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Therefore increased monitoring of valproate and concomitant drug concentrations and dosage adjustment are indicated whenever enzyme-inducing or inhibiting drugs are introduced or withdrawn (7.1) • Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended (7.1) • Coadministration of valproate can affect the pharmacokinetics of other drugs (e.g., diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein binding displacement (7.2) • Patients stabilized on rufinamide should begin valproate therapy at a low dose, and titrate to clinically effective dose (7.2) • Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with divalproex sodium delayed-release tablets (7.2) • Topiramate: Hyperammonemia and encephalopathy (5.10, 7.3) • Cannabidiol: ALT and/or AST elevation (7.4) Use In Specific Populations • Pregnancy: Divalproex sodium delayed-release tablets can cause congenital malformations including neural tube defects, decreased IQ, and neurodevelopmental disorders (5.2, 5.3, 8.1) • Geriatric: Reduce starting dose

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