Pregabalin (Lyrica): Indications and Dosing
FDA-Approved Indications
Pregabalin is FDA-approved for five specific conditions: neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for partial-onset seizures (ages 1 month and older), fibromyalgia, and neuropathic pain associated with spinal cord injury. 1
Dosing by Indication
Diabetic Peripheral Neuropathy
Start at 50 mg three times daily (150 mg/day) and increase to 100 mg three times daily (300 mg/day) within 1 week based on efficacy and tolerability. 1
- The maximum recommended dose is 300 mg/day 1
- Doses of 600 mg/day were studied but showed no additional benefit and were less well tolerated 1
- Treatment above 300 mg/day is not recommended due to dose-dependent adverse reactions 1
- At 300 mg/day, the NNT for substantial benefit is 5.0 (4.0 to 6.6) 2
Postherpetic Neuralgia
Start at 75 mg twice daily or 50 mg three times daily (150 mg/day), then increase to 150 mg twice daily or 100 mg three times daily (300 mg/day) within 1 week. 1, 2
- For patients without sufficient pain relief after 2-4 weeks at 300 mg/day who tolerate the medication well, may increase to 600 mg/day (300 mg twice daily or 200 mg three times daily) 1, 2
- Reserve dosing above 300 mg/day only for patients with ongoing pain who are tolerating 300 mg/day 1
- At 300 mg/day, 50% of patients achieve at least 30% pain reduction versus 25% with placebo (NNT 3.9) 2
- At 600 mg/day, 62% achieve at least 30% pain reduction versus 24% with placebo (NNT 2.7) 2
Fibromyalgia
Start at 75 mg twice daily (150 mg/day), increase to 150 mg twice daily (300 mg/day) within 1 week, with a target dose of 300-450 mg/day. 1
- Patients without sufficient benefit at 300 mg/day may increase to 225 mg twice daily (450 mg/day) 1
- Maximum dose is 450 mg/day for fibromyalgia (not 600 mg/day as in neuropathic pain) 1
- Doses above 450 mg/day are not recommended due to dose-dependent adverse reactions 1
- The NNT for substantial benefit at 600 mg/day is 11 (7.1 to 21), much higher than for neuropathic pain conditions 2
Spinal Cord Injury-Related Neuropathic Pain
Start at 75 mg twice daily (150 mg/day), increase to 150 mg twice daily (300 mg/day) within 1 week. 1
- For patients without sufficient pain relief after 2-3 weeks at 300 mg/day who tolerate pregabalin, may increase to 300 mg twice daily (600 mg/day) 1
- Dose range is 150-600 mg/day 1
Partial-Onset Seizures (Adjunctive Therapy)
Adults (≥17 years): Start at 150 mg/day, maximum 600 mg/day in 2-3 divided doses. 1
- Pediatric patients ≥30 kg: Start at 2.5 mg/kg/day, maximum 10 mg/kg/day (not exceeding 600 mg/day) in 2-3 divided doses 1
- Pediatric patients <30 kg: Start at 3.5 mg/kg/day, maximum 14 mg/kg/day in 3 divided doses (ages 1 month to <4 years) or 2-3 divided doses (ages ≥4 years) 1
- Increase dosage approximately weekly based on clinical response and tolerability 1
Critical Dosing Principles
Optimal Therapeutic Dose
For most neuropathic pain conditions, 300 mg/day provides the optimal benefit-to-risk ratio, with 600 mg/day reserved only for patients with inadequate response at 300 mg/day who tolerate the medication well. 2, 1
- Higher doses (>300 mg/day) often don't provide additional benefits but significantly increase side effects and treatment discontinuation 2
- Allow a minimum of 2-4 weeks at 300 mg/day to assess adequate response before considering dose escalation 2
Pharmacokinetic Advantages
Pregabalin has linear pharmacokinetics with 90% oral bioavailability, making dosing predictable and straightforward. 2, 3
- Pain relief can occur within 1.5-3.5 days, with noticeable effects within 1 week 2, 4
- Full assessment of efficacy is possible after 4 weeks at therapeutic dose 2, 4
- This is faster than gabapentin, which requires 2+ months for adequate trial 2
Special Population Considerations
Elderly Patients
Start with lower doses and implement slower titration in elderly patients due to increased risk of dizziness, somnolence, confusion, balance disorders, and falls. 2, 1
- Common side effects in elderly include dizziness (23-46%), somnolence (15-25%), and peripheral edema (10%) 2
- These effects are dose-dependent and manageable with dose reduction 2
Renal Impairment
Mandatory dose reduction is required in patients with reduced renal function, as pregabalin is eliminated primarily unchanged by the kidneys. 2, 1
- For CrCl 30-60 mL/min: Reduce total daily dose by approximately 50% 2
- For CrCl 15-30 mL/min: Reduce total daily dose by approximately 75% 2
- For CrCl <15 mL/min: Reduce total daily dose by approximately 85-90% 2
- For hemodialysis patients: Adjust daily dose based on renal function plus supplemental dose immediately following every 4-hour hemodialysis treatment 1
Administration and Discontinuation
Administration
Administer pregabalin orally in 2-3 divided doses per day, with or without food. 2, 1
- Twice-daily dosing: 150 mg BID for 300 mg/day target 2
- Three-times-daily dosing: 100 mg TID for 300 mg/day target 2
Discontinuation
When discontinuing pregabalin, taper gradually over a minimum of 1 week to avoid withdrawal symptoms. 2, 1
- Abrupt discontinuation should be avoided 2
Common Side Effects
The most common side effects are dizziness (23-46%), somnolence (15-25%), dry mouth, constipation, peripheral edema, and weight gain. 2, 5
- Side effects are generally dose-dependent and manageable with dose reduction 2
- At 300 mg/day: somnolence 16% vs 5.5% placebo, dizziness 29% vs 8.1% placebo 2
- At 600 mg/day: somnolence 25% vs 5.8% placebo, dizziness 35% vs 8.8% placebo 2
- Gradual titration over 1 week minimizes these side effects 2
Critical Safety Warnings
Serious breathing problems can occur when pregabalin is combined with opioid pain medications, benzodiazepines, or other CNS depressants. 2
- Monitor all patients for dizziness, somnolence, and neurological side effects, especially during dose titration 2
- Be particularly cautious in elderly patients who may be more susceptible to falls 2
Comparison with Gabapentin
Pregabalin has more predictable absorption and linear pharmacokinetics compared to gabapentin's nonlinear, saturable absorption. 2
- When switching from gabapentin to pregabalin, start at 50 mg three times daily or 75 mg twice daily 2
- Maximum dose: pregabalin 600 mg/day versus gabapentin 3600 mg/day 2
- Both medications have nearly identical adverse effect profiles 2
- The combination of pregabalin and gabapentin should be avoided due to additive sedative effects, especially in elderly patients or those with fall risk. 2
- The efficacy of adjunctive pregabalin in patients taking gabapentin has not been evaluated in controlled trials 1
Evidence Quality by Condition
Postherpetic neuralgia and painful diabetic neuropathy have the strongest evidence for pregabalin efficacy (moderate-quality evidence), with NNTs generally 6 and below for 300-600 mg/day. 2, 5