APO-Sodium

What it is

APO-Sodium is sodium valproate available in tablet form . The registered strengths are 200 mg and 500 mg tablets in blister pack format .

Approved indications

APO-Sodium is used for the treatment of patients with epilepsy or mania, who would normally be maintained on oral sodium valproate . — Epilepsy . — Mania .

Dosing overview

Daily dosage requirements vary according to age and body weight. Patients already satisfactorily treated with sodium valproate may be continued at their current dosage. For adults, patients stabilised on 25 mg/kg administered daily should continue with a dose of 1 mg/kg/hr, or alternatively may be given a dose usually of 400–800 mg depending on body weight (up to 10 mg/kg) followed by maintenance dosing 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 . In the elderly, dosage should be determined by control of symptoms .

Key safety warnings

Cases of life-threatening pancreatitis have 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 . 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, with incidents usually occurring during the first six months of therapy . Jaundice, serious or fatal hepatotoxicity may be preceded by nonspecific symptoms of sudden onset, such as loss of seizure control, malaise, asthenia, weakness, lethargy, facial oedema, anorexia, vomiting, abdominal pain, drowsiness . 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. Pooled analyses of placebo-controlled clinical trials showed that patients randomised to one of the antiepileptic drugs had approximately twice the risk of suicidal thinking or behaviour compared to patients randomised to placebo, representing an increase of approximately one case of suicidal thinking or behaviour for every 530 patients treated . Patients, their caregivers, and families should be informed that antiepileptic drugs increase the risk of suicidal thoughts and behaviour and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behaviour, or the emergence of suicidal thoughts, behaviour, or thoughts about self-harm . Valproate has a high teratogenic potential and children exposed in utero to valproate have a high risk for congenital malformations and neurodevelopmental disorders . Data from a meta-analysis has shown that 10.73% of children of epileptic women exposed to valproate monotherapy during pregnancy suffer from congenital malformations, which is a greater risk of major malformations than for the general population, for whom the risk is about 2–3% .

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 . For treatment of mania, valproate is contraindicated in pregnancy 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 . Known hypersensitivity to the medicine is a contraindication . Known urea cycle disorders are contraindicated . Known hepatic porphyria is contraindicated . Patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding mitochondrial enzyme polymerase γ (POLG, for example Alpers-Huttenlocher Syndrome) and children under two years of age who are suspected of having POLG-related disorder are contraindicated .

Regulatory history

APO-Sodium Valproate 200 mg and 500 mg tablets were first listed on the Australian Register of Therapeutic Goods on 13 April 2022 under licence category RE .