VALPROIC acid = VPA = SODIUM VALPROATE oral

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      Last updated: October 2024

     

    Prescription under medical supervision

     

     

     

     
    • VPA must not be used in pregnancy or in women and girls of childbearing age. The risk of foetal harm is higher than with other antiseizure medications.
    • Due to the numerous and potentially severe adverse effects of VPA, patients should be kept under close surveillance.

     

    Therapeutic action

    • Antiseizure (antiepileptic), mood stabilizer

    Indications

    • Epilepsy: generalised tonic-clonic seizures, focal (partial) seizures and absence seizures
    • Prevention of recurrence of bipolar disorder 

    Forms and strengths

    • 200 mg and 500 mg enteric-coated tablets
    • 200 mg/5 ml oral solution, to be administered using a measuring device (oral syringe, measuring spoon, or cup with graduations).

    Dosage

    Start with a low dose then increase gradually based on patient's response and tolerance.

     

    Epilepsy

    • Child 2 to 11 years: start with 10 to 15 mg/kg once daily or 5 to 7.5 mg/kg 2 times daily; increase the daily dose by increments of 5 to 10 mg/kg every week, up to 12.5 to 15 mg/kg 2 times daily if necessary (max. 600 mg 2 times daily).
    • Child 12 years and over and adult: start with 500 to 600 mg once daily; increase the daily dose by increments of 200 mg every 3 days, up to 500 mg to 1 g 2 times daily if necessary (max. 2.5 g daily).

    Prevention of recurrence of bipolar disorder 

    • Adult: start with 200 mg 2 times daily; increase the daily dose until the optimal individual dose is reached, usually around 500 mg 2 times daily (max. 1g 2 times daily).

    Duration

    • As long as required. Do not stop treatment abruptly, even if changing treatment to another medication.

    Contra-indications, adverse effects, precautions

    • Do not administer:
      • to women and girls of childbearing age. If the treatment is necessary and if there is no alternative, a negative blood pregnancy test and effective contraception are required;
      • 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 (caution when driving/operating machinery), extrapyramidal symptoms, behavioural disturbances, confusional state, insomnia;
      • weight gain, menstrual irregularities, gastrointestinal disturbances, vitamin D deficiency (consider supplementation), osteoporosis,thrombocytopenia;
      • rarely: pancreatitis, hepatic disorders (e.g. elevated liver enzymes), prolonged bleeding time, hypersensitivity reactions (including severe cutaneous reactions such as Stevens-Johnson, Lyell and DRESS syndromes), hyperammonemic encephalopathy. In these cases, stop treatment. Early symptoms such as fever, rash, mouth ulcers and bleeding require immediate medical attention. 
      • respiratory depression and coma in the event of overdose.
    • If possible, perform at least FBC, liver enzymes and serum sodium levels, at baseline then regularly during treatment; check prothrombin time before surgical procedures.
    • 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);
      • drugs containing alcohol, benzodiazepines, opioid analgesics, antipsychotics, first-generation antihistamines (hydroxyzine, promethazine), antidepressants, other antiseizure medications, etc. (increased sedation).
    • Avoid alcohol during treatment (increased risk of adverse effects).
    • Pregnancy: do not use (risk of neural tube defects; urogenital, limb and facial malformations; neurodevelopmental disorders).
      • In case of pregnancy during treatment, change to a safer drug (levetiracetam). If VPA is the only option, provide counselling about the risks to the child; use the lowest effective dose and divide doses over the day to minimize peaks in plasma concentrations.
      • Administer folic acid high dose (5 mg daily) during the first trimester. Start as soon as possible, including during the preconception period in case of planned pregnancy. 
    • Breast-feeding: administer with caution (excreted in milk); monitor the child (risk of hepatotoxicity and bleeding).

    Remarks

    • Take with meals.
    • VPA can be used with contraceptive implants and oral contraceptives, although estrogens may decrease VPA plasma concentrations.

    Storage 

     
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    – Below 25 °C