Home › NDC Lookup › Ingredients › Divalproex Sodium › 71335-2158-02
Divalproex Sodium 500 mg Tablet, Delayed Release, 30-count — NDC 71335-2158-02 package photo

Divalproex Sodium 500 mg Tablet, Delayed Release, 30-count

by Bryant Ranch Prepack · 30 TABLET, DELAYED RELEASE in 1 BOTTLE (71335-2158-2)
NDC 71335-2158-02
🏷️ FDA NDC (as labeled) 71335-2158-2 billing pads the package segment with a zero
This package
Contains30-count Pack sizes5 compare ↓
Also priced by: Part D plans $0.1520/unit — full pricing hub ↓
Also comes in: 60 tablets 71335-2158-01 90 tablets 71335-2158-03 120 tablets 71335-2158-05 180 tablets 71335-2158-04
Rx only Generic On market Non-controlled
🗂️ Data synced 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

⚠️
Other active recalls for Divalproex Sodium (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Jun 26, 2026 — Presence of Foreign Tablets/Capsules (Bionpharma Inc.) · FDA recall D-0742-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 71335-2158-2
Product NDC 71335-2158
11-digit billing NDC 71335215802
NCPDP billing unit EA — each (per item)
RxCUI 1099870
UNII 644VL95AO6
Application # ANDA090554
SPL Set ID fbaff0ae-431e-4e83-81c2-41eb4b18ee87
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 2014-10-24
Route ORAL
Dosage form TABLET, DELAYED RELEASE
Substance DIVALPROEX SODIUM
GCN Seq No 004540
GCN 17291
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 500 MG TAB
FDB brand name Divalproex Sodium
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 71335-2158-2 — a 5-4-1 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 package segment → 71335-2158-02. 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.

🏭 Manufacturer & labeler

LabelerBryant Ranch Prepack
Application holderAUROBINDO PHARMA LIMITED
FDA applicationANDA090554 (ANDA)
Labeler code71335
First marketedOct 2014
Product typeHuman Prescription Drug
Portfolio4,431 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.

🩺 Clinical

Label name DIVALPROEX SOD DR 500 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
  • Divalproex is used for three main things: controlling certain types of seizures (epilepsy), treating acute manic or mixed episodes in bipolar disorder, and preventing migraines. Wh...
  • What exactly is divalproex used for — my doctor prescribed it but I'm not totally sure why.
  • That depends on your specific form. If you're taking the extended-release tablet, you take it once a day and should swallow it whole — don't crush or chew it. The delayed-release t...
  • How should I take it — does it matter when during the day or whether I eat first?
📖 Read our full Divalproex guide →
1
Nutrient depletion considerations

Divalproex Sodium may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Divalproex Sodium nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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.

💊 What it looks like

Color Pink
ShapeOval
ImprintD;86
Size19 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 M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII UF064M00AF
    Diethyl phthalate is a clear, colorless liquid made from phthalic acid. It's used in medicines as a plasticizer to make tablet coatings flexible and as a solvent to help dissolve and distribute active ingredients evenly throughout the product.
  • UNII L06K8R7DQK
    A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
  • UNII WZB9127XOA
    A synthetic red dye used to color medications and make them easier to identify. It serves as a colorant in tablets, capsules, and liquid formulations.
  • 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 36SFW2JZ0W
    Hypromellose 2910 is a plant-based thickening agent derived from cellulose. In medicines, it forms a protective coating on tablets or capsules and controls how quickly the drug dissolves and releases into your body.
  • UNII ND2M416302
    Isopropyl alcohol is a clear liquid solvent derived from petroleum. In medicines, it dissolves active ingredients and other components, helps the product flow smoothly, and aids in sterilization during manufacturing.
  • UNII 1DI56QDM62
    A natural fatty substance from soybeans that helps mix oil and water-based ingredients together. It acts as an emulsifier and lubricant in medicines to improve texture and help the product break down properly in your body.
  • UNII 2165RE0K14
    A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
  • 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 OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII G2M7P15E5P
    Polyethylene glycol 3350 is a synthetic polymer used as a solvent, humectant, and thickening agent in medicines. It helps dissolve other ingredients, retain moisture in the product, and achieve the desired consistency.
  • UNII 532B59J990
    Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
  • UNII U725QWY32X
    Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the 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 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 CHI530446X
    Vanillin is a natural or synthetic aromatic compound that gives vanilla flavor. It's used in medicines as a flavoring agent to mask bitter tastes and improve how the medicine tastes.

