| Sec 4.2 - the following has been added
In patients with renal insufficiency: It may be necessary to decrease dosage. Dosage should be adjusted according to clinical monitoring since monitoring of plasma concentrations may be misleading.
In patients with hepatic insufficiency: Salicylates should not be used concomitantly with sodium valproate since they employ the same metabolic pathway (see section 4.4 Special Warnings and Precautions for Use and 4.8 Undesirable Effects).
Liver dysfunction, including hepatic failure resulting in fatalities, has occurred in patients whose treatment included valproic acid (see section 4.3 Contraindications and 4.4 Special Warnings and Precautions for Use).
Salicylates should not be used in children under 16 years (see aspirin/salicylate product information on Reye’s syndrome). In addition in conjunction with sodium valproate, concomitant use in children under 3 years can increase the risk of liver toxicity (see section 4.4 Special Warnings).
Combined Therapy: When starting Episenta® in patients already on anticonvulsants, these should be tapered slowly; initiation of Episenta® treatment should then be gradual, with target dose being reached after about 2 weeks.
Once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose of Episenta®.
N.B. In children requiring doses higher than 40 mg/kg/day clinical chemistry and haematological parameters should be monitored.
Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary. However, a method for measurement of plasma levels is available and may be helpful where there is poor control or side effects are suspected (see section 5.2 Pharmacokinetic Properties).
Sec 4.2 - the following has been added
Although there is no specific evidence of sudden recurrence of underlying symptoms following withdrawal of valproate, discontinuation should normally only be done under the supervision of a specialist in a gradual manner. This is due to the possibility of sudden alterations in plasma concentrations giving rise to a recurrence of symptoms.
Sec 4.5.1 - the following has been added
In particular, a clinical study has suggested that adding olanzapine to valproate or lithium therapy may significantly increase the risk of certain adverse events associated with olanzapine e.g. neutropenia, tremor, dry mouth, increased appetite and weight gain, speech disorder and somnolence.
Co-administration of temozolomide and sodium valproate may cause a small decrease in the clearance of temozolomide that is not thought to be clinically relevant.
Sec 4.5.2 - the following has been added
On the other hand, combination of felbamate and sodium valproate may increase valproic acid plasma concentration. Episenta® dosage should be monitored.
Decrease in plasma valproate levels, sometimes associated with convulsions, has been observed when imipenem or meropenem were combined
Rifampicin may decrease the valproate blood levels resulting in a lack of therapeutic effect. Therefore, valproate dosage adjustment may be necessary when it is co-administered with rifampicin.
Sec 4.5.3 the following has been added
Sodium valproate usually has no enzyme-inducing effect; as a cosequence, Episenta® does not reduce efficacy of oestroprogestative agents in women receiving hormonal contraception, including the oral contraceptive pill.
Concomitant administration of valproate and topiramate has been associated with encephalopathy and/or hyperammonaemia. In patients taking these two drugs, careful monitoring of signs and symptoms is advised in particularly at-risk patients such as those with pre-existing encephalopathy.
Sec 4.5.3 the following has been deleted
The effect of hormonal contraceptives ("the pill") is not reduced by sodium valproate.
Sec 4.6 the following has been added
Women of childbearing potential should not be started on Episenta® without specialist neurological advice.
Adequate counselling should be made available to all women with epilepsy of childbearing potential regarding the risks associated with pregnancy because of the potential teratogenic risk to the foetus (see section 4.6.1 Pregnancy). Women who are taking Episenta® and who may become pregnant should receive specialist neurological advice and the benefits of its use should be weighed against the risks.
Sodium valproate is the antiepileptic of choice in patients with certain types of epilepsy such as generalised epilepsy ± mycolonus/photosensitivity. For partial epilepsy, Episenta® should be used only in patients resistant to other treatment.
If pregnancy is planned, consideration should be given to cessation of Episenta® treatment, if appropriate.
When Episenta® treatment is deemed necessary, precautions to minimize the potential teratogenic risks should be followed (see section 4.6.1 paragraph entitled ‘In view of the above data’).
Sec 10 - the date of revision has been changed to November 2009
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