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venlafaxine 112.5 mg Tablet, Extended Release, 30-count — NDC 52427-0632-30 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

venlafaxine 112.5 mg Tablet, Extended Release, 30-count — NDC 52427-632-30 (Billing 52427-0632-30)

by Almatica Pharma LLC · 30 TABLET, EXTENDED RELEASE in 1 BOTTLE

This is a package of 30 tablets of venlafaxine 112.5 mg Tablet, Extended Release from Almatica Pharma LLC, marketed since Jun 2022 and currently FDA-listed; retail pharmacies pay about $6.23 per tablet (NADAC). It is this product's only package size.

NDC 52427-0632-30
🏷️ FDA NDC (as labeled) 52427-632-30 billing pads the product segment with a zero
Rx only Brand 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

NDC database record

One package, one record: these facts belong to NDC 52427-632-30 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
52427 labeler · 632 product · 30 package
Package marketed since
Aug 1, 2022
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
30 EA per package
Barcode (UPC)
0352427632303
Medicaid fills, this package
2,069 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 52427-632-30
Product NDC 52427-632
11-digit billing NDC 52427063230
NCPDP billing unit EA — each (per item)
RxCUI 2605950
UNII 18XP3YT5NH
UPC 0352427632303
Application # NDA215429
SPL Set ID e81a2daf-b8b2-7c05-b532-bc775700b100
Established class (EPC) Serotonin and Norepinephrine Reuptake Inhibitor
Mechanism of action Norepinephrine Uptake Inhibitors; Serotonin Uptake Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-06-30
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance VENLAFAXINE BESYLATE MONOHYDRATE

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

GPI-14 58180090057520
GCN Seq No 083520
GCN 52506
HICL code 048091
Ingredient (HICL) Venlafaxine Besylate
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H7
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 1)
HIC3 code H7C
Therapeutic class — specific (HIC3) Serotonin-Norepinephrine Reuptake-Inhib (Snris)
AHFS code 28:16.04.16
AHFS class Sel.serotonin,Norepi Reuptake Inhibitor
FDB label name VENLAFAXINE BES ER 112.5 MG TB
FDB brand name Venlafaxine Besylate Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 083520
  • GCN: 52506
  • GPI-14 (Medi-Span): 58180090057520
  • HICL (First Databank): 048091
  • AHFS class code: 28:16.04.16
  • RxCUI (RxNorm): 2605950
Why two NDCs? The FDA registers this code as 52427-632-30 — 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 → 52427-0632-30. 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 Serotonin and Norepinephrine Reuptake Inhibitor class.

Pharmacologic class Serotonin and Norepinephrine Reuptake Inhibitor
Drug family (ATC) Other antidepressants
How it works Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors
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 VENLAFAXINE BES ER 112.5 MG TB Ingredient Venlafaxine Besylate
📖 What it is MedlinePlus · NLM

Venlafaxine is used to treat depression, generalized anxiety disorder (GAD; excessive worrying that is difficult to control), social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life), and panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks). Venlafaxine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental bala...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats major depressive disorder. Depending on the product, it is also used for social anxiety disorder, generalized anxiety disorder and panic disorder. Your pharmacist can con...
  • Take extended-release forms once a day with food, at about the same time each day. Swallow tablets and capsules whole. A capsule can be opened onto applesauce if swallowing is hard...
  • Nausea, sleepiness, dry mouth, sweating, constipation and loss of appetite are common. Some people have sexual side effects. Call your doctor if side effects are severe or don’t ea...
  • Please don’t stop suddenly. Stopping or cutting the dose quickly can cause dizziness, nausea, anxiety, insomnia and electric-shock feelings. Your prescriber will lower the dose gra...
📖 Read our full Venlafaxine guide →
1
Nutrient depletion considerations

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

🧪 Full Venlafaxine 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.

