What is the recommended dose of pregabalin (Lyrica) for various conditions, including epilepsy, fibromyalgia, and neuropathic pain, in patients with normal and impaired renal function?

Pregabalin Dosing Across Various Conditions

Pregabalin dosing is condition-specific and ranges from 150-600 mg/day divided into 2-3 doses, with most conditions requiring 300 mg/day as the standard effective dose, though fibromyalgia may require 300-450 mg/day for optimal benefit. 1

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 are less well tolerated 1
• The 600 mg/day dose studied showed no evidence of additional significant benefit 1

Postherpetic Neuralgia

• Start at 75 mg twice daily or 50 mg three times daily (150 mg/day) 1, 2
• Increase to 150 mg twice daily or 100 mg three times daily (300 mg/day) within 1 week 1, 2
• For patients with inadequate pain relief after 2-4 weeks on 300 mg/day who tolerate the medication well, may increase to 600 mg/day (300 mg twice daily or 200 mg three times daily) 1, 2
• Reserve doses above 300 mg/day only for patients with ongoing pain who are tolerating 300 mg/day 1, 3

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 therapeutic dose is 300-450 mg/day 1
• For insufficient benefit at 300 mg/day, may increase to 225 mg twice daily (450 mg/day) 1
• The 600 mg/day dose showed no additional benefit and was less well tolerated 1
• Treatment above 450 mg/day is not recommended 1

Adjunctive Therapy for Partial-Onset Seizures

Adults (17 years and older)

• Start at 150 mg/day divided into 2-3 doses 1
• Maximum dose is 600 mg/day in 2-3 divided doses 1
• Increase dosage approximately weekly based on clinical response and tolerability 1

Pediatric Patients (1 month and older)

For children weighing ≥30 kg:

• Start at 2.5 mg/kg/day in 2-3 divided doses 1
• Maximum dose is 10 mg/kg/day (not to exceed 600 mg/day) 1

For children weighing <30 kg:

• Start at 3.5 mg/kg/day 1
• Maximum dose is 14 mg/kg/day 1
• Ages 1 month to <4 years: administer in 3 divided doses 1
• Ages ≥4 years: administer in 2-3 divided doses 1

Neuropathic Pain Associated with Spinal Cord Injury

• 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 150-600 mg/day 1
• For patients without sufficient pain relief after 2-3 weeks on 300 mg/day who tolerate pregabalin, may increase to 300 mg twice daily (600 mg/day) 1

Dosing in Renal Impairment

Dose adjustment is mandatory in adult patients with reduced renal function, as pregabalin is eliminated primarily by renal excretion 1, 2

Dosing Based on Creatinine Clearance:

• CLcr ≥60 mL/min: Use standard dosing as above 1
• CLcr 30-60 mL/min: Reduce total daily dose by approximately 50% 1
• CLcr 15-30 mL/min: Reduce total daily dose by approximately 75% 1
• CLcr <15 mL/min: Reduce total daily dose by approximately 85-90% 1

Hemodialysis Patients:

• Adjust daily dose based on renal function as above 1
• Administer supplemental dose immediately following every 4-hour hemodialysis treatment 1

Special Populations

Elderly Patients

• Consider lower starting doses and slower titration due to increased risk of adverse effects including dizziness, somnolence, and confusion 3, 2
• Elderly patients are more susceptible to falls due to dizziness 3

Titration Strategy and Timeline

• Pregabalin has linear pharmacokinetics, making dosing more straightforward than gabapentin 2, 4
• Most patients can start at 150 mg/day in 2-3 divided doses 2
• The initial 150 mg/day dose has been found efficacious in some trials 2
• Pregabalin may provide analgesia more quickly than gabapentin - noticeable effects may occur within 1 week, whereas gabapentin may require 2 months or more 2, 4
• An adequate trial requires 4 weeks at therapeutic dose 2

Discontinuation

• Taper gradually over a minimum of 1 week when discontinuing pregabalin to avoid withdrawal symptoms 1, 5

Common Pitfalls and Caveats

• Doses above 300 mg/day are not consistently more effective than 300 mg/day for most neuropathic pain conditions and are associated with higher rates of adverse effects 2, 3
• Do not use pregabalin above 450 mg/day for fibromyalgia - no additional benefit demonstrated 1
• Common dose-dependent side effects include dizziness (23-46%), somnolence (15-25%), peripheral edema (10%), dry mouth, and constipation 3, 6
• These side effects can be minimized by starting with lower doses and implementing slow dose escalation 3, 2
• Weight gain may be more problematic in long-term use 7
• The efficacy of pregabalin when used with gabapentin has not been evaluated, so no dosing recommendations exist for combination therapy 1