from 'off' episodes with onset within 20 minutes 2
- Duration of effect is approximately 100 minutes 2
- In clinical studies, patients required a mean of approximately 3 rescue doses per day 2
- Apomorphine is particularly suited for patients requiring rapid, reliable relief of unpredictable and predictable 'off' periods 3
- Also beneficial for patients with levodopa absorption or gastric emptying problems, or for rapid relief of early morning dystonia or akinesia 3
Common Side Effects and Management
- Injection-site reactions, yawning, dyskinesias, drowsiness, nausea/vomiting, dizziness, and rhinorrhea are common (occurring in ≥20% of patients) 2
- Skin problems, hypotension, confusion, and hallucinations may occur with long-term use 4
- Close medical supervision is recommended when initiating therapy 2
By following this dosing regimen and administration protocol, apomorphine can effectively manage 'off' episodes in patients with advanced Parkinson's disease who experience motor fluctuations despite optimized oral medication regimens.