What is the dosing guideline for Lyrica (pregabalin)?

Pregabalin (Lyrica) Dosing Guidelines

The recommended starting dose of pregabalin (Lyrica) is 150 mg/day, which can be titrated up to 600 mg/day based on efficacy and tolerability, with dose adjustments required for patients with renal impairment. 1, 2

General Dosing Recommendations

Neuropathic Pain

• Starting dose: 150 mg/day (divided into 2-3 doses)
• Titration: Can increase to 300 mg/day within 1 week based on efficacy and tolerability
• Maximum dose:
  • 450 mg/day for diabetic peripheral neuropathy (no additional benefit at 600 mg/day with increased side effects) 2
  • 600 mg/day for postherpetic neuralgia and spinal cord injury-related pain 1, 2

Dosing Schedule

• Divided doses: BID (twice daily) or TID (three times daily)
• Can be taken with or without food (food does not significantly affect absorption) 3

Renal Dosing Adjustments

Pregabalin is eliminated primarily through renal excretion, requiring dose adjustments in patients with impaired renal function 2:

Creatinine Clearance (mL/min)	Total Daily Dose Range (mg/day)	Dose Regimen
≥60	150-600	BID or TID
30-59	75-300	BID or QD
15-29	25-150	QD or BID
<15	25-75	QD

For hemodialysis patients: Administer supplemental dose immediately following each 4-hour hemodialysis session 2

Efficacy by Condition

Postherpetic Neuralgia

• Most effective condition for pregabalin treatment
• NNT for 50% pain reduction: 3.9 at 600 mg/day 4
• Recommended dose: 150-600 mg/day 1

Diabetic Peripheral Neuropathy

• Effective at 300-450 mg/day
• NNT for 50% pain reduction: 5.0 at 600 mg/day 4
• 450 mg/day is maximum recommended dose 2

Neuropathic Pain Associated with Spinal Cord Injury

• Starting dose: 75 mg twice daily (150 mg/day)
• May increase to 300 mg twice daily (600 mg/day) 2

Central Neuropathic Pain

• NNT for 50% pain reduction: 5.6 at 600 mg/day 4

Fibromyalgia

• Less effective than for neuropathic conditions
• NNT for 50% pain reduction: 11 at 600 mg/day 4

Common Side Effects

• Dizziness: 27-46% at 600 mg/day (dose-dependent) 5, 4
• Somnolence: 15-25% at 600 mg/day (dose-dependent) 5, 4
• Other common effects: peripheral edema, weight gain, dry mouth, blurred vision 1
• Treatment discontinuation due to adverse events: 18-28% 5

Important Considerations

1. Titration approach: Start low and titrate based on response and tolerability
2. Avoid abrupt discontinuation: Taper gradually over at least 1 week
3. Monitor for abuse potential: Higher risk in patients with history of substance abuse; 9.6% of patients use >600 mg/day for extended periods 6
4. Elderly patients: Start at lower doses and titrate more slowly
5. Pharmacokinetics:
   • Bioavailability: ~90%
   • Half-life: ~6 hours
   • No significant hepatic metabolism (95% excreted unchanged in urine) 3, 7
6. No significant drug interactions: Pregabalin is not metabolized by cytochrome P450 enzymes 7

Treatment Failure Considerations

If inadequate response after 2-3 weeks at maximum tolerated dose, consider:

1. Adding another first-line agent (SNRI, TCA)
2. Switching to alternative first-line agent
3. Referral to pain specialist if complex management is needed 1

Pregabalin shows no evidence of benefit in HIV neuropathy and limited evidence in neuropathic back pain, cancer pain, or polyneuropathy 4.