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Divalproex Sodium D/R 250 mg Tablet, Delayed Release, 60-count — NDC 72189-0636-60 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Divalproex Sodium D/R 250 mg Tablet, Delayed Release, 60-count — NDC 72189-636-60 (Billing 72189-0636-60)

by Direct_Rx · 60 TABLET, DELAYED RELEASE in 1 BOTTLE

This is a package of 60 tablets of Divalproex Sodium D/R 250 mg Tablet, Delayed Release from Direct_Rx, marketed since Jul 2025 and currently FDA-listed. It is this product's only package size.

NDC 72189-0636-60
🏷️ FDA NDC (as labeled) 72189-636-60 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 72189-636-60
Product NDC 72189-636
11-digit billing NDC 72189063660
NCPDP billing unit EA — each (per item)
RxCUI 1099678
UNII 644VL95AO6
Application # ANDA078597
SPL Set ID 3aff8f08-d8e8-cd13-e063-6394a90aa00c
Established class (EPC) Anti-epileptic Agent; Mood Stabilizer
Physiologic effect Decreased Central Nervous System Disorganized Electrical Activity
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-07-28
Route ORAL
Dosage form TABLET, DELAYED RELEASE
Substance DIVALPROEX SODIUM
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 004539
GCN 17290
HICL code 001884
Ingredient (HICL) Divalproex Sodium
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H4
Therapeutic class — intermediate (HIC2) Anticonvulsants
HIC3 code H4B
Therapeutic class — specific (HIC3) Anticonvulsants
AHFS code 28:12.28.00
AHFS class Gaba-Mediated Anticonvulsants
FDB label name DIVALPROEX SOD DR 250 MG TAB
FDB brand name Divalproex Sodium
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 004539
  • GCN: 17290
  • HICL (First Databank): 001884
  • AHFS class code: 28:12.28.00
  • RxCUI (RxNorm): 1099678
Why two NDCs? The FDA registers this code as 72189-636-60 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 72189-0636-60. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Mood Stabilizer class.

Pharmacologic class Mood Stabilizer, Anti-epileptic Agent
Drug family (ATC) Fatty acid derivatives
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name DIVALPROEX SOD DR 250 MG TAB Ingredient Divalproex Sodium
📖 What it is MedlinePlus · NLM

