Maximum Recommended Dose of Pregabalin (Lyrica)
The maximum recommended dose of pregabalin (Lyrica) is 600 mg per day, typically divided into 2-3 doses. 1, 2
Dosing Guidelines by Indication
Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
- Starting dose: 50 mg three times daily (150 mg/day)
- Maximum recommended dose: 100 mg three times daily (300 mg/day) 2
- Higher doses (600 mg/day) do not confer additional benefits and are associated with more adverse effects 2
Postherpetic Neuralgia
- Starting dose: 75 mg twice daily or 50 mg three times daily (150 mg/day)
- Initial maximum: 300 mg/day (can be reached within 1 week)
- Extended maximum: Up to 600 mg/day (300 mg twice daily or 200 mg three times daily) for patients who:
- Do not experience sufficient pain relief after 2-4 weeks at 300 mg/day
- Can tolerate the medication
- Have ongoing pain 2
Fibromyalgia
- Starting dose: 75 mg twice daily (150 mg/day)
- Recommended dose range: 300-450 mg/day
- Maximum dose: 450 mg/day (225 mg twice daily) 2
- Although studied at 600 mg/day, there is no evidence of additional benefit at this dose, and it was less well tolerated 2
Adjunctive Therapy for Partial-Onset Seizures
- Adults: Starting at 150 mg/day with maximum of 600 mg/day 2
- Pediatric patients ≥30 kg: Maximum 10 mg/kg/day (not to exceed 600 mg/day) 2
- Pediatric patients <30 kg: Maximum 14 mg/kg/day 2
Dosing Considerations
Renal Impairment
Pregabalin is eliminated primarily by renal excretion (98%), requiring dose adjustments in patients with reduced renal function 2, 3:
| Creatinine Clearance (mL/min) | Total Daily Dose Range (mg/day) | Dose Regimen |
|---|---|---|
| ≥60 | 900-3600 | 300-1200 mg TID |
| >30-59 | 400-1400 | 200-700 mg BID |
| >15-29 | 200-700 | 200-700 mg QD |
| ≤15 | 100-300 | 100-300 mg QD |
Titration Recommendations
- Begin with lower doses and gradually increase to minimize adverse effects 1
- For most indications, allow 1 week between dose increases 2
- When discontinuing, taper gradually over a minimum of 1 week to avoid withdrawal symptoms 2
Efficacy and Dose-Response Relationship
The efficacy of pregabalin is dose-dependent, but so are adverse effects:
- In postherpetic neuralgia, significant pain reduction is seen even at 150 mg/day 4
- In diabetic neuropathy, 300 mg/day is typically required for significant pain reduction 3, 4
- For mixed neuropathic pain conditions, 600 mg/day shows better efficacy than lower doses 4
- Doses above 300 mg/day are associated with higher rates of adverse effects without consistently better efficacy 1, 2
Common Adverse Effects
Adverse effects are dose-dependent and include:
- Dizziness: 13-46% (increasing with dose) 4, 5
- Somnolence: 11-32% (increasing with dose) 4, 5
- Peripheral edema: 10.4% 3
These side effects are generally mild to moderate and can often be managed with dose reduction rather than discontinuation 3.
Important Considerations
- Pregabalin has a high oral bioavailability (approximately 90%) 6
- It can be taken with or without food 2
- Plasma half-life is about 6 hours 6
- While rare, some patients may use pregabalin above recommended dosages (9.6% used >600 mg/day for 6+ months in one study) 7
- Male gender and concurrent use of antipsychotics or benzodiazepines are associated with higher risk of using above-recommended dosages 7
Pregabalin's maximum dose of 600 mg/day should be reserved for specific indications and patients who have not achieved adequate pain relief at lower doses, while carefully monitoring for adverse effects.