Topiramate Disease Interactions

Oligohidrosis (decreased sweating) and hyperthermia have been reported in association with the use of some carbonic anhydrase inhibitor anticonvulsants such as topiramate and zonisamide. Most of the reports have been in children. Caution and close monitoring of body temperature is advised when prescribing these drugs, especially in patients with a fever, in hot weather, or if combined with other drugs that predispose to heat related disorders. Zonisamide is not approved for use in pediatric patients in the U.S.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

The major route of elimination of carbonic anhydrase inhibitors is through the kidney. These drugs should be administered cautiously in patients with reduced renal function and a dose adjustment might be required depending on the level of impairment.

Reduced plasma bicarbonate levels and, in some instances, elevated plasma chloride levels may result in metabolic acidosis during long-term therapy with carbonic anhydrase inhibitors. Therapy with carbonic anhydrase inhibitors should be administered cautiously in patients with metabolic or hyperchloremic acidosis or with conditions that predispose to acidosis (renal disease, severe respiratory disorders, diarrhea). The measurement of baseline and periodic serum bicarbonate is recommended. If metabolic acidosis develops (it may be corrected by administration of sodium bicarbonate), and persists, a dose reduction or treatment discontinuation should be considered.

A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving topiramate. Symptoms include acute onset of decreased visual acuity and/or ocular pain. It typically occurs within 1 month of treatment initiation and it has been reported in both pediatric and adult patients. Caution is recommended when prescribing topiramate in patients with elevated intraocular pressure regardless of the etiology.

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than that in a normal individual. To avoid rapid drops in topiramate plasma level during hemodialysis, a supplemental dose may be required. The actual adjustment should consider 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.

Plasma clearance of topiramate decreased a mean of 26% in patients with moderate to severe liver dysfunction. After a single dose of phentermine 15 mg-topiramate 92 mg, pharmacokinetics of topiramate were not affected in patients with mild (Child-Pugh score 5 to 6) and moderate (Child-Pugh score 7 to 9) liver dysfunction when compared with healthy subjects. Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at increased risk for hyperammonemia with or without encephalopathy. Although not studied, use of topiramate may exacerbate existing defects or unmask deficiencies in susceptible patients.

The use of topiramate increases the risk of kidney stones. The reported incidence was 1.5% during premarketing use, which is about 2 to 4 times that expected in a similar, untreated population. Topiramate is a 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, especially those with predisposing factors (e.g., history of nephrolithiasis), to minimize the risk of kidney stone formation. The concomitant use of topiramate with any other drug producing metabolic acidosis, or potentially in patients on a ketogenic diet, may create a physiological environment that increases the risk of kidney stone formation and 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.