Divalproex Sodium
Tablet, Delayed Release · Oral
Uses
Divalproex sodium extended-release tablets are indicated for: Acute treatment of manic or mixed episodes associated with bipolar disorder, with or without psychotic features ( 1.1 ) Monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1.2 ) Prophylaxis of migraine headaches ( 1.3 ) 1.1 Mania Divalproex sodium extended-release tablets are valproate and are indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. A mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode (depressed mood, loss of interest or pleasure in nearly all activities). The efficacy of divalproex sodium extended-release tablets is based in part on studies of divalproex sodium delayed-release tablets in this indication, and was confirmed in a 3-week trial with patients meeting DSM-IV TR criteria for bipolar I disorder, manic or mixed type, who were hospitalized for acute mania [see Clinical Studies ( 14.1 )]. The effectiveness of valproate for long-term use in mania, i.e., more than 3 weeks, has not been demonstrated in controlled clinical trials. Therefore, healthcare providers who elect to use divalproex sodium extended-release tablets for extended periods should continually reevaluate the long-term risk-benefits of the drug for the individual patient. 1.2 Epilepsy Divalproex sodium extended-release tablets are indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. Divalproex sodium extended-release tablets are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures in adults and children 10 years of age or older, and adjunctively in adults and children 10 years of age or older with multiple seizure types that include absence seizures. Simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. Complex absence is the term used when other signs are also present. 1.3 Migraine Divalproex sodium extended-release tablets are indicated for prophylaxis of migraine headaches. There is no evidence that divalproex sodium extended-release tablets are useful in the acute treatment of migraine headaches. 1.4 Important Limitations Because of the risk to the fetus of decreased IQ, neurodevelopmental disorders, neural tube defects, and other major congenital malformations, which may occur very early in pregnancy, valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. Valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 ), Use in Specific Populations ( 8.1 ), and Patient Counseling Information ( 17 )]. For prophylaxis of migraine headaches, divalproex sodium extended-release tablets are contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see Contraindications ( 4 )].
Dosage and administration
Divalproex sodium extended-release tablets are an extended-release product intended for once-a-day oral administration. Divalproex sodium extended-release tablets should be swallowed whole and should not be crushed or chewed. Divalproex sodium extended-release tablets are intended for once-a-day oral administration. Divalproex sodium extended-release tablets should be swallowed whole and should not be crushed or chewed ( 2.1 , 2.2 ). Mania: Initial dose is 25 mg/kg/day, increasing as rapidly as possible to achieve therapeutic response or desired plasma level ( 2.1 ). The maximum recommended dosage is 60 mg/kg/day ( 2.1 , 2.2 ). Complex Partial Seizures: Start at 10 to 15 mg/kg/day, increasing at 1 week intervals by 5 to 10 mg/kg/day to achieve optimal clinical response; if response is not satisfactory, check valproate plasma level; see full prescribing information for conversion to monotherapy ( 2.2 ). The maximum recommended dosage is 60 mg/kg/day ( 2.1 , 2.2 ). Absence Seizures: Start at 15 mg/kg/day, increasing at 1 week intervals by 5 to 10 mg/kg/day until seizure control or limiting side effects ( 2.2 ). The maximum recommended dosage is 60 mg/kg/day ( 2.1 , 2.2 ). Migraine: The recommended starting dose is 500 mg/day for 1 week, thereafter increasing to 1,000 mg/day ( 2.3 ). 2.1 Mania Divalproex sodium extended-release tablets are administered orally. The recommended initial dose is 25 mg/kg/day given once daily. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In a placebo-controlled clinical trial of acute mania or mixed type, patients were dosed to a clinical response with a trough plasma concentration between 85 and 125 mcg/mL. The maximum recommended dosage is 60 mg/kg/day. There is no body of evidence available from controlled trials to guide a clinician in the longer term management of a patient who improves during divalproex sodium extended-release tablets treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no data to support the benefits of divalproex sodium extended-release tablets in such longer-term treatment (i.e., beyond 3 weeks). 2.2 Epilepsy Divalproex sodium extended-release tablets are administered orally, and must be swallowed whole. As divalproex sodium extended-release tablets dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions ( 7.2 )]. Complex Partial Seizures For adults and children 10 years of age or older. Monotherapy (Initial Therapy) Divalproex sodium extended- release tablets have not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions. Conversion to Monotherapy Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 - 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of divalproex sodium extended-release tablets therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency. Adjunctive Therapy Divalproex sodium extended-release tablets may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to valproate, no adjustment of carbamazepine or phenytoin dosage was needed [see Clinical Studies ( 14.2 )] . However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see Drug Interactions ( 7 )].
