PREEMPT Dosing Protocol for Chronic Migraine
Administer onabotulinumtoxinA 155-195 units across 31-39 injection sites every 12 weeks following the standardized PREEMPT protocol. 1, 2
Specific Dosing Parameters
- Total dose range: 155-195 units per treatment session 1, 2
- Number of injection sites: 31-39 sites distributed across specific head and neck muscle groups 1, 2
- Treatment interval: Every 12 weeks (approximately 3 months) 1, 3
- Administration route: Intramuscular injection using the fixed-site, fixed-dose PREEMPT injection pattern 2
PREEMPT Injection Protocol Distribution
The PREEMPT protocol requires injecting specific anatomical sites across seven head and neck muscle areas 2:
- Frontalis: 20 units divided into 4 sites (5 units per site) 2
- Corrugator: 10 units divided into 2 sites (5 units per site) 2
- Procerus: 5 units in 1 site 2
- Occipitalis: 30 units divided into 6 sites (5 units per site) 2
- Temporalis: 40 units divided into 8 sites (5 units per site) 2
- Trapezius: 30 units divided into 6 sites (5 units per site) 2
- Cervical paraspinal muscles: 20 units divided into 4 sites (5 units per site) 2
This accounts for the base dose of 155 units. The additional 40 units (up to 195 units total) can be administered using a "follow-the-pain" approach to areas of predominant pain, distributed across the temporalis, occipitalis, and trapezius muscles 2.
Treatment Evaluation Timeline
- Initial assessment period: Patients require at least 2-3 treatment cycles (24-36 weeks) before being classified as non-responders 1, 3
- Response criteria: A reduction of at least 30% in monthly headache days is required to define treatment response 3, 2
- Efficacy assessment: Evaluate response after 6-9 months (2-3 treatment cycles at 12-week intervals) 3
- Documentation at each visit: Record headache frequency, intensity, cumulative headache hours, acute medication usage, and quality of life measures 1, 3
Expected Clinical Outcomes
The PREEMPT trials demonstrated that onabotulinumtoxinA produces 4, 5:
- Reduction in headache days: Mean decrease of 8.4 days per month from baseline at 24 weeks (compared to 6.6 days with placebo) 4
- Reduction in migraine days: Statistically significant decrease of approximately 1.9-3.1 days per month compared to placebo 1
- Long-term efficacy: Real-world data shows reduction from baseline mean of 20.6 headache days to 7.4 days at the 8th administration visit 6
- Quality of life improvement: Significant improvements in all Migraine-Specific Quality of Life domains and health-related quality of life scores 1, 6
Critical Treatment Considerations
Patient selection criteria before initiating onabotulinumtoxinA 1, 3:
- Confirmed diagnosis of chronic migraine (≥15 headache days per month for at least 3 months, with headaches lasting ≥4 hours) 1, 3
- Failure of 2-3 oral preventive medications (topiramate, propranolol, amitriptyline, valproate, or venlafaxine) 1, 3
- Not indicated for episodic migraine (<15 headache days per month) 1
Medication overuse headache management 1:
- Address concurrent medication overuse by limiting simple analgesics to <15 days per month and triptans to <10 days per month 1
- OnabotulinumtoxinA can be initiated while addressing medication overuse; withdrawal and preventive therapy can be managed in parallel 1
Discontinuation Criteria
- Less than 30% reduction in headache days per month after 2-3 treatment cycles 3, 2
- Patient achieves reduction to <10 headache days per month for 3 consecutive months 2
- Re-evaluate patients 4-5 months after stopping to ensure they have not returned to chronic migraine status 2
Safety Profile
- Adverse events occur in approximately 62% of treated patients, with most being mild to moderate in severity 4
- Most common adverse drug reactions: eyelid ptosis (5.4%), neck pain (2.8%), and musculoskeletal stiffness (2.7%) 6
- Discontinuation rate due to adverse events is low (3.8%) 4
- Long-term treatment through 5 cycles (56 weeks) demonstrates continued safety with no new safety concerns 7