sodium valproate: clinical use

Prescribing considerations

• Initiation in patients under 55 is subject to current specialist and second-specialist requirements.
• Apply the Pregnancy Prevention Programme to relevant female patients.
• Avoid abrupt withdrawal.
• Plasma valproate measurement is not routinely required but may help with poor control, suspected toxicity or significant interactions.
• Assess formulation, release characteristics, indication and excipients before switching products.

Contraindications and cautions

• Hypersensitivity to sodium valproate or formulation excipients
• Active liver disease or a personal or family history of severe hepatic dysfunction, particularly drug-related
• Known urea-cycle disorder or porphyria
• Known POLG-related mitochondrial disease, or suspected POLG-related disease in a child younger than two years
• Uncorrected systemic primary carnitine deficiency
• Pregnancy and reproductive circumstances specified by the indication-specific licence and Pregnancy Prevention Programme

Monitoring

• Before treatment: body mass index, full blood count, platelets, liver function and coagulation testing; pregnancy testing where applicable.
• Continue liver-function monitoring until stable; once stable, monitor body mass index, full blood count and liver function periodically.
• Check full blood count and coagulation before surgery or when spontaneous bruising or bleeding occurs.
• Investigate promptly for features of liver injury, pancreatitis, hyperammonaemia, blood dyscrasia or severe skin reaction.

Clinical pharmacology

Valproate is a broad-spectrum anticonvulsant whose activity includes potentiation of inhibitory GABA signalling. It is highly protein-bound, undergoes extensive hepatic metabolism and has clinically important concentration- and interaction-dependent pharmacokinetics.

Formulation and product differences

• Prolonged-release capsules contain granules; selected capsules may be opened and the intact granules mixed with suitable food or drink.
• Prolonged-release tablets provide smoother plasma concentrations and should not be crushed or chewed.
• Gastro-resistant tablets release sodium valproate after passing through the stomach and must be swallowed whole.
• Oral liquids support administration where tablets or capsules are unsuitable; follow supplied measuring devices and product-specific dilution instructions.
• The intravenous product is for hospital use when oral treatment is temporarily impossible and must be administered separately from other intravenous additives.

Gastro-resistant tablet

Route: Oral

Strengths: 200 mg, 500 mg

Granules

Route: Oral

Strengths: 500 mg, 1000 mg