EPILIM

What it is

Sodium Valproate Wockhardt (EPILIM) is used for the treatment of patients with epilepsy or mania, who would normally be maintained on oral sodium valproate, and for whom oral therapy is temporarily not possible. It is supplied as a solution for injection containing 100 mg/mL sodium valproate, available in 4 mL ampoules containing 400 mg and 10 mL ampoules containing 1000 mg. The product is a clear and colourless solution for injection in a Type I glass ampoule.

Approved indications

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

Dosing overview

Dosage requirements vary according to age and body weight. 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, and 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. The medicine may be given by direct slow intravenous injection or by slow intravenous infusion in 0.9% NaCl (normal saline), 5% glucose solution or glucose saline, using a separate intravenous line. EPILIM should be replaced by oral sodium valproate therapy as soon as practicable.

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 and others after several years of use. Some cases have been described as haemorrhagic with rapid progression from initial symptoms to death. 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. If pancreatitis is diagnosed, sodium valproate should be discontinued and alternative treatment for the underlying medical condition initiated as clinically indicated. Severe liver damage and/or hepatic failure resulting in fatalities have occurred in patients whose treatment included 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. The incidents usually occurred during the first six months of therapy, with the period of maximum risk being 2 to 12 weeks. Clinical symptoms such as loss of seizure control, malaise, asthenia, weakness, lethargy, facial oedema, anorexia, vomiting, abdominal pain, drowsiness and jaundice are an indication for immediate withdrawal of the medicine. Patients should be monitored closely for the appearance of these symptoms and should immediately report any such signs to the clinician. Antiepileptic drugs, including sodium valproate, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication. Patients treated with any antiepileptic drug for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or any unusual changes in mood or behaviour, and appropriate treatment should be considered. Prolongation of bleeding time, sometimes with thrombocytopenia, has occurred with sodium valproate therapy. Platelet function should be monitored before surgery is undertaken in patients receiving sodium valproate. Valproate has a high teratogenic potential and children exposed in utero to valproate have a high risk for congenital malformations and neurodevelopmental disorders. Valproate should not be used in female children and women of child-bearing potential unless other treatments are ineffective or not tolerated.

Contraindications

For treatment of epilepsy, valproate is contraindicated in pregnancy unless there is no suitable alternative treatment, and in women of childbearing potential unless the physician has provided information regarding the potential effects of valproate during pregnancy. For treatment of mania, valproate is contraindicated in pregnancy and in women of childbearing potential unless the physician has provided information regarding the potential effects of valproate during pregnancy. For all indications, valproate is contraindicated in patients with pre-existing, acute or chronic hepatic dysfunction or family history of severe hepatitis, particularly medicine-related. Valproate is contraindicated in patients with known hypersensitivity to the medicine. Valproate is contraindicated in patients with known urea cycle disorders. Valproate is contraindicated in patients with 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, such as Alpers-Huttenlocher Syndrome) and in children under two years of age who are suspected of having POLG-related disorder. Sodium valproate IV should not be injected intramuscularly as it may produce tissue necrosis.

Regulatory history

EPILIM was first registered on the Australian Register of Therapeutic Goods on 30 September 1991, with registrations for oral formulations including syrup, crushable tablet, and enteric-coated tablets (ARTG 15372, 15373, 15370, 15369). A sugar-free liquid formulation was registered on 30 June 2000 (ARTG 74711), and an intravenous powder for injection formulation was registered on 8 November 2005 (ARTG 104416).