displayName: BOXED WARNING SECTION
FDA Article Code: 34066-1
HEPATOTOXICITYHEPATIC FAILURE RESULTING IN FATALITIES HAS OCCURRED IN PATIENTS RECEIVING VALPROIC ACID AND ITS DERIVATIVES. EXPERIENCE HAS INDICATED THAT CHILDREN UNDER THE AGE OF TWO YEARS ARE AT A CONSIDERABLY INCREASED RISK OF DEVELOPING FATAL HEPATOTOXICITY, ESPECIALLY THOSE ON MULTIPLE ANTICONVULSANTS, THOSE WITH CONGENITAL METABOLIC DISORDERS, THOSE WITH SEVERE SEIZURE DISORDERS ACCOMPANIED BY MENTAL RETARDATION, AND THOSE WITH ORGANIC BRAIN DISEASE. WHEN DIVALPROEX SODIUM IS USED IN THIS PATIENT GROUP, IT SHOULD BE USED WITH EXTREME CAUTION AND AS A SOLE AGENT. THE BENEFITS OF THERAPY SHOULD BE WEIGHED AGAINST THE RISKS. ABOVE THIS AGE GROUP, EXPERIENCE IN EPILEPSY HAS INDICATED THAT THE INCIDENCE OF FATAL HEPATOTOXICITY DECREASES CONSIDERABLY IN PROGRESSIVELY OLDER PATIENT GROUPS.THESE INCIDENTS USUALLY HAVE OCCURRED DURING THE FIRST SIX MONTHS OF TREATMENT. SERIOUS OR FATAL HEPATOTOXICITY MAY BE PRECEDED BY NON-SPECIFIC SYMPTOMS SUCH AS MALAISE, WEAKNESS, LETHARGY, FACIAL EDEMA, ANOREXIA, AND VOMITING. IN PATIENTS WITH EPILEPSY, A LOSS OF SEIZURE CONTROL MAY ALSO OCCUR. PATIENTS SHOULD BE MONITORED CLOSELY FOR APPEARANCE OF THESE SYMPTOMS. LIVER FUNCTION TESTS SHOULD BE PERFORMED PRIOR TO THERAPY AND AT FREQUENT INTERVALS THEREAFTER, ESPECIALLY DURING THE FIRST SIX MONTHS.TERATOGENICITYVALPROATE CAN PRODUCE TERATOGENIC EFFECTS SUCH AS NEURAL TUBE DEFECTS (E.G., SPINA BIFIDA)ACCORDINGLY, THE USE OF DIVALPROEX SODIUM DELAYED-RELEASE TABLETS IN WOMEN OF CHILDBEARING POTENTIAL REQUIRES THAT THE BENEFITS OF ITS USE BE WEIGHED AGAINST THE RISK OF INJURY TO THE FETUS. THIS IS ESPECIALLY IMPORTANT WHEN THE TREATMENT OF A SPONTANEOUSLY REVERSIBLE CONDITION NOT ORDINARILY ASSOCIATED WITH PERMANENT INJURY OR RISK OF DEATH (E.G., MIGRAINE) IS CONTEMPLATED. SEE WARNINGS, INFORMATION FOR PATIENTS.AN INFORMATION SHEET DESCRIBING THE TERATOGENIC POTENTIAL OF VALPROATE IS AVAILABLE FOR PATIENTS.PANCREATITISCASES OF LIFE-THREATENING PANCREATITIS HAVE BEEN REPORTED IN BOTH CHILDREN AND ADULTS RECEIVING VALPROATE. SOME OF THE CASES HAVE BEEN DESCRIBED AS HEMORRHAGIC WITH A RAPID PROGRESSION FROM INITIAL SYMPTOMS TO DEATH. CASES HAVE BEEN REPORTED SHORTLY AFTER INITIAL USE AS WELL AS AFTER SEVERAL YEARS OF USE. PATIENTS AND GUARDIANS SHOULD BE WARNED THAT ABDOMINAL PAIN, NAUSEA, VOMITING, AND/OR ANOREXIA CAN BE SYMPTOMS OF PANCREATITIS THAT REQUIRE PROMPT MEDICAL EVALUATION. IF PANCREATITIS IS DIAGNOSED, VALPROATE SHOULD ORDINARILY BE DISCONTINUED. ALTERNATIVE TREATMENT FOR THE UNDERLYING MEDICAL CONDITION SHOULD BE INITIATED AS CLINICALLY INDICATED. (See WARNINGS and PRECAUTIONS.)
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Divalproex sodium is a stable co-ordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralization of valproic acid with 0.5 equivalent of sodium hydroxide. Chemically it is designated as sodium hydrogen bis(2-propylpentanoate). Divalproex sodium has the following structure:Divalproex sodium occurs as a white powder with a characteristic odor.Divalproex sodium delayed-release tablets are for oral administration. Divalproex sodium delayed-release tablets are supplied in three dosage strengths containing divalproex sodium equivalent to 125 mg, 250 mg, or 500 mg of valproic acid.Inactive IngredientsDivalproex sodium delayed-release tablets: pregelatinized starch, povidone, microcrystalline cellulose, silicon dioxide, opadry clear, methacrylic acid co-polymer, sodium hydroxide, simethicone emulsion, triethyl citrate, talc, vanilla flavor and opacode black.In addition, individual tablets contain:250 mg tablets: Ferric oxide.500 mg tablets: FD&C Blue No. 1.The components of opadry clear are hypromellose and polyethylene glycol 6000 and the components of opacode black are shellac glaze, iron oxide black, n-butyl alcohol, industrial methylated spirit, lecithin (soya), antifoam DC 1510 (food grade).
