Drug Class Description
Carboxylic acid derivatives (anticonvulsants / anti- epileptics).

Generic Name
Generic

Drug Description
Tablets/syrup.

Presentation
Tablets, e/c, sodium valproate 200mg , 500mg . Available from APS, Cox, CP (Orlept R ), Generics UK, Hillcross, Norton, Sterwin. Tablets, crushable, sodium valproate 100mg . Available from Hillcross. Syrup, sodium valproate 200mg/5mL . Available from Norton (sugar- free), Sterwin.

Indications
Epilepsy.

Adult Dosage
Initially 600 mg daily usually in two divided doses increasing by 200 mg at three day intervals; usual maintenance, 1 - 2 g daily. Maximum daily dose, 2 .5 g daily.

Child Dosage
Under 20 kg, initially 20 mg/kg bodyweight daily, increase in severe cases only if plasma levels can be monitored. Above 40 mg/kg daily, also monitor clinical chemistry and haematology. Over 20 kg, initially 400 mg daily. Increase gradually until control achieved, usually 20 - 30 mg/kg daily; maximum 35 mg/kg daily.

Contra Indications
Hypersensitivity to sodium valproate. Active liver disease; family history of severe hepatic dysfunction, particularly drug related; porphyria.

Special Precautions
Children with severe epilepsy associated with mental retardation, brain damage or congenital metabolic defects; monotherapy preferred in this group. Perform liver function tests before commencing treatment and in first 6 months in those patients for clinical symptoms of hepatic failure.Renal insufficiency; adjust dose according to clinical monitoring. Major surgery; monitor platelet function. False positives for ketones in urine testing for diabetes. Pregnancy.

Interactions
Other anticonvulsants (including phenobarbital [phenobarbitone], phenytoin, primidone, carbamazepine, lamotrigine), neuroleptics, MAOIs, benzodiazepines, antidepressants, zidovudine, warfarin, felbamate, cimetidine, mefloquine, colestyramine (cholestyramine), salicylates.

Adverse Reactions
Congenital and familial/genetic disorders:Hepato-biliary disorders: rare cases of liver dysfunction, Severe liver damage, including hepatic failure sometimes resulting in death, has been reported. Increased liver enzymes are common, particularly early in treatment, and may be transient.Gastrointestinal disorders (nausea, gastralgia, diarrhoea) frequently occur at the start of treatment, but they usually disappear after a few days without discontinuing treatment. These problems can usually be overcome by taking sodium valproate with or after food or by using Enteric Coated Sodium Valproate.Very rare cases of pancreatitis, sometimes lethal, have been reported.Nervous system disorders: Sedation has been reported occasionally, usually when in combination with other anticonvulsants. In monotherapy it occurred early in treatment on rare occasions and is usually transient. Rare cases of lethargy occasionally progressing to stupor, sometimes with associated hallucinations or convulsions have been reported. Encephalopathy and coma have very rarely been observed. These cases have often been associated with too high a starting dose or too rapid a dose escalation or concomitant use of other anticonvulsants, notably phenobarbital or topiramate. They have usually been reversible on withdrawal of treatment or reduction of dosage.Very rare cases of reversible extrapyramidal symptoms including parkinsonism, or reversible dementia associated with reversible cerebral atrophy have been reported. Dose-related ataxia and fine postural tremor have occasionally been reported.An increase in alertness may occur; this is generally beneficial but occasionally aggression, hyperactivity and behavioural deterioration have been reported.Metabolic disorders:Cases of isolated and moderate hyperammonaemia without change in liver function tests may occur frequently, are usually transient and should not cause treatment discontinuation. However, they may present clinically as vomiting, ataxia, and increasing clouding of consciousness. Should these symptoms occur sodium valproate should be discontinued. Very rare cases of hyponatraemia have been reported.Hyperammonaemia associated with neurological symptoms has also been reported. In such cases further investigations should be considered.Blood and lymphatic system disorders:Frequent occurrence of thrombocytopenia, rare cases of anaemia, leucopenia or pancytopenia. The blood picture returned to normal when the drug was discontinued.Bone marrow failure, including red cell aplasia.Agranulocytosis.Isolated findings of a reduction in blood fibrinogen and/or an increase in prothrombin time have been reported, usually without associated clinical signs and particularly with high doses (sodium valproate has an inhibitory effect on the second phase of platelet aggregation). Spontaneous bruising or bleeding is an indication for withdrawal of medication pending investigations.Skin and subcutaneous tissue disorders:ash rarely occur with valproate. In very rare cases toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme have been reported.Transient hair loss, which may sometimes be dose-related, has often been reported. Regrowth normally begins within six months, although the hair may become more curly than previously. Hirsutism and acne have been very rarely reported.Reproductive system and breast disorders:Amenorrhoea and irregular periods have been reported. Very rarely gynaecomastia has occurred.Vascular disorders:The occurrence of vasculitis has occasionally been reported.Ear disorders: Hearing loss, either reversible or irreversible has been reported rarely; however a cause and effect relationship has not been established.Renal and urinary disorders: There have been isolated reports of a reversible Fanconi's syndrome (a defect in proximal renal tubular function giving rise to glycosuria, amino aciduria, phosphaturia, and uricosuria), but the mode of action is as yet unclear.Very rare cases of enuresis have been reported.Immune system disorders: Angioedema, Drug Rash with Eosinophilia, Systemic Symptoms (DRESS) syndrome, and allergic reactions (ranging from rash to hypersensitivity reactions) have been reported.General disorders: Very rare cases of non-severe peripheral oedema have been reported.Increase in weight may also occur. Weight gain being a risk factor for polycystic ovary syndrome, it should be carefully monitored.

Drug Availability
(POM)

Updated
04 March 2010