Depakine/Depakine Chrono

Depakine/Depakine Chrono Special Precautions

valproic acid

Manufacturer:

Sanofi-Aventis

Distributor:

DKSH
Full Prescribing Info
Special Precautions
Liver Dysfunction: Conditions of Occurrence: Severe liver damage resulting sometimes in fatalities have been exceptionally reported. Patients most at risk especially in cases of multiple anticonvulsant therapy are infants and young children <3 years with severe seizure disorders, particularly those with brain damage, mental retardation and/or congenital metabolic or degenerative disease. After the age of 3, the incidence of occurrence is significantly reduced and progressively decreases with age.
In most cases, such liver damage occurred during the first 6 months of therapy.
Suggestive Signs: Clinical symptoms are essential for early diagnosis. In particular, the following conditions which may precede jaundice should be taken into consideration, especially in patients at risk: Nonspecific symptoms, usually of sudden onset eg, asthenia, anorexia, lethargy, drowsiness, which are sometimes associated with repeated vomiting and abdominal pain and recurrence of seizures.
Patients (or their family or children) should be instructed to report immediately any such signs to a physician should they occur. Investigations including clinical examination and biological assessment of liver function should be undertaken immediately.
Detection: Liver function should be periodically monitored during the first 6 months of therapy. Amongst usual investigations, tests which reflect protein synthesis particularly prothrombin rate, are most relevant. Confirmation of an abnormally low prothrombin rate, particularly in association with other biological abnormalities (significant decrease in fibrinogen and coagulation factors; increased bilirubin level and raised transaminases) requires cessation of Depakine therapy. As a matter of precaution and in case they are taken concomitantly, salicylates should also be discontinued since they employ the same metabolic pathway.
Liver function test should be carried out before therapy (see Contraindications) and periodically during the first 6 months especially in patients at risk.
As with most antiepileptic drugs, increased liver enzymes may be noted, particularly at the beginning of the therapy; they are transient and isolated, without clinical sign.
More extensive biological investigations (including prothrombin rate) are recommended in those patients; an adjustment of dosage may be considered when appropriate, and tests should be repeated as necessary.
Monotherapy is recommended in children <1 year when prescribing Depakine, but the potential benefit of Depakine should be weighed against the risk of liver damage in such patients prior to initiation of therapy. The concomitant use of salicylates should be avoided in those children <1 year due to the risk of liver toxicity.
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 Adverse Reactions).
In patients with renal insufficiency, it may be necessary to decrease dosage as a result of increase in free serum valproic acid levels.
Although immune disorders have been only exceptionally noted during the use of Depakine, the potential benefit of Depakine should be weighed against its potential risk in patients with systemic lupus erythematosus.
Exceptional cases of pancreatitis have been reported; therefore, patients experiencing acute abdominal pain should have their serum amylase estimated prior to surgery.
Use in Pregnancy: Risk Associated with Epilepsy and Antiepileptics: In offsprings born to mothers with epilepsy receiving any epileptic treatment, the global rate of malformations has been demonstrated to be 2-3 times higher than the rate (approximately 3%) reported in formation. Although an increased number of children with malformations has been reported in case of multiple drug therapy, the respective part of treatments and disease has not been formally established. Malformations most frequently encountered are labial clefts and cardiovascular malformations.
Sudden discontinuation in the antiepileptic therapy may be associated with a worsening of the disease in the mother and subsequent untoward effects in the foetus.
Risk Associated with Sodium Valproate: In animals: Teratogenic effects have been demonstrated in the mouse, rat and rabbit.
In humans: The global risk of malformations in women receiving valproate during the 1st trimester of pregnancy is not higher than the risk described with other antiepileptics. A few cases of multiple malformations and facial dysmorphia have been reported. The frequency of those effects has not yet been clearly established. Nevertheless sodium valproate preferably induces neutral tube defects: Myelomeningocele, spina bifida and malformations of which antenatal diagnosis is possible. The frequency of this effect is estimated to be 1-2%.
In view of the aforementioned; should a woman expect to become pregnant, review the indication for antiepileptic therapy; folate supplementation may be considered.
During pregnancy, valproate antiepileptic treatment should not be discontinued if it has been effective.
Monotherapy is to be recommended; the minimum effective daily dosage should be used, in several divided doses over the day. Nevertheless, specialized antenatal monitoring should be instituted in order to detect the possible occurrence of neutral tube effect.
Use in Lactation: Excretion of valproate in breast milk is low, with a concentration between 1-10% of maternal serum levels: Up to now, breastfed children that have been monitored during the neonatal period have not experienced clinical effects.
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