Dosage forms and strengths
Divalproex sodium extended-release tablets USP, 250 mg are available as pink colored, oval shaped, biconvex film coated tablets imprinted with "U 380" on one side and plain on the other. Each film-coated extended-release tablet contains divalproex sodium, USP equivalent to 250 mg of valproic acid. Divalproex sodium extended-release tablets USP, 500 mg are available as yellow colored, oval shaped, biconvex film coated tablets imprinted with "U 381" on one side and plain on the other. Each film-coated extended-release tablet contains divalproex sodium, USP equivalent to 500 mg of valproic acid. Tablets: 250 mg and 500 mg ( 3 )
Contraindications
Divalproex sodium extended-release tablets are contraindicated in patients: with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions ( 5.1 )]. known to have mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; e.g., Alpers-Huttenlocher Syndrome) and children under two years of age who are suspected of having a POLG-related disorder [see Warnings and Precautions ( 5.1 )] with known hypersensitivity to divalproex sodium, sodium valproate, or valproic acid. Reactions have included multiorgan hypersensitivity, serious dermatologic reactions, and angioedema [see Warnings and Precautions ( 5.12 , 5.13 , 5.14 )]. with known urea cycle disorders [see Warnings and Precautions ( 5.6 )]. being treated for prophylaxis of migraine headaches: who are pregnant or in women of childbearing potential who are not using effective contraception [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 ) and Use in Specific Populations ( 8.1 )]. Hepatic disease or significant hepatic dysfunction ( 4 , 5.1 ) Known mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG) ( 4 , 5.1 ) Suspected POLG-related disorder in children under two years of age ( 4 , 5.1 ) Known hypersensitivity to the drug ( 4 , 5.12 ) Urea cycle disorders ( 4 , 5.6 ) Prophylaxis of migraine headaches: Pregnant women, women of childbearing potential not using effective contraception ( 4 , 8.1 )
Warnings and precautions
Birth defects, decreased IQ, and neurodevelopmental disorders following in utero exposure; Should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant or to treat a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable ( 5.2 , 5.3 , 5.4 ) Pancreatitis; Divalproex sodium extended-release tablets should ordinarily be discontinued ( 5.5 ) Suicidal behavior or ideation; Antiepileptic drugs, including divalproex sodium extended-release tablets, increase the risk of suicidal thoughts or behavior ( 5.7 ) Bleeding and other hematopoietic disorders; Monitor platelet counts and coagulation tests ( 5.8 ) Hyperammonemia and hyperammonemic encephalopathy; Measure ammonia level if unexplained lethargy and vomiting or changes in mental status, and also with concomitant topiramate use; consider discontinuation of valproate therapy ( 5.6 , 5.9 , 5.10 ) Hypothermia; Hypothermia has been reported during valproate therapy with or without associated hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate ( 5.11 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reaction, serious dermatologic reactions, and angioedema: Discontinue divalproex sodium extended-release tablets unless an alternate etiology is established ( 5.12 , 5.13 , 5.14 ) 5.1 Hepatotoxicity General Information on Hepatotoxicity Hepatic failure resulting in fatalities has occurred in patients receiving valproate. 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. Serum liver tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months of valproate therapy. However, healthcare providers should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination. Caution should be observed when administering valproate products to patients with a prior history of hepatic disease. Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk. See below, "Patients with Known or Suspected Mitochondrial Disease." Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions. When divalproex sodium extended-release tablet 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. In progressively older patient groups experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably. Patients with Known or Suspected Mitochondrial Disease Divalproex sodium extended-release tablets are contraindicated in patients known to have mitochondrial disorders caused by POLG mutations and children under two years of age who are clinically suspected of having a mitochondrial disorder [see Contraindications ( 4 )]. Valproate-induced acute liver failure and liver-related deaths have been reported in patients with hereditary neurometabolic syndromes caused by mutations in the gene for mitochondrial DNA polymerase γ (POLG) (e.g., Alpers- Huttenlocher Syndrome) at a higher rate than those without these syndromes. Most of the reported cases of liver failure in patients with these syndromes have been identified in children and adolescents. POLG-related disorders should be suspected in patients with a family history or suggestive symptoms of a POLG-related disorder, including but not limited to unexplained encephalopathy, refractory epilepsy (focal, myoclonic), status epilepticus at presentation, developmental delays, psychomotor regression, axonal sensorimotor neuropathy, myopathy cerebellar ataxia, ophthalmoplegia, or complicated migraine with occipital aura. POLG mutation testing should be performed in accordance with current clinical practice for the diagnostic evaluation of such disorders. The A467T and W748S mutations are present in approximately 2/3 of patients with autosomal recessive POLG-related disorders. In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, divalproex sodium extended-release tablets should only be used after other anticonvulsants have failed. This older group of patients should be closely monitored during treatment with divalproex sodium extended-release tablets for the development of acute liver injury with regular clinical assessments and serum liver test monitoring. The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent. In some cases, hepatic dysfunction has progressed in spite of discontinuation of drug [see Box Warning and Contraindications ( 4 )] . 5.2 Structural Birth Defects Valproate can cause fetal harm when administered to a pregnant woman. Pregnancy registry data show that maternal valproate use can cause neural tube defects and other structural abnormalities (e.g., craniofacial defects, cardiovascular malformations, hypospadias, limb malformations). The rate of congenital malformations among babies born to mothers using valproate is about four times higher than the rate among babies born to epileptic mothers using other anti-seizure monotherapies.