Valproic acid is used to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). It is also used to prevent migraine headaches, but not to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. It works by increasing the amount of a certain natural substance in the brain.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats seizures, manic episodes of bipolar disorder, and prevents migraines. Which uses apply depends on the product. Capsules are only for seizures. Ask me to check which one y...
  • Swallow tablets whole and never crush or chew them. Extended-release tablets are once a day. Capsules can be swallowed whole or sprinkled on soft food and swallowed right away. Tak...
  • For delayed-release tablets, take it as soon as you remember unless it is almost time for the next dose. Do not double up. Ask your prescriber if you take another form.
  • Nausea, stomach upset, sleepiness, dizziness, tremor, headache and hair loss are common. Call your doctor if they bother you a lot. Call right away for severe stomach pain, vomitin...
📖 Read our full Divalproex guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $0.1520 $9.12 / 60 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
72189-0636-60 You're viewing this Main listing 60 TABLET, DELAYED RELEASE in 1 BOTTLE 2025-07-28 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Divalproex Sodium 250 mg 00832-7123-01 Upsher-Smith 1 tablet $0.086 AB Availability likely —
Divalproex Sodium 250 mg 00904-6860-61 Major 1 tablet $0.086 AB Availability likely —
Divalproex Sodium 250 mg 29300-0139-01 Unichem 100 tablets $0.086 AB Availability likely —
Divalproex Sodium 250 mg 57237-0047-01 Rising 100 tablets $0.086 AB Availability likely —
Divalproex Sodium 250 mg 60687-0868-01 American 1 tablet $0.086 AB Availability likely —
Divalproex Sodium 250 mg 68001-0473-00 BluePoint 100 tablets $0.086 AB Availability likely —
Divalproex Sodium 250 mg 68084-0776-01 American 1 tablet $0.086 AB Discontinued —
Depakote 250 mg 00074-7326-13 AbbVie 100 tablets $4.046 AB Availability likely —
divalproex sodium 250 mg 00615-8587-39 NCS 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 17856-0797-01 ATLANTIC 1 tablet — AB FDA listed —
Divalproex Sodium 250 mg 50090-1123-00 A-S 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 50090-2007-00 A-S 30 tablets — AB FDA listed —
divalproex sodium 250 mg 50090-7763-00 A-S 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 51655-0365-52 Northwind 30 tablets — AB FDA listed —
divalproex sodium 250 mg 55111-0530-01 Dr.Reddy's 100 tablets — AB FDA listed —
Divalproex Sodium 250 mg 55154-4154-00 Cardinal 1 tablet — AB FDA listed —
Divalproex Sodium 250 mg 55154-7145-00 Cardinal 1 tablet — AB Discontinued —
Divalproex Sodium 250 mg 60760-0698-60 St. 60 tablets — AB FDA listed —
Divalproex Sodium 250 mg 62756-0797-08 Sun 100 tablets — AB FDA listed —
Divalproex Sodium 250 mg 63187-0742-30 Proficient 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 65862-0402-01 Aurobindo 100 tablets — AB FDA listed —
Divalproex Sodium 250 mg 67046-1571-03 Coupler 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 68071-3553-06 NuCare 60 tablets — AB FDA listed —
divalproex sodium 250 mg 68788-4079-03 Preferred 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 68788-8609-03 Preferred 30 tablets — AB FDA listed —
divalproex sodium 250 mg 69452-0434-13 Bionpharma 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 70518-3055-00 REMEDYREPACK 30 tablets — AB Discontinued —
Divalproex Sodium 250 mg 70518-3431-00 REMEDYREPACK 60 tablets — AB FDA listed —
Divalproex Sodium 250 mg 71335-0008-01 Bryant 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 71335-2277-01 Bryant 30 tablets — AB FDA listed —
divalproex sodium 250 mg 71335-2783-01 Bryant 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 71335-2862-01 Bryant 100 tablets — AB FDA listed —
Divalproex Sodium 250 mg 71335-2885-01 Bryant 500 tablets — AB FDA listed —
Divalproex Sodium 250 mg 71610-0031-60 Aphena 90 tablets — AB FDA listed —
Divalproex Sodium 250 mg 72162-2316-01 Bryant 100 tablets — AB FDA listed —
Divalproex Sodium 250 mg 72162-2460-01 Bryant 100 tablets — AB FDA listed —
Divalproex Sodium D/R 250 mgthis 72189-0636-60 Direct_Rx 60 tablets — AB FDA listed —
Divalproex Sodium 250 mg 72789-0353-01 PD-Rx 100 tablets — AB FDA listed —
divalproex sodium 250 mg 82804-0233-30 Proficient 30 tablets — AB FDA listed —
Divalproex Sodium 250 mg 87441-0027-01 Unit 30 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2025
On the market since
Jul 2025
📍
2026
Currently FDA-listed
1 year listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color orange
ShapeOval
Imprint797
Size15 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 5138Q19F1X
    Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
  • UNII 8PJ61P6TS3
    Butyl alcohol is a clear liquid organic solvent derived from petroleum or natural sources. In medicines, it helps dissolve active ingredients and serves as a solvent in liquid formulations and some topical products.
  • UNII H77VEI93A8
    A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
  • UNII EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • UNII XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII NX76LV5T8J
    A synthetic plastic polymer made from methacrylic acid and ethyl acrylate. It's used as a coating or binder to control how and where the medicine dissolves in your digestive system.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 46N107B71O
    Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 8MDF5V39QO
    A white powder form of baking soda that acts as a buffer and pH regulator in medicines. It helps maintain the right acid-base balance and may aid tablet disintegration.
  • UNII 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
  • UNII O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
  • UNII XHX3C3X673
    Triacetin is a clear, oily liquid made from glycerin and acetic acid. It works as a plasticizer and solvent in medicines, helping soften coatings and improve how liquids mix together in formulations.
  • UNII 8Z96QXD6UM
    Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.

