What is the recommended titration schedule for Gabapentin (Neurontin)?

Gabapentin Titration Schedule

The recommended titration schedule for gabapentin starts with 100-300 mg at bedtime or 100-300 mg three times daily, with dose increments of 100-300 mg every 1-7 days as tolerated, aiming for an effective dose range of 900-3600 mg/day in divided doses. 1

Initial Dosing and Titration

For Neuropathic Pain:

• Starting dose: 100-300 mg at bedtime or 100-300 mg three times daily 1
• Titration rate: Increase by 100-300 mg every 1-7 days as tolerated 1
• Target maintenance dose: 900-3600 mg/day in divided doses (2-3 times daily) 1
• Duration of titration: 3-8 weeks for titration plus 2 weeks at maximum dose to assess efficacy 1

For Postherpetic Neuralgia (FDA-approved indication):

• Day 1: Single 300 mg dose 2
• Day 2: 600 mg/day (300 mg twice daily) 2
• Day 3: 900 mg/day (300 mg three times daily) 2
• Subsequent titration: Increase as needed for pain relief up to 1800 mg/day (600 mg three times daily) 2
• Maximum dose: Although efficacy was demonstrated across 1800-3600 mg/day, additional benefit beyond 1800 mg/day was not demonstrated in clinical studies 2

For Epilepsy (FDA-approved indication):

• Adults and children 12 years and older: Start with 300 mg three times daily 2
• Maintenance dose: 300-600 mg three times daily 2
• Maximum dose: Up to 2400 mg/day has been well tolerated in long-term studies; doses up to 3600 mg/day have been administered for short durations 2

Special Populations

Elderly Patients:

• Consider lower starting dosages and slower titration 1
• Starting dose: 100-200 mg/day 1
• Increase incrementally at longer intervals to allow monitoring of effects 1

Patients with Renal Impairment:

• Dosage adjustment required based on creatinine clearance 1, 2
• For creatinine clearance 30-59 mL/min: 400-1400 mg/day in divided doses 2
• For creatinine clearance 15-29 mL/min: 200-700 mg/day in divided doses 2
• For creatinine clearance <15 mL/min: 100-300 mg once daily 2
• Supplemental dose after hemodialysis is recommended 2

Clinical Considerations

Pharmacokinetics:

• Gabapentin has nonlinear pharmacokinetics due to saturable absorption, requiring careful titration 1
• Maximum time between doses should not exceed 12 hours 2

Adverse Effects:

• Most common: dizziness, somnolence, and sedation 1, 3
• These effects can be reduced by starting with lower doses and titrating cautiously 1
• Adverse effects are typically mild to moderate and usually subside within approximately 10 days from initiation 4

Efficacy Considerations:

• An adequate trial requires 3-8 weeks for titration plus 2 weeks at maximum dose 1
• Higher doses (1800-3600 mg/day) may provide greater efficacy in some patients 4, 3
• Some patients may respond to rapid titration, with treatment started at 900 mg/day (300 mg three times daily) from day 1 5

Practical Approach to Titration

1. Initial phase: Start with 100-300 mg at bedtime or 100-300 mg three times daily 1
2. Gradual increase: Titrate by 100-300 mg every 1-7 days as tolerated 1
3. Assessment: Evaluate pain relief and side effects at each dose level 4
4. Maintenance: Continue titration until adequate pain relief is achieved, side effects become unmanageable, or maximum dose of 3600 mg/day is reached 1, 4

Common Pitfalls and Caveats

• Underdosing: Many patients are maintained on suboptimal doses; higher doses may be required for adequate pain control 4, 3
• Premature discontinuation: An adequate trial requires at least 3-8 weeks plus 2 weeks at maximum dose 1
• Abrupt discontinuation: If gabapentin needs to be discontinued, it should be tapered gradually over at least 1 week to avoid withdrawal symptoms 2
• Divided dosing: Administering gabapentin in divided doses (2-3 times daily) is important for optimal efficacy due to its short half-life 2, 4
• Renal function: Failure to adjust dosing based on renal function can lead to excessive side effects 1, 2