Consumer medicine information

1. Why am I using Epilim?

Epilim contains the active ingredient sodium valproate. Epilim is used to treat epilepsy in adults and children and mania in adults.
For more information, see Section 1. Why am I using Epilim? in the full CMI.

2. What should I know before I use Epilim?

Do not use if you have ever had an allergic reaction to Epilim or any of the ingredients listed at the end of the CMI.
Epilim can seriously harm an unborn child when taken during pregnancy. If you are a female able to have a baby, you must use an effective method of birth control (contraception) during your entire treatment with Epilim. Schedule an urgent appointment with your doctor if you want to become pregnant or if you think you became pregnant. Do not stop taking Epilim unless your doctor tells you to, as it may be dangerous for you.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use Epilim? in the full CMI and read the patient guide available electronically through QR code on the carton (www.sanofi.com.au/valproate).

3. What if I am taking other medicines?

Some medicines may interfere with Epilim and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Epilim?

• Your doctor will tell you how much to take. This may depend on your age, your condition and whether or not you are taking any other medicines.

5. What should I know while using Epilim?

6. Are there any side effects?

All medicines have some unwanted side effects. Mostly these are mild and short-lived. Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Epilim.
Tell your doctor immediately or go to the Accident and Emergency department of your nearest hospital :

• If you or your child develops a sudden illness and particularly if it includes repeated vomiting, extreme tiredness, abdominal pain, drowsiness, weakness, loss of appetite, upper stomach pain, nausea, jaundice (yellowing of the skin or whites of the eyes), swelling of the legs or worsening of your epilepsy or a general feeling of being unwell

• If you or your child taking Epilim develops problems with balance and co-ordination, feeling lethargic or less alert, vomiting,

• If seizures become worse or happen more frequently

• If you have any thoughts of harming yourself or committing suicide

• If you think you are pregnant

1 Name of Medicine

Sodium valproate.

2 Qualitative and Quantitative Composition

Crushable tablets, sodium valproate 100 mg.
Enteric-coated tablets, sodium valproate 200 mg.
Enteric-coated tablets, sodium valproate 500 mg.
Syrup, sodium valproate 200 mg/5 mL. Excipients of known effects: sucrose, saccharin sodium and sorbitol.
Sugar free liquid, sodium valproate 200 mg/5 mL. Excipients of known effects: saccharin sodium, sorbitol solution (70%) (non-crystallising), sodium methyl hydroxybenzoate and sodium propyl hydroxybenzoate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Crushable tablets, 100 mg (white, scored).
Tablets, 200 mg (lilac, enteric-coated).
Tablets, 500 mg (lilac enteric-coated).
Syrup, 200 mg/5 mL (red, cherry flavoured).
Sugar free liquid, 200 mg/5 mL (red, cherry flavoured).

4 Clinical Particulars

4.9 Overdose

Cases of accidental and suicidal overdosage have been reported. Fatalities are rare.
Symptoms. Symptoms of overdosage may include serious CNS depression and impairment of respiration. In cases of overdose, long half-lives up to 30 hours have been reported. Signs of an acute massive overdose usually include coma, with muscular hypotonia, hyporeflexia and miosis, impaired respiratory functions and metabolic acidosis, hypotension and circulatory collapse/shock. Symptoms may however be variable and seizures have been reported in the presence of very high plasma levels. Cases of intracranial hypertension related to cerebral oedema have been reported. Deaths have occurred following massive overdose; nevertheless, a favourable outcome is usual. The presence of sodium content in the valproate formulations may lead to hypernatraemia when taken in overdose.
Treatment. Establish airway and breathing and evaluate circulatory status. Assisted mechanical ventilation may be required in cases of respiratory depression. Activated charcoal may reduce the absorption of the medicine if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube, once the airway is protected. Haemodialysis and haemoperfusion have been used successfully. Intravenous naloxone has also been used sometimes in association with activated charcoal given orally. In case of valproate overdose resulting in hyperammonemia, carnitine can be given through IV route to attempt to normalize ammonia levels.
Provided that adequate supportive treatment is given, full recovery usually occurs. Particular attention should be given to the maintenance of an adequate urinary output. Hepatic and pancreatic function should be monitored.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Genotoxicity. Valproate was not mutagenic in bacteria (Ames test), or mouse lymphoma L5178Y cells at thymidine kinase locus (mouse lymphoma assay), and did not induce DNA repair activity in primary culture of rat hepatocytes. After oral administration, valproate did not induce either chromosome aberrations in rat bone marrow, or dominant lethal effects in mice.
Statistically significant higher incidences of sister-chromatid exchange (SCE) have been observed in patients exposed to valproate as compared to healthy subjects not exposed to valproate. However, these data may have been impacted by confounding factors. Two published studies examining SCE frequency in epileptic patients treated with valproate versus untreated epileptic patients, provided contradictory results. The biological significance of an increase in SCE frequency is not known.
Toxicology. No significant toxic effects were seen in rats receiving 270 mg/kg/day for 3 months or in dogs receiving 90 mg/kg/day for 12 months. At higher doses sedation, ataxia and various histopathological effects (testicular atrophy and reduction in lymphoid tissue) were observed at levels of 256 to 568 microgram/mL (1.78 to 3.94 mmol/L).
Testicular function. In sub-chronic/chronic toxicity studies, testicular degeneration/atrophy or spermatogenesis abnormalities and a decrease in testes weight were reported in adult rats and dogs after oral administration of valproate. The dose without an effect on the testes was similar to the maximum recommended human dose of 50 mg/kg/day on a mg/m² basis.
In a fertility study in rats, valproate at doses up to 350 mg/kg/day did not alter male reproductive performance. This dose was about 1.3 times the maximum recommended human dose of 50 mg/kg/day on a mg/m² basis.
In juvenile rats, a decrease in testes weight and testicular degeneration were observed at doses that also elicited substantial general systemic toxicity. The relevance of the testicular findings to the paediatric population is unknown because the fertility of animals exposed to valproate as pre-pubertal juveniles has not been investigated.
Carcinogenicity. Carcinogenesis. Sodium valproate was administered in the diet to Sprague-Dawley rats and ICR (HA/ICR) mice at approximate dosage levels of 0, 80 and 160 mg/kg/day for up to 2 years. There was equivocal evidence of an increased incidence of subcutaneous fibrosarcomas in male rats and of bronchoalveolar adenomas in male mice. The presence of these tumours was not considered to be biologically significant because of the published variable incidence of spontaneously occurring fibrosarcomas and pulmonary adenomas in rats and mice respectively and the fact that statistical significance of tumour incidence was only attained in males. The significance of these findings for humans is unknown at present.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Sodium valproate is a white, odourless, crystalline powder with a saline taste. It is highly soluble in water and alcohol. It is quite dissimilar to other established anticonvulsants such as barbiturates, hydantoins, succinamides, oxazolidinediones and acetylureas in that it has no nitrogen or aromatic moiety.
Chemical name: Sodium di-n-propylacetic acid.
Its molecular weight is 166.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSSOVALP.gif CAS number. 1069-66-5.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes

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