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 eaPer package
Retail pharmacies payNADAC · weekly $6.230 $186.89 / 30 tablets
Medicaid paysCMS SDUD · 12 mo $6.35 $190.50 / 30 tablets
Medicare drug plans payPart D · Q2 2026 $6.37 $191.14 / 30 tablets
NADAC price history (per ea) — tap or hover for the price & month
Dec 2025 Mar 2026 Jun 2026 Sep 2026 $6.230 $6.172
▲ Up 1% over the last 10 months.
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
52427-0632-30 You're viewing this Main listing 30 TABLET, EXTENDED RELEASE in 1 BOTTLE 2022-08-01 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
venlafaxine 112.5 mgthis 52427-0632-30 Almatica 30 tablets $6.230 — Availability likely —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
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

🏛️
2022
First FDA approval
Jun 2022
📍
2026
Currently FDA-listed
4 years listed
🛡️
2028
Latest patent/protection listed
not a guaranteed launch date
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through May 2028. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jun 29, 2022 RLD RS ⏳ ~1.6 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 7776358 — drug product
2022 2024 2026 2028
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (1)
PatentTypeUse codeExpires
US 7776358 ↗ Drug product — May 16, 2028
Common questions
Is there a generic version of VENLAFAXINE BES ER 112.5 MG TB?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for VENLAFAXINE BES ER 112.5 MG TB. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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 White
ShapeRound
ImprintALM;632
Size9 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.

🧪 Avoiding an ingredient? See Venlafaxine inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 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 8GQS4E66YY
    A synthetic polymer made from acrylic compounds. It forms a coating on tablets or capsules to control how and where the medicine releases in the digestive system.
  • 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 92RU3N3Y1O
    Dimethicone is a silicone-based oil that acts as an anti-foaming agent and lubricant in medicines. It reduces gas bubbles in liquid formulations and helps coat and protect the stomach lining when ingested.
  • 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 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 EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • 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 3WJQ0SDW1A
    Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
  • 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.

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

LabelerAlmatica Pharma LLC
Application holderALMATICA PHARMA LLC
FDA applicationNDA215429 (NDA)
Labeler code52427
First marketedJun 2022
Product typeHuman Prescription Drug
Portfolio26 products on file

More NDCs from Almatica Pharma LLC labeler code 52427

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 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 124 words ▾

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and emergence of suicidal thoughts and behaviors [see Warnings and Precautions ( 5.1 )]. Venlafaxine Extended-Release Tablets are not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 )].

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors ( 5.1 ).

Venlafaxine Extended-Release Tablets are not approved for use in pediatric patients ( 8.4 )

🎯 Indications and Usage 55 words ▾

1 INDICATIONS AND USAGE Venlafaxine Extended-Release Tablets are indicated in adults for the treatment of: Major depressive disorder (MDD) Generalized Anxiety Disorder (GAD) Venlafaxine Extended-Release Tablets are a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated in adults for the treatment of: Major Depressive Disorder (MDD) ( 1 ) Generalized Anxiety Disorder (GAD) ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Do not initiate treatment with Venlafaxine Extended-Release Tablets. Use another venlafaxine extended-release product for initial dosage, titration, and dosages below 112.5 mg once daily ( 2.1 ). Take once daily with food.

Swallow tablets whole with fluid. Do not divide, crush, chew, or place in water ( 2.1 ). Venlafaxine Extended-Release Tablets can be initiated at 112.5 mg once daily in patients who have received at least 75 mg of another venlafaxine extended-release product for at least 4 days ( 2.2 , 2.3 ).

Maximum recommended dosage is 225 mg once daily ( 2.2 , 2.3 ). When discontinuing treatment, reduce the dose gradually. Gradual dosage reduction will require the use of another venlafaxine extended-release product ( 2.8 , 5.7 ).

Hepatic and Renal impairment: Maximum recommended dosage of Venlafaxine Extended-Release Tablets is 112.5 mg once daily. Switch to another venlafaxine extended-release product if doses lower than 112.5 mg are needed ( 2.6 , 2.7 ).

2.1Important Dosing and Administration Information Do not initiate venlafaxine treatment, titrate by doses less than 112.5 mg, or taper treatment with Venlafaxine Extended-Release Tablets, as dosing is not possible in these scenarios because Venlafaxine Extended-Release Tablets are only available in a 112.5 mg strength. Use another venlafaxine extended-release product for dosage initiation, titration, administration of dosages below 112.5 mg once daily, and to taper during discontinuation [see Dosage and Administration ( 2.6 , 2.7 , 2.8 )] .