23 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.

💲 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 $4.56 / 30 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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Divalproex Sodium 500 mg 00832-7124-01 Upsher-Smith 1 tablet $0.161 AB Availability likely —
Divalproex Sodium 500 mg 00904-6861-61 Major 1 tablet $0.161 AB Availability likely —
Divalproex Sodium 500 mg 29300-0140-01 Unichem 100 tablets $0.161 AB Availability likely —
Divalproex Sodium 500 mg 57237-0048-01 Rising 100 tablets $0.161 AB Availability likely —
Divalproex Sodium 500 mg 60687-0879-61 American 1 tablet $0.161 AB Availability likely —
Divalproex Sodium 500 mg 68001-0474-00 BluePoint 100 tablets $0.161 AB Availability likely —
Divalproex Sodium 500 mg 68084-0782-61 American 1 tablet $0.164 AB Discontinued —
Depakote 500 mg 00074-7327-13 AbbVie 100 tablets $7.453 AB Availability likely —
divalproex sodium 500 mg 00615-8588-39 NCS 30 tablets — AB FDA listed —
divalproex sodium 500 mg 55111-0531-01 Dr.Reddy's 100 tablets — AB FDA listed —
Divalproex Sodium 500 mg 55154-2336-00 Cardinal 1 tablet — AB FDA listed —
Divalproex Sodium 500 mg 55154-4679-00 Cardinal 1 tablet — AB Discontinued —
Divalproex Sodium 500 mg 55154-5633-00 Cardinal 1 tablet — AB FDA listed —
Divalproex Sodium 500 mg 60760-0798-60 St. 60 tablets — AB FDA listed —
Divalproex Sodium 500 mg 61919-0249-60 DirectRx 60 tablets — AB FDA listed —
Divalproex Sodium 500 mg 62756-0798-08 Sun 100 tablets — AB FDA listed —
Divalproex Sodium 500 mg 63187-0743-30 Proficient 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 63629-4278-01 Bryant 60 tablets — AB FDA listed —
Divalproex Sodium 500 mg 65862-0403-01 Aurobindo 100 tablets — AB FDA listed —
divalproex sodium 500 mg 67046-1647-03 Coupler 30 tablets — AB FDA listed —
divalproex sodium 500 mg 69452-0435-13 Bionpharma 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 70518-1558-00 REMEDYREPACK 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 70518-2357-00 REMEDYREPACK 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 70518-2626-00 REMEDYREPACK 1 tablet — AB Discontinued —
Divalproex Sodium 500 mg 70518-2674-02 REMEDYREPACK 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 70518-4575-00 REMEDYREPACK 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 71335-2124-01 Bryant 60 tablets — AB FDA listed —
Divalproex Sodium 500 mgthis 71335-2158-02 Bryant 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 71335-2344-01 Bryant 60 tablets — AB FDA listed —
divalproex sodium 500 mg 71335-2782-01 Bryant 60 tablets — AB FDA listed —
Divalproex Sodium 500 mg 71610-0032-53 Aphena 60 tablets — AB FDA listed —
Divalproex Sodium 500 mg 72789-0354-01 PD-Rx 100 tablets — AB FDA listed —
Divalproex Sodium 500 mg 87441-0028-01 Unit 30 tablets — AB FDA listed —
Divalproex Sodium 500 mg 68180-0267-01 Lupin 100 tablets — — Discontinued —
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

🏛️
2014
On the market since
Oct 2014
📍
2026
Currently FDA-listed
12 years 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.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Divalproex Sodium — the program that covers self-administered drugs. 14 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Divalproex Sodium. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$32.54M
Claims incl. refills
863.4K
Beneficiaries
312.7K
Spend / beneficiary
$104.05
Spend / claim
$37.68
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Divalproex Sodium — the ingredient across all brands.

