Which of the following drugs may cause hyperchloremic acidosis?

a. Nitrofurantoin
b. Amlodipine
c. Zonisamide
d. Capecitabine
e. Adalimumab

Answer: (c). Zonisamide (Zonegran)is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. It is supplied for oral administration as capsules containing 25 mg or 100 mg Zonisamide.

Zonisamide is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy. It can be taken with or without food. The initial dose of ZONEGRAN should be 100 mg daily. After two weeks, the dose may be increased to 200 mg/day for at least two weeks. It can be increased to 300 mg/day and 400 mg/day, with the dose stable for at least two weeks to achieve steady state at each level. Evidence from controlled trials suggests that Zonegran doses of 100-600 mg/day are effective, but there is no suggestion of increasing response above 400 mg/day.

Zonisamide causes hyperchloremic, non-anion gap, metabolic acidosis (i.e., decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis).This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of zonisamide on carbonic anhydrase.

Generally, Zonisamide-induced metabolic acidosis occurs early in treatment, but it can develop at any time during treatment. Metabolic acidosis generally appears to be dose-dependent and can occur at doses as low as 25 mg daily.

Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, ketogenic diet, or specific drugs) may be additive to the bicarbonate lowering effects of zonisamide.

Some manifestations of acute or chronic metabolic acidosis include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae including cardiac arrhythmias or stupor. Chronic, untreated, metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis.

Somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration are also reported side effects of Zonisamide.

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