18 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerDirect_Rx
Application holderSUN PHARMACEUTICAL INDUSTRIES LTD
FDA applicationANDA078597 (ANDA)
Labeler code72189
First marketedJul 2025
Product typeHuman Prescription Drug
Portfolio355 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🆘 Overdosage 🧬 Clinical Pharmacology 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Medication Guide 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📚 References 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~3 min read ▾

WARNING: LIFE THREATENING ADVERSE REACTIONS Hepatotoxicity General Population: Hepatic failure resulting in fatalities has occurred in patients receiving valproate and its derivatives. 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 [see Warnings and Precautions (5.1)].

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.

The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. Patients with Mitochondrial Disease: There is an increased risk of valproate-induced acute liver failure and resultant deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA Polymerase γ (POLG) gene (e.g., Alpers Huttenlocher Syndrome). Divalproex sodium delayed-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)].

In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, divalproex sodium delayed-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 delayed-release tablets for the development of acute liver injury with regular clinical assessments and serum liver testing. POLG mutation screening should be performed in accordance with current clinical practice [see Warnings and Precautions (5.1)].

Fetal Risk Valproate can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). In addition, valproate can cause decreased IQ scores and neurodevelopmental disorders following in utero exposure. Valproate is therefore contraindicated for prophylaxis of migraine headaches in pregnant women and in women of childbearing potential who are not using effective contraception [see Contraindications (4)].

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. In such situations, effective contraception should be used [see Warnings and Precautions (5.2, 5.3, 5.4)].

A Medication Guide describing the risks of valproate is available for patients [see Patient Counseling Information (17)]. 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 ev… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage ~2 min read ▾

1.1Mania Divalproex sodium is a valproate and is indicated for the treatment of the manic episodes associated with bipolar disorder. 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.

The efficacy of divalproex sodium delayed-release tablets was established in 3-week trials with patients meeting DSM-III-R criteria for bipolar disorder who were hospitalized for acute mania [see Clinical Studies (14.1)]. The safety and effectiveness of divalproex sodium delayed-release tablets 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 delayed-release tablets for extended periods should continually reevaluate the long-term usefulness of the drug for the individual patient.

1.2Epilepsy Divalproex sodium delayed-release tablets are indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. Divalproex sodium delayed-release tablets are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients 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.

1.3Migraine Divalproex sodium delayed-release tablets are indicated for prophylaxis of migraine headaches. There is no evidence that divalproex sodium delayed-release tablets are useful in the acute treatment of migraine headaches.

1.4Important 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 is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see Contraindications (4)].

⏱️ Dosage and Administration ~3 min read ▾

Divalproex sodium delayed-release tablets are intended for oral administration. Divalproex sodium delayed-release tablets should be swallowed whole and should not be crushed or chewed. Patients should be informed to take divalproex sodium delayed-release tablets every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.

2.1Mania Divalproex sodium delayed-release tablets are administered orally. The recommended initial dose is 750 mg daily in divided doses. 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 placebo-controlled clinical trials of acute mania, patients were dosed to a clinical response with a trough plasma concentration between 50 and 125 mcg/mL. Maximum concentrations were generally achieved within 14 days. 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 delayed-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 delayed-release tablets in such longer-term treatment.

Although there are no efficacy data that specifically address longer-term antimanic treatment with divalproex sodium delayed-release tablets, the safety of divalproex sodium delayed-release tablets in long-term use is supported by data from record reviews involving approximately 360 patients treated with divalproex sodium delayed-release tablets for greater than 3 months.

2.2Epilepsy Divalproex sodium delayed-release tablets are administered orally. Divalproex sodium delayed-release tablets are indicated as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures. As the divalproex sodium delayed-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 delayed-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 to 100 mcg/mL).… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 85 words ▾

Divalproex sodium delayed-release tablets 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. 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. 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.

⛔ Contraindications 128 words ▾

Divalproex sodium is 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)].

⚠️ Warnings and Cautions ~3 min read ▾

5.1Hepatotoxicity 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 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.

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 delayed-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 delayed-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 delayed-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 Boxed Warning and Contraindications (4)].

5.2Structural Birth Defect… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

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 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.

