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
–
– Below 25 °C