Refer to the Prescribing Information of other venlafaxine extended-release products for the recommended dosage of those products in these dosing scenarios. Venlafaxine Extended-Release Tablets can be initiated in patients who have received at least 75 mg per day of another venlafaxine extended-release product for at least 4 days [see Dosage and Administration ( 2.2 , 2.3 )] . Administer Venlafaxine Extended-Release Tablets as once daily with food, either in the morning or in the evening at approximately the same time each day [see Clinical Pharmacology ( 12.3 )] .

Swallow tablets whole with fluid. Do not divide, crush, chew, or place in water.

2.2Recommended Dosage for the Treatment of Major Depressive Disorder Initiate Venlafaxine Extended-Release Tablets at a dosage of 112.5 mg once daily in patients who have received at least 75 mg per day of another venlafaxine extended-release product for at least 4 days [see Dosage and Administration ( 2.1 )] . Patients not responding to their current venlafaxine dosage may benefit from dose increases to a maximum of 225 mg per day. Increase the dosage in increments of up to 75 mg per day, as needed, using another venlafaxine extended-release product at intervals of 4 days or more.

2.3Recommended Dosage for the Treatment of Generalized Anxiety Disorder Initiate Venlafaxine Extended-Release Tablets at a dosage of 112.5 mg once daily in patients who have received at least 75 mg per day of another venlafaxine extended-release product for at least 4 days [see Dosage and Administration ( 2.1 )] . Patients not responding to their current venlafaxine dosage may benefit from dose increases to a maximum of 225 mg per day. Increase the dosage in increments of up to 75 mg per day, as needed, using another venlafaxine extended-release product at intervals of 4 days or more.

2.4Screen for Bipolar Disorder Prior to Starting Venlafaxine Extended-Release Tablets Prior to initiating treatment with Venlafaxine Extended-Release Tablets, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.6 )] .

2.5Switching Patients from Venlafaxine Tablets (Immediate-Release Formulation) Patients who are currently receiving venlafaxine tablets (immediate-release formulation) may be switched to Venlafaxine Extended-Release Tablets at the nearest equivalent dose (mg per day) if the total daily dosage is either 112.5 mg or 225… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 37 words ▾

3 DOSAGE FORMS AND STRENGTHS Extended-release tablets: 112.5 mg, white, round, biconvex tablet, with “ALM” over “632” printed in black ink on one side, and plain on the other side. Extended-Release tablets: 112.5 mg ( 3 ).

⛔ Contraindications 116 words ▾

4 CONTRAINDICATIONS Venlafaxine Extended-Release Tablets are contraindicated in patients: with known hypersensitivity to venlafaxine besylate, venlafaxine hydrochloride, desvenlafaxine succinate or to any excipients in Venlafaxine Extended-Release Tablets [see Adverse Reactions ( 6.2 )] . taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of increased risk of serotonin syndrome [see Dosage and Administration ( 2.9 ), Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.1 )] .

Hypersensitivity to venlafaxine besylate, venlafaxine hydrochloride, desvenlafaxine succinate, or any excipients in Venlafaxine Extended-Release Tablets ( 4 ). Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI ( 4 , 5.2 , 7.1 ).

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue Venlafaxine Extended-Release Tablets and serotonergic agents and initiate supportive treatment ( 4 , 5.2 , 7.1 ). Elevated Blood Pressure: Control hypertension before initiating treatment.

Monitor blood pressure regularly during treatment ( 5.3 ). Increased Risk of Bleeding: Concomitant use of aspirin, NSAIDs, other antiplatelet drugs, warfarin, and other anticoagulants may increase risk ( 5.4 ). Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.5 ).

Activation of Mania/Hypomania: Screen patients for bipolar disorder ( 2.4 , 5.6 ). Discontinuation Syndrome: Taper dose and monitor for discontinuation symptoms ( 5.7 ). Seizure: Can occur.