6.1Mania The incidence of treatment-emergent events has been ascertained based on combined data from two three week placebo-controlled clinical trials of divalproex sodium delayed-release tablets in the treatment of manic episodes associated with bipolar disorder. The adverse reactions were usually mild or moderate in intensity, but sometimes were serious enough to interrupt treatment. In clinical trials, the rates of premature termination due to intolerance were not statistically different between placebo, divalproex sodium delayed-release tablets and lithium carbonate.

A total of 4%, 8% and 11% of patients discontinued therapy due to intolerance in the placebo, divalproex sodium delayed-release tablets and lithium carbonate groups, respectively. Table 2 summarizes those adverse reactions reported for patients in these trials where the incidence rate in the divalproex sodium delayed-release tablets-treated group was greater than 5% and greater than the placebo incidence, or where the incidence in the divalproex sodium delayed-release tablets-treated group was statistically significantly greater than the placebo group.

Vomiting was the only reaction that was reported by significantly (p ≤ 0.05) more patients receiving divalproex sodium delayed-release tablets compared to placebo. Table 2. Adverse Reactions Reported by > 5% of Divalproex Sodium Delayed-Release Tablets-Treated Patients During Placebo-Controlled Trials of Acute Mania* Adverse Reaction Divalproex Sodium Delayed-Release Tablets (n=89) % Placebo (n=97) % * The following adverse reactions occurred at an equal or greater incidence for placebo than for divalproex sodium delayed-release tablets: back pain, headache, constipation, diarrhea, tremor, and pharyngitis.

Nausea 22 15 Somnolence 19 12 Dizziness 12 4 Vomiting 12 3 Accidental Injury 11 5 Asthenia 10 7 Abdominal Pain 9 8 Dyspepsia 9 8 Rash 6 3 The following additional adverse reactions were reported by greater than 1% but not more than 5% of the 89 divalproex sodium delayed-release tablets-treated patients in controlled clinical trials: Body as a Whole: Chest pain, chills, chills and fever, fever, neck pain, neck rigidity. Cardiovascular System: Hypertension, hypotension, palpitations, postural hypotension, tachycardia, vasodilation.

Digestive System: Anorexia, fecal incontinence, flatulence, gastroenteritis, glossitis, periodontal abscess. Hemic and Lymphatic System: Ecchymosis. Metabolic and Nutritional Disorders: Edema, peripheral edema.

Musculoskeletal System: Arthralgia, arthrosis, leg cramps, twitching. Nervous System: Abnormal dreams, abnormal gait, agitation, ataxia, catatonic reaction, confusion, depression, diplopia, dysarthria, hallucinations, hypertonia, hypokinesia, insomnia, paresthesia, reflexes increased, tardi… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

7.1Effects of Coadministered 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 coadministration 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. Caution should be observed if valproate and aspirin are to be coadministered. 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 coadministration 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 coadministered w… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including divalproex sodium delayed-release tablets, during pregnancy. Encourage women who are taking divalproex sodium delayed-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 (Human)].

Epidemiological studies have indicated that children exposed to valproate in utero have lower IQ scores and a higher risk of neurodevelopmental disorders compared to children exposed to either another AED in utero or to no AEDs in utero [see Warnings and Precautions (5.3) and Data (Human)]. 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 valpr… [Excerpted — this section continues on DailyMed.]

🆘 Overdosage 120 words ▾

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.

🧬 Clinical Pharmacology ~3 min read ▾

12.1Mechanism 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).

12.2Pharmacodynamics The relationship between plasma concentration and clinical response is not well documented. One contributing factor is the nonlinear, concentration dependent protein binding of valproate which affects the clearance of the drug. Thus, monitoring of total serum valproate cannot provide a reliable index of the bioactive valproate species.

For example, because the plasma protein binding of valproate is concentration dependent, the free fraction increases from approximately 10% at 40 mcg/mL to 18.5% at 130 mcg/mL. Higher than expected free fractions occur in the elderly, in hyperlipidemic patients, and in patients with hepatic and renal diseases. Epilepsy The therapeutic range in epilepsy is commonly considered to be 50 to 100 mcg/mL of total valproate, although some patients may be controlled with lower or higher plasma concentrations.