Top reported reactions

Seizure2,620
Weight Increased2,168
Nausea2,109
Fatigue1,963
Somnolence1,901
Pain1,897
Tremor1,823

Age at onset

Neonate136
Infant29
Child316
Adolescent207
Adult3,203
Elderly633

Reporter sex

46,266 reports
Male · 48%
Female · 52%
Unknown · 1%

Serious outcomes

Hospitalization15,089
Death2,569
Life-threatening1,724
Disabling1,369
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 2,256 909
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
71335-2158-01 60 TABLET, DELAYED RELEASE in 1 BOTTLE (71335-2158-1) 2022-08-22 Active
71335-2158-02 You're viewing this 30 TABLET, DELAYED RELEASE in 1 BOTTLE (71335-2158-2) 2022-08-22 Active
71335-2158-03 90 TABLET, DELAYED RELEASE in 1 BOTTLE (71335-2158-3) 2022-08-22 Active
71335-2158-04 180 TABLET, DELAYED RELEASE in 1 BOTTLE (71335-2158-4) 2022-08-22 Active
71335-2158-05 120 TABLET, DELAYED RELEASE in 1 BOTTLE (71335-2158-5) 2022-08-22 Active

You're viewing the smallest of 5 pack sizes for this product.

Pack size FAQ

What quantity is in NDC 71335-2158-02?
NDC 71335-2158-02 is a 30-count package — 30 tablet, delayed release in 1 bottle.
What is the difference between NDC 71335-2158-02 and NDC 71335-2158-01?
Both are Divalproex Sodium 500 mg Tablet, Delayed Release — the drug itself is identical. NDC 71335-2158-02 is the 30-count package, while NDC 71335-2158-01 is the 60 tablets package.
What NDC number is used to bill for this package of Divalproex Sodium 500 mg Tablet, Delayed Release?
Bill NDC 71335-2158-02 — the 11-digit billing format is 71335215802. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 71335-2158-2, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 71335-2158-02, written without dashes as 71335215802. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 71335-2158-02, the first segment (71335) is the labeler code FDA assigned to Bryant Ranch Prepack; the middle segment (2158) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (02) identifies this exact package size and type. Together they name one specific package of one specific product.
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 Bryant Ranch Prepack. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 4 other package presentations of this same product, including 60 tablets (71335-2158-01), 90 tablets (71335-2158-03), 120 tablets (71335-2158-05). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Bryant Ranch Prepack 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. 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 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide
🚨 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…

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE Divalproex sodium is an anti-epileptic drug indicated for: Treatment of manic episodes associated with bipolar disorder (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)

1.1Mania Divalproex sodium delayed-release tablets are a valproate and are 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 delayed-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 ~3 min read ▾

2 DOSAGE AND ADMINISTRATION 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. Divalproex sodium delayed-release tablets are administered orally in divided doses.

Divalproex sodium delayed-release tablets should be swallowed whole and should not be crushed or chewed (2.1, 2.2) . Mania: Initial dose is 750 mg daily, 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 250 mg twice daily, thereafter increasing to a maximum of 1,000 mg/day as needed (2.3) .

