Topiramate encephalopathy

Hyperammonemia and encephalopathy associated with concomitant valproic acid use Administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. In most cases, symptoms and signs abated with discontinuation of either drug. 

In two other cases the addition of topiramate was thought to have precipitated valproate-induced hyperammonemic encephalopathy (1172). Recovery occurred after withdrawal of valproate or topiramate. The authors suggested that topiramate may have contributed to the hyperammonemia by inhibiting carbonic anhydrase and cerebral glutamine synthetase. 

Valproate-induced hyperammonemic encephalopathy in the presence of topiramate. Neurology 2000 54(l) 230-2. 

Encephalopathy has been reported in patients given topiramate with or without valproate. One study found no clinically relevant pharmacokinetic interaction between topiramate and valproate. 

Six patients with severe epilepsy developed stuporous encephalopathy with marked cognitive impairment when taking topiramate with valproate (5 patients) or when taking topiramate alone (1 patient). Four of the patients had hyperammonaemia which resolved when topiramate or valproate were withdrawn. The toxicity was possibly due to a synergistic effect of valproate and topiramate on liver ornithine metabolism resulting in hyperammonaemia. It was also possible that the encephalopathy was due to topiramate toxicity in at-risk patients such as those with pre-existing chronic encephalopathy. ... 

The pharmacokinetic study suggests that dosage adjustments and special precautions are not required during concurrent use. However, the report of encephalopathy with topiramate and valproate indicates that particularly for af-risk patients such as those with pre-existing encephalopathy care-fid monitoring is advised in these patients. ... 

Antiepileptic drug-induced encephalopathies have been reviewed [50 ]. These complications have been reported with phenytoin, carbamazepine, and valproate and less often with vigabatrin, lamotrigine, and topiramate. 

Filippi L, Poggi C, la Marca G, Furlanetto S, Fiorini P, Cavallaro G, Plantulli A, Donzelli G, Guerrini R. Oral topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia a safety study. J Pediatr 2010 157(3) 361-6. 

In one patient there was a possible synergistic interaction of valproic acid and topir-amate with respect to the emergence of hyperammonemic encephalopathy [316 ]. The authors speculated that inhibition of carbonic anhydrase by topiramate might be the basis of this, since HCO is used in the sjmthesis of carbamoylphosphate in the urea cycle. 

Deutsch SI, Burket JA, Rosse RB. Valproate-induced hyperammonemic encephalopathy and normal liver functions possible synergism with topiramate. Clin Neuropharmacol 2009 32(6) 350-2. 

The combination of topiramate 100 mg/day and VPA 500 mg/day led to acute encephalopathy, including drowsiness, disorientation, and stupor in a 37-year-old man. Serum ammonia level was elevated. The symptoms resolved after topiramate was withdrawn. Re-challenging the patient witii VPA alone did not cause encephalopatiry. It has been suggested that tiiere may be a pharmacodynamic synergism between topiramate and VPA, leading to hyperammonemia [175 ]. 

Chakor RT, Bharote HS. Topiramate-valproate-induced encephalopathy in migraine. Headache September 2012 52(8) 1321-2. 

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