Initial Dosing of Pregabalin (Lyrica)
The recommended initial dose of pregabalin (Lyrica) is 75 mg twice daily (150 mg/day) for most indications, with slower titration starting at 25-50 mg at bedtime recommended to minimize side effects. 1, 2
Dosing by Indication
Neuropathic Pain
- Starting dose: 75 mg twice daily (150 mg/day)
- Titration: May increase to 300 mg/day within 1 week based on efficacy and tolerability
- Maximum dose: 300-600 mg/day (divided into 2-3 doses)
- Maintenance: 300 mg/day is often sufficient; doses above 300 mg/day should be reserved for patients with ongoing pain who tolerate lower doses 1
Fibromyalgia
- Starting dose: 75 mg twice daily (150 mg/day)
- Titration: May increase to 300 mg/day within 1 week
- Maximum dose: 300-450 mg/day
- Note: Although 600 mg/day was studied, there is no evidence of additional benefit, and this dose was less well tolerated 1, 3
Practical Dosing Approach
- Initial dosing: Start with 25-50 mg at bedtime to minimize side effects 2
- Gradual titration: Increase by 25-50 mg every 3-7 days as tolerated
- Target dose: Work toward 150-300 mg/day in divided doses (BID or TID)
Renal Adjustment
Pregabalin is eliminated primarily by renal excretion, so dose adjustment is required in patients with reduced renal function:
| Creatinine Clearance (mL/min) | Total Daily Dose Adjustment |
|---|---|
| ≥60 | No adjustment needed |
| 30-59 | Reduce to 50% of normal dose |
| 15-29 | Reduce to 25-50% of normal dose |
| <15 | Reduce to 25% of normal dose |
Side Effects to Monitor
- Common side effects: Dizziness (27-46%), somnolence (15-25%), peripheral edema (7-8%), weight gain 2, 1
- Neuropsychiatric effects: Monitor for emergence or worsening of depression, suicidal thoughts or behavior 1
- Cognitive effects: Attention, memory, and language problems may occur, especially in elderly patients 2
Important Considerations
- Pregabalin has faster titration (days) compared to gabapentin (weeks) 2
- Bioavailability is >90% (dose-independent), unlike gabapentin which has decreasing bioavailability with increasing doses 2
- Time to steady state is 24-48 hours 2
- Pregabalin can be safely combined with other medications due to minimal protein binding and negligible hepatic metabolism 4
- Use caution when combining with CNS depressants due to additive sedative effects 2
Discontinuation
Pregabalin should be discontinued gradually over at least 1 week to minimize withdrawal symptoms 3
Comparison to Gabapentin
| Parameter | Pregabalin | Gabapentin |
|---|---|---|
| Bioavailability | >90% (dose-independent) | Decreases with increasing dose |
| Dosing | 2-3 times daily | 3 times daily |
| Titration | Faster (days) | Slower (weeks) |
| Therapeutic dose | Lower (150-600 mg/day) | Higher (900-3600 mg/day) |
| Time to steady state | 24-48 hours | 1-2 days |