Side effects
The following serious adverse reactions are described below and elsewhere in the labeling: Hepatic Failure [see Warnings and Precautions ( 5.1 )] Birth Defects [see Warnings and Precautions ( 5.2 )] Decreased IQ and Neurodevelopmental Disorders following in utero exposure [see Warnings and Precautions ( 5.3 )] Pancreatitis [see Warnings and Precautions ( 5.5 )] Hyperammonemic Encephalopathy [see Warnings and Precautions ( 5.6 , 5.9 , 5.10 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.7 )] Bleeding and Other Hematopoietic Disorders [see Warnings and Precautions ( 5.8 )] Hypothermia [see Warnings and Precautions ( 5.11 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [see Warnings and Precautions ( 5.12 )] Serious Dermatologic Reactions [see Warnings and Precautions ( 5.13 )] Angioedema [see Warnings and Precautions ( 5.14 )] Somnolence in the Elderly [see Warnings and Precautions ( 5.16 )] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Information on pediatric adverse reactions is presented in section 8. Most common adverse reactions (reported ≥15% for any indication) are abdominal pain, alopecia, asthenia, diarrhea, diplopia, dizziness, dyspepsia, headache, infection, insomnia, nausea, somnolence, thrombocytopenia, tremor, vomiting ( 6.1 , 6.2 , 6.3 ). The safety and tolerability of valproate in pediatric patients were shown to be comparable to those in adults ( 8.4 ). To report SUSPECTED ADVERSE REACTIONS, contact Unichem Pharmaceuticals (USA), Inc., at 1-866-562-4616 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Mania The incidence of treatment-emergent events has been ascertained based on combined data from two three week placebo-controlled clinical trials of divalproex sodium extended-release tablets in the treatment of manic episodes associated with bipolar disorder. Table 3 summarizes those adverse reactions reported for patients in these trials where the incidence rate in the divalproex sodium extended-release tablets-treated group was greater than 5% and greater than the placebo incidence. Table 3. Adverse Reactions Reported by > 5% of Divalproex Sodium Extended-Release Tablets-Treated Patients During Placebo-Controlled Trials of Acute Mania 1 Adverse Event Divalproex Sodium Extended-Release Tablets (n = 338) % Placebo (n = 263) % Somnolence 26 14 Dyspepsia 23 11 Nausea 19 13 Vomiting 13 5 Diarrhea 12 8 Dizziness 12 7 Pain 11 10 Abdominal Pain 10 5 Accidental Injury 6 5 Asthenia 6 5 Pharyngitis 6 5 1 The following adverse reactions/event occurred at an equal or greater incidence for placebo than for divalproex sodium extended-release tablets: headache The following additional adverse reactions were reported by greater than 1% of the Divalproex sodium extended-release tablets-treated patients in controlled clinical trials: Body as a Whole : Back Pain, Chills, Chills and Fever, Drug Level Increased, Flu Syndrome, Infection, Infection Fungal, Neck Rigidity. Cardiovascular System : Arrhythmia, Hypertension, Hypotension, Postural Hypotension. Digestive System : Constipation, Dry Mouth, Dysphagia, Fecal Incontinence, Flatulence, Gastroenteritis, Glossitis, Gum Hemorrhage, Mouth Ulceration. Hemic and Lymphatic System: Anemia, Bleeding Time Increased, Ecchymosis, Leucopenia. Metabolic and Nutritional Disorders: Hypoproteinemia, Peripheral Edema. Musculoskeletal System: Arthrosis, Myalgia. Nervous System: Abnormal Gait, Agitation, Catatonic Reaction, Dysarthria, Hallucinations, Hypertonia, Hypokinesia, Psychosis, Reflexes Increased, Sleep Disorder, Tardive Dyskinesia, Tremor. Respiratory System: Hiccup, Rhinitis. Skin and Appendages: Discoid Lupus Erythematosus, Erythema Nodosum, Furunculosis, Maculopapular Rash, Pruritus, Rash, Seborrhea, Sweating, Vesiculobullous Rash. Special Senses: Conjunctivitis, Dry Eyes, Eye Disorder, Eye Pain, Photophobia, Taste Perversion. Urogenital System: Cystitis, Urinary Tract Infection, Menstrual Disorder, Vaginitis. 6.2 Epilepsy Based on a placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures, divalproex sodium delayed-release tablets were generally well tolerated with most adverse reactions rated as mild to moderate in severity. Intolerance was the primary reason for discontinuation in the divalproex sodium delayed-release tablets-treated patients (6%), compared to 1% of placebo-treated patients. Table 4 lists treatment-emergent adverse reactions which were reported by ≥ 5% of divalproex sodium delayed-release tablets-treated patients and for which the incidence was greater than in the placebo group, in the placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures. Since patients were also treated with other antiepilepsy drugs, it is not possible, in most cases, to determine whether the following adverse reactions can be ascribed to divalproex sodium delayed-release tablets alone, or the combination of divalproex sodium delayed-release tablets and other antiepilepsy drugs. Table 4.
Drug interactions
Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. Therefore increased monitoring of valproate and concomitant drug concentrations and dosage adjustment are indicated whenever enzyme-inducing or inhibiting drugs are introduced or withdrawn ( 7.1 ) Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended ( 7.1 ) Co-administration of valproate can affect the pharmacokinetics of other drugs (e.g. diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein binding displacement ( 7.2 ) Patients stabilized on rufinamide should begin valproate therapy at a low dose, and titrate to clinically effective dose ( 7.2 ) Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with divalproex sodium extended-release tablets ( 7.2 ) Topiramate: Hyperammonemia and encephalopathy ( 5.10 , 7.3 ) Cannabidiol: ALT and/or AST elevation ( 7.4 ) 7.1 Effects of Co-Administered Drugs on Valproate Clearance Drugs that affect the level of expression of hepatic enzymes, particularly those that elevate levels of glucuronosyltransferases (such as ritonavir), may increase the clearance of valproate. For example, phenytoin, carbamazepine, and phenobarbital (or primidone) can double the clearance of valproate. Thus, patients on monotherapy will generally have longer half-lives and higher concentrations than patients receiving polytherapy with antiepilepsy drugs. In contrast, drugs that are inhibitors of cytochrome P450 isozymes, e.g., antidepressants, may be expected to have little effect on valproate clearance because cytochrome P450 microsomal mediated oxidation is a relatively minor secondary metabolic pathway compared to glucuronidation and beta-oxidation. Because of these changes in valproate clearance, monitoring of valproate and concomitant drug concentrations should be increased whenever enzyme inducing drugs are introduced or withdrawn. The following list provides information about the potential for an influence of several commonly prescribed medications on valproate pharmacokinetics. The list is not exhaustive nor could it be, since new interactions are continuously being reported. Drugs for which a potentially important interaction has been observed Aspirin A study involving the co-administration of aspirin at antipyretic doses (11 to 16 mg/kg) with valproate to pediatric patients (n=6) revealed a decrease in protein binding and an inhibition of metabolism of valproate. Valproate free fraction was increased 4-fold in the presence of aspirin compared to valproate alone. The β-oxidation pathway consisting of 2-E-valproic acid, 3-OH-valproic acid, and 3-keto valproic acid was decreased from 25% of total metabolites excreted on valproate alone to 8.3% in the presence of aspirin. Whether or not the interaction observed in this study applies to adults is unknown, but caution should be observed if valproate and aspirin are to be co-administered. Carbapenem Antibiotics A clinically significant reduction in serum valproic acid concentration has been reported in patients receiving carbapenem antibiotics (for example, ertapenem, imipenem, meropenem; this is not a complete list) and may result in loss of seizure control. The mechanism of this interaction is not well understood. