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 in patients 1 month of age 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 total) 1
- Increase to 100 mg three times daily (300 mg/day) within 1 week based on efficacy and tolerability 1
- Maximum recommended dose is 300 mg/day - doses of 600 mg/day were studied but showed no additional benefit and were less well tolerated 1
- The optimal benefit-to-risk ratio is achieved at 300 mg/day, with NNT of 5.99 at this dose 2
Postherpetic Neuralgia
- Start at 75 mg twice daily or 50 mg three times daily (150 mg/day total) 1, 3
- Increase to 150 mg twice daily or 100 mg three times daily (300 mg/day) within 1 week 1, 3
- For patients with inadequate pain relief after 2-4 weeks at 300 mg/day who tolerate the medication well, may increase to 300 mg twice daily or 200 mg three times daily (600 mg/day) 1, 3
- Reserve doses above 300 mg/day only for patients with ongoing pain who tolerate 300 mg/day, as higher doses cause significantly more adverse effects without consistent additional benefit 1, 3
- This is the condition with strongest efficacy data: NNT of 3.9-5.3 for substantial benefit 3, 2
Fibromyalgia
- Start at 75 mg twice daily (150 mg/day) 2, 1
- Recommended dose range is 300-450 mg/day 2, 1
- May increase to 225 mg twice daily (450 mg/day) if insufficient benefit at 300 mg/day 1
- Maximum dose is 600 mg/day, but doses above 450 mg/day are not recommended due to lack of additional benefit and increased adverse effects 1
- NNT for patient-reported improvement is 4.8 2
Spinal Cord Injury-Related Neuropathic Pain
- Start at 75 mg twice daily (150 mg/day) 1
- 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
- Recommended dose range is 150-600 mg/day 1
Partial-Onset Seizures (Adjunctive Therapy)
Adults (17 years and older):
- Start at 150 mg/day in 2-3 divided doses 1
- Maximum dose is 600 mg/day in 2-3 divided doses 1
- Increase dosage approximately weekly based on clinical response and tolerability 1
Pediatric patients (1 month and older):
- Dosing is weight-based and complex - refer to FDA labeling for specific pediatric dosing tables 1
Critical Dosing Principles
The 300 mg/day Sweet Spot
For most neuropathic pain conditions, 300 mg/day provides the optimal benefit-to-risk ratio. 3, 1
- Doses above 300 mg/day are not consistently more effective but cause significantly greater adverse effects and higher treatment discontinuation rates 3, 1
- 600 mg/day should be reserved only for patients with inadequate pain relief at 300 mg/day who tolerate the medication well 3, 1
- Allow a minimum of 2-4 weeks at 300 mg/day before considering dose escalation 3
Pharmacokinetic Advantages
- Pregabalin has linear pharmacokinetics with 90% oral bioavailability, making dose titration predictable 3
- Effects are noticeable within 1 week, with pain relief occurring within 1.5-3.5 days 3, 2
- This is significantly faster than gabapentin, which requires 2+ months for adequate trial 3
- No hepatic metabolism and no cytochrome P-450 interactions 4
Special Population Dosing
Renal Impairment
Dose adjustment is mandatory in adult patients with reduced renal function, as pregabalin is eliminated primarily by renal excretion (95% unchanged). 3, 1
- CrCl 30-60 mL/min: Reduce total daily dose by approximately 50% 3, 2
- CrCl 15-30 mL/min: Reduce total daily dose by approximately 75% 3, 2
- CrCl <15 mL/min: Reduce total daily dose by 85-90% 3, 2
- For hemodialysis patients, administer supplemental dose immediately following every 4-hour hemodialysis treatment 1
Elderly Patients
Consider lower starting doses and slower titration in elderly patients due to increased risk of adverse effects. 3, 2
- Elderly patients are at higher risk for dizziness (23-46%), somnolence (15-25%), confusion, falls, peripheral edema, balance disorder, tremor, and coordination abnormalities 3, 2
- Start at the lowest recommended dose and titrate more gradually than in younger adults 3, 5
Administration Guidelines
General Principles
- Administer orally with or without food 1
- Divide total daily dose into 2-3 administrations per day 3, 1
- When discontinuing, taper gradually over a minimum of 1 week to avoid withdrawal symptoms 3, 1
- Allow adequate trial of 4 weeks at therapeutic dose before declaring treatment failure 3
Titration Strategy
- Start low and increase weekly to minimize adverse effects 3, 1
- Gradual titration over 1 week minimizes dose-dependent side effects like dizziness and somnolence 3
- Most patients can start at 150 mg/day in 2-3 divided doses 3
Critical Safety Warnings
Respiratory Depression
Serious breathing problems can occur when pregabalin is combined with opioid pain medications, benzodiazepines, or other CNS depressants. 2
- Monitor for increased somnolence or decreased respiratory rate when initiating or increasing pregabalin dose, especially in combination with opioids 2
- This is particularly dangerous in elderly patients 3
Common Adverse Effects
The most common dose-dependent adverse effects are: 3, 6, 4
- Dizziness (23-46%)
- Somnolence (15-25%)
- Peripheral edema (10%)
- Dry mouth
- Constipation
- Weight gain (14% at 600 mg/day) 7
- Ataxia and diplopia 6
These adverse effects can often be managed by dose reduction without discontinuing therapy. 3
Suicidality Risk
- Pregabalin may cause suicidal thoughts or actions in approximately 1 in 500 people 2
- Do not abruptly discontinue without consulting healthcare provider 2
Abuse Potential
- Pregabalin is a Schedule V controlled substance due to potential for abuse and dependence 4
- Male gender and concurrent prescription of antipsychotics and benzodiazepines are associated with increased risk of use above recommended dosages 8
Comparison with Gabapentin
When to Choose Pregabalin Over Gabapentin
Pregabalin has more predictable absorption and linear pharmacokinetics compared to gabapentin's nonlinear, saturable absorption. 3, 5
- Pregabalin provides faster pain relief (within 1 week vs. 2+ months for gabapentin) 3
- Pregabalin dosing is more straightforward due to linear kinetics 3, 5
- Maximum dose: pregabalin 600 mg/day vs. gabapentin 3600 mg/day 3, 5
Adverse Effect Profiles
Both medications have nearly identical adverse effect profiles, including dizziness, somnolence, peripheral edema, and weight gain at similar rates. 3, 5
- Switching from one to the other may not reduce side effects like dizziness 3
- Do not combine pregabalin with gabapentin - this creates unacceptable sedative burden, especially in elderly patients or those at risk for falls 3
Switching from Gabapentin to Pregabalin
- Start pregabalin 75 mg twice daily while continuing morning dose of gabapentin for first few days 3
- Gradually taper gabapentin over several days to weeks to avoid withdrawal symptoms 3
- For elderly or renally impaired patients, use lower doses and slower titration 3
Clinical Pitfalls to Avoid
Do not routinely prescribe 600 mg/day as standard dose - 300 mg/day provides optimal benefit-to-risk ratio for most patients 3, 1
Do not use standard doses in renal impairment - mandatory dose reduction required based on creatinine clearance 3, 2, 1
Do not abruptly discontinue - taper over minimum of 1 week to avoid withdrawal symptoms 3, 1
Do not combine with gabapentin - creates excessive sedative burden without established benefit 3
Do not underdose the trial period - allow minimum 4 weeks at therapeutic dose (typically 300 mg/day) before declaring treatment failure 3
Do not ignore fall risk in elderly - start lower and titrate slower in this population 3, 2
Do not combine carelessly with opioids or benzodiazepines - serious respiratory depression can occur 2