Topiramate Disease Interactions

There are 5 disease interactions with topiramate:

The use of topiramate is associated with hyperchloremic, nonanion-gap metabolic acidosis, which is characterized by decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis. The condition usually occurs early in treatment and is caused by renal bicarbonate loss due to the inhibitory effect of topiramate on carbonic anhydrase. Bicarbonate decreases are generally mild to moderate, averaging 4 mEq/L at dosages of 400 mg/day in adults and approximately 6 mg/kg/day in pediatric patients. However, metabolic acidosis has been observed at dosages as low as 50 mg/day in adults and in patients as young as 5 months old, especially at dosages above 5 mg/kg/day. Rarely, patients may experience severe decrements to values below 10 mEq/L. Therapy with topiramate should be administered cautiously in patients with conditions that predispose to acidosis, including severe respiratory disease, renal disease, poorly controlled diabetes, alcoholism, congestive heart failure requiring pharmacologic treatment (especially unstable or acute CHF where there is risk of hypoperfusion and hypoxemia), and any condition associated with hypoxemia (e.g., severe anemia, myocardial infarction, asphyxia, shock), dehydration (e.g., severe diarrhea or vomiting), or sepsis. All patients prescribed topiramate should have serum bicarbonate measured at baseline and periodically, and be advised of the significance of nonspecific symptoms such as malaise, anorexia, respiratory distress, increasing somnolence, and gastrointestinal disturbances that may indicate early acidosis. More marked acidosis may be associated with cardiac arrhythmias and stupor. Chronic, untreated metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis, and may also cause osteomalacia, osteoporosis, and reduced growth rates in pediatric patients. If metabolic acidosis develops and persists, consideration should be given to reducing the dosage or discontinuing topiramate. If the decision is made to continue topiramate, alkali treatment should be considered.

Topiramate is primarily eliminated unchanged by the kidney. The plasma clearance of topiramate may be decreased and the half-life prolonged in patients with impaired renal function. Therapy with topiramate should be administered cautiously in patients with significant renal dysfunction. The manufacturer recommends initiating therapy at one-half the usual dosage in patients with moderate to severe renal impairment. Such patients will also require a longer time to reach steady-state at any given dosage.

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than that in a normal individual. A prolonged period of dialysis may cause plasma topiramate level to fall below that required to maintain an anti-seizure effect, thus a supplemental dose may be required in patients undergoing hemodialysis. The actual adjustment should take into account the duration of dialysis, the clearance rate of the dialysis system being used, and the effective renal clearance of topiramate in the patient being dialyzed.

Topiramate is partially metabolized by the liver and may accumulate in patients with impaired hepatic function. Therapy with topiramate should be administered cautiously in patients with liver disease.

The use of topiramate may infrequently be associated with the development of kidney stones. The reported incidence was 1.5% (32 of 2,086 patients) during premarketing use, which is about 2 to 4 times that expected in a similar, untreated population. Topiramate is a weak carbonic anhydrase inhibitor and may promote stone formation by reducing urinary citrate excretion and increasing urinary pH. Therapy with topiramate should be administered cautiously with adequate hydration in patients with a history of nephrolithiasis. The concomitant use of topiramate with other carbonic anhydrase inhibitors should be avoided. Patients who are dehydrated may be at increased risk for the development of nephrolithiasis and should be encouraged to consume additional amounts of liquid during topiramate therapy.

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