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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. General Because of reports of thrombocytopenia (see WARNINGS), 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 DEPAKOTE be monitored for platelet count and coagulation parameters prior to planned surgery. In a clinical trial of DEPAKOTE 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 10 9 /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. Since DEPAKOTE may interact with concurrently administered drugs which are capable of enzyme induction, periodic plasma concentration determinations of valproate and concomitant drugs are recommended during the early course of therapy where clinically appropriate (see PRECAUTIONS -Drug Interactions). Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test. Text Continues Below
There have been reports of altered thyroid function tests associated with valproate. The clinical significance of these is unknown. There are in vitro studies that suggest valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequence, if any, is not known. Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. Nevertheless, these data should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.
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