Gabapentinoids: Recommended Uses and Dosing
FDA-Approved Indications
Gabapentinoids are FDA-approved for postherpetic neuralgia, neuropathic pain (pregabalin for diabetic neuropathy), and adjunctive treatment of partial-onset seizures, with pregabalin also approved for fibromyalgia. 1, 2
Gabapentin Approved Uses:
- Postherpetic neuralgia 1
- Adjunctive therapy for partial-onset seizures in adults and children ≥3 years 1
Pregabalin Approved Uses:
- Postherpetic neuralgia 2
- Diabetic peripheral neuropathy 2
- Adjunctive therapy for partial-onset seizures in patients ≥1 month 2
- Fibromyalgia 3
Gabapentin Dosing
For Neuropathic Pain (Postherpetic Neuralgia)
Start gabapentin at 300 mg on Day 1, increase to 300 mg twice daily on Day 2, then 300 mg three times daily (900 mg/day) on Day 3, with target therapeutic dose of 1800-3600 mg/day in three divided doses. 4, 1
Titration Schedule:
- Day 1: 300 mg once daily (at bedtime) 4, 1
- Day 2: 300 mg twice daily (600 mg/day) 1
- Day 3: 300 mg three times daily (900 mg/day) 1
- Subsequent titration: Increase by 300 mg every 3-7 days until reaching 1800-3600 mg/day 4
Target Doses:
- Minimum effective dose: 1800 mg/day (600 mg three times daily) 4
- Maximum dose: 3600 mg/day (1200 mg three times daily) 4, 1
- Maximum single dose: 1200 mg 5
Critical Dosing Considerations:
- Three times daily dosing is mandatory due to saturable, nonlinear absorption pharmacokinetics 4
- Maximum interval between doses should not exceed 12 hours 1
- Efficacy may require 2 months or more for full effect 4, 5
- Doses >1800 mg/day showed comparable effects in clinical trials, with additional benefit not clearly demonstrated 1
For Partial-Onset Seizures
Adults: Start 300 mg three times daily, with maintenance dose of 300-600 mg three times daily (900-1800 mg/day); maximum 3600 mg/day 1
Pediatric (3-11 years): Start 10-15 mg/kg/day in three divided doses, titrate over 3 days to maintenance dose of 25-35 mg/kg/day (ages 5-11) or 40 mg/kg/day (ages 3-4) 1
Pregabalin Dosing
For Neuropathic Pain
Start pregabalin at 75 mg twice daily or 50 mg three times daily (150 mg/day), increase to 150 mg twice daily (300 mg/day) within 1 week, with maximum dose of 600 mg/day only for patients with inadequate response who tolerate 300 mg/day well. 3, 2
Titration Schedule:
- Initial dose: 75 mg twice daily or 50 mg three times daily (150 mg/day) 3
- Week 1: Increase to 150 mg twice daily or 100 mg three times daily (300 mg/day) 3
- If needed after 2-4 weeks: May increase to 300 mg twice daily or 200 mg three times daily (600 mg/day) 3
Key Dosing Points:
- Standard effective dose: 300 mg/day (150 mg twice daily) 3
- Maximum dose: 600 mg/day 3, 2
- Higher doses (>300 mg/day) often don't provide additional benefits but increase side effects 3
- Pregabalin has linear pharmacokinetics, making dosing more predictable than gabapentin 3
- Effects noticeable within 1 week; adequate trial requires 4 weeks at therapeutic dose 3
For Partial-Onset Seizures
Adults: 150-600 mg/day in 2-3 divided doses 2
Pediatric (4-<17 years): 2.5-10 mg/kg/day (maximum 600 mg/day) in two divided doses; increase dose by 40% for patients <30 kg 2
Pediatric (1 month-<4 years): 7-14 mg/kg/day in three divided doses 2
For Fibromyalgia
Dosing range: 300-450 mg/day in divided doses, maximum 600 mg/day 3
Renal Dose Adjustments
Gabapentin Renal Dosing 1
| CrCl (mL/min) | Total Daily Dose | Regimen |
|---|---|---|
| ≥60 | 900-3600 mg/day | 300-1200 mg TID |
| 30-59 | 400-1400 mg/day | 200-700 mg BID |
| 15-29 | 200-700 mg/day | 200-700 mg QD |
| <15 | 100-300 mg/day | 100-300 mg QD |
| Hemodialysis | Maintenance dose based on CrCl + supplemental post-HD dose | 125-350 mg after each 4-hour HD session |
Pregabalin Renal Dosing 3
Dose reductions required for renal impairment (pregabalin is 98% renally excreted): 3
