What is the dosing schedule for pregabalin for neuropathic pain, fibromyalgia, generalized anxiety disorder, and seizures, and how should it be adjusted for elderly patients and renal impairment?

Pregabalin Dosing Guidelines

Start pregabalin at 75 mg twice daily (150 mg/day total) and increase to 300 mg/day within one week for most neuropathic pain conditions, fibromyalgia, and anxiety disorders; elderly patients and those with renal impairment require lower starting doses and slower titration. 1

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Standard Dosing by Indication

Neuropathic Pain (Postherpetic Neuralgia, Diabetic Peripheral Neuropathy)

• Initial dose: 75 mg twice daily or 50 mg three times daily (150 mg/day total) 1
• Target therapeutic dose: 300 mg/day (150 mg twice daily or 100 mg three times daily) within 1 week 1
• Maximum dose: 600 mg/day (300 mg twice daily or 200 mg three times daily), reserved only for patients with inadequate pain relief at 300 mg/day who tolerate the medication well 1
• Critical point: 300 mg/day provides the optimal benefit-to-risk ratio; doses above 300 mg/day are not consistently more effective but cause significantly more adverse effects 1
• Duration of adequate trial: Minimum 4 weeks at therapeutic dose (300 mg/day) before declaring treatment failure 1
• Onset of efficacy: Pain relief occurs within 1.5-3.5 days, significantly faster than gabapentin which requires 2+ months 1

Fibromyalgia

• Dosing range: 300-450 mg/day in divided doses 1
• Maximum dose: 600 mg/day 1
• Evidence: Patients more likely to report improvement with NNT of 4.8 1

Generalized Anxiety Disorder

• Dosing range: 200-600 mg/day divided into 2-3 daily doses 2
• Evidence: Significant reduction in Hamilton Anxiety Scale scores compared to placebo (P ≤ 0.01) 2

Seizures (Adjunctive Therapy for Partial-Onset)

• Dosing range: 150-600 mg/day divided into 2-3 doses 2
• Evidence: Significantly fewer seizures than placebo (P ≤ 0.001) 2

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Administration Schedule

• Frequency: Administer in 2-3 divided doses per day 1
• Food interaction: May be taken without regard to meals; food reduces rate but not extent of absorption 3
• Steady state: Achieved within 24-48 hours (1-2 days) of repeated administration 1, 3

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Elderly Patient Considerations

• Starting dose: Consider 75 mg at bedtime or 50 mg twice daily 1
• Titration: Slower titration with weekly increases as tolerated 1
• Rationale: Increased risk of dizziness (23-46%), somnolence (15-25%), confusion, balance disorder, tremor, coordination abnormalities, and falls 1
• Renal function: Elderly patients invariably have reduced renal function even with normal serum creatinine due to reduced muscle mass; always calculate creatinine clearance before initiating therapy 1

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Renal Impairment Dose Adjustments

Mandatory dose reduction required because pregabalin is eliminated 95-98% unchanged by the kidneys 1, 3, 4

Creatinine Clearance (CLcr)	Total Daily Dose Reduction	Example Dosing
30-60 mL/min	Reduce by ~50%	75 mg twice daily (150 mg/day)
15-30 mL/min	Reduce by ~75%	25-75 mg once or twice daily
<15 mL/min	Reduce by 85-90%	25-75 mg once daily

• Critical: Calculate creatinine clearance using Cockcroft-Gault equation before initiating therapy 1
• Elderly patients: Creatinine-based equations can misclassify kidney disease by one stage in >30% of elderly patients due to reduced muscle mass; consider CKD-EPI creatinine-cystatin C equation 1
• Severe impairment example: At CLcr 18 mL/min, AUC increases 6.3-fold and half-life doubles to 28 hours, necessitating maximum dose of 75 mg/day 1

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Pharmacokinetic Advantages Over Gabapentin

• Linear pharmacokinetics: Dose increases produce proportional increases in blood levels, making titration predictable 1, 3, 4
• High bioavailability: ~90% oral bioavailability, independent of dose 3, 4
• Rapid absorption: Peak plasma concentrations at 0.7-1.3 hours 3
• No hepatic metabolism: Not subject to CYP450 interactions; excreted virtually unchanged by kidneys 3, 4
• Faster efficacy: Noticeable effects within 1 week versus gabapentin requiring 2+ months 1

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Common Adverse Effects and Management

• Dizziness: 23-46% of patients, dose-dependent 1
• Somnolence: 15-25% of patients, dose-dependent 1
• Peripheral edema: 10% of patients 1
• Weight gain, dry mouth, constipation: Common but manageable 1
• Management strategy: Start with lower doses and implement gradual titration to minimize peak-related side effects; most adverse effects can be managed by dose reduction without discontinuing therapy 1, 5

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Critical Safety Warnings

• CNS depressant interactions: Serious breathing problems can occur when combined with opioid pain medications, benzodiazepines, or other CNS depressants 1
• Elderly vulnerability: Synergistic sedative effects increase fall risk, confusion, and respiratory depression 1
• Discontinuation: Taper gradually over minimum of 1 week to avoid withdrawal symptoms; never discontinue abruptly 1

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Common Pitfalls to Avoid

• Do not routinely prescribe 600 mg/day as standard dose: Evidence clearly shows 300 mg/day provides optimal benefit-to-risk ratio; 600 mg/day reserved only for subset with ongoing pain despite adequate trial at 300 mg/day 1
• Do not assume normal renal function in elderly based on serum creatinine alone: Always calculate CLcr 1
• Do not combine with gabapentin: No evidence supports combining two gabapentinoids; creates unacceptable additive sedative burden without established efficacy benefits 1
• Do not declare treatment failure before 4 weeks at therapeutic dose: Allow adequate trial period 1
• Do not use standard doses in renal impairment: Mandatory dose reduction required 1

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Switching from Gabapentin to Pregabalin

• Starting dose: 75 mg twice daily or 50 mg three times daily 1
• Transition plan: Start pregabalin 75 mg twice daily while continuing morning dose of gabapentin for first few days, then gradually taper gabapentin over several days to weeks 1
• Rationale: Pregabalin has more predictable absorption and linear pharmacokinetics compared to gabapentin 1
• Maximum dose comparison: Gabapentin 3600 mg/day versus pregabalin 600 mg/day 1

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Long-Term Use Considerations

• Duration: Pregabalin is intended for long-term, ongoing use to maintain pain control; not for short-term courses (e.g., 12 weeks) 1
• Frail elderly: Even in frail older adults with limited life expectancy, continuing pregabalin for neuropathic pain is "often adequate" 1
• No routine discontinuation: No guideline recommends stopping after specific time period if adequate pain relief achieved 1