What are the uses and dosage of Pregabalin (Pregaba NT) for conditions like epilepsy, neuropathic pain, and anxiety disorders?

Pregabalin (Pregaba NT): Uses and Dosage

Pregabalin is FDA-approved for neuropathic pain (diabetic peripheral neuropathy and postherpetic neuralgia), partial-onset seizures, and fibromyalgia, with dosing ranging from 150-600 mg/day in divided doses, starting at 75 mg twice daily or 50 mg three times daily. 1

FDA-Approved Indications

Neuropathic Pain Associated with Diabetic Peripheral Neuropathy

• Start at 50 mg three times daily (150 mg/day) 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 above this provide no additional benefit and increase adverse effects 1
• The 600 mg/day dose studied in trials was less well tolerated without additional efficacy 1
• Number needed to treat (NNT) is 5.99 for 300 mg/day and 4.04 for 600 mg/day 2

Postherpetic Neuralgia

• Start at 75 mg twice daily or 50 mg three times daily (150 mg/day) 1
• Increase to 150 mg twice daily or 100 mg three times daily (300 mg/day) within 1 week 1
• For patients with inadequate pain relief after 2-4 weeks on 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
• Reserve doses above 300 mg/day only for patients with ongoing pain who tolerate 300 mg/day 1
• Effects are noticeable within 1 week, with full efficacy assessment possible after 4 weeks 3

Partial-Onset Seizures (Adjunctive Therapy)

• Adults: Start at 150 mg/day, maximum 600 mg/day in 2-3 divided doses 1
• Pediatric patients ≥30 kg: Start at 2.5 mg/kg/day, maximum 10 mg/kg/day (not exceeding 600 mg/day) 1
• Pediatric patients <30 kg: Start at 3.5 mg/kg/day, maximum 14 mg/kg/day 1
• Dose escalation should occur approximately weekly based on response and tolerability 1

Fibromyalgia

• Start at 75 mg twice daily (150 mg/day) 1
• Increase to 150 mg twice daily (300 mg/day) within 1 week 1
• Recommended dose range is 300-450 mg/day 4, 1
• Maximum dose is 600 mg/day 4
• NNT for patient-reported improvement is 4.8 4

Off-Label Use: Central Poststroke Pain

• Pregabalin is considered a second-line treatment for central poststroke pain after amitriptyline and lamotrigine 2
• Two clinical trials found pregabalin was not significantly better than placebo for daily pain reporting, though it improved sleep and anxiety 2
• This represents mixed evidence, making it a reasonable option only after first-line agents fail 2

Administration Guidelines

Dosing Schedule

• Administer in 2-3 divided doses per day 4
• Can be taken with or without food 1
• Linear pharmacokinetics make dosing more predictable than gabapentin 4, 5

Titration Strategy

• Start low and titrate gradually over 1 week intervals 4
• Most patients can start at 150 mg/day with noticeable effects within 1 week 4
• Allow 4 weeks at therapeutic dose for adequate trial 4, 3

Discontinuation

• Taper gradually over a minimum of 1 week to avoid withdrawal symptoms 1, 4
• Abrupt discontinuation can cause anxiety, convulsions, and other withdrawal symptoms 6

Special Populations

Elderly Patients

• Use lower starting doses and slower titration 4
• Increased risk of dizziness (23-46%), somnolence (15-25%), confusion, falls, and peripheral edema (10%) 4
• Side effects are dose-dependent and manageable with dose reduction 4

Renal Impairment

• Dose adjustment is mandatory as pregabalin is eliminated primarily by renal excretion 4, 1
• Reduce total daily dose by approximately 50% for CrCl 30-60 mL/min 4
• Reduce by 75% for CrCl 15-30 mL/min 4
• Reduce by 85-90% for CrCl <15 mL/min 4

Common Side Effects

• Dizziness (23-46%), somnolence (15-25%), peripheral edema (10%) 4
• Headache, weight gain, dry mouth, constipation 2, 4
• Side effects are generally dose-dependent and transient 2
• Minimize side effects by starting with lower doses and slow escalation 4

Critical Safety Warnings

• Serious breathing problems can occur when combined with opioids, benzodiazepines, or other CNS depressants 4
• Male gender and concurrent prescription of antipsychotics and benzodiazepines increase risk of use above recommended dosages 7
• Abuse potential exists, particularly in patients with history of substance use disorder 6

Comparison with Gabapentin

• Pregabalin has more predictable absorption and linear pharmacokinetics compared to gabapentin's nonlinear profile 4
• Maximum dose: pregabalin 600 mg/day vs gabapentin 3600 mg/day 4
• When switching from gabapentin, start pregabalin at 75 mg twice daily while continuing morning gabapentin dose for first few days, then taper gabapentin over several days to weeks 4
• Both medications have nearly identical adverse effect profiles 4