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop significantly or seizure control deteriorates [see Warnings and Precautions ( 5.15 )] . Estrogen-Containing Hormonal Contraceptives Estrogen-containing hormonal contraceptives may increase the clearance of valproate, which may result in decreased concentration of valproate and potentially increased seizure frequency. Prescribers should monitor serum valproate concentrations and clinical response when adding or discontinuing estrogen containing products. Felbamate A study involving the co-administration of 1,200 mg/day of felbamate with valproate to patients with epilepsy (n=10) revealed an increase in mean valproate peak concentration by 35% (from 86 to 115 mcg/mL) compared to valproate alone. Increasing the felbamate dose to 2,400 mg/day increased the mean valproate peak concentration to 133 mcg/mL (another 16% increase). A decrease in valproate dosage may be necessary when felbamate therapy is initiated. Methotrexate Methotrexate may decrease serum valproate levels and potentially result in increased frequency of seizures or bipolar symptoms. Prescribers should monitor serum valproate concentrations and clinical response when adding or discontinuing methotrexate and adjust valproate dosage, if necessary. Rifampin A study involving the administration of a single dose of valproate (7 mg/kg) 36 hours after 5 nights of daily dosing with rifampin (600 mg) revealed a 40% increase in the oral clearance of valproate. Valproate dosage adjustment may be necessary when it is co-administered with rifampin. 7.2 Effects of Valproate on Other Drugs Valproate has been found to be a weak inhibitor of some P450 isozymes, epoxide hydrase, and glucuronosyltransferases. The following list provides information about the potential for an influence of valproate co administration on the pharmacokinetics or pharmacodynamics of several commonly prescribed medications. The list is not exhaustive, since new interactions are continuously being reported.
Use in specific populations
Pregnancy: Divalproex sodium extended-release tablets can cause congenital malformations including neural tube defects, decreased IQ, and neurodevelopmental disorders ( 5.2 , 5.3 , 8.1 ) Geriatric: Reduce starting dose; increase dosage more slowly; monitor fluid and nutritional intake, and somnolence ( 5.16 , 8.5 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including divalproex sodium extended-release tablets, during pregnancy. Encourage women who are taking divalproex sodium extended-release tablets during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling toll-free 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/ . This must be done by the patient herself. Risk Summary For use in prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see Contraindications ( 4 )]. For use in epilepsy or bipolar disorder, valproate should not be used to treat women who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see Boxed Warning and Warnings and Precautions ( 5.2 , 5.3 )] . Women with epilepsy who become pregnant while taking valproate should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. Maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects including spina bifida, but also malformations involving other body systems (e.g., craniofacial defects including oral clefts, cardiovascular malformations, hypospadias, limb malformations). This risk is dose-dependent; however, a threshold dose below which no risk exists cannot be established. In utero exposure to valproate may also result in hearing impairment or hearing loss. Valproate polytherapy with other AEDs has been associated with an increased frequency of congenital malformations compared with AED monotherapy. The risk of major structural abnormalities is greatest during the first trimester; however, other serious developmental effects can occur with valproate use throughout pregnancy. The rate of congenital malformations among babies born to epileptic mothers who used valproate during pregnancy has been shown to be about four times higher than the rate among babies born to epileptic mothers who used other anti-seizure monotherapies [see Warnings and Precautions ( 5.2 ) and Data ] . Epidemiological studies have indicated that children exposed to valproate in utero have lower IQ scores and a higher risk of neurodevelopmental disorders (NDDs) , including autism spectrum disorder (ASD), intellectual disability (ID, defined as an IQ <70), and attention deficit/ hyperactivity disorder (ADHD) compared to children exposed to either another AED in utero or to no AEDs in utero [see Warnings and Precautions ( 5.3 ) and Data ] . An observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders [see Data ( Human )]. In animal studies, valproate administration during pregnancy resulted in fetal structural malformations similar to those seen in humans and neurobehavioral deficits in the offspring at clinically relevant doses [see Data ( Animal )] . There have been reports of hypoglycemia in neonates and fatal cases of hepatic failure in infants following maternal use of valproate during pregnancy. Pregnant women taking valproate may develop hepatic failure or clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see Warnings and Precautions ( 5.1 , 5.8 )] . Available prenatal diagnostic testing to detect neural tube and other defects should be offered to pregnant women using valproate. Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. It is not known whether the risk of neural tube defects or decreased IQ in the offspring of women receiving valproate is reduced by folic acid supplementation. Dietary folic acid supplementation both prior to conception and during pregnancy should be routinely recommended for women of childbearing potential using valproate [see Warnings and Precautions ( 5.2 , 5.4 )]. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including valproate, due to the risk of status epilepticus or severe seizures, which may be life-threatening.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including divalproex sodium extended-release tablets, during pregnancy. Encourage women who are taking divalproex sodium extended-release tablets during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling toll-free 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/ . This must be done by the patient herself. Risk Summary For use in prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see Contraindications ( 4 )]. For use in epilepsy or bipolar disorder, valproate should not be used to treat women who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see Boxed Warning and Warnings and Precautions ( 5.2 , 5.3 )] . Women with epilepsy who become pregnant while taking valproate should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. Maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects including spina bifida, but also malformations involving other body systems (e.g., craniofacial defects including oral clefts, cardiovascular malformations, hypospadias, limb malformations). This risk is dose-dependent; however, a threshold dose below which no risk exists cannot be established. In utero exposure to valproate may also result in hearing impairment