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Advanced Neurology Seizures and CKD

carbamazepine is excreted through the kidneys, and it is worldwide, most likely because of its cost and availability.
suggested that no dosing adjustments are necessary for The majority of this AED is rapidly metabolized to the
patients receiving HD [9,130,135] . There is no indication for S-enantiomer S-licarbazepine, which is also the metabolite
supplemental dosing [131,135] . Being an auto-inducing AED, of oxcarbazepine [145] . The plasma protein binding capacity
carbamazepine can enhance its own metabolism, and that of of eslicarbazepine is around 40%. It is mostly excreted
other medications including warfarin, oral contraceptives, in urine. In the US, reduced dose administration is
digoxin, corticosteroids, tacrolimus, and cyclosporine. indicated for patients with eGFR <50mL/min/1.73m 2[9,145] .
Macrolides and valproic acid, another AED to be discussed Full dose supplementation for patients receiving HD is
in the next section, are hepatic enzyme inhibitors, which recommended, because it is thought that eslicarbazepine
can increase carbamazepine levels, potentially causing is usually effectively removed during a HD session [135] .
carbamazepine toxicity [142] . There are many side effects For eGFR between 30 and 60 mL/min/1.73 m , the RDH
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to consider when prescribing carbamazepine. It may recommends an initial 400 mg dose every 48 h or 200 mg
contribute toward an adverse lipid profile, similar to other once daily dose, which can eventually be increased to
hepatic-inducing medications [132,133] . Carbamazepine use 400 mg daily [130] . For eGFR <30 mL/min/1.73 m , the RDH
2
is associated with the development of interstitial nephritis suggests starting with 400 mg on alternate days for 2 weeks,
(including rarer reports of acute granulomatous interstitial administered after HD session, and increasing to 400 mg
nephritis) and hyponatremia [135] . Hyponatremia is believed once daily, with the maximum dose being 600 mg daily [130] .
to be secondary to syndrome of inappropriate antidiuretic It notes that the manufacturer does not recommend its use
hormone secretion, enhanced sensitivity of the collecting in GFR <30 mL/min/1.73 m .
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duct to vasopressin, or a reset osmostat [135] . Further studies
are needed to confirm the exact pathophysiological 4.4. Valproic acid
mechanism of hyponatremia. Because of these side effects, Table 6 presents a summary of valproic acid [9,130,135,146] .
many guidelines recommend routine monitoring of sodium Valproic acid has traditionally been one of the most common
concentration levels pre-treatment and after 3 months of AEDs prescribed for focal and generalized seizures, status
carbamazepine treatment in patients living with CKD, in epilepticus, and generalized seizures of genetic origin. It
the elderly, and in those taking other medications that have is also used to treat bipolar disorder and as a prophylactic
the potential to alter sodium concentration [139] . Although treatment for migraine disorders. Valproic acid acts by the
the RDH recommends no particular dosing adjustments, blockade of voltage-gated sodium and calcium channels
it suggests starting with a low dose and titrating according and enhancement of GABAergic systems [135] . Metabolized
to clinical response [130] . by the liver, valproic acid is typically 90% protein-bound,
Oxcarbazepine is primarily prescribed for treating and increased free serum levels of valproic acid are noted
focal seizures. Structurally similar to carbamazepine, in uremia [135] . US-based practice guideline recommends
oxcarbazepine is metabolized in the liver and is a no dose reduction in CKD, given that <3% of valproic
physiologically active AED through R- and S-licarbazepine acid is renally excreted [9,135] . The RDH concurs with
and its monohydroxy metabolites (MHD) [143] . It is reported these recommendations, but suggests starting with a low
that around 40% of the MHD metabolite is protein bound dose and titrating according to response [130] . Intermittent
and approximately 50% is excreted in urine [131] . In the US, removal of valproic acid has been observed during HD
current guidance recommends a 50% dose reduction for sessions [146] . The effect of HD on active valproic drug
patients with eGFR <30 mL/min/1.73 m 2[9,131] . The RDH levels is transient, because the majority of valproic acid
suggests dosing should be as per normal kidney function redistributes back from the tissues into the bloodstream,
even when eGFR <30 mL/min/1.73 m , but recommends and plasma levels increase again after a couple of hours [146] .
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prescriptions should start at 300 mg daily and thereafter Potentially serious adverse effects of valproic acid in CKD
be slowly titrated up [130] . Compared to carbamazepine, include tubulointerstitial nephritis, Fanconi syndrome,
oxcarbazepine is a significantly weaker CYP450-inducing hyponatremia, liver failure progressing to hepatorenal
AED. It is also a weak CYP450-2A9 inhibitor, which syndrome, and hyperammonemic encephalopathy [135] .
may raise phenytoin levels in the situation of concurrent
use [139] . Oxcarbazepine has a superior adverse effects 4.5. Levetiracetam and brivaracetam
profile compared with carbamazepine, with reduced risks Table 7 presents a summary of levetiracetam and
of interstitial nephritis and hyponatremia (which often brivaracetam [9,129-131,147-155] . Levetiracetam (sold under brand
presents asymptomatically) [139,144] . name Keppra) has emerged as one of the most popular first-
Eslicarbazepine acetate (eslicarbazepine) is less line options for focal and generalized seizure treatment,
prescribed compared to carbamazepine and oxcarbazepine including status epilepticus, in recent years. This is mostly

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Volume 2 Issue 2 (2023) olume 2 Issue 2 (2023) 22 https://doi.org/10.36922/an.314
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https://doi.org/10.36922/an.314