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
DIVALPROEX SODIUM SHOULD NOT BE ADMINISTERED TO PATIENTS WITH HEPATIC DISEASE OR SIGNIFICANT HEPATIC DYSFUNCTION.Divalproex sodium is contraindicated in patients with known hypersensitivity to the drug.Divalproex sodium is contraindicated in patients with known urea cycle disorders (See WARNINGS).
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
Overdosage with valproate may result in somnolence, heart block, and deep coma. Fatalities have been reported; however patients have recovered from valproate levels as high as 2120 mcg/mL.In overdose situations, the fraction of drug not bound to protein is high and hemodialysis or tandem hemodialysis plus hemoperfusion may result in significant removal of drug. The benefit of gastric lavage or emesis will vary with the time since ingestion. General supportive measures should be applied with particular attention to the maintenance of adequate urinary output.Naloxone has been reported to reverse the CNS depressant effects of valproate overdosage. Because naloxone could theoretically also reverse the antiepileptic effects of valproate, it should be used with caution in patients with epilepsy.
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Divalproex sodium delayed-release tablets,USP are supplied as:125 mg tablets: White to off white colored modified oval biconvex enteric film coated tablet imprinted with on one side in black ink and plain on the other side.Bottles of 100 NDC 0228-2142-11Unit dose packages of 100 (10×10) NDC 0228-2142-75250 mg tablets: Pale brown colored with mottled appearance modified oval biconvex enteric film coated tablet imprinted with on one side in black ink and plain on the other side.Bottles of 100 NDC 0228-2144-11Bottles of 500 NDC 0228-2144-50Unit dose packages of 100 (10×10) NDC 0228-2144-75500 mg tablets: Blue colored modified oval biconvex enteric film coated tablet imprinted with on one side in black ink and plain on the other side.Bottles of 100 NDC 0228-2145-11Bottles of 500 NDC 0228-2145-50Unit dose packages of 100 (10×10) NDC 0228-2145-75
displayName: STORAGE AND HANDLING SECTION
FDA Article Code: 44425-7
Store at 20° to 25 ° C (68 ° to 77 ° F). [see USP Controlled Room Temperature].
Patient Information Leaflet
displayName: SUPPLEMENTAL PATIENT MATERIAL SECTION
FDA Article Code: 38056-8
Important Information for Women Who Could Become Pregnant About the Use of Divalproex Sodium Delayed-Release Tablets.Please read this leaflet carefully before you take divalproex sodium delayed-release tablets. This leaflet provides a summary of important information about taking divalproex sodium delayed-release tablets to women who could become pregnant. If you have any questions or concerns, or want more information about divalproex sodium delayed-release tablets, contact your doctor or pharmacist.Information For Women Who Could Become PregnantDivalproex sodium delayed-release tablets can be obtained only by prescription from your doctor. The decision to use divalproex sodium delayed-release tablets is one that you and your doctor should make together, taking into account your individual needs and medical condition.Before using divalproex sodium delayed-release tablets, women who can become pregnant should consider the fact that divalproex sodium delayed-release tablets have been associated with birth defects, in particular, with spina bifida and other defects related to failure of the spinal canal to close normally. Approximately 1 to 2% of children born to women with epilepsy taking divalproex sodium in the first 12 weeks of pregnancy had these defects (based on data from the Centers for Disease Control, a U.S. agency based in Atlanta). The incidence in the general population is 0.1 to 0.2%.Divalproex sodium delayed-release tablets have also been associated with other birth defects such as defects of the heart, the bones, and other parts of the body. Information suggests that birth defects may be more likely to occur with divalproex sodium delayed-release tablets than some other drugs that treat your medical condition.Information For Women Who Are Planning to Get Pregnant
Information For Women Who Become Pregnant
- Women taking divalproex sodium delayed-release tablets who are planning to get pregnant should discuss the treatment options with their doctor.
Other Important Information
- If you become pregnant while taking divalproex sodium delayed-release tablets you should contact your doctor immediately.
Facts About Birth DefectsIt is important to know that birth defects may occur even in children of individuals not taking any medications or without any additional risk factors.This summary provides important information about the use of divalproex sodium delayed-release tablets to women who could become pregnant. If you would like more information about the other potential risks and benefits of divalproex sodium delayed-release tablets , ask your doctor or pharmacist to let you read the professional labeling and then discuss it with them. If you have any questions or concerns about taking these medications, you should discuss them with your doctor.Manufactured byOrchid Healthcare(A Division of Orchid Chemicals & Pharmaceuticals Ltd.)Irungattukottai – 602 105, IndiaManufactured forActavis Elizabeth LLC200 Elmora Avenue,Elizabeth, NJ 07207 USAIssued: February 2007
- Your medication should be taken exactly as prescribed by your doctor to get the most benefit from your medication and reduce the risk of side effects.
- If you have taken more than the prescribed dose of your medication, contact your hospital emergency room or local poison center immediately.
- Your medication was prescribed for your particular condition. Do not use it for another condition or give the drug to others.