or hearing loss. Valproate polytherapy with other AEDs has been associated with an increased frequency of congenital malformations compared with AED monotherapy. The risk of major structural abnormalities is greatest during the first trimester; however, other serious developmental effects can occur with valproate use throughout pregnancy. The rate of congenital malformations among babies born to epileptic mothers who used valproate during pregnancy has been shown to be about four times higher than the rate among babies born to epileptic mothers who used other anti-seizure monotherapies [see Warnings and Precautions ( 5.2 ) and Data ] . Epidemiological studies have indicated that children exposed to valproate in utero have lower IQ scores and a higher risk of neurodevelopmental disorders (NDDs) , including autism spectrum disorder (ASD), intellectual disability (ID, defined as an IQ <70), and attention deficit/ hyperactivity disorder (ADHD) compared to children exposed to either another AED in utero or to no AEDs in utero [see Warnings and Precautions ( 5.3 ) and Data ] . An observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders [see Data ( Human )]. In animal studies, valproate administration during pregnancy resulted in fetal structural malformations similar to those seen in humans and neurobehavioral deficits in the offspring at clinically relevant doses [see Data ( Animal )] . There have been reports of hypoglycemia in neonates and fatal cases of hepatic failure in infants following maternal use of valproate during pregnancy. Pregnant women taking valproate may develop hepatic failure or clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see Warnings and Precautions ( 5.1 , 5.8 )] . Available prenatal diagnostic testing to detect neural tube and other defects should be offered to pregnant women using valproate. Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. It is not known whether the risk of neural tube defects or decreased IQ in the offspring of women receiving valproate is reduced by folic acid supplementation. Dietary folic acid supplementation both prior to conception and during pregnancy should be routinely recommended for women of childbearing potential using valproate [see Warnings and Precautions ( 5.2 , 5.4 )]. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Epilepsy, with or without exposure to antiepileptic drugs, has been associated with several adverse outcomes during pregnancy, including preeclampsia, preterm labor, antepartum and postpartum hemorrhage, placental abruption, poor fetal growth, prematurity, fetal death, and maternal mortality. The risk of maternal or fetal injury may be greatest for patients with untreated or poorly controlled convulsive seizures. Women with epilepsy who become pregnant should not abruptly discontinue antiepileptic drugs, including valproate, due to the risk of status epilepticus or severe seizures, which may be life-threatening. Maternal adverse reactions Pregnant women taking valproate may develop clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see Warnings and Precautions ( 5.8 )] . If valproate is used in pregnancy, the clotting parameters should be monitored carefully in the mother. If abnormal in the mother, then these parameters should also be monitored in the neonate.
Pediatric use
8.4 Pediatric Use Experience has indicated that pediatric patients under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions [see Boxed Warning and Warnings and Precautions ( 5.1 )] . When divalproex sodium extended-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 the age of 2 years, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. Younger children, especially those receiving enzyme inducing drugs, will require larger maintenance doses to attain targeted total and unbound valproate concentrations. Pediatric patients (i.e., between 3 months and 10 years) have 50% higher clearances expressed on weight (i.e., mL/min/kg) than do adults. Over the age of 10 years, children have pharmacokinetic parameters that approximate those of adults. The variability in free fraction limits the clinical usefulness of monitoring total serum valproic acid concentrations. Interpretation of valproic acid concentrations in children should include consideration of factors that affect hepatic metabolism and protein binding. Pediatric Clinical Trials Divalproex sodium delayed-release tablets were studied in seven pediatric clinical trials. Two of the pediatric studies were double-blinded placebo-controlled trials to evaluate the efficacy of divalproex sodium extended-release tablets for the indications of mania (150 patients aged 10 to 17 years, 76 of whom were on divalproex sodium extended-release tablets) and migraine (304 patients aged 12 to 17 years, 231 of whom were on divalproex sodium extended-release tablets). Efficacy was not established for either the treatment of migraine or the treatment of mania. The most common drug-related adverse reactions (reported >5% and twice the rate of placebo) reported in the controlled pediatric mania study were nausea, upper abdominal pain, somnolence, increased ammonia, gastritis and rash. The remaining five trials were long term safety studies. Two six-month pediatric studies were conducted to evaluate the long-term safety of divalproex sodium extended-release tablets for the indication of mania (292 patients aged 10 to 17 years). Two twelve-month pediatric studies were conducted to evaluate the long-term safety of divalproex sodium extended-release tablets for the indication of migraine (353 patients aged 12 to 17 years). One twelve-month study was conducted to evaluate the safety of depakote Sprinkle Capsules in the indication of partial seizures (169 patients aged 3 to 10 years). In these seven clinical trials, the safety and tolerability of divalproex sodium delayed-release tablets in pediatric patients were shown to be comparable to those in adults [see Adverse Reactions ( 6 )]. Juvenile Animal Toxicology In studies of valproate in immature animals, toxic effects not observed in adult animals included retinal dysplasia in rats treated during the neonatal period (from postnatal day 4) and nephrotoxicity in rats treated during the neonatal and juvenile (from postnatal day 14) periods. The no-effect dose for these findings was less than the maximum recommended human dose on a mg/m 2 basis.
Geriatric use
8.5 Geriatric Use No patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. In a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. A higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. Discontinuation of valproate was occasionally associated with the latter two events. It is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients. A study of elderly patients with dementia revealed drug related somnolence and discontinuation for somnolence [see Warnings and Precautions ( 5.16 )] . The starting dose should be reduced in these patients, and dosage reductions or discontinuation should be considered in patients with excessive somnolence [see Dosage and Administration ( 2.5 )] . There is insufficient information available to discern the safety and effectiveness of valproate for the prophylaxis of migraines in patients over 65. The capacity of elderly patients (age range: 68 to 89 years) to eliminate valproate has been shown to be reduced compared to younger adults (age range: 22 to 26 years) [see Clinical Pharmacology ( 12.3 )] .
Overdosage
Overdosage with valproate may result in somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported; however patients have recovered from valproate levels as high as 2,120 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.
