Risperidone/valproic acid interactions
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Various toxicities: case report A boy [age not stated] developed gingival hypertrophy, and megaloblastic anaemia with megakaryocytic dysplasia and pancytopenia following concomitant administration of valproic acid and risperidone for autism and epilepsy. The boy, who had a history of epilepsy and autism, was referred to the clinic with a history of petechiae, ecchymosis and pallor at the age of 15 years. He had been receiving valproic acid and risperidone daily [routes and doses not stated] for 8 years. He did not follow-up regularly and had impairment of feeding. At presentation, he was agitated and had hypertrophic gingiva with large amounts of tooth decay. He also had several ecchymosis and petechiae on the extremities and trunk. No hepatosplenomegaly or lymphadenopathy was reported. His complete blood count revealed the following: haemoglobin of 3.6 g/dL, WBC count of 1.4 x103/mm3, absolute neutrophil count of 730 /mm3, mean corpuscular volume of 117fL and platelet count of 8000 /mm3. His serum LDH level was 1637 U/L, and total bilirubin level was 1.46 mg/dL with 0.66 mg/dL of it was unconjugated form. The reticulocyte count was 1.89%, while the anti-globin test was negative. His renal function tests, serum electrolytes and liver function tests were normal. His serum valproic acid level was high at 146 mg/dL. Peripheral blood smear showed hyper-segmented neutrophils and macrocytic erythrocytes. Bone marrow aspiration showed hyperplasia in the erythroid series with the presence of immature nuclei. Hyper-segmented neutrophils were found during the examination. Also, dysplasia was noted in all series, which was assessed as bone marrow with megaloblastic changes. The flow cytometry showed no phenotypic pattern associated with malignancy, and bone marrow biopsy showed reactive erythroid hyperplasia. Epstein-Barr virus, parvovirus B19 and cytomegalovirus DNA PCR were negative. His vitamin B12 and folic acid levels were low, while homocysteine level was high [durations of treatments to reactions onsets not stated]. Hence, the boy received treatment with plasma, erythrocyte and thrombocyte transfusions. Treatment with risperidone and valproic acid was stopped, and he was prescribed with levetiracetam. His flow cytometry and bone marrow biopsy analysis were negative for leukaemia. Therefore, a diagnosis of valproic acid-associated megaloblastic anaemia with megakaryocytic dysplasia and pancytopenia was made. High valproic acid levels also contributed to his gingival hypertrophy. He also started receiving supportive treatment with folic and vitamin B12. In the second week of treatment, his laboratory test results were as follows: haemoglobin of 13.6 g/dL, WBC count of 4.35 x103/mm3, platelet count of 371 x103/mm3, MCV of 95fL and folic acid of 20.8 µg/L. His condition improved with mood and appetite improvement. It was concluded that, the interaction between risperidone and valproic acid led to high levels of valproic acid, which subsequently caused gingival hypertrophy, and megaloblastic anaemia with megakaryocyti
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