Valproate semisodium precautions

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

List of precautions

General

Hyperammonemia

Urine ketone test

Altered thyroid function

Suicidal ideation

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General

Because of reports of thrombocytopenia, inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters, (e.g., low fibrinogen), platelet counts and coagulation tests are recommended before initiating therapy and at periodic intervals. It is recommended that patients receiving Valproate semisodium be monitored for platelet count and coagulation parameters prior to planned surgery. In a clinical trial of Valproate semisodium as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets < 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of > 110 μg/mL (females) or > 135 μg/mL (males). Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy. Return to top

Hyperammonemia

Hyperammonemia has been reported in association with valproate therapy and may be present despite normal liver function tests. In patients who develop unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. If ammonia is increased, valproate therapy should be discontinued. Appropriate interventions for treatment of hyperammonemia should be initiated, and such patients should undergo investigation for underlying urea cycle disorders. Asymptomatic elevations of ammonia are more common and when present, require close monitoring of plasma ammonia levels. If the elevation persists, discontinuation of valproate therapy should be considered. Return to top

Urine ketone test

Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. Return to top

Altered thyroid function

There have been reports of altered thyroid function tests associated with valproate. The clinical significance of these is unknown. Return to top

Suicidal ideation

Suicidal ideation may be a manifestation of certain psychiatric disorders, and may persist until significant remission of symptoms occurs. Close supervision of high risk patients should accompany initial drug therapy. Return to top

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The content of this page is taken from the FDA package insert for this drug and should not be edited.