Description
Divalproex sodium, USP 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), oligomer. Divalproex sodium, USP has the following structure: Divalproex sodium, USP occurs as a white to off-white powder. Divalproex sodium extended-release tablets, USP 250 mg and 500 mg are for oral administration. Divalproex sodium extended-release tablets, USP contain divalproex sodium in a once-a-day extended-release formulation equivalent to 250 and 500 mg of valproic acid. Inactive Ingredients Divalproex sodium extended-release tablets USP, 250 mg and 500 mg: Colloidal silicon dioxide, ethylcellulose, hypromellose, lactose monohydrate, propyl gallate, stearic acid and talc. The film coating contains ferric oxide red (for 250 mg), ferric oxide yellow (for 500 mg), hypromellose, lactose monohydrate, titanium dioxide, and triacetin. Imprinting ink Opacode ® S-1-277001 Black contains iron oxide black, propylene glycol and shellac glaze. Meets USP Dissolution Test 12. Image
Mechanism of action
12.1 Mechanism of Action Divalproex sodium dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its therapeutic effects have not been established. It has been suggested that its activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA).
How supplied
Divalproex sodium extended-release tablets USP, 250 mg available as pink colored, oval shaped, biconvex film coated tablets imprinted with "U 380" on one side and plain on the other. Each divalproex sodium extended-release tablet contains divalproex sodium, USP equivalent to 250 mg of valproic acid in the following package sizes: NDC 68001-646-00: Bottles of 100 NDC 68001-646-03: Bottles of 500 Divalproex sodium extended-release tablets USP, 500 mg available as yellow colored, oval shaped, biconvex film coated tablets imprinted with "U 381" on one side and plain on the other. Each divalproex sodium extended-release tablet contains divalproex sodium, USP equivalent to 500 mg of valproic acid in the following packaging sizes: NDC 68001-647-00: Bottles of 100 NDC 68001-647-03: Bottles of 500 Recommended Storage: Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Hepatotoxicity Warn patients and guardians that nausea, vomiting, abdominal pain, anorexia, diarrhea, asthenia, and/or jaundice can be symptoms of hepatotoxicity and, therefore, require further medical evaluation promptly [see Warnings and Precautions ( 5.1 )]. Pancreatitis Warn patients and guardians that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis and, therefore, require further medical evaluation promptly [see Warnings and Precautions ( 5.5 )]. Birth Defects, Decreased IQ, and Neurodevelopmental Disorders Inform pregnant women and women of childbearing potential (including girls beginning the onset of puberty) that use of valproate during pregnancy increases the risk of birth defects, decreased IQ, and neurodevelopmental disorders in children who were exposed in utero[see Warnings and Precautions ( 5.2 , 5.3 , 5.4 ) and Use in Specific Populations ( 8.1 )]. Advise women to use effective contraception while taking valproate. When appropriate, counsel these patients about alternative therapeutic options. This is particularly important when valproate use is considered for a condition not usually associated with permanent injury or death such as prophylaxis of migraine headache [see Contraindications ( 4 )] . Advise patients to read the Medication Guide, which appears as the last section of the labeling [seeWarnings and Precautions ( 5.2 , 5.3 , 5.4 ) and Use in Specific Populations ( 8.1 )] . Pregnancy Registry Advise women of childbearing potential to discuss pregnancy planning with their doctor and to contact their doctor immediately if they think they are pregnant. Encourage women who are taking divalproex sodium extended-release tablets to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 or visit the website, http://www.aedpregnancyregistry.org/ [see Use in Specific Populations ( 8.1 )] . Suicidal Thinking and Behavior Counsel patients, their caregivers, and families that AEDs, including divalproex sodium extended-release tablets, may increase the risk of suicidal thoughts and behavior and to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to the healthcare providers [see Warnings and Precautions ( 5.7 )]. Hyperammonemia Inform patients of the signs and symptoms associated with hyperammonemic encephalopathy and to notify the prescriber if any of these symptoms occur [see Warnings and Precautions ( 5.9 , 5.10 )]. CNS Depression Since valproate products may produce CNS depression, especially when combined with another CNS depressant (e.g., alcohol), advise patients not to engage in hazardous activities, such as driving an automobile or operating dangerous machinery, until it is known that they do not become drowsy from the drug. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions Instruct patients that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related. Advise patients to report such reactions to a healthcare provider immediately [see Warnings and Precautions ( 5.12 )]. Serious Dermatologic Reactions Advise patients of the early signs and symptoms of severe cutaneous adverse reactions and to report any occurrence immediately to a healthcare provider [see Warnings and Precautions ( 5.13 )]. Angioedema Advise patients to discontinue divalproex sodium extended-release tablets and seek immediate medical care if they develop signs or symptoms of angioedema, such as facial, perioral, or upper airway swelling [see Warnings and Precautions ( 5.14 )]. Medication Residue in the Stool Instruct patients to notify their healthcare provider if they notice a medication residue in the stool [see Warnings and Precautions ( 5.20 )]. Brands listed are the trademarks of their respective owners. Manufactured by: UNICHEM LABORATORIES LTD. Pilerne Ind. Estate, Pilerne, Bardez, Goa 403 511, India. For: BluePoint Laboratories Revised: 06/2026 13016901
Label text from the FDA structured product label by BluePoint Laboratories (revised Aug 12, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Divalproex Sodium in 168 products
- Valproate Sodium in 16 products
Divalproex Sodium NDC products (184)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-4861 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | A-S Medication Solutions | ANDA |
| 50090-7841 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | A-S Medication Solutions | ANDA |
| 50090-7763 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | A-S Medication Solutions | ANDA |
| 50090-7635 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | A-S Medication Solutions | ANDA |
| 50090-7121 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | A-S Medication Solutions | ANDA |
| 50090-6074 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | A-S Medication Solutions | ANDA |
| 50090-1123 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | A-S Medication Solutions | ANDA |
| 50090-2007 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | A-S Medication Solutions | ANDA |
| 50090-4737 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | A-S Medication Solutions | ANDA |
| 27241-115 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | Ajanta Pharma USA Inc. | ANDA |
| 62332-821 | Divalproex Sodium 125 mg/1 Capsule, Delayed Release | Alembic Pharmaceuticals Inc. | ANDA |
| 46708-821 | Divalproex Sodium 125 mg/1 Capsule, Delayed Release | Alembic Pharmaceuticals Limited | ANDA |
| 68084-782 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | American Health Packaging | ANDA |
| 68084-776 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | American Health Packaging | ANDA |
| 60687-915 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | American Health Packaging | ANDA |
| 68084-415 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | American Health Packaging | ANDA |
| 68084-313 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | American Health Packaging | ANDA |
| 60687-904 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | American Health Packaging | ANDA |
