Apomorphine Injection Dosing for Parkinson's Disease
For treating 'off' episodes in Parkinson's disease, start apomorphine subcutaneous injection at 2 mg (0.2 mL) as a test dose, then titrate in 1 mg increments to an effective dose typically ranging from 2-6 mg per injection, with most patients requiring 3-4 mg per dose administered as needed for 'off' episodes (maximum 5 injections per day not exceeding 20 mg total daily dose). 1, 2
Initial Test Dosing and Titration
- Begin with a supervised test dose of 2 mg (0.2 mL) subcutaneously in a clinical setting to assess response and tolerability 1, 2
- If the 2 mg dose produces inadequate response after 20 minutes, increase by 1 mg increments at subsequent test sessions (typically separated by at least 2 hours) until an effective dose is identified 1
- The therapeutic rescue dose typically ranges from 2-6 mg per injection, with a mean effective dose of approximately 3.4-3.7 mg 3, 2
- Most patients achieve optimal benefit with 3-4 mg per injection 1, 3
Maintenance Dosing Parameters
- Administer the individualized effective dose subcutaneously as needed when 'off' episodes occur 1, 2
- Patients typically require an average of 3 rescue doses per day during maintenance therapy 1
- Maximum frequency: 5 injections per day 1
- Maximum total daily dose: 20 mg (cumulative from all injections) 1
- Onset of effect occurs within 10-20 minutes, with duration of action approximately 90-100 minutes 1, 4
Administration Technique
- Use subcutaneous injection sites with rotation to minimize skin complications 3
- Clean the injection site with alcohol before each administration 5
- The pen-injection formulation allows for self-administration after proper training 2
Mandatory Antiemetic Prophylaxis
- Initiate trimethobenzamide 300 mg three times daily starting 3 days before the first apomorphine dose to prevent severe nausea and vomiting 1
- Continue antiemetic prophylaxis during dose titration and for at least the first 2 months of therapy 1
- Close medical supervision is required when initiating apomorphine therapy 1
Clinical Indications for Apomorphine Injection
- Severe unpredictable 'off' periods despite optimized oral medications (most common indication in 75.7% of patients) 3
- Predictable 'off' episodes requiring rapid, reliable relief 6
- Delayed or failed 'on' response due to levodopa absorption or gastric emptying problems 6
- Early morning dystonia or akinesia requiring rapid relief 6
- Consider switching to continuous infusion if rescue injections are needed more than 4-6 times per day 6
Common Adverse Effects
- Injection-site reactions occur in >20% of patients and may include subcutaneous nodules 1, 3, 2
- Nausea and vomiting (mitigated by antiemetic prophylaxis) 1, 2
- Dyskinesias (may increase in frequency) 1, 2
- Yawning, drowsiness, dizziness or postural hypotension 1
- Rhinorrhea 1
- Serious neuropsychiatric effects are uncommon: only 1 patient developed new confusion and 5 developed new hallucinations in a 10-year audit of 107 patients 3
Critical Safety Considerations
- Do not use apomorphine with 5-HT3 antagonist antiemetics (ondansetron, granisetron, etc.) due to risk of profound hypotension and loss of consciousness 1
- Monitor for symptomatic hypotension, particularly during dose titration 3
- Rotate injection sites to prevent skin complications (occurred in 16 of 107 patients in long-term use) 3
- Apomorphine has linear pharmacokinetics with tmax ranging from 5-45 minutes and does not change with repeat dosing 2
Long-Term Efficacy
- Apomorphine injection reduces mean daily duration of 'off' periods by 51-58% compared to placebo 2
- The effect remains stable over time, with mean duration of intermittent injection use of 48.2 months in long-term follow-up 3
- Approximately 85% of patients continue long-term use, with only 16 of 107 patients discontinuing completely in a 10-year audit 3
- Patient satisfaction is high, with 72.2% preferring sublingual apomorphine formulation over subcutaneous when both are available, though both are effective 4