VALWOK

What it is

VALWOK is sodium valproate solution for injection, available in ampoules containing 100 mg/mL. Each 4 mL ampoule contains 400 mg sodium valproate and each 10 mL ampoule contains 1000 mg sodium valproate. The product is a clear and colourless solution for injection in a Type I glass ampoule.

Approved indications

— Treatment of patients with epilepsy who would normally be maintained on oral sodium valproate and for whom oral therapy is temporarily not possible. — Treatment of patients with mania who would normally be maintained on oral sodium valproate and for whom oral therapy is temporarily not possible.

Dosing overview

VALWOK may be given by direct slow intravenous injection or by slow intravenous infusion in 0.9% NaCl, 5% glucose solution or glucose saline, using a separate intravenous line. The recommended concentration of the intravenous infusion solution is 4 mg/mL, with 8 mg/mL being the maximum concentration. For adults with epilepsy, patients already satisfactorily treated with sodium valproate may be continued at their current dosage using continuous infusion, for example, a patient stabilised on 25 mg/kg administered daily should be continued with an infusion at the rate of 1 mg/kg/hr. Other patients may be given a slow intravenous injection over 3–5 minutes, usually 400–800 mg depending on body weight (up to 10 mg/kg) followed by continuous infusion of 1–2 mg/kg/hr up to a maximum of 2500 mg/day, according to the patient's clinical response. For children, the daily requirement is usually in the range 20–30 mg/kg/day. Where adequate control is not achieved within this range the dose may be increased up to 40 mg/kg/day but only in patients in whom plasma valproic acid levels can be monitored. In the elderly, dosage should be determined by control of symptoms.

Key safety warnings

Life-threatening pancreatitis has been reported in both children and adults receiving sodium valproate, with some cases occurring shortly after initial use while others have occurred after several years of use. Young children are at particular risk but this risk decreases with increasing age. Patients and guardians should be warned that acute abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical attention. Severe liver damage and/or hepatic failure resulting in fatalities have occurred in patients whose treatment included valproic acid or sodium valproate. Patients most at risk are those on multiple anticonvulsant therapy and children, particularly those under the age of 3 years and those with congenital metabolic or degenerative disorders, organic brain disease or severe seizure disorders associated with brain damage and/or mental retardation. Jaundice, serious or fatal hepatotoxicity may be preceded by nonspecific symptoms, usually of sudden onset, such as loss of seizure control, malaise, asthenia, weakness, lethargy, facial oedema, anorexia, vomiting, abdominal pain, drowsiness, and jaundice. Antiepileptic drugs, including sodium valproate, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication, and patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or any unusual changes in mood or behaviour. Valproate has a high teratogenic potential and children exposed in utero to valproate have a high risk for congenital malformations and neurodevelopmental disorders.

Contraindications

Valproate is contraindicated in pregnancy for treatment of epilepsy unless there is no suitable alternative treatment, and in women of childbearing potential unless the physician has provided information in regard to the potential effects of valproate during pregnancy. Valproate is contraindicated in pregnancy for treatment of mania and in women of childbearing potential unless the physician has provided information in regard to the potential effects of valproate during pregnancy. Valproate is contraindicated in pre-existing, acute or chronic hepatic dysfunction or family history of severe hepatitis, particularly medicine-related. Valproate is contraindicated in known hypersensitivity to the medicine. Valproate is contraindicated in known urea cycle disorders. Valproate is contraindicated in known hepatic porphyria. Valproate is contraindicated in patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding mitochondrial enzyme polymerase γ (POLG) and in children under two years of age who are suspected of having POLG-related disorder.

Regulatory history

VALWOK sodium valproate 400 mg/4 mL solution for injection ampoule was first listed on the ARTG on 2 June 2017. VALWOK sodium valproate 1000 mg/10 mL solution for injection ampoule was first listed on the ARTG on 2 June 2017.