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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drug concentrations and dosage adjustment are indicated whenever enzyme-inducing or inhibiting drugs are introduced or withdrawn (7.1) Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended (7.1) Co-administration 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 extended-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 extended-release tablets can cause congenital malformations including neural tube defects, decreased IQ, and neurodevelopmental disorders

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Lastly, the majority of best-selling drugs and essential medicines target the product of circadian genes [111]

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