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 cli…

💊 Dosage Forms and Strengths 96 words ▾

3 DOSAGE FORMS AND STRENGTHS Divalproex sodium delayed-release tablets, USP are supplied as: 125 mg is pink-red colored, oval shaped enteric-coated tablets, imprinted with “D 84” on one side with black edible ink and plain on other side. 250 mg is peach colored, oval shaped enteric-coated tablets, imprinted with “D 85”on one side with black edible ink and plain on other side. 500 mg is pink colored, oval shaped enteric-coated tablets, imprinted with “D 86” on one side with black edible ink and plain on other side.

Tablets: 125 mg, 250 mg and 500 mg (3)

⛔ Contraindications ~1 min read ▾

4 CONTRAINDICATIONS Divalproex sodium delayed-release tablets should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions (5.1) ] . Divalproex sodium delayed-release tablets are contraindicated in patients 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) ] .

Divalproex sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to the drug [see Warnings and Precautions (5.12) ] . Divalproex sodium delayed-release tablets are contraindicated in patients with known urea cycle disorders [see Warnings and Precautions (5.6) ] . For use in prophylaxis of migraine headaches: Divalproex sodium delayed-release tablets are contraindicated in women who are pregnant and 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 Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Hepatotoxicity; evaluate high risk populations and monitor serum liver tests ( 5.1 ) 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 delayed-release tablets should ordinarily be discontinued (5.5) Suicidal behavior or ideation; Antiepileptic drugs, including divalproex sodium delayed-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; discontinue divalproex sodium delayed-release tablets (5.12) Somnolence in the elderly can occur. Divalproex sodium delayed-release tablets dosage should be increased slowly and with regular monitoring for fluid and nutritional intake (5.14)

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.,…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS 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) ] Somnolence in the elderly [see Warnings and Precautions (5.14) ] 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.

Most common adverse reactions (reported >5%) are abdominal pain, accidental injury, alopecia, amblyopia/blurred vision, amnesia, anorexia, asthenia, ataxia, back pain, bronchitis, constipation, depression, diarrhea, diplopia, dizziness, dyspepsia, dyspnea, ecchymosis, emotional lability, fever, flu syndrome, headache, increased appetite, infection, insomnia, nausea, nervousness, nystagmus, peripheral edema, pharyngitis, rash, rhinitis, somnolence, thinking abnormal, thrombocytopenia, tinnitus, tremor, vomiting, weight gain, weight loss (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 Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 1 Adverse Reaction Divalproex Sodium Delayed-Release Tablets (n = 89) % Placebo (n = 97) % 1 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 c…

🔄 Drug Interactions ~2 min read ▾

7 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 delayed-release tablets (7.2) Topiramate: Hyperammonemia and encephalopathy (5.10, 7.3) Cannabidiol: ALT and/or AST elevation ( 7.4 )

7.1Effects 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. 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 (5.13) ] .

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 freq…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: Divalproex sodium delayed-release tablets can cause congenital malformations including neural tube defects, decreased IQ, and neurodevelopmental disorders (5.2, 5.3, 8.1) Pediatric: Children under the age of two years are at considerably higher risk of fatal hepatotoxicity (5.1, 8.4) Geriatric: Reduce starting dose; increase dosage more slowly; monitor fluid and nutritional intake, and somnolence (5.14, 8.5)

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 Prec…

🤰 Pregnancy ~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 recei…

🧒 Pediatric Use ~2 min read ▾

8.4Pediatric 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 delayed-release tablets are used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks.

Above 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 was studied in seven pediatric clinical trials. Two of the pediatric studies were double-blinded placebo-controlled trials to evaluate the efficacy of divalproex sodium ER for the indications of mania (150 patients aged 10 to 17 years, 76 of whom were on divalproex sodium ER) and migraine (304 patients aged 12 to 17 years, 231 of whom were on divalproex sodium ER). 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 ER 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 ER for the indication of migraine (353 patients aged 12 to 17 years). One twelve-month study was conducted to evaluate the safety of divalproex sodium 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 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 169 words ▾

8.5Geriatric 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 (5.14) ] .

