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Advanced Neurology Seizures and CKD

Dialysis‑related dose adjustments US: Consider 50% of daily dose in PD and as post-HD supplement UK: Contraindicated in dialysis patients US: 30% supplemental dose prior to HD sessions, or a full dose post-HD UK: Dose reduction by 25 – 50% initially, and avoidance of very large single dose

eGFR (mL/min/ 1.73 m 2 ) related dose adjustments US: Monitor with caution – dose reduction may be needed in an individual basis UK: A 25–50% dose reduction is recommended in mild and moderate CKD, and contraindicated with severe CKD US: Monitor with caution – dose reduction may be needed in an individual basis UK: When eGFR < 10, dose reduction by 25 – 50% initially, and avoidance of very large sin

Potential nephrotoxicities Interstitial nephritis with antiepileptic hypersensitivity syndrome Exacerbate anemia and Vitamin D deficiency for CKD patients Interstitial nephritis with antiepileptic hypersensitivity syndrome Exacerbate anemia and vitamin D deficiency for CKD patients

Interactions with other AEDs Reduces carbamazepine, clobazam, ethosuximide, lamotrigine, felbamate, lacosamide, levetiracetam, oxcarbazepine, primidone, pregabalin, topiramate, valproic acid, phenytoin and zonisamide levels Reduces carbamazepine, clobazam, ethosuximide, lamotrigine, felbamate, lacosamide, levetiracetam, oxcarbazepine, primidone, pregabalin, topiramate, valproic acid, pheny

% of urinary excretion Approximately 25% Approximately 40% AED: Antiepileptic drug; CKD: Chronic kidney disease; eGFR: estimated glomerular filtration rate; GABA: Gamma-aminobutyric acid; HD: Hemodialysis; PD: Peritoneal dialysis;

Table 4. Properties and metabolism of ;henobarbital and ;rimidone
Metabolism Hepatic metabolism through the CYP450 system Metabolized by the liver to phenobarbital and phenylethylmalonamide, another less active metabolite

Protein binding Approximately 55% Between 10% and 30%

Primary mechanism of action Positive allosteric regulation of the barbiturate- binding site of the GABA-A receptor Positive allosteric regulation of the barbiturate- binding site of the GABA-A receptor

AED (reference range in mg/L) Phenobarbital [9,130,135,137-139] (10 – 40) Primidone [9,130,131,140,141] (5 – 12) UK: United Kingdom; US: United States

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