| 60687-879 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | American Health Packaging | ANDA |
| 60687-868 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | American Health Packaging | ANDA |
| 60687-857 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | American Health Packaging | ANDA |
| 68084-310 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | American Health Packaging | ANDA |
| 65162-755 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | Amneal Pharmaceuticals LLC | ANDA |
| 65162-757 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | Amneal Pharmaceuticals LLC | ANDA |
| 71610-031 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-032 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-030 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-707 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-289 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-249 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-205 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-157 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 17856-0109 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | ATLANTIC BIOLOGICALS CORP. | ANDA |
| 17856-0797 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | ATLANTIC BIOLOGICALS CORP. | ANDA |
| 65862-403 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Aurobindo Pharma Limited | ANDA |
| 65862-402 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Aurobindo Pharma Limited | ANDA |
| 65862-959 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Aurobindo Pharma Limited | ANDA |
| 65862-594 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 65862-595 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 50268-259 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | AvPAK | ANDA |
| 50268-260 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | AvPAK | ANDA |
| 69452-435 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Bionpharma Inc. | ANDA |
| 69452-434 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bionpharma Inc. | ANDA |
| 69452-433 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Bionpharma Inc. | ANDA |
| 68001-646 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | BluePoint Laboratories | ANDA |
| 68001-647 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | BluePoint Laboratories | ANDA |
| 68001-474 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | BluePoint Laboratories | ANDA |
| 68001-473 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | BluePoint Laboratories | ANDA |
| 68001-472 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | BluePoint Laboratories | ANDA |
| 68001-106 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | BluePoint Laboratories | ANDA |
| 68001-105 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | BluePoint Laboratories | ANDA |
| 71335-2782 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 72162-2460 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 72162-2316 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 72162-2515 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 72162-2516 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 71335-2885 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 71335-2862 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 71335-2783 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 71335-2535 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 63629-4698 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 71335-0008 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 63629-4278 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 71335-2277 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 71335-1883 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 71335-2124 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 71335-2344 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 71335-2158 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Bryant Ranch Prepack | ANDA |
| 31722-022 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-021 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Camber Pharmaceuticals, Inc. | ANDA |
| 55154-3552 | Divalproex Sodium 125 mg/1 Capsule, Delayed Release | Cardinal Health 107, LLC | ANDA |
| 55154-5633 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Cardinal Health 107, LLC | ANDA |
| 55154-4759 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | Cardinal Health 107, LLC | ANDA |
| 55154-4154 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Cardinal Health 107, LLC | ANDA |
| 55154-2345 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | Cardinal Health 107, LLC | ANDA |
| 55154-2336 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Cardinal Health 107, LLC | ANDA |
| 67046-1647 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Coupler LLC | ANDA |
| 67046-1631 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Coupler LLC | ANDA |
| 67046-1595 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Coupler LLC | ANDA |
| 67046-1571 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Coupler LLC | ANDA |
| 67046-2021 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | Coupler LLC | ANDA |
| 67046-1683 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Coupler LLC | ANDA |
| 61919-249 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | DirectRx | ANDA |
| 55111-533 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Dr. Reddy's Laboratories Ltd | ANDA |
| 55111-532 | Divalproex Sodium 125 mg/1 Capsule, Delayed Release | Dr. Reddy's Laboratories Ltd | ANDA |
| 55111-534 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Dr. Reddy's Laboratories Ltd | ANDA |
| 55111-531 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Dr.Reddy's Laboratories Limited | ANDA |
| 55111-530 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Dr.Reddy's Laboratories Limited | ANDA |
| 55111-529 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Dr.Reddy's Laboratories Limited | ANDA |
| 81469-492 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | First Nation Group, LLC | ANDA |
| 70756-447 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | Lifestar Pharma LLC | ANDA |
| 68180-265 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-267 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-266 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-261 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-260 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 0904-7182 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | Major Pharmaceuticals | ANDA |
| 0904-6861 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Major Pharmaceuticals | ANDA |
| 0904-6860 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Major Pharmaceuticals | ANDA |
| 0904-6615 | Divalproex Sodium 125 mg/1 Capsule, Delayed Release | Major Pharmaceuticals | ANDA |
| 0904-6363 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Major Pharmaceuticals | ANDA |
| 51079-766 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Mylan Institutional Inc. | ANDA |
| 51079-767 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Mylan Institutional Inc. | ANDA |
| 0378-0473 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Mylan Pharmaceuticals Inc. | ANDA |
| 0378-0472 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Mylan Pharmaceuticals Inc. | ANDA |
| 0615-8588 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 0615-8237 | Divalproex Sodium 125 mg/1 Capsule | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 0615-8376 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 0615-8377 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 0615-8586 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 0615-8587 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 16714-485 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | NorthStar Rx LLC | ANDA |
| 16714-484 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | NorthStar Rx LLC | ANDA |
| 72603-260 | Divalproex Sodium 125 mg/1 Capsule, Delayed Release | NorthStar Rx LLC | ANDA |
