What is the recommended conversion dose from Lyrica (pregabalin) to gabapentin for neuropathic pain management?

Lyrica to Gabapentin Conversion

There is no established evidence-based conversion ratio between pregabalin (Lyrica) and gabapentin, so you must discontinue pregabalin and initiate gabapentin using standard titration protocols starting at 300 mg once daily or at bedtime, then titrate upward to therapeutic doses of 1800-3600 mg/day in three divided doses over 3-8 weeks. 1

Why No Direct Conversion Exists

• Pregabalin and gabapentin have fundamentally different pharmacokinetic profiles that prevent dose-for-dose conversion. 1
• Gabapentin has nonlinear, saturable absorption pharmacokinetics, making dose titration less predictable than pregabalin's linear pharmacokinetics 1
• Pregabalin has approximately 90% oral bioavailability regardless of dose, while gabapentin's bioavailability decreases as doses increase due to saturable intestinal transport mechanisms 2
• Despite both being α2δ ligands with similar mechanisms of action, their clinical dosing requirements differ substantially 3

Recommended Gabapentin Initiation Protocol

Starting Dose

• Begin gabapentin at 300 mg once daily or at bedtime on day 1 1, 4
• For elderly or medically frail patients, start at the lower end (100-300 mg at bedtime) with slower titration 1, 4

Titration Schedule

• Increase to 300 mg three times daily (900 mg/day total) by day 3 1
• Continue titrating upward by 300 mg increments every 3-7 days as tolerated 1, 4
• Target therapeutic dose range is 1800-3600 mg/day in three divided doses 1
• The minimum effective dose for most neuropathic pain conditions is 1800 mg/day (600 mg three times daily) 1
• Maximum dose of 3600 mg/day (1200 mg three times daily) may be needed for optimal pain relief 1

Time to Therapeutic Effect

• Allow 3-8 weeks for titration plus 2 weeks at maximum tolerated dose to properly evaluate efficacy 1, 4
• An adequate therapeutic trial may require 2 months or more to reach optimal effect 1, 4
• Do not declare treatment failure prematurely—efficacy for neuropathic pain develops gradually over several weeks 1

Critical Dosing Requirements for Gabapentin

• Three times daily dosing is mandatory for standard gabapentin due to saturable absorption—do not use once-daily or twice-daily schedules 1
• Doses must be spaced no more than 12 hours apart 4
• This differs fundamentally from pregabalin, which can be dosed twice daily due to its linear pharmacokinetics 5

Efficacy Data Supporting Target Doses

• In postherpetic neuralgia, gabapentin at 1200 mg/day or greater provided substantial benefit (≥50% pain relief) in 32% versus 17% with placebo (NNT 6.7) 6
• In painful diabetic neuropathy, gabapentin at 1200 mg/day or greater provided substantial benefit in 38% versus 21% with placebo (NNT 5.9) 6
• Doses of 1800-3600 mg/day are required for optimal efficacy in most neuropathic pain conditions 2

Renal Function Assessment (Non-Negotiable)

• Calculate creatinine clearance using the Cockcroft-Gault equation before initiating gabapentin therapy 4
• Gabapentin is eliminated primarily by renal excretion (98%), requiring mandatory dose reduction based on creatinine clearance 1, 4
• This is particularly critical in elderly patients who invariably have reduced renal function 4

Expected Adverse Effects

• Common adverse effects include dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (9%) 1, 6
• These effects are typically mild to moderate, dose-dependent, and often transient, usually subsiding within approximately 10 days 1, 2
• Adverse event withdrawals occur in 11% versus 8.2% with placebo (NNH 30) 6

Critical Pitfalls to Avoid

• Never start at high doses without gradual titration—this dramatically increases the risk of intolerable adverse effects, particularly falls in elderly patients 1, 4
• Do not rush titration in elderly patients, as this increases fall risk from dizziness 1
• Do not discontinue abruptly—taper gradually over at least 1 week to avoid withdrawal symptoms 1
• Do not fail to assess renal function before initiating therapy 4
• Do not assume lack of efficacy if adequate time for titration and therapeutic trial has not been allowed 4

Pregabalin Discontinuation

• While the evidence does not provide specific tapering protocols for pregabalin discontinuation, gradual tapering is prudent to avoid withdrawal symptoms 1
• You can overlap the pregabalin taper with gabapentin initiation, though combination therapy is not standard practice and lacks robust evidence for routine use 3