sodium valproate + valproic acid: clinical use

Prescribing considerations

• Apply current reproductive-risk measures and avoid abrupt withdrawal.
• Exercise caution in young children, polytherapy, renal impairment, systemic lupus erythematosus, and risk of carnitine deficiency, hyperammonaemia or pancreatitis.
• Consider sodium content where clinically relevant.

Contraindications and cautions

• Hypersensitivity to valproate or an excipient.
• Active liver disease or personal or family history of severe hepatic dysfunction.
• Known urea-cycle disorder or porphyria.
• Known POLG-related mitochondrial disorder; suspected POLG-related disease in children under two years.
• Uncorrected systemic primary carnitine deficiency.
• Pregnancy or childbearing potential where product-specific exceptions and Pregnancy Prevention Programme conditions are not fulfilled.

Monitoring

• Assess liver function before treatment and periodically during the first six months.
• Check full blood count, platelets and coagulation before treatment, before surgery and with spontaneous bruising or bleeding.
• Monitor weight, seizure control, sedation, gastrointestinal symptoms, hepatic warning signs and reproductive safety requirements.
• Investigate ammonia and carnitine status when compatible symptoms or risk factors are present.

Clinical pharmacology

Both components provide the active valproate moiety. Prolonged-release formulations reduce peak concentrations and plasma fluctuation compared with immediate-release presentations.

Formulation and product differences

• Dyzantil and Epilim Chrono are prolonged-release tablets that must be swallowed whole.
• Epilim Chronosphere is a modified-release granule formulation that must not be crushed, chewed, heated or stored after mixing.
• An inert tablet or granule matrix may be visible in stools after active ingredient release.