Typical maintenance dosing of antiseizure medications in adults with chronic kidney disease*

Antiseizure medication	GFR >60 mL/minute/1.73 m²	CKD stage 3 GFR 30 to 59 mL/minute/1.73 m²	CKD stage 4 GFR 15 to 29 mL/minute/1.73 m²	CKD stage 5 GFR <15 mL/minute/1.73 m²	ESKD with dialysis
Carbamazepine	400 to 1600 mg orally per day in two or three divided doses.	No adjustment necessary.	No adjustment necessary.	No adjustment necessary.	Usually no adjustment necessary.
Cenobamate	100 to 400 mg once per day (consider dose adjustment with GFR <90).	Use with caution; dose reduction may be needed.	Use with caution; dose reduction may be needed.	Use is not recommended (has not been studied).	Use is not recommended (has not been studied).
Gabapentin^¶	900 to 3600 mg orally per day in three divided doses.	400 to 1400 mg orally per day in two divided doses.	200 to 700 mg orally once per day.	100 to 300 mg orally once per day. Use with caution.	200 to 300 mg supplement after each IHD session^¶.
Lacosamide	100 to 400 mg orally per day in two divided doses.	No adjustment necessary^Δ.	Gradually titrate from low initial dose. Maximum 300 mg per day in divided doses^Δ.	Gradually titrate from low initial dose. Maximum 300 mg per day in divided doses^Δ.	50% of daily dose as supplement after each IHD session^Δ.
Lamotrigine	Varies due to indication and concomitant antiseizure medications (eg, without enzyme-inducing drug: 225 to 375 mg orally per day in two divided doses).	Use with caution; dose reduction may be needed.	Use with caution; dose reduction may be needed.	Use with caution; dose reduction may be needed.	Give dose after IHD. Consider post-HD supplemental dosing.
Levetiracetam	1000 to 3000 mg orally per day in two divided doses.	500 to 1500 mg orally per day in two divided doses.	500 to 1000 mg orally per day in two divided doses.	500 to 1000 mg orally per day in two divided doses.	500 to 1000 mg orally per day. Give 50% of daily dose as post-IHD supplement.
Oxcarbazepine	600 to 2400 mg orally per day in two divided doses.	No adjustment necessary.	Initiate at half of usual daily dose.	Initiate at half of usual daily dose.	Supplemental dose not needed.
Phenobarbital	120 to 300 mg orally per day in two or three divided doses. Carefully individualize dose according to seizure control and serum concentrations, refer to clinical topic for detail.	Use with caution; dose reduction may be needed.	Use with caution; dose reduction may be needed.	Use with caution; dose reduction may be needed.	High-flux dialyzers can likely remove drug; however, findings are variable, and no clear consensus on supplemental dose is available. Consider giving up to 50% of daily dose as supplement after IHD or PD.
Phenytoin	300 to 600 mg orally per day in two or three divided doses. Carefully individualize dose according to seizure control and serum concentrations, refer to clinical topic for detail.	No change. Oral loading dose usually not given.	No change. Oral loading dose usually not given.	No change. Oral loading dose usually not given. Protein binding may be decreased; consider assessing free phenytoin levels.	No change^◊. Oral loading dose usually not given. Protein binding may be decreased; consider assessing free phenytoin levels.
Pregabalin^¶	150 to 600 mg orally per day in two or three divided doses.	75 to 300 mg orally per day in two or three divided doses.	25 to 150 mg orally once per day in a single or two divided doses.	25 to 75 mg orally once per day.	25 to 150 mg supplement after each IHD session^¶.
Topiramate	200 to 400 mg orally per day in two divided doses.	50% dose reduction.	50% dose reduction.	50% dose reduction.	Give dose after IHD or 50% of daily dose as post-HD supplement.
Valproic acid (valproate)	15 to 60 mg/kg orally per day in two or three divided doses. Standard dose (usual upper limit of weight-based dosing): ≤2500 mg per day.	No adjustment necessary.	No adjustment necessary.	No adjustment necessary.	Supplementation usually not given. High-flux dialyzers can likely remove drug. Protein binding may be decreased; consider assessing free valproic acid levels.
Zonisamide	100 to 400 mg orally once per day.	No adjustment necessary. Gradually titrate from low initial dose.	Unclear. Gradually titrate from low initial dose.	Unclear. Gradually titrate from low initial dose.	Give dose after IHD. Supplement needed for post-IHD seizures.

Typical adult maintenance dosing in epilepsy (ie, not for status epilepticus or other indications) of oral immediate-release formulations; initial dosing is usually the lowest maintenance dose, which may need to be titrated to improve tolerability and according to seizure control. Details for initiating and adjustment of dose vary by each agent. Refer to the Lexicomp drug monographs and appropriate UpToDate clinical reviews for detailed information on individual agents.

GFR: glomerular filtration rate; CKD: chronic kidney disease; ESKD: end-stage kidney disease; IHD: intermittent hemodialysis; PD: peritoneal dialysis.

* Dose is adjusted according to seizure control. Drug levels may be useful for establishing an individual therapeutic range when the patient is in remission and for guiding dose adjustments (eg, when kidney function is changing or there is an alteration in drug formulation or change in regimen involving an interacting medication). Refer to UpToDate clinical reviews of epilepsy treatment.

¶ Clearance dependent upon kidney function; low protein binding, low volume of distribution (Vd), and cleared efficiently by dialysis. Postdialysis supplemental dosing is necessary.

Δ Patients with CKD who are taking medications that are strong CYP3A4 and CYP2C9 inhibitors may have increased exposure to lacosamide; a further dose reduction may be needed. Specific interactions may be determined by using the Lexi-Interact program included within UpToDate.

◊ Seizures have been reported in a small number of patients after high-flux IHD. Individualized supplementation may be needed.

Adapted from: Bansal AD, Hill CE, Berns JB. Use of antiepileptic drugs in patients with chronic kidney disease and end stage renal disease. Semin Dial 2015; 28:404.

Additional data from:

Israni R, Kasbekar N, Haynes K, Berns J. Use of antiepileptic drugs in patients with kidney disease. Semin Dial 2006; 19:408.
Perucca E. Clinical pharmacology and therapeutic use of the new antiepileptic drugs. Fundam Clin Pharmacol 2001; 15:405.
Asconapé JJ. Use of antiepileptic drugs in hepatic and renal disease. Handb Clin Neurol 2014; 119:417.
Diaz A, Deliz B, Benbadis S. The use of newer antiepileptic drugs in patients with renal failure. Expert Rev Neurother 2014; 12:99.

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Typical maintenance dosing of antiseizure medications in adults with chronic kidney disease*