Section 06 · Monograph

Pregabalin

Reviewed Nov 2026FDA label

LyricaGabapentinoid

Indications

Management of neuropathic pain associated with diabetic peripheral neuropathyFDA-labeled
Management of postherpetic neuralgiaFDA-labeled
Management of fibromyalgiaFDA-labeled
Management of neuropathic pain associated with spinal cord injuryFDA-labeled
Adjunctive therapy for partial-onset seizures, age 1 month and olderFDA-labeled

Gabapentinoid that binds with high affinity to the alpha-2-delta subunit of voltage-gated calcium channels in the CNS, reducing calcium influx at nerve terminals and decreasing release of excitatory neurotransmitters (glutamate, norepinephrine, substance P)
Does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors despite structural similarity to GABA

Diabetic peripheral neuropathy: initiate 50mg TID (150mg/day); may increase within 1 week to max 100mg TID (300mg/day) based on efficacy/tolerability
Postherpetic neuralgia: initiate 75mg BID or 50mg TID (150mg/day); may increase within 1 week to 300mg/day, and further to a max of 600mg/day if needed and tolerated
Fibromyalgia: initiate 75mg BID (150mg/day); may increase within 1 week to 150mg BID (300mg/day); max recommended dose 450mg/day
Spinal cord injury neuropathic pain: initiate 75mg BID; may increase to 150mg BID within 1 week, up to a max of 300mg BID (600mg/day) as tolerated
Schedule V controlled substance — taper gradually over at least 1 week when discontinuing rather than abrupt withdrawal

Renal impairment: dose reduction required based on creatinine clearance per label dosing table; supplemental dose recommended after hemodialysis

Adjunctive seizure therapy: dosed by weight in pediatric patients; adults typically 150-600mg/day in divided doses

Known hypersensitivity to pregabalin or any component of the formulation (including history of angioedema with pregabalin)

Additive CNS depression (sedation, respiratory depression) with opioids, benzodiazepines, alcohol, and other CNS depressants — FDA warning regarding respiratory depression risk when combined with opioids, particularly in opioid-naive or elderly patients
Additive risk of peripheral edema when combined with thiazolidinedione antidiabetic agents
No clinically significant CYP-mediated pharmacokinetic interactions; primarily renally eliminated unchanged

Common: dizziness (~30%), somnolence (~23%), peripheral edema, weight gain, dry mouth, blurred vision
Angioedema (facial, perioral, and laryngeal swelling) — can be life-threatening; discontinue immediately if it occurs
Weight gain and peripheral edema, more common with higher doses and longer duration
CNS depression additive with opioids and alcohol; respiratory depression risk, especially in combination with opioids
Increased risk of suicidal ideation/behavior (class effect across AEDs)
Potential for misuse, abuse, and physical dependence — Schedule V controlled substance
Rare creatine kinase elevation/rhabdomyolysis; thrombocytopenia; PR-interval prolongation
Withdrawal symptoms (insomnia, nausea, headache, anxiety, diarrhea) with abrupt discontinuation

Signs/symptoms of angioedema (facial/lip/throat swelling)
Weight and evidence of fluid retention/peripheral edema, especially in patients with heart failure
Respiratory status and sedation level when co-prescribed with opioids or other CNS depressants
Mental status for mood changes or suicidal ideation
Renal function for dose adjustment
Signs of misuse or dependence given controlled substance status

May cause fetal harm based on animal data (developmental toxicity at clinically relevant exposures); limited human data
Encourage enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334)
Present in human milk; breastfeeding not generally recommended due to limited safety data in infants