BOX WARNING
id: 51a43cac-235b-4248-a101-26c654a1d6d6
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 DELAYED-RELEASE TABLETS ARE
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.
TERATOGENICITY
VALPROATE 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.
A PATIENT
INFORMATION LEAFLET DESCRIBING THE TERATOGENIC POTENTIAL OF VALPROATE IS AVAILABLE
FOR PATIENTS.
PANCREATITIS
CASES 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
.)
DESCRIPTION
id: 9dcc14c9-0970-499f-9db5-b72e6526bc6e
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. 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 USP are supplied in three dosage strengths containing divalproex sodium, USP equivalent to 125 mg, 250 mg, or 500 mg of valproic acid.
Inactive Ingredients
Divalproex sodium delayed-release tablets: colloidal silicon dioxide, corn starch, povidone, pregelatinized starch, hypromellose, titanium dioxide, triacetin, methacrylic acid copolymer type C, talc, triethyl citrate, colloidal anhydrous silica, sodium bicarbonate, and sodium lauryl sulfate.
Imprinting ink contains shellac, iron oxide black, N-butyl alcohol, industrial methylated spirit, propylene glycol, purified water and isopropyl alcohol.
In addition, individual tablets contain:
125 mg tablets: FD&C Red #40, and FD&C Blue #2
250 mg tablets: FD&C Yellow #6, and iron oxide yellow
500 mg tablets: D&C Red #30, FD&C Blue #2, and iron oxide red
CONTRAINDICATIONS
id: c834ae4d-ef96-4061-8b25-fe68232d7e76
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
).
OVERDOSAGE
id: f467e991-0f2a-4908-b0b2-e2f23c221778
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 µg/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.
HOW SUPPLIED
id: dbd2f856-83a6-4f2b-bdca-b11e99314598
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Divalproex sodium delayed-release tablets USP are supplied as:
The 125 mg tablets are pink colored, oval shaped, biconvex coated tablets imprinted ‘796’ with black ink on one side and plain on the other side.
Bottles of 30’s with Child Resistant Cap………………NDC 62756-796-83
Bottles of 100’s with Child Resistant Cap ……..… NDC 62756-796-88
Bottles of 100’s with Non Child Resistant Cap……..NDC 62756-796-08
Bottles of 500’s with Non Child Resistant Cap……..NDC 62756-796-13
Bottles of 1000’s with Non Child Resistant Cap……NDC 62756-796-18
The 250 mg tablets are orange colored, oval shaped, biconvex coated tablets imprinted ‘797’ with black ink on one side and plain on the other side.
Bottles of 30’s with Child Resistant Cap………………NDC 62756-797-83
Bottles of 100’s with Child Resistant Cap ……..… NDC 62756-797-88
Bottles of 100’s with Non Child Resistant Cap……..NDC 62756-797-08
Bottles of 500’s with Non Child Resistant Cap……..NDC 62756-797-13
Bottles of 1000’s with Non Child Resistant Cap……NDC 62756-797-18
The 500 mg tablets are pink colored, oval shaped, biconvex coated tablets imprinted ‘798’ with black ink on one side and plain on the other side.
Bottles of 30’s with Child Resistant Cap………………NDC 62756-798-83
Bottles of 100’s with Child Resistant Cap ……..… NDC 62756-798-88
Bottles of 100’s with Non Child Resistant Cap……..NDC 62756-798-08
Bottles of 500’s with Non Child Resistant Cap……..NDC 62756-798-13
Bottles of 1000’s with Non Child Resistant Cap……NDC 62756-798-18
Recommended storage: Store at 20° – 25°C (68° – 77°F); excursions permitted to 15° – 30° C (59° – 86° F) [see USP Controlled Room Temperature].
PATIENT INFORMATION
id: 05287852-7c1d-41fa-9508-53da1353b0a6
displayName: SPL PATIENT PACKAGE INSERT SECTION
FDA Article Code: 42230-3
The following wording is contained in a separate leaflet provided for patients.
PATIENT INFORMATION LEAFLET
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 any of these medications. This leaflet provides a summary of important information about taking these medications to women who could become pregnant. If you have any questions or concerns, or want more information about these medications, contact your doctor or pharmacist.
Information For Women Who Could Become Pregnant
These medications can be obtained only by prescription from your doctor. The decision to use any of these medications is one that you and your doctor should make together, taking into account your individual needs and medical condition.
Before using
any of these medications, women who can become pregnant should consider the fact that these medications 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 delayed-release tablets 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%.
These medications 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 these medications than some other drugs that treat your medical condition.
Information For Women Who Are Planning to Get Pregnant
- Women taking any of these medications who are planning to get pregnant should discuss the treatment options with their doctor.
Information For Women Who Become Pregnant
- If you become pregnant while taking any of these medications, you should contact your doctor immediately.
Other Important Information
- 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.
Facts About Birth Defects
It 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 these medications, 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.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
