Dosage and administration

Before initiating treatment with valproate, a medical history and physical examination should be performed, with careful attention to any hepatic, haematological, and neurological problems. The patient should be educated about the signs and symptoms of hepatic toxicity, pancreatitis, and blood dyscrasias, and told to contact the physician immediately if these should arise. The patient should also be warned of the teratogenic effects of valproate. Baseline laboratory tests should include a complete blood count and liver function tests, and, if appropriate, a pregnancy test. Blood counts and liver function tests should be performed monthly for the first 3 months, and, if no abnormalities are found, every 6 to 12 months thereafter. If hepatic transaminase levels increase to more than three times normal, valproate should be discontinued. If the transaminase levels eventually return to baseline and the patient responded to valproate previously, rechallenge can be considered. If hepatic transaminase levels increase, but are less than three times normal, monitoring should be increased to once every 1 to 2 weeks until transaminase levels stabilize, and then monthly thereafter/2)

The initial starting dose of valproate in adults is 250 to 1000 mg per day, given in two or three divided doses (see Table.1 for dosage forms). The dose may be increased every 1 to 3 days depending on the patient's response and tolerance. The usual therapeutic concentration is between 50 and 150 pg/ml (drawn 12 h after the last dose) for both psychiatric and neurological disorders. Some clinicians give the entire daily dose of valproate at bedtime. In patients with seizure disorders or acute mania, an oral-loading strategy can be used. (1J In this situation, the patient receives 20 mg/kg as a bolus on the first day, resulting in rapid achievement of therapeutic levels. However, psychiatric patients who are not acutely manic usually have difficulty tolerating the oral loading strategy.

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