Pivmecillinam Valproate

There is a report of hyperammonaemic encephalopathy which developed in a 72-year-old woman taking valproate monotherapy for partial epilepsy after she started treatment with pivmecillinam 600 mg daily. She recovered after discontinuation of valproate and use of cefuroxime instead of pivmecillinam. Valproate may reduce serum carnitine, for reasons that are not well understood. Valproate-induced hyperammonaemic encephalopathy may be due to reduced carnitine levels. ... 

A 72-year-old woman taking valproate as monotherapy for her epilepsy developed a urinary tract infection and was given pivmecillinam 600 mg/day. During the next few days she became stuporose her serum ammonia concentration was high (113 mmol/1) but liver function was normal. Pivmecillinam and valproate were withdrawn and she recovered rapidly. 

The authors recommended caution when treating patients taking valproate with pivmecillinam because of the risk of hyperammonemic encephalopathy. It seems reasonable... 

An isolated report describes hyperammonaemic encephalopathy in an elderly patient during treatment with valproate and pivmecillinam. The manufacturers of both pivmecillinam and pivampicillin advise the avoidance of concurrent valproate because of the increased risk of carnitine deficiency. 

The authors of the report advise caution if pivmecillinam is added to treatment with valproate. Although this appears to be the only report of an adverse effect due to the combined effects of pivmecillinam and valproate on carnitine levels, the manufacturers advise the avoidance of both pivampicillin or pivmecillinam with valproic acid or valproate or other medication liberating pivalic acid. " ... 

Lokrantz C-M, Eriksson B, Rosen I, Asztely F. Hyperammonemic encephalopathy induced by a combination of valproate and pivmecillinam. Acta Neurol Scand(200A) 109, 297-301. 

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