Mania In placebo-controlled clinical trials of acute mania, patients were dosed to clinical response with trough plasma concentrations between 50 and 125 mcg/mL [see Dosage and Administration (2.1)].

12.3Pharmacokinetics Absorption/Bioavailability Equivalent oral doses of divalproex sodium products and valproic acid capsules deliver equivalent quantities of valproate ion systemically. Although the rate of valproate ion absorption may vary with the formulation administered (liquid, solid, or sprinkle), conditions of use (e.g., fasting or postprandial) and the method of administration (e.g., whether the contents of the capsule are sprinkled on food or the capsule is taken intact), these differences should be of minor clinical importance under the steady state conditions achieved in chronic use in the treatment of epilepsy.

However, it is possible that differences among the various valproate products in Tmax and Cmax could be important upon initiation of treatment. For example, in single dose studies, the effect of feeding had a greater influence on the rate of absorption of the tablet (increase in Tmax from 4 to 8 hours) than on the absorption of the sprinkle capsules (increase in Tmax from 3.3 to 4.8 hours). While the absorption rate from the G.I. tract and fluctuation in valproate plasma concentrations vary with dosing regimen and formulation, the efficacy of valproate as an anticonvulsant in chronic use is unlikely to be affected.

Experience employing dosing regimens from once-a-day to four-times-a-day, as well as studies in primate epilepsy models involving constant rate infusion, indicate that total daily systemic bioavailability (extent of absorption) is the primary determinant of seizure control and that differences in the ratios of plasma peak to trough concentrations between valproate formulations are inconsequential from a practical clinical standpoint. Whether or not rate of absorption influences the efficacy of valproate as an antimanic or antimigraine agent is unknown.

Coadministration of oral valproate products with food and substitution among the various divalproex sodium and valproic acid formulations should cause no clinical problems in the management of patients with epilepsy [see Dosage and Administration (2.2)]. Nonetheless, any changes in dosage administration, or the addition or discontinuance of concomitant drugs should ordinarily be accompanied by close monitoring of clinical status and valproate plasma concentrations. Distribution Protein Binding The plasma protein binding of valproate is concentration dependent and the free fraction increases from approximately 10% at 40 mcg/mL to 18.5% at 130 mcg/mL.

Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairm… [Excerpted — this section continues on DailyMed.]

📦 How Supplied / Storage and Handling 185 words ▾

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 with Child Resistant Cap, NDC 62756-796-83 Bottles of 100 with Child Resistant Cap, NDC 62756-796-88 Bottles of 100, NDC 62756-796-08 Bottles of 500, NDC 62756-796-13 Bottles of 1,000, 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 60 with Child Resistant Cap, NDC 72189-636-60 Bottles of 100 with Child Resistant Cap, NDC 62756-797-88 Bottles of 100, NDC 62756-797-08 Bottles of 500, NDC 62756-797-13 Bottles of 1,000, 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 with Child Resistant Cap, NDC 62756-798-83 Bottles of 100 with Child Resistant Cap, NDC 62756-798-88 Bottles of 100, NDC 62756-798-08 Bottles of 500, NDC 62756-798-13 Bottles of 1,000, NDC 62756-798-18

📦 Storage and Handling 26 words ▾

Recommended Storage: Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30° C (59° to 86° F) [see USP Controlled Room Temperature].

📋 Description 169 words ▾

Divalproex sodium is a stable coordination 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: [spl-divalproex-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 maize 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 glaze, iron oxide black, N-butyl alcohol, propylene glycol, and ammonium hydroxide. 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

💬 Medication Guide ~3 min read ▾

Dispense with Medication Guide available at: https://www.sunpharma.com/usa/products MEDICATION GUIDE Divalproex Sodium (dye val' proe ex soe' dee um) Delayed-Release Tablets, USP, for oral use What is the most important information I should know about divalproex sodium delayed-release tablets? Do not stop divalproex sodium delayed-release tablets without first talking to a healthcare provider. Stopping divalproex sodium delayed-release tablets suddenly can cause serious problems.

Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus). Divalproex sodium delayed-release tablets can cause serious side effects, including: 1. Serious liver damage that can cause death, especially in children younger than 2 years old and patients with mitochondrial disorders.

The risk of getting this serious liver damage is more likely to happen within the first 6 months of treatment. Call your healthcare provider right away if you get any of the following symptoms: feeling very weak, tired or uncomfortable (malaise) swelling of your face not feeling hungry nausea or vomiting that does not go away diarrhea pain on the right side of your stomach (abdomen) dark urine yellowing of your skin or the whites of your eyes loss of seizure control in people with epilepsy In some cases, liver damage may continue even though the medicine is stopped.

Your healthcare provider will do blood tests to check your liver before and during treatment with divalproex sodium delayed-release tablets. 2. Divalproex sodium delayed-release tablets may harm your unborn baby.

If you take divalproex sodium delayed-release tablets during pregnancy for any medical condition, your baby is at risk for serious birth defects that affect the brain and spinal cord (such as spina bifida or neural tube defects). These defects can begin in the first month, even before you know you are pregnant. Other birth defects that affect the structures of the heart, head, arms, legs, and the opening where the urine comes out (urethra) on the bottom of the penis can also happen.

Decreased hearing or hearing loss can also happen. Birth defects may occur even in children born to women who are not taking any medicines and do not have other risk factors. Taking folic acid supplements before getting pregnant and during early pregnancy can lower the chance of having a baby with a neural tube defect.

If you take divalproex sodium delayed-release tablets during pregnancy for any medical condition, your child is at risk for having lower IQ and may be at risk for developing autism or attention deficit/hyperactivity disorder. There may be other medicines to treat your condition that have a lower chance of causing birth defects, decreased IQ, or other disorders in your child. Women who are pregnant must not take divalproex sodium delayed-release tablets to prevent migraine headaches.

All women of childbearing age (including girls from the start of puberty) should talk to their healthcare provider about using other possible treatments instead of divalproex sodium delayed-release tablets. If the decision is made to use divalproex sodium delayed-release tablets, you should use effective birth control (contraception). Tell your healthcare provider right away if you become pregnant while taking divalproex sodium delayed-release tablets.

You and your healthcare provider should decide if you will continue to take divalproex sodium delayed-release tablets while you are pregnant. Pregnancy Registry: If you become pregnant while taking divalproex sodium delayed-release tablets, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. You can enroll in this registry by calling toll-free 1-888-233-2334 or by visiting the website, http://www.aedpregnancyregistry.org/.

The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. 3. Swelling (Inf… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14.1Mania The effectiveness of divalproex sodium delayed-release tablets for the treatment of acute mania was demonstrated in two 3-week, placebo controlled, parallel group studies. (1) Study 1: The first study enrolled adult patients who met DSM-III-R criteria for bipolar disorder and who were hospitalized for acute mania. In addition, they had a history of failing to respond to or not tolerating previous lithium carbonate treatment.

Divalproex sodium delayed-release tablets were initiated at a dose of 250 mg tid and adjusted to achieve serum valproate concentrations in a range of 50 to 100 mcg/mL by day 7. Mean divalproex sodium delayed-release tablets doses for completers in this study were 1,118, 1,525, and 2,402 mg/day at Days 7, 14, and 21, respectively. Patients were assessed on the Young Mania Rating Scale (YMRS; score ranges from 0 to 60), an augmented Brief Psychiatric Rating Scale (BPRS-A), and the Global Assessment Scale (GAS).

Baseline scores and change from baseline in the Week 3 endpoint (last-observation-carry-forward) analysis were as follows: Table 6. Study 1 * Mean score at baseline † Change from baseline to Week 3 (LOCF) ‡ Difference in change from baseline to Week 3 endpoint (LOCF) between divalproex sodium delayed-release tablets and placebo YMRS Total Score Group Baseline* BL to Wk 3† Difference‡ Placebo 28.8 +

0.2Divalproex sodium delayed-release tablets 28.5 - 9.5

9.7BPRS-A Total Score Group Baseline* BL to Wk 3† Difference‡ Placebo 76.2 +

1.8Divalproex sodium delayed-release tablets 76.4 -17

18.8GAS Score Group Baseline* BL to Wk 3† Difference‡ Placebo 31.8 0 Divalproex sodium delayed-release tablets 30.3 + 18.1

