Topiramate and fulminant liver failure

Topiramate‐Induced Acute Liver Failure in a Pediatric Patient

“…Our patient's topiramate level, however, was >4‐fold higher than it had ever been before, with no changes in his medications and no supplements, which, we hypothesize, mimics a “new drug” effect. Bjoro et al (6) described an adult with ALF requiring a liver allograft 4 months after topiramate was added to a stable regimen of carbamazepine and days after a dose increase. Similarly, Doan and Clendenning (7) reported a case of ALF in a young adult for whom topiramate was added to a long‐standing valproate regimen.…”

Adding topiramate to valproate therapy may cause reversible hepatic failure

“…Histological investigation of the liver showed massive centrilobular necrosis compatible with druginduced liver failure [4]. It has been speculated that the disturbances of liver function may be due to a direct toxic effect of TPM to an enhancement of the propensity of VPA or CBZ to cause hepatotoxic effects [2][3][4]. However, the mechanisms leading to the potential of TPM to aggravate hepatotoxic effects of VPA or CBZ remains to be elucidated.…”

“…In these patients, liver enzyme tests remained normal except for a slightly increased gamma‐GT [2]. Clinically relevant interactions of TPM with CBZ have also been reported [5], and one case of fulminant liver failure, severe encephalopathy and renal failure caused by adjunctive TPM in a patient who tolerated CBZ well has been documented [4]. Histological investigation of the liver showed massive centrilobular necrosis compatible with drug‐induced liver failure [4].…”

“…Clinically relevant interactions of TPM with CBZ have also been reported [5], and one case of fulminant liver failure, severe encephalopathy and renal failure caused by adjunctive TPM in a patient who tolerated CBZ well has been documented [4]. Histological investigation of the liver showed massive centrilobular necrosis compatible with drug‐induced liver failure [4]. It has been speculated that the disturbances of liver function may be due to a direct toxic effect of TPM to an enhancement of the propensity of VPA or CBZ to cause hepatotoxic effects [2‐4].…”

“…In children, there have been three cases where liver disturbances were caused by TPM add-on therapy with no evidence of hepatic failure while treated with valproate (VPA) alone or in combination with other drugs [3]. Another patient who was treated with carbamazepine (CBZ) without any signs of liver disease developed severe liver failure requiring liver transplantation during adjunctive therapy with TPM [4]. We report a further adult patient who tolerated VPA well but developed symptoms and signs of hepatic failure when VPA was combined with TPM.…”