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 (2.4) ] . There is insufficient information available to discern the safety and effectiveness of valproate for the prophylaxis of migraines in patients over 65.

🆘 Overdosage 122 words ▾

10 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.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

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 T max and C max 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 T max from 4 to 8 hours) than on the absorption of the sprinkle capsules (increase in T max 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.

Co-administration 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 disea…

🧬 Mechanism of Action 47 words ▾

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).

📦 How Supplied / Storage and Handling 111 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Divalproex sodium delayed-release tablets, USP are supplied as: Divalproex Sodium Delayed-Release Tablets USP, 500 mg are pink colored, oval shaped enteric-coated tablets, imprinted with “D 86” on one side with black edible ink and plain on other side. NDC 71335-2158-1: 60 TABLETs in a BOTTLE NDC 71335-2158-2: 30 TABLETs in a BOTTLE NDC 71335-2158-3: 90 TABLETs in a BOTTLE NDC 71335-2158-4: 180 TABLETs in a BOTTLE NDC 71335-2158-5: 120 TABLETs in a BOTTLE 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].

Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

📋 Description ~1 min read ▾

11 DESCRIPTION Divalproex sodium is a stable co-ordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship. Chemically it is designated as sodium hydrogen bis(2-propylpentanoate). Divalproex sodium has the following structure: Divalproex sodium USP occurs as a white crystalline powder with a characteristic odor.

Divalproex sodium delayed-release tablets, USP 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, USP: silicon dioxide, microcrystalline cellulose, croscarmellose sodium, povidone (Kollidon 30), hydroxypropyl cellulose low substituted, talc, methacrylic acid and ethyl acrylate copolymer dispersion, and diethyl phthalate.

In addition, 125 mg tablets are coated with opadry clear 04K59023 and opadry II complete film coating system 86G540000 pink. Opadry clear 04K59023 contains hypromellose and triacetin, opadry II complete film coating system 86G540000 pink contains polyvinyl alcohol, talc, titanium dioxide, macrogol/PEG 3350, FD&C Red #40, lecithin (soya), and vanillin. 250 mg tablets are coated with opadry clear 04K59023 and opadry II 86G53866 orange.

Opadry clear 04K59023 contains hypromellose and triacetin, opadry II 86G53866 orange contains polyvinyl alcohol, talc, titanium dioxide, macrogol/PEG 3350, lecithin (soya), vanillin, FD&C Yellow #6, and iron oxide yellow. 500 mg tablets are coated with opadry clear 04K59023 and opadry II 86G84795 pink. Opadry clear 04K59023 contains hypromellose and triacetin, opadry II 86G84795 pink contains polyvinyl alcohol, talc, titanium dioxide, macrogol/PEG 3350, lecithin (soya), FD&C Red #40, vanillin, and FD&C Blue #2.

The tablets are printed with opacode black S-1-17823 containing shellac glaze in ethanol, isopropyl alcohol, iron oxide black, N-butyl alcohol, propylene glycol, and ammonium hydroxide.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING 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 and Decreased IQ 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 . 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 [see Warnings 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 delayed-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 delayed-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.

Multiorgan Hypersensitivity Reactions Instruct patients that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related and should be reported to the physician immediately [see Warnings and Precautions (5.12) ] . 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 (5.18) ]. Dispense with Medication Guide available at: http://www.risingpharma.com/med-guides.html Distributed by: Rising Pharma Holdings, Inc.

East Brunswick, NJ 08816 Made in India Code: TS/DRUGS/19/1993 Revised: 07/2024

💬 Medication Guide ~3 min read ▾

Dispense with Medication Guide available at: http://www.risingpharma.com/med-guides.html MEDICATION GUIDE Divalproex Sodium (dye val' proe ex soe' dee um) Delayed-Release Tablets, USP 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 (Inflammati…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 71335-2157-01 · Bryant 71335-2160-01 · Bryant →
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.