Pregabalin

Pregabalin is a gabapentinoid used for neuropathic pain, adjunct treatment of focal seizures and generalised anxiety disorder, and, in some regions, fibromyalgia. Unlike gabapentin it has linear, predictable absorption and a quicker titration, but shares sedation, dizziness, oedema and misuse risk, and requires renal dose adjustment.

Mechanism. Binds the alpha-2-delta subunit of voltage-gated calcium channels and reduces release of excitatory neurotransmitters.

Pharmacokinetics. Bioavailability is 90% or more at all doses. It is not protein bound or metabolised, and 90 to 99% is excreted unchanged in urine. Half-life is about 6 hours. Food delays absorption without clinical effect.

First-line use. Neuropathic pain in adults.

• Oral pregabalin: start 150 mg daily in two or three divided doses. After 3 to 7 days increase to 300 mg daily, and after a further 7 days to a maximum of 600 mg daily if needed. Duration depends on benefit; review at 4 weeks on the effective dose.

• Some labels limit painful diabetic neuropathy to a maximum of 300 mg daily.

Alternative use.

• Adjunct for focal seizures in adults: 150 mg daily in two or three doses, increased to 300 mg after 1 week, maximum 600 mg daily.

• Generalised anxiety disorder in adults: 150 mg daily, increased at weekly steps of 150 mg, usual 150 to 600 mg daily, maximum 600 mg daily.

• Fibromyalgia (where licensed): 75 mg twice daily, increased to 150 mg twice daily within a week, maximum 450 mg daily.

Specialist use. Children with focal seizures are dosed by weight under specialist care. A commonly used schedule starts at 2.5 mg/kg daily at 30 kg or more and 3.5 mg/kg daily under 30 kg, divided into doses, with maximums of 10 mg/kg and 14 mg/kg daily, not over 600 mg daily.

Kidney function. Adult daily dose by creatinine clearance:

• Haemodialysis: give a supplemental dose of 25 to 100 mg after each 4-hour session.

• Liver: no adjustment.

• Older adults: start at the lower dose and titrate by kidney function.

Contraindications. Hypersensitivity.

Serious adverse effects. Angioedema, respiratory depression with opioids or other sedatives, suicidal ideation, peripheral oedema with heart failure worsening, raised creatine kinase, visual disturbance, misuse and dependence, and withdrawal symptoms or seizures if stopped abruptly.

Common adverse effects. Dizziness, somnolence, ataxia, blurred vision, weight gain, peripheral oedema, euphoria and dry mouth.

Interactions. Opioids, benzodiazepines, alcohol and other sedatives add to central nervous system and respiratory depression. Thiazolidinediones add oedema and weight gain. No cytochrome P450 interactions.

Common prescribing errors. Not reducing for kidney impairment. Combining with opioids without warning. Quick stopping. Prescribing to someone with a history of misuse without a plan.

Special groups.

• Pregnancy: avoid unless essential, since data are limited and some suggest a small increase in malformation risk.

• Breastfeeding: infant exposure is low, but manufacturers advise avoidance; weigh benefit against risk and monitor the infant for drowsiness.

• Older adults: falls, confusion and sedation are frequent.

• Regional: diversion and misuse occur in some settings; supply in small amounts and review regularly.

Formulations. Capsules 25, 50, 75, 100, 150, 200, 225 and 300 mg. Oral solution 20 mg/mL. Prolonged-release tablets exist. Take with or without food.

Monitoring.

• Baseline: creatinine clearance, oedema, heart failure status, falls risk, concurrent sedatives, mood and substance use.

• Ongoing: pain or anxiety scores, sedation, weight, oedema, vision and renal function. Levels are not used.

Stopping. Taper over at least 1 week. Stop and reassess for angioedema.

Referral and escalation. Refer for pain not controlled by two adequate drug trials or by single agents at maximum tolerated dose. Urgent review for angioedema, respiratory depression or suspected misuse.