- CrCl 30-60 mL/min: Reduce total daily dose by ~50%
- CrCl 15-30 mL/min: Reduce total daily dose by ~75%
- CrCl <15 mL/min: Reduce total daily dose by ~85-90%
Special Populations
Elderly Patients
Start at lower doses with slower titration in elderly patients due to increased risk of falls, confusion, dizziness, and somnolence. 4, 3
- For gabapentin: Start 100 mg at bedtime, increase by 300 mg every 3-7 days 4
- For pregabalin: Consider lower starting doses and slower titration 3
- Dose adjustment based on creatinine clearance is mandatory, as elderly patients often have decreased renal function 4, 1
Hemodialysis Patients
Use gabapentinoids judiciously in hemodialysis patients, as they are associated with significantly increased risk of altered mental status (50% higher), falls (55% higher), and fractures (38% higher) even at low doses. 6
- Gabapentin doses >100 mg/day associated with 31-41% higher hazard of altered mental status 6
- Supplemental post-hemodialysis dosing required for gabapentin 1
Switching Between Gabapentinoids
Transitioning from Gabapentin to Pregabalin
Start pregabalin 75 mg twice daily while continuing the morning dose of gabapentin for the first few days, then gradually taper gabapentin over several days to weeks. 3
- Pregabalin has more predictable absorption and linear pharmacokinetics compared to gabapentin 3
- Both medications have nearly identical adverse effect profiles 3
- In clinical practice, patients prescribed pregabalin achieve therapeutic doses more rapidly than those prescribed gabapentin (69% vs 3.5% by first prescription) 7
Discontinuation
Taper gabapentinoids gradually over a minimum of 1 week when discontinuing to avoid withdrawal symptoms; longer tapering periods may be needed at prescriber's discretion. 3, 1
- Abrupt cessation may induce withdrawal symptoms including anxiety, insomnia, nausea, pain, and sweating 8
- Dependence may develop with chronic use 8
Common Side Effects
Both gabapentin and pregabalin cause dizziness (23-46%), somnolence (15-25%), peripheral edema (10%), dry mouth, constipation, and weight gain, with side effects being dose-dependent. 3, 9
Strategies to Minimize Side Effects:
- Start with lower doses and titrate slowly 4, 5
- Use divided dosing to minimize peak-related effects 3
- Consider dose reduction if side effects are intolerable 9
- Be particularly cautious in elderly patients due to increased fall risk 4, 6
Critical Safety Warnings
Serious breathing problems can occur when pregabalin is combined with opioid pain medications, benzodiazepines, or other CNS depressants. 3
- Monitor for respiratory depression when combining with CNS depressants 3
- Both medications have potential for nonmedical use due to euphoria, sedation, and disinhibition effects 8
- Widespread nonmedical use has increased incidence of accidental and deliberate poisonings 8
Clinical Pearls
Gabapentin:
- Nonlinear pharmacokinetics make dose titration less predictable 4
- Once-daily or twice-daily dosing is inadequate; three times daily is essential 4
- Allow full 2-month trial period before declaring treatment failure 4
- Minimal drug interactions due to lack of hepatic metabolism 4
Pregabalin:
- Linear pharmacokinetics allow more straightforward dosing 3
- Can be dosed twice or three times daily 3, 2
- Faster titration to therapeutic doses compared to gabapentin 7
- In postherpetic neuralgia, 300 mg/day is standard; higher doses may not provide additional benefit 3
Off-Label Uses with Limited Evidence:
- Chronic nonspecific back pain and nonradicular leg pain have limited evidence 8
- Unexplained chronic cough: 300 mg once daily, escalate to maximum 1800 mg/day in two divided doses 4
- HIV-associated neuropathic pain: Gabapentin titrated to 2400 mg/day over 4 weeks (strong recommendation, moderate-quality evidence) 4