What is known about fever as a side effect of topiramate? Is it temporary or dose dependent?

Fråga: What is known about fever as a side effect of topiramate? Is it temporary or dose dependent?

Sammanfattning: We have not found any information about whether hyperthermia caused by topiramate may subside spontaneously or with dose reduction. However, it might be useful to measure blood drug levels of topiramate to ensure the patient is within the therapeutic range. On the other hand, there are case reports of patients who have experienced severe damage after long-lasting hyperthermia. Disrupted body temperature control in a young child prone to getting infections potentially leading to a further increase in body temperature - seems risky and we recommended discontinuation of topiramate.

Svar: Topiramate (Topamax) is an anticonvulsant drug licensed for treatment from the age of 2 years (1). According to the SPC hyperthermia is a known, uncommon (1/100-1/1000 patients) side effects that only appears in children (1). In the Swedish adverse reaction register, Swedis, there are two reports of fever as a side effect of topiramate (2). In one case (an adult patient) the fever disappeared upon withdrawal of topiramate, and recurred upon rechallenge. The treatment was then permanently discontinued. In the second report (a child) it is not clear whether the treatment was discontinued or not.

A review of the scientific literature revealed several studies and case reports of hyperthermia during topiramate therapy. The hyperthermia is suspected to be due to a reduced ability to sweat, which is a known adverse reactions to topiramate (3). Hyperthermia has been observed in up to 10.5 % of topiramate patients (4). Young age (< 6 years), higher doses (> 6 mg/kg) and warm environmental temperature has been seen to increase the risk (4). There are also case reports of permanent neurological damage and rhabdomyolysis after topiramate induced hyperthermia (5.6).

When looking for potential interactions between the patient´s medicines, we found a class C interaction (i.e. clinically relevant interaction that can be handled through e.g. dose adjustment) between topiramate and phenobarbital. This interaction can result in decreasing serum concentrations of topiramate (7). This should not lead to side effects of topiramate, and we do not suspect any interaction in this case. Topimax. Fass (cited 2014-01-08) Swedis Ben-Zeev B, Watemberg N, Augarten A, Brand N, Yahav Y, Efrati O, Topper L, Blatt I. Oligohydrosis and hyperthermia: pilot study of a novel topiramate adverse effect. J Child Neurol 20013;18(4):254-7 Ziad el K, Rahi AC, Hamdan SA, Mikati MA. Age, dose, and environmental temperature are risk factors for topiramate-related hyperthermia. Neurology 2005;65(7):1139-40 Strawn JR, Adler CM, Strakowski SM, DelBello MP. Hyperthermia and rhabdomyolysis in an adolescent treated with topiramate and olanzapine. J Child Adolesc Psychopharmacol 2008;18(1):116-8 Galicia SC, Lewis SL, Metman LV. Severe topiramate-associated hyperthermia resulting in persistent neurological dysfunction. Clin Neuropharmacol 2005;28(2):94-5 Läkemedelsinteraktioner (SFINX) (cited 2013-10-17)