18.1Divalproex sodium delayed-release tablets were statistically significantly superior to placebo on all three measures of outcome. (2) Study 2: The second study enrolled adult patients who met Research Diagnostic Criteria for manic disorder and who were hospitalized for acute mania. Divalproex sodium delayed-release tablets were initiated at a dose of 250 mg tid and adjusted within a dose range of 750 mg/day to 2,500 mg/day to achieve serum valproate concentrations in a range of 40 to 150 mcg/mL.

Mean divalproex sodium delayed-release tablets doses for completers in this study were 1,116, 1,683, and 2,006 mg/day at Days 7, 14, and 21, respectively. Study 2 also included a lithium group for which lithium doses for completers were 1,312, 1,869, and 1,984 mg/day at Days 7, 14, and 21, respectively. Patients were assessed on the Manic Rating Scale (MRS; score ranges from 11 to 63), and the primary outcome measures were the total MRS score, and scores for two subscales of the MRS, i.e., the Manic Syndrome Scale (MSS) and the Behavior and Ideation Scale (BIS).

Baseline scores and change from baseline in the Week 3 endpoint (last-observation-carry-forward) analysis were as follows: Table 7. Study 2 * Mean score at baseline † Change from baseline to Day 21 (LOCF) ‡ Difference in change from baseline to Day 21 endpoint (LOCF) between divalproex sodium delayed-release tablets and placebo and lithium and placebo MRS Total Score Group Baseline* BL to Day 21† Difference‡ Placebo 38.9 -

4.4Lithium 37.9 -10.5

6.1Divalproex sodium delayed-release tablets 38.1 - 9.5

5.1MSS Total Score Group Baseline* BL to Day 21† Difference‡ Placebo 18.9 -

2.5Lithium 18.5 - 6.2

3.7Divalproex sodium delayed-release tablets 18.9 - 6.0

3.5BIS Total Score Group Baseline* BL to Day 21† Difference‡ Placebo 16.4 -

1.4Lithium 16.0 - 3.8

2.4Divalproex sodium delayed-release tablets 15.7 - 3.2

1.8Divalproex sodium delayed-release tablets were statistically significantly superior to placebo on all three measures of outcome. An exploratory analysis for age and gender effects on outcome did not suggest any differential responsiveness on the basis of age or gender. A comparison of the percentage of patients showing ≥ 30% reduction in the symptom score from baseline in each treatment group, separated by study, is shown in F… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis Valproate was administered orally to rats and mice at doses of 80 and 170 mg/kg/day (less than the maximum recommended human dose on a mg/m2 basis) for two years. The primary findings were an increase in the incidence of subcutaneous fibrosarcomas in high-dose male rats receiving valproate and a dose-related trend for benign pulmonary adenomas in male mice receiving valproate. Mutagenesis Valproate was not mutagenic in an in vitro bacterial assay (Ames test), did not produce dominant lethal effects in mice, and did not increase chromosome aberration frequency in an in vivo cytogenetic study in rats.

Increased frequencies of sister chromatid exchange (SCE) have been reported in a study of epileptic children taking valproate; this association was not observed in another study conducted in adults. Impairment of Fertility In chronic toxicity studies in juvenile and adult rats and dogs, administration of valproate resulted in testicular atrophy and reduced spermatogenesis at oral doses of 400 mg/kg/day or greater in rats (approximately equal to or greater than the maximum recommended human dose (MRHD) on a mg/m2 basis) and 150 mg/kg/day or greater in dogs (approximately equal to or greater than the MRHD on a mg/m2 basis).

Fertility studies in rats have shown no effect on fertility at oral doses of valproate up to 350 mg/kg/day (approximately equal to the MRHD on a mg/m2 basis) for 60 days.

📚 References 31 words ▾

1. Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurology 2013; 12 (3):244-252.

📄 Package Label / Principal Display Panel 1 words ▾

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Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Direct_Rx. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Direct_Rx is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
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For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.