EPIROL Tablet Ref.[115236] Active ingredients: Valproic acid

Combined medication

Owing to the interaction known to occur with other anti-epileptic compounds it may sometimes be necessary to reduce the dosage of other drugs when adding Epirol to existing therapy. If the sedative effects of barbiturates are found to be enhanced, dosage of these compounds should be reduced. Like many other drugs, Epirol may also potentiate the effect of monoamine oxidase inhibitors (MAO) and other antidepressants, and dosage of such compounds should therefore also be reduced.

Diabetic patients

Epirol is eliminated mainly through the kidneys, partially in the form of ketone bodies, and this may give false positive readings in the urine-testing of possible diabetics.

Woman of childbearing age

EPIROL had been associated with teratogenicity when given to women in the first trimester of pregnancy. Its use should be avoided in pregnant women and women likely to become pregnant unless its continued use is considered essential by the doctor. Women who have been exposed to Epirol in the first trimester of pregnancy should be informed of the risk and offered prenatal counselling.

Side effects and special precautions

Liver dysfunction, including hepatic failure resulting in fatalities has occurred in patients whose treatment included valproic acid or sodium valproate. These incidents occurred during the first six months of therapy, the period of maximum risk being 2-12 weeks. No deaths have occurred in patients receiving the drug continuously for more than 6 months. Biochemical tests may not always become abnormal early in the evaluation of hepatic failure; non-specific findings such as loss of seizure control, malaise, anorexia and vomiting, developing after a period of satisfactory Epirol treatment alert the clinician to the possibility of hepatic damage.

Epirol should not be administered to patients with pre-existing hepatic dysfunction. All patients for whom treatment with Epirol is contemplated should have base line liver function assessed (including serum fibrinogen and albumin levels) prior to commencement of therapy. Liver function should be carefully monitored, particularly during the first six months of therapy, and when dosage is being titrated upwards. Patients with a prior history of liver disease or with severe or unusual seizure disorders, e.g. those accompanied by mental retardation and/or organic brain disease, should be followed particularly carefully.

Transient elevations of liver enzymes are not uncommon during early treatment with Epirol. However, if liver enzymes, elevations are accompanied by other evidence of hepatic dysfunction; especially raised serum bilirubin or lowered serum fibrinogen then the drug should be immediately withdrawn.

Hyperammonaemia without hepatic damage can occur in patients during treatment with valproic acid or sodium valproate. It has been suggested that this may be related to interference with propionic acid metabolism. This may manifest clinically as vomiting, ataxia and increasing clouding of consciousness. Should these symptoms occur, Epirol should be discontinued. Valproic acid inhibits second stage of platelet aggregation.

Reversible prolongation of bleeding time, sometimes with thrombo-cytopenia, has occurred rarely at high dosage. Spontaneous bruising or bleeding is an indication for withdrawal of medication pending investigation. It is recommended that patients receiving Epirol should be monitored for platelet function before surgery.

Red cell hypoplasia and leucopenia have been reported with Epirol.

The blood picture returned to normal when the drug was discontinued.

There have been reports of pancreatitis occurring in patients receiving valproic acid or sodium valproate. Patients experiencing acute abdominal pain should have the serum amylase estimated.

No cardiac effects attributed to Epirol have been reported. Minor gastric irritation, and, less frequently, nausea have been observed in some patients at the start of treatment, but these problems can usually be overcome by administering Epirol tablets with or after food. Should such symptoms persist they can be relieved by standard medication.

Transient hair loss has been noted in some patients. This effect does not appear to be dose-related and regrowth normally begins within 6 months, although the hair may become more curly than previously. Tremor has occasionally been observed at high dosages which may be controlled by reduction of dosage.

Oedema has been reported. Increase in alertness, appetite and mass may occur.