What are the uses and dosages of Pregabalin (Lyrica)?

Pregabalin (Lyrica): Uses and Dosing

Pregabalin is FDA-approved for neuropathic pain (diabetic neuropathy, postherpetic neuralgia, spinal cord injury), fibromyalgia, and partial-onset seizures in patients ≥1 month old, with standard dosing starting at 150 mg/day (75 mg twice daily or 50 mg three times daily) and titrating to 300-600 mg/day based on response. 1

FDA-Approved Indications

Pregabalin is indicated for: 1

• Neuropathic pain associated with diabetic peripheral neuropathy
• Postherpetic neuralgia
• Adjunctive therapy for partial-onset seizures (patients ≥1 month old)
• Fibromyalgia
• Neuropathic pain associated with spinal cord injury

Standard Dosing Regimens

Neuropathic Pain (Diabetic Neuropathy, Postherpetic Neuralgia)

Initial dosing: Start at 75 mg twice daily or 50 mg three times daily (150 mg/day total). 2, 3

Titration schedule: 2, 3

• Increase to 300 mg/day (150 mg twice daily or 100 mg three times daily) within 3-7 days based on tolerability
• If pain relief remains insufficient after 2-4 weeks at 300 mg/day and the patient tolerates the medication well, increase to 600 mg/day (300 mg twice daily or 200 mg three times daily)
• Maximum dose: 600 mg/day 2

Key dosing principle: 300 mg/day is the standard moderate dose for postherpetic neuralgia; higher doses (>300 mg/day) often provide minimal additional benefit but increase side effects. 2

Fibromyalgia

Dosing range: 300-450 mg/day in divided doses, with maximum of 600 mg/day. 4

Evidence note: The EULAR guidelines found pregabalin effective for fibromyalgia with a "weak for" recommendation, noting patients were more likely to report improvement (NNT 4.8). 4

Partial-Onset Seizures

Initial dosing: 75 mg twice daily or 50 mg three times daily (150 mg/day). 2

Titration: Increase to maximum 600 mg/day based on individual response and tolerability. 5

Pharmacokinetic Advantages

Pregabalin has linear pharmacokinetics, making dosing more predictable than gabapentin: 2, 6

• Rapid and nearly complete absorption
• No protein binding
• No hepatic metabolism or cytochrome P-450 interactions
• Primarily renal excretion
• Noticeable effects within 1 week; full efficacy assessment at 4 weeks 3

Special Population Dosing

Renal Impairment (Mandatory Dose Adjustment)

Pregabalin is eliminated primarily by renal excretion, requiring dose reductions: 2, 1

• CrCl 30-60 mL/min: Reduce total daily dose by approximately 50%
• CrCl 15-30 mL/min: Reduce total daily dose by 75%
• CrCl <15 mL/min: Reduce total daily dose by 85-90%

Elderly Patients

Lower starting doses and slower titration are recommended due to increased risk of: 2, 1

• Dizziness, somnolence, confusion
• Balance disorder, tremor, coordination abnormalities
• Falls risk
• Age-related decline in renal function (requiring dose adjustment)

Common Side Effects (Dose-Dependent)

The most frequent adverse effects include: 2, 1, 7

• Dizziness (23-46%)
• Somnolence (15-25%)
• Peripheral edema (10%)
• Dry mouth, constipation
• Weight gain (14% at 600 mg/day)
• Ataxia, diplopia

Clinical strategy: Start with lower doses and implement slow titration to minimize peak-related side effects. 2

Critical Safety Warnings

Life-Threatening Risks (FDA Boxed Warnings)

Do not drive or operate machinery until you know how pregabalin affects you. 1

Serious breathing problems can occur when combined with: 1

• Opioid pain medications (e.g., oxycodone)
• Benzodiazepines (e.g., lorazepam)
• Other CNS depressants
• Pre-existing respiratory conditions

Suicidal thoughts/actions: Like all antiepileptic drugs, pregabalin carries risk (~1 in 500 patients). Monitor for new or worsening depression, anxiety, agitation, or suicidal ideation. 1

Serious allergic reactions (angioedema): Stop immediately if swelling of face, mouth, lips, tongue, throat, or difficulty breathing occurs. 1

Drug Interactions

Higher risk of adverse effects when combined with: 1

• ACE inhibitors: Increased risk of swelling and hives
• Thiazolidinediones (rosiglitazone, pioglitazone): Increased weight gain and peripheral edema
• Opioids or sedatives: Increased dizziness, sleepiness, respiratory depression

Discontinuation Protocol

Never abruptly discontinue pregabalin. Taper gradually over minimum of 1 week to avoid withdrawal symptoms. 2, 6

Efficacy Timeline

Therapeutic assessment: 3

• Noticeable effect on neuropathic pain: Within 1 week
• Full efficacy evaluation: 4 weeks at therapeutic dose
• If inadequate response after 4 weeks at maximum tolerated dose, consider alternative therapy

Comparative Efficacy by Condition

Best NNT for ≥50% pain relief with 600 mg/day: 8

• Postherpetic neuralgia: 3.9 (highest efficacy)
• Painful diabetic neuropathy: 5.0
• Central neuropathic pain: 5.6
• Fibromyalgia: 11 (lowest efficacy, requiring higher NNT)

Clinical implication: Pregabalin demonstrates strongest evidence for peripheral neuropathic pain conditions; fibromyalgia requires more patients to treat for benefit. 8

Pregnancy and Fertility Considerations

Pregnancy Category: Animal studies showed birth defects and male fertility impairment. 1

• Enroll in North American Antiepileptic Drug Pregnancy Registry (1-888-233-2334) if pregnant
• Breastfeeding not recommended (pregabalin passes into breast milk) 1

Controlled Substance Status

Schedule V controlled substance due to potential for abuse and dependence. 5