Valparin XR 500 Special Precautions

Liver damage resulting in fatalities has been exceptionally reported. Patients most-at-risk, especially in cases of multiple anti-convulsant therapy, are infants and young children under the age of 3 with severe seizure disorders. After the age of 3 the incidences reduces significantly and progressively decreases with age. Mono-therapy is recommended in children under 3 years of age, but the potential benefit of Sodium Valproate + Valproic acid should be weighed against the risk of liver damage. Liver function tests are required before beginning treatment as is periodic monitoring during the first 6 months, especially in-at-risk patients. It should be underlined that like most antiepileptics, there may be an isolated and transient increase in liver enzymes, in the absence of any clinical signs especially at the beginning of treatment. In such cases, a complete laboratory workup should be performed (including prothrombin time), dosage may be reconsidered and workups should be repeated on the basis of the changes in the parameters. In children, under 3 years of age salicylates should not be prescribed concurrently due to risk of liver toxicity.
In patients with renal insufficiency, increased serum concentrations of free valproic acid should be taken into account, and dosage should be consequently be adjusted. In case of acute abdominal pain, serum amylase level should be determined before deciding on surgery, as exceptional cases of pancreatitis have been reported. Blood tests including cell count, platelet count, bleeding time and coagulation tests are recommended prior to initiation of therapy and surgery, and in case of spontaneous bruising and bleeding. Immune disorders have been noted only exceptionally and hence benefit Sodium Valproate + Valproic Acid should be weighed against potential risk in patients with SLE.
Hyperammonemia has been reported in association with valproate therapy and may be present despite normal liver function tests. In patients who develop unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. Hyperammonemia should be also be considered in patients who present with hypothermia. If ammonia is increased, sodium valproate + valproic acid therapy should be discontinued. Appropriate interventions for treatment of hyperammonemia should be initiated, and such patients should undergo investigation for underlying urea cycle disorders. Asymptomatic elevations of ammonia are more common and when present, require close monitoring of plasma ammonia levels. If the elevation persists, discontinuation of valproate therapy should be considered.
Hypothermia has been reported in association with sodium valproate + valproic acid therapy both in conjunction with and in the absence of hyperammmonemia.
Sodium Valproate + Valproic Acid is partially eliminated partially eliminated in the urine as keto-metabolite which may lead to a false interpretation of the urine ketone test. Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents in several indications. Patients should be monitored for signs of suicidal ideation and behaviors and appropriate treatment should be considered. Patients and caregivers of patients should be advised to seek medical advice should signs of suicidal ideation or behavior emerge.
Sodium Valproate + Valproic Acid should not be used in children, in female adolescents, in women of childbearing potential and pregnant women unless alternative treatments are ineffective or not tolerated because of its high teratogenic potential and risk of development disorders in infants exposed in utero to valproate. The benefit and risk should be carefully reconsidered at a regular treatment reviews, at puberty and urgently when a woman of childbearing potential treated with Sodium Valproate + Valproic Acid plans a pregnancy or if she becomes pregnant. Women of childbearing potential must use effective contraception during treatment and be informed of the risks associated with the use of Sodium Valproate + Valproic Acid (Valparin XR 500) during pregnancy.
Use in Pregnancy & Lactation: Sodium Valproate + Valproic Acid (Valparin XR 500) should not be used in female children, in women of childbearing potential and in pregnant women unless other treatments are ineffective or not tolerated. Women of childbearing potential have to use effective contraception during treatment. In women planning to become pregnant all efforts should be made to switch to appropriate alternative treatment prior to conception, if possible. Valproate is excreted in human milk with a concentration between 1% and 10% of maternal serum level, up to now children breastfed. A decision must be made whether to discontinue breast-feeding or to discontinue /abstain from valproate therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.