Antiepileptic Dosing in Kidney Disease

Antiepileptic drugs differ widely in kidney dependence. Levetiracetam, gabapentin, pregabalin, topiramate and lacosamide need adjustment. Phenytoin, valproate and carbamazepine are eliminated in the liver but are highly protein bound, so total levels mislead in uraemia and low albumin.

Loading doses. They are not reduced, and apply in status epilepticus whatever the kidney function.

Dialysis. Levetiracetam, gabapentin, pregabalin and topiramate are removed by haemodialysis and need a supplemental dose after each session. Phenytoin, valproate and carbamazepine are not meaningfully removed.

Preferred. Levetiracetam and lamotrigine, with dose adjustment where needed.

Use with care. Phenytoin and valproate, using free levels. Carbamazepine, which may cause hyponatraemia. Topiramate, because it causes acidosis and stones.

Special groups.

• Pregnancy: levetiracetam and lamotrigine are favoured, and valproate should be avoided.

• Children: dose by mg/kg and check levels.

• Older adults: start low.

• East Africa: phenytoin, phenobarbital and carbamazepine are often the available agents, and enzyme induction reduces the exposure of antiretrovirals and other drugs.

• Levetiracetam: clearance 50 to 80, 500 to 1000 mg every 12 hours. 30 to 50, 250 to 750 mg every 12 hours. Under 30, 250 to 500 mg every 12 hours. Dialysis, 500 to 1000 mg once daily with 250 to 500 mg after each session. Status epilepticus loading 60 mg/kg intravenously (maximum 4500 mg).

• Phenytoin: loading 20 mg/kg intravenously at no more than 50 mg/min (25 mg/min in older adults), then 3 to 5 mg/kg daily. Total target 10 to 20 mg/L, free target 1 to 2 mg/L. If only a total level is available, adjusted level = observed level divided by (0.2 × albumin in g/dL + 0.1), or with clearance under 10 mL/min divided by (0.1 × albumin in g/dL + 0.1).

• Valproate: no dose change, but interpret total levels (50 to 100 mg/L) with caution because the free fraction is higher.

• Carbamazepine: no adjustment, with sodium monitoring.

• Lamotrigine: no change in mild disease, with slower titration and lower maintenance in severe disease.

• Oxcarbazepine: clearance under 30, start 300 mg daily and increase slowly.

• Topiramate: half the usual dose when clearance is under 70 mL/min, with a supplement after dialysis.

• Lacosamide: maximum 300 mg daily when clearance is under 30 mL/min, with a supplement of up to half the dose after dialysis.

• Gabapentin and pregabalin: use the renal bands, for example gabapentin 200 to 700 mg once daily at 15 to 29 mL/min.

Monitoring. Check sodium, bicarbonate, albumin, free levels and seizure control, and recheck after any change in function or dialysis.

Stop rules. Reduce the dose for toxicity (ataxia, nystagmus, sedation, myoclonus). Do not stop an antiepileptic abruptly, and switch gradually.

Referral and escalation. Seek neurology advice for seizures not controlled on two agents, status epilepticus, pregnancy planning, and dialysis patients on more than one agent.

Common errors. Reducing the loading dose, using total phenytoin levels with low albumin, omitting post-dialysis levetiracetam, and giving valproate to women who may become pregnant.