A patient taking pregabalin (Lyrica) 200 mg three times daily needs to be switched to gabapentin; what is the appropriate starting dose of gabapentin?

Gabapentin Starting Dose When Switching from Pregabalin 200 mg TID

Start gabapentin at 300 mg three times daily (900 mg/day total) on day 1, then titrate upward by 300 mg every 3–7 days as tolerated, targeting a therapeutic dose of 1800–3600 mg/day in three divided doses. 1, 2

Rationale for Initial 900 mg/Day Dose

• The FDA-approved gabapentin titration schedule begins at 300 mg on day 1, increases to 600 mg/day (300 mg twice daily) on day 2, and reaches 900 mg/day (300 mg three times daily) by day 3. 2 However, when switching from pregabalin 600 mg/day (200 mg TID), starting directly at 900 mg/day (300 mg TID) is appropriate because the patient is already tolerating a therapeutic dose of a gabapentinoid. 1

• Pregabalin 600 mg/day represents the maximum recommended dose and is at the upper end of the therapeutic range, typically reserved for patients with inadequate pain relief at 300 mg/day. 3 This suggests the patient requires robust gabapentinoid therapy.

• There is no established conversion ratio between pregabalin and gabapentin because they have different pharmacokinetic profiles—pregabalin has linear, predictable absorption with >90% bioavailability, while gabapentin has nonlinear, saturable absorption that becomes less efficient at higher doses. 1, 3

Target Therapeutic Dose Range

• The minimum effective dose for neuropathic pain is 1800 mg/day (600 mg three times daily), with a target therapeutic range of 1800–3600 mg/day in three divided doses. 1, 4 Doses of 1800–3600 mg/day provide moderate-quality evidence for efficacy, with 32–38% of patients achieving ≥50% pain reduction versus 17–21% with placebo. 1

• Titrate gabapentin by 300 mg increments every 3–7 days as tolerated until reaching the target dose of at least 1800 mg/day. 1, 2 For example: start at 900 mg/day (300 mg TID), increase to 1200 mg/day (400 mg TID) after 3–7 days, then to 1800 mg/day (600 mg TID) after another 3–7 days. 1

• Allow 3–8 weeks for titration plus 2 weeks at maximum tolerated dose before declaring treatment failure, as an adequate trial of gabapentin can require 2 months or more, with efficacy developing gradually over several weeks. 1, 4

Critical Dosing Requirements

• Gabapentin must be administered three times daily because of its nonlinear, saturable absorption; the interval between doses must not exceed 12 hours. 1, 2 Once-daily or twice-daily regimens lead to subtherapeutic levels and treatment failure. 1

• Mandatory renal function assessment is required before initiating gabapentin, as the drug is eliminated primarily by renal excretion and dose reduction is mandatory based on creatinine clearance. 1, 4, 2 Calculate creatinine clearance using the Cockcroft-Gault equation. 1, 2

Renal Dose Adjustments

Creatinine Clearance	Total Daily Dose	Dosing Frequency
≥60 mL/min	900–3600 mg	Three times daily
30–59 mL/min	400–1400 mg	Twice daily
15–29 mL/min	200–700 mg	Once daily
<15 mL/min	100–300 mg	Once daily

1, 2

Transition Strategy from Pregabalin

• Begin gabapentin 300 mg three times daily (900 mg/day) while continuing the morning dose of pregabalin for at least the first few days, then gradually taper off pregabalin over several days to weeks to avoid withdrawal symptoms. 3 This overlap minimizes the risk of breakthrough pain during the transition.

• Taper pregabalin gradually over a minimum of 1 week when discontinuing, as abrupt discontinuation can cause withdrawal symptoms. 3, 2 For example, reduce pregabalin from 200 mg TID to 100 mg TID for 3–4 days, then to 50 mg TID for 3–4 days, then discontinue. 3

Special Population Considerations

• In elderly patients (≥65 years), start with lower doses (100–200 mg/day) and titrate more slowly (increments every 3–7 days or longer) to minimize adverse effects including dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (9%), which increase fall risk. 1, 4

• Elderly patients often have reduced renal function masked by normal serum creatinine due to reduced muscle mass, so always calculate creatinine clearance rather than relying on serum creatinine alone. 3

Common Pitfalls to Avoid

• Do not start at high doses (such as 1800 mg/day) without gradual titration, as this dramatically increases the risk of intolerable adverse effects, particularly dizziness and somnolence. 4, 5

• Do not declare treatment failure before completing the full 2-month trial at therapeutic doses (≥1800 mg/day), as efficacy develops gradually over weeks. 1, 4

• Do not use once-daily or twice-daily dosing for standard gabapentin, as three-times-daily administration is essential due to saturable absorption. 1

• Do not assume gabapentin will work if pregabalin failed—patients may respond to pregabalin, gabapentin, both, or neither, and there is no evidence supporting sequential gabapentinoid use. 3 However, switching is reasonable if pregabalin was discontinued due to intolerable side effects rather than lack of efficacy. 3

Expected Outcomes and Adverse Effects

• Common adverse effects include dizziness, somnolence, peripheral edema, and gait disturbance, which are typically mild to moderate, dose-dependent, and often transient, usually subsiding within approximately 10 days. 1, 5

• About 32–38% of patients achieve at least 50% pain reduction with gabapentin at therapeutic doses (1800–3600 mg/day), compared to 17–21% with placebo. 1 Adverse event withdrawals occur in 11% of patients versus 8.2% with placebo. 4

• Gabapentin and pregabalin have nearly identical adverse effect profiles, so if the patient experienced intolerable side effects with pregabalin, switching to gabapentin may not necessarily reduce these effects. 3