Pregabalin (Lyrica): Indications, Dosages, and Alternatives
Pregabalin is indicated for neuropathic pain (diabetic peripheral neuropathy, postherpetic neuralgia, and spinal cord injury-associated pain), adjunctive therapy for partial-onset seizures, and fibromyalgia, with dosing based on indication and renal function. 1, 2
Indications
FDA-Approved Indications:
- Neuropathic Pain
- Diabetic peripheral neuropathy
- Postherpetic neuralgia
- Neuropathic pain associated with spinal cord injury
- Epilepsy: Adjunctive therapy for partial-onset seizures in patients 1 month of age and older
- Fibromyalgia
Dosing Recommendations by Indication
1. Diabetic Peripheral Neuropathy
- Starting dose: 50 mg three times daily (150 mg/day)
- Target dose: 300 mg/day (maximum recommended)
- Titration: May increase to 300 mg/day within 1 week based on efficacy and tolerability 2
2. Postherpetic Neuralgia
- Starting dose: 75 mg twice daily or 50 mg three times daily (150 mg/day)
- Target dose: 150-300 mg/day
- Maximum dose: 600 mg/day
- Titration: May increase to 300 mg/day within 1 week; doses above 300 mg/day should be reserved for patients with ongoing pain who tolerate 300 mg/day 2
3. Neuropathic Pain Associated with Spinal Cord Injury
- Starting dose: 75 mg twice daily (150 mg/day)
- Target dose: 300-600 mg/day
- Titration: May increase to 300 mg/day within 1 week; may further increase to 600 mg/day after 2-3 weeks if needed 2
4. Adjunctive Therapy for Partial-Onset Seizures
- Adults: Starting dose 150 mg/day, maximum 600 mg/day, divided into 2-3 doses
- Pediatric patients ≥30 kg: 2.5 mg/kg/day initially, maximum 10 mg/kg/day (not exceeding 600 mg/day)
- Pediatric patients <30 kg: 3.5 mg/kg/day initially, maximum 14 mg/kg/day 2
Dosing in Renal Impairment
Pregabalin requires dose adjustment in renal impairment as it is eliminated primarily by renal excretion 1, 2:
| Creatinine Clearance (mL/min) | Total Daily Dose Adjustment |
|---|---|
| ≥60 | No adjustment needed |
| 30-59 | 150-300 mg/day |
| 15-29 | 75-150 mg/day |
| <15 | 25-75 mg/day |
For hemodialysis patients, administer a supplemental dose immediately following every 4-hour hemodialysis treatment 2.
Administration Guidelines
- Pregabalin can be taken with or without food
- Administer in 2-3 divided doses per day depending on indication
- When discontinuing, taper gradually over at least 1 week to minimize withdrawal symptoms 2
Pharmacology and Pharmacokinetics
- Mechanism of action: Binds to voltage-gated calcium channels at the α2-δ subunit, inhibiting neurotransmitter release 3
- Absorption: Linear pharmacokinetics with ~90% bioavailability
- Protein binding: Minimal
- Metabolism: Not significantly metabolized
- Elimination: Primarily renal excretion of unchanged drug (95%) 4
- Half-life: Approximately 6 hours 4
Alternatives to Pregabalin
For Neuropathic Pain:
First-line alternatives:
- Gabapentin: 100-300 mg at bedtime initially, titrated to 900-3600 mg/day in divided doses 3, 1
- Tricyclic antidepressants: Nortriptyline or desipramine 25 mg at bedtime initially, titrated to 150 mg/day 3, 1
- SNRIs: Duloxetine (30 mg daily initially, target 60-120 mg daily) or venlafaxine (37.5 mg once or twice daily initially, target 75-225 mg daily) 3, 1
- Topical lidocaine: 5% patch, up to 3 patches daily for 12-18 hours 3, 1
Second-line alternatives:
Adverse Effects and Monitoring
- Common adverse effects: Dizziness (27-46%), somnolence (15-25%), peripheral edema, weight gain 3, 1, 5
- Monitoring:
- Renal function (adjust dose accordingly)
- Weight changes
- Visual field changes (rare but reported) 6
- Withdrawal symptoms if discontinued abruptly
Clinical Pearls and Pitfalls
- Pregabalin may provide analgesia more quickly than gabapentin due to linear pharmacokinetics and more straightforward dosing 3
- In the United States, pregabalin is a Schedule V controlled substance due to potential for abuse 3
- For most neuropathic pain conditions, doses of 150 mg/day are generally ineffective; 300-600 mg/day are typically needed for efficacy 5
- Only a minority of patients will have substantial benefit with pregabalin; NNTs for 50% pain relief range from 3.9 for postherpetic neuralgia to 11 for fibromyalgia 5
- Avoid monotherapy fixation—many patients benefit from combination therapy with other agents 1
- Pregabalin has not shown clear evidence of benefit in acute postoperative pain 5