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Advanced Neurology Seizures and CKD

Dialysis‑related dose adjustments US: No dose adjustments needed. Consider avoiding lorazepam in dialysis patients UK: No dose adjustments needed Dialysis‑related dose US: No dose adjustments UK: No dose adjustments

(mL/min/1.73 m 2 ) related dose adjustments adjustments needed in majority of cases. Consider avoiding lorazepam with adjustments needed, but to start at small doses and titrate upwards as per adjustments needed needed

eGFR US: No dose eGFR GFR UK: No dose response eGFR (mL/min/1.73 m 2 ) related dose adjustments

Potential nephrotoxicities Rarely reported cases of interstitial nephritis and crystal nephropathy US: No dose adjustments needed UK: No dose adjustments needed

Interactions with other AEDs Benzodiazepine levels could be reduced by carbamazepine, oxcarbazepine, eslicarbazepine, phenytoin and phenobarbital Potential nephrotoxicities Not reported

% of urinary excretion >95% Interactions with other AEDs Could either reduce or increase phenytoin levels

Metabolism Hepatic metabolism with majority of benzodiazepines metabolized through the CYP450-3A4 system AED: Antiepileptic drug; CYP450: Cytochrome P450; eGFR: estimated glomerular filtration rate; GABA: Gamma-aminobutyric acid; UK: United Kingdom; US: United States % of urinary excretion Approximately 94%

Protein binding Clonazepam: approximately 85% Diazepam: >95% Lorazepam: between 85% and 91% Midazolam: approximately 97% Metabolism Hepatic metabolism through the CYP450-3A4 system AED: Antiepileptic drug; CYP450: Cytochrome P450; eGFR: estimated glomerular filtration rate; UK: United Kingdom; US: United States
Table 13. Properties and metabolism of benzodiazepines

Primary mechanism of action Binding to the benzodiazepine site of the GABA-A receptor and increasing its opening frequency, increasing GABA currents and promoting neuron inhibition Table 14. Properties and metabolism of clobazam Protein Primary mechanism binding of action Approx. Similar to other 86% benzodiazepines, but is a long-acting 1,5-benzodiazepine

AED (reference range in mg/L) Benzodiazepines [9,130,131,135,166] i.e., clonazepam, diazepam, lorazepam and midazolam (clonazepam: 0.02 – 0.08; diazepam: 0.1 – 1.0; lorazepam: 2–6; midazolam: 0.03–0.1) AED (reference range in mg/L) Clobazam [9,129,130,168] (0.03 – 0.3)

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