Can valproic acid or olanzapine cause isolated hypoalbuminemia?/nA patient in her twenties, of Ethi

Fråga: Can valproic acid or olanzapine cause isolated hypoalbuminemia?

A patient in her twenties, of Ethiopian origin, with a psychotic disorder, is found to have hypoalbuminemia (32 g/L normal range 34-47). Her ALP is slightly elevated (4.9 ukal/L normal range 0.8-4.6). The transaminases are normal, as are other routine serum tests. She is on medication with olanzapine and, since August 2003, valproic acid. Her latest valproic acid concentration was subtherapeutic.

Sammanfattning: Valproic acid has been described as a possible cause of hypoalbuminemia in children. The documentation for this, however, is limited to a small case series of severely neurologically impaired patients on enteral nutrition. In the absence of further documentation or a mechanistic explanation, valproic acid therapy seems an unlikely cause of hypoalbuminemia in a young Ethiopian woman. There is no evidence in the literature that olanzapine therapy would be associated with isolated hypoalbuminemia.

Svar: Both olanzapine and valproic acid have rarely been associated with fulminant hepatitis, of which hypoalbuminemia is often a feature (1). This patient however, presents with hypoalbuminemia in the absence of other signs of significant liver affection. A literature search identified one case series where five severely handicapped children with enteral nutrition were shown to have hypoalbuminemia, in some cases with concomitant edema, while on valproic acid therapy. Removal of this medication, without any alteration of the enteral diet constitution, led to normalisation of serum albumin levels (2). No other references to this phenomenon were found in the literature. Concerning olanzapine, the search of the medical literature did not identify any association with hypoalbuminemia.

Valproic acid is approximately 90% bound to plasma proteins, mainly albumin. This binding is saturable within the therapeutic concentration range of valproic acid at normal concentrations of albumin. Therefore a higher free fraction of serum valproic acid is seen at higher concentrations. Two case reports describe valproic acid toxicity at therapeutic concentrations, due to supratherapeutic free drug concentrations in the presence of hypoalbuminemia (3,4). Monitoring of free valproic acid concentration thus seems indicated in the presence of hypoalbuminemia.

A further medical workup in this patient might include a full medical history, clinical examination, urinary protein levels, PK-INR, inflammatory parameters, a full blood count, a chest film for TB, and faecal microscopy for intestinal parasitosis. Free valproic acid concentration should be monitored.