Steady-state pharmacokinetic data indicate that the peak concentration (CValproate was neither mutagenic in bacteria, nor in the mouse lymphoma assay Non-clinical data reveal no special hazard for humans based on conventional carcinogenicity studies.Valproate induced teratogenic effects (malformations of multiple organ systems) in mice, rats and rabbits.Behavioural abnormalities have been reported in first generation offspring of mice and rats after Violet coat (Opadry 04-S-6705), containing: titanium dioxide (E171), erythrosine BS aluminium lake (E127), indigo carmine aluminium lake (E132), iron oxide black (E172), hypromellose (E464), macrogol 400, Purified water*. Contents of the pack and other information 1. Clinical monitoring is recommended especially at the beginning of combined therapy with dosage adjustment when appropriate.Epilim decreases phenytoin total plasma concentration. Young children are at particular risk; this risk decreases with increasing age. At plasma concentrations of up to 5 – 6 times the maximum therapeutic levels, there are unlikely to be any symptoms other than nausea, vomiting and dizziness.Signs of acute massive overdose, i.e. • In women of childbearing potential unless the conditions of the pregnancy prevention programme are fulfilled (see sections 4.3 and 4.6). Therefore, clinical monitoring is recommended, and dosages should be adjusted (lamotrigine dosage decreased) when appropriate.

Haematological disorders have been shown in breastfed newborns/infants of treated women (see section 4.8). Hepatic failure with pancreatitis increases the risk of fatal outcome. • Cases of hypothyroidism have been reported in neonates whose mothers have taken valproate during pregnancy. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.The concomitant use of valproate and carbapenem agents is not recommended.Valproate may trigger or worsen clinical signs of underlying mitochondrial diseases caused by mutations of mitochondrial DNA as well as the nuclear encoded POLG gene. Dosage should be adjusted according to clinical monitoring since monitoring of plasma concentrations may be misleading (see section 5.2).Salicylates should not be used concomitantly with Epilim since they employ the same metabolic pathway (see sections 4.4 and 4.8).Liver dysfunction, including hepatic failure resulting in fatalities, has occurred in patients whose treatment included valproic acid (see sections 4.3 and 4.4). Sodium valproate and valproic acid are anti-convulsants. Valproate serum concentration in the umbilical cord, representing that in the fetuses, was similar to or slightly higher than that in the mothers.The major pathway of valproate biotransformation is glucuronidation (~ 40%), mainly via UGT1A6, UGT1A9, and UGT2B7.The half-life of Epilim is usually reported to be within the range of 8 – 20 hours. Increased liver enzymes are common, particularly early in treatment, and may be transient (see section 4.4.1).The above adverse events frequently occur at the start of treatment, but they usually disappear after a few days without discontinuing treatment. Epilim Liquid (sugar-free) or Epilim Syrup are alternatives. What Epilim is and what it is used for 2. In particular the following conditions, which may precede jaundice, should be taken into consideration, especially in patients at risk (see above: 'Conditions of occurrence'): - non-specific symptoms, usually of sudden onset, such as asthenia, malaise, anorexia, lethargy, oedema and drowsiness, which are sometimes associated with repeated vomiting and abdominal pain.These are an indication for immediate withdrawal of the drug.Patients (or their family for children) should be instructed to report immediately any such signs to a physician should they occur. • Valproate is contraindicated in patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme polymerase γ (POLG), e.g. Spontaneous bruising or bleeding is an indication for withdrawal of medication pending investigations (see section 4.6).Reporting suspected adverse reactions after authorisation of the medicinal product is important. The tablets should be swallowed whole and not crushed or chewed. Blood tests (blood cell count, including platelet count, bleeding time and coagulation tests) are recommended prior to initiation of therapy or before surgery, and in case of spontaneous bruising or bleeding (see section 4.8).In patients with renal insufficiency, it may be necessary to decrease dosage. What you need to know before you take Epilim Chrono 3.