| 51655-365 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Northwind Health Company, LLC | ANDA |
| 68071-3553 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | NuCare Pharmaceuticals,Inc. | ANDA |
| 72789-354 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 72789-353 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 72789-286 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 68788-4079 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-4100 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-8609 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-8358 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | Preferred Pharmaceuticals, Inc. | ANDA |
| 63187-743 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Proficient Rx LP | ANDA |
| 82804-233 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Proficient Rx LP | ANDA |
| 63187-742 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Proficient Rx LP | ANDA |
| 70518-4557 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-4575 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-3183 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-4553 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-3683 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-3477 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-3457 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | REMEDYREPACK INC. | ANDA |
| 70518-3431 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-3055 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-2674 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-2626 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-2357 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-2036 | Divalproex Sodium 500 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-1897 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-2003 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-1138 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-1556 | Divalproex Sodium 250 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-1558 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70518-1749 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | REMEDYREPACK INC. | ANDA |
| 70518-1781 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | REMEDYREPACK INC. | ANDA |
| 57237-106 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Rising Pharma Holdings, Inc. | ANDA |
| 57237-048 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Rising Pharma Holdings, Inc. | ANDA |
| 57237-047 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Rising Pharma Holdings, Inc. | ANDA |
| 48433-033 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Safecor Health, LLC | ANDA |
| 48433-034 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Safecor Health, LLC | ANDA |
| 60760-798 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | St. Mary's Medical Park Pharmacy | ANDA |
| 60760-698 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | St. Mary's Medical Park Pharmacy | ANDA |
| 62756-798 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 62756-796 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 62756-797 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 29300-138 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-139 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-140 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-380 | Divalproex Sodium 250 mg/1 Tablet, Film Coated, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-381 | Divalproex Sodium 500 mg/1 Tablet, Film Coated, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 87441-028 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Unit Dose Solutions, Inc. | ANDA |
| 87441-027 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Unit Dose Solutions, Inc. | ANDA |
| 0832-7124 | Divalproex Sodium 500 mg/1 Tablet, Delayed Release | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-7123 | Divalproex Sodium 250 mg/1 Tablet, Delayed Release | Upsher-Smith Laboratories, LLC | ANDA |
| 0832-7122 | Divalproex Sodium 125 mg/1 Tablet, Delayed Release | Upsher-Smith Laboratories, LLC | ANDA |
| 65841-639 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | Zydus Lifesciences Limited | ANDA |
| 68382-106 | Divalproex Sodium 125 mg/1 Capsule, Coated Pellets | Zydus Pharmaceuticals USA Inc. | ANDA |
| 37662-0729 | Valproate Sodium 200 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2862 | Valproate Sodium 6 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2863 | Valproate Sodium 12 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2864 | Valproate Sodium 30 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2865 | Valproate Sodium 100 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-0732 | Valproate Sodium 1 [hp_Q]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-0731 | Valproate Sodium 1 [hp_M]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-0730 | Valproate Sodium 500 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2869 | Valproate Sodium 10 [hp_M]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2868 | Valproate Sodium 1 [hp_M]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2867 | Valproate Sodium 500 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-2866 | Valproate Sodium 200 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-0728 | Valproate Sodium 100 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-0727 | Valproate Sodium 30 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-0726 | Valproate Sodium 12 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
| 37662-0725 | Valproate Sodium 6 [hp_C]/1 Pellet | Hahnemann Laboratories, INC. | UNAPPROVED HOMEOPATHIC |
Divalproex Sodium recalls
- D-0742-2026 Jul 29, 2026 · Class II · Ongoing
Presence of Foreign Tablets/Capsules - D-0426-2024 Apr 3, 2024 · Class II · Terminated
Failed dissolution specifications - D-1362-2022 Aug 31, 2022 · Class II · Terminated
Failed dissolution specifications. - D-1291-2022 Aug 3, 2022 · Class II · Terminated
Failed Dissolution Specifications: Failure occurred during routine stability testing of dissolution test. - D-1583-2019 Aug 7, 2019 · Class II · Terminated
cGMP deviations: Product was exposed above 50% relative humidity levels during packaging operations. - D-0507-2019 Feb 27, 2019 · Class II · Terminated
Failed Dissolution Specifications: Out of specification results observed for high dissolution. - D-0228-2018 Jan 24, 2018 · Class II · Terminated
Cross Contamination With Other Products: metronidazole powder was found in one bottle of Divalproex Sodium. - D-1135-2015 Jun 24, 2015 · Class II · Terminated
Failed Dissolution Specifications; exceeded specification at the 9 hour time point - D-1136-2015 Jun 24, 2015 · Class II · Terminated
Failed Dissolution Specifications; exceeded specification at the 9 hour time point
Frequently asked questions
What is Divalproex Sodium used for?
Divalproex sodium extended-release tablets are indicated for: Acute treatment of manic or mixed episodes associated with bipolar disorder, with or without psychotic features ( 1.1 ) Monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1.2 ) Prophylaxis of…
What are the side effects of Divalproex Sodium?
The following serious adverse reactions are described below and elsewhere in the labeling: Hepatic Failure [see Warnings and Precautions ( 5.1 )] Birth Defects [see Warnings and Precautions ( 5.2 )] Decreased IQ and Neurodevelopmental Disorders following in utero exposure [see Warnings and Precautions ( 5.3 )] Pancreatitis [see Warnings and Precautions ( 5.5 )] Hyperammonemic Encephalopathy [see… See the full label for the complete list.
Who makes Divalproex Sodium?
Divalproex Sodium is listed by 44 labelers in the FDA NDC directory, including A-S Medication Solutions, Ajanta Pharma USA Inc., Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited.
Has Divalproex Sodium been recalled?
The FDA enforcement database lists 9 recalls for Divalproex Sodium, most recently D-0742-2026 (class ii): Presence of Foreign Tablets/Capsules