Maintenance regimens.
| Drug | Dose and route | Hepatic and kidney adjustment |
|---|
| Levetiracetam | 500 mg orally twice daily, increase by 500 mg twice daily every 2 weeks to a maximum of 1.5 g twice daily | Creatinine clearance 50 to 79: 500 to 1000 mg every 12 hours; 30 to 49: 250 to 750 mg every 12 hours; under 30: 250 to 500 mg every 12 hours. In severe hepatic impairment, creatinine clearance overestimates kidney function, so reduce the daily dose by about 50% |
| Lacosamide | 50 mg orally twice daily, increase by 50 mg twice daily weekly | Maximum 300 mg daily in mild to moderate hepatic impairment; avoid in severe |
| Lamotrigine | 25 mg orally daily for 2 weeks, then 50 mg daily for 2 weeks, then increase slowly | Reduce initial, escalation and maintenance doses by about 25% in moderate to severe impairment without ascites and about 50% in severe impairment with ascites |
| Gabapentin | 100 to 300 mg orally at night, titrate to 300 to 600 mg three times daily | Adjust to creatinine clearance; maximum 700 mg daily if creatinine clearance is 30 to 59 mL/min |
| Brivaracetam | 25 to 50 mg orally twice daily | Maximum 150 mg daily in all stages of hepatic impairment |
| Perampanel | 2 mg orally at night, increase by 2 mg every 2 weeks | Maximum 6 mg daily in mild and 4 mg in moderate impairment; avoid in severe |
| Phenobarbital | 60 to 180 mg orally at night (1 to 3 mg/kg daily) | Reduce dose in cirrhosis; avoid in Child-Pugh C because of sedation and encephalopathy |
Acute seizure. - Lorazepam 4 mg intravenously (0.1 mg/kg), repeated once after 10 minutes if seizures continue. - Levetiracetam 60 mg/kg intravenously (maximum 4500 mg) over 10 minutes as the loading dose, with no hepatic reduction needed. - Phenytoin 20 mg/kg intravenously (maximum 2 g) at no more than 50 mg/minute with ECG and blood pressure monitoring if levetiracetam is not available. Aim for a free level of 1 to 2 mg/L. - Treat reversible causes at the same time: glucose, sodium, calcium, alcohol withdrawal, thiamine.
Pregnancy. Valproate is contraindicated. Levetiracetam and lamotrigine are preferred; lamotrigine clearance rises in pregnancy, so monitor levels. Folic acid 5 mg orally daily from before conception.
Breastfeeding. Levetiracetam, lamotrigine and gabapentin pass into milk; observe the infant for sedation and poor feeding.
Older adults. Start at half the usual dose and move slowly; falls and cognitive effects are common.
Children. Valproate is contraindicated in suspected POLG mitochondrial disease and is hazardous under 2 years. Dosing should be set with paediatric neurology and hepatology.
Kidney impairment. Dose levetiracetam, gabapentin and lacosamide to creatinine clearance, interpreted with caution.
Interactions. Phenytoin, carbamazepine and phenobarbital make hepatitis C direct-acting antivirals ineffective and lower tacrolimus, apixaban and rivaroxaban levels. Valproate with lamotrigine raises lamotrigine levels about twofold.
East Africa. Phenobarbital is widely available and used for epilepsy; in liver disease use the lowest dose that controls seizures, and review need for an alternative where levetiracetam is obtainable. Neurocysticercosis and cerebral malaria are regional causes of seizures to consider.
