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Advanced Neurology Seizures and CKD

Dialysis‑related dose adjustments Dialysis‑related dose adjustments US: Dosing supplementation usually not given. High-flux dialysis may remove the drug UK: Dosing supplementation usually not given. High-flux dialysis may remove the drug

(mL/min/1.73 m 2 ) related dose adjustments would eventually be increased to 400 mg daily is recommended. For eGFR < 30, starting with 400 mg on alternate days for 2 weeks, increasing to 400 mg once daily; the maximum dose, i.e., 600 mg daily, is eGFR (mL/min/1.73 m 2 ) related dose adjustments US: No dose adjustments UK: No dose adjustments needed, but to start with a low dose and titrating according to response

eGFR recommended needed

Potential nephrotoxicities Potential nephrotoxicities Tubulointerstitial nephritis Fanconi syndrome Hyponatremia

Interactions with other AEDs Interactions with other AEDs Reduces topiramate levels Increases free fraction phenytoin, diazepam, carbamazepine-10,11 epoxide, felbamate, lamotrigine, lorazepam, midazolam, phenobarbital, rufinamide and ethosuximide levels Valproic acid levels could increase felbamate. Its levels could be decreased by ethosuximide and AED inducers

% of urinary excretion AED: Antiepileptic drug; CYP450: Cytochrome P450; eGFR: estimated glomerular filtration rate; GABA: Gamma-aminobutyric acid; MHD: Monohydroxy derivative; UK: United Kingdom; % of urinary excretion Between 1% and 3% AED: Antiepileptic drug; CYP450: Cytochrome P450; eGFR: estimated glomerular filtration rate; GABA: Gamma-aminobutyric acid; UK: United Kingdom; US: United States

Metabolism Metabolism Hepatic metabolism through CYP450 system

Table 6. Properties and metabolism of valproic acid
Protein binding Protein binding Approximately 90%; binding decreases in

Primary mechanism of action uremia

Primary mechanism of action Blockade of voltage-gated sodium and calcium channels and enhancement of GABAergic systems

Table 5. (Continued) AED (reference range in mg/L) US: United States AED (reference range in mg/L) Valproic acid [9,130,135,146] (50–100)

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