What laboratory tests are required before initiating Depakote (valproate) therapy in a patient, particularly in those with pre-existing liver or renal disease, or in female patients of childbearing age?

Laboratory Testing Before Starting Depakote (Valproate)

Before initiating Depakote therapy, obtain baseline liver function tests (AST, ALT, bilirubin), complete blood count with platelet count, and a pregnancy test in all females of reproductive age. 1, 2

Essential Baseline Laboratory Tests

Hepatic Function Panel

• Measure serum AST (SGOT), ALT (SGPT), and bilirubin before starting valproate therapy 1, 2
• Baseline liver testing is particularly critical in patients with:
  • History of liver disease (hepatitis B or C, alcoholic hepatitis, cirrhosis) 3
  • HIV infection 3
  • Regular alcohol use 3
  • Pregnancy or within 3 months postpartum 3
  • Concurrent use of other hepatotoxic medications 1
• Valproate hepatotoxicity can occur at any time during therapy, though most common early in treatment, and may present with cholestatic or hepatocellular patterns 4

Hematologic Testing

• Obtain complete blood count (CBC) with platelet count and differential at baseline 1, 2
• Platelet counts and coagulation parameters are essential due to risk of thrombocytopenia and inhibition of platelet aggregation 2
• In clinical trials, 27% of patients receiving approximately 50 mg/kg/day had at least one platelet count ≤75 × 10⁹/L 2
• Neutropenia, though rare, can develop even after years of stable therapy 5

Renal Function Assessment

• Measure serum creatinine, BUN, and obtain urinalysis before initiating therapy 3, 1
• Renal function testing helps establish baseline parameters and guides dosing adjustments 1
• Valproate-associated reversible renal insufficiency has been documented 4

Pregnancy Testing

• Mandatory pregnancy test for all females of reproductive age before starting valproate 1, 2
• Valproate is a known teratogen with significant risk of neural tube defects and other malformations 2
• Counsel patients on effective contraception methods, noting that rifampin reduces oral contraceptive efficacy if used concurrently 3

Additional Baseline Considerations

Metabolic Screening

• Serum chemistry panel including electrolytes should be obtained 1
• Consider ammonia level if patient has history of unexplained encephalopathy, mental retardation, cyclical vomiting, protein avoidance, or family history of urea cycle disorders 2
• Evaluation for urea cycle disorders is critical before initiation in patients with unexplained encephalopathy or family history of unexplained infant deaths 2

Weight Documentation

• Record accurate body weight for proper dose calculation, as initial dosing is typically 20 mg/kg/day for acute mania 1

High-Risk Populations Requiring Enhanced Baseline Testing

Patients in the following categories warrant more comprehensive baseline evaluation:

• Infants under 2 years on polytherapy - highest risk for hepatotoxicity 1
• Patients with suspected or confirmed urea cycle disorders - valproate is contraindicated in this population 2
• Those with history of unexplained encephalopathy, elevated ammonia, or low BUN 2
• Patients with bleeding disorders or on anticoagulation - require coagulation studies 2

Critical Clinical Pitfalls to Avoid

• Do not skip pregnancy testing in any female of reproductive age, regardless of reported sexual activity, as valproate causes severe birth defects 2
• Do not initiate therapy without liver function tests in patients with any liver disease risk factors, as hepatotoxicity can be life-threatening 2, 4
• Do not assume normal baseline values eliminate the need for ongoing monitoring, as adverse effects like neutropenia can develop after years of stable therapy 5
• Screen for urea cycle disorder symptoms before starting therapy, as hyperammonemic encephalopathy can be fatal in these patients 2