VALPROIC acid = VPA = SODIUM VALPROATE injectable

Last updated: October 2024

Therapeutic action

• Antiseizure (anticonvulsant)

Indications

• Second-line treatment of convulsive status epilepticus

Forms and strengths, route of administration

• 400 mg in 4 ml ampoule (100 mg/ml) for slow IV injection or IV infusion in 0.9% sodium chloride or 5% glucose
• DO NOT ADMINISTER BY IM INJECTION (risk of necrosis).

Dosage and duration

• Loading dose:
  • Child 2 years and over: 
    • Use diluted solution: add 4 ml (400 mg) of VPA to 6 ml of 0.9% NaCl to obtain 10 ml of solution containing 40 mg of VPA per ml.
    • Administer 20 mg/kg (max. 1.5 g) over 5 minutes by IV infusion using a syringe pump or by slow IV injection.
    • If seizures do not stop after the end of the first dose, readminister the same dose: 20 mg/kg (max. 1.5 g) as above. 
    • Do not exceed the total dose of 40 mg/kg or 3 g. 
  • Adult: 
    • 40 mg/kg (max. 3 g) single dose over 10 minutes 
    • Use diluted solution as above (40 mg/ml) if administered by IV infusion using a syringe pump.
    • Use undiluted solution if administered by IV infusion in a bag of 100 ml of 0.9% NaCl. 

In children and adults, do not exceed an infusion rate of 6 mg/kg/minute.

• If maintenance treatment is indicated after the loading dose: change to oral route as soon as possible.

Contra-indications, adverse effects, precautions

• Do not administer:
  • to women and girls of childbearing age;
  • to children under 2 years (increased risk of hepatotoxicity);
  • to patients with pancreatitis, hepatic disease or history of hepatic disease.
• Reduce dosage in patients with renal impairment.
• May cause:
  • drowsiness, extrapyramidal symptoms, behavioural disturbances, confusional state;
  • menstrual irregularities, gastrointestinal disturbances, thrombocytopenia;
  • rarely: pancreatitis, hepatic disorders (e.g. elevated liver enzymes), prolonged bleeding time, hypersensitivity reactions sometimes severe, hyperammonemic encephalopathy. In these cases, stop treatment.
  • respiratory depression and coma in the event of overdose.
• Avoid or monitor the combination with:
  • mefloquine, carbapenems, tricyclic antidepressants, rifampicin, protease inhibitors, other antiseizure medications (reduced effect of VPA);
  • acetylsalicylic acid, erythromycin, isoniazid (increased VPA toxicity);

  • benzodiazepines, opioid analgesics, antipsychotics, first-generation antihistamines (hydroxyzine, promethazine), antidepressants, other antiseizure medications, etc. (increased sedation).

• Pregnancy: do not use except if vital and no alternative is available (risk of neural tube defects; urogenital, limb and facial malformations; neurodevelopmental disorders). Use a safer drug if possible (levetiracetam).
• Breast-feeding: administer with caution (excreted in milk); monitor the child (risk of hepatotoxicity and bleeding).

Remarks

• Do not mix with other drugs in the same syringe or infusion.

Storage