Use with caution in patients with seizure disorder ( 5.8 ). Hyponatremia: Can occur in association with SIADH ( 5.9 ). Interstitial Lung Disease and Eosinophilic Pneumonia: Can occur ( 5.12 ).

Sexual Dysfunction: Venlafaxine Extended-Release Tablets may cause symptoms of sexual dysfunction ( 5.13 ).

5.1Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied.

There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric* and Adult Patients *Venlafaxine Extended-Release Tablets are not approved for use in pediatric patients.

Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts and Behaviors per 1,000 Patients Treated Increases Compared to Placebo < 18 years old 14 additional patients 18–24 years old 5 additional patients Decreases Compared to Placebo 25–64 years old 1 fewer patient ≥ 65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing Venlafaxine Extended-Release Tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

5.2Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs), including Venlafaxine Extended-Release Tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Hypersensitivity [see Contraindications ( 4 )] Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Elevated Blood Pressure [see Warnings and Precautions ( 5.3 )] Increased Risk of Bleeding [see Warnings and Precautions ( 5.4 )] Angle-Closure Glaucoma [see Warnings and Precautions ( 5.5 )] Activation of Mania/Hypomania [see Warnings and Precautions ( 5.6 )] Discontinuation Syndrome [see Warnings and Precautions ( 5.7 )] Seizures [see Warnings and Precautions ( 5.8 )] Hyponatremia [see Warnings and Precautions ( 5.9 )] Weight and Height Changes in Pediatric Patients [see Warnings and Precautions ( 5.10 )] Appetite Changes in Pediatric Patients [see Warnings and Precautions ( 5.11 )] Interstitial Lung Disease and Eosinophilic Pneumonia [see Warnings and Precautions ( 5.12 )] Sexual Dysfunction [see Warnings and Precautions ( 5.13 )] Most common adverse reactions (incidence ≥5% and at least twice the rate of placebo): nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, impotence (men), and libido decreased ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact Almatica Pharma LLC at 1-877-447-7979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Studies Experience 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. The safety of Venlafaxine Extended-Release Tablets for the treatment of MDD and GAD is based on adequate and well controlled studies of venlafaxine extended-release capsules. Below is a display of adverse reactions of venlafaxine extended-release capsules from those adequate and well-controlled studies in MDD, GAD, and other indications.

Most Common Adverse Reactions The most commonly observed adverse reactions in the clinical study database in venlafaxine extended-release capsules treated patients in MDD, GAD, and other indications (incidence ≥ 5% and at least twice the rate of placebo) were: nausea (30.0%), somnolence (15.3%), dry mouth (14.8%), sweating (11.4%), abnormal ejaculation (9.9%), anorexia (9.8%), constipation (9.3%), impotence (5.3%) and decreased libido (5.1%). Adverse Reactions Reported as Reasons for Discontinuation of Treatment Combined across short-term, placebo-controlled premarketing studies for MDD, GAD, and other indications, 12% of the 3,558 patients who received venlafaxine extended-release capsules within a dosage range of 37.5 mg to 225 mg discontinued treatment due to an adverse reaction, compared with 4% of the 2,197 placebo-treated patients in those studies [Venlafaxine Extended-Release Tablets are only available as 112.5 mg dosage strength].

The most common adverse reactions leading to discontinuation in ≥ 1% of the venlafaxine extended-release capsules treated patients in the short-term studies (up to 12 weeks) in MDD, GAD, and other indications are shown in Table 7. Table 7: Adverse Reactions Leading to Discontinuation in Venlafaxine Extended-Release Capsule Placebo-controlled Clinical Studies (up to 12 Weeks Duration) Body System Adverse Reaction Venlafaxine Extended-Release Capsules n = 3,558 Placebo n = 2,197 Body as a whole Asthenia 1.7

0.5Headache 1.5

0.8Digestive system Nausea 4.3

0.4Nervous system Dizziness 2.2

0.8Insomnia 2.1

0.6Somnolence 1.7

0.3Skin and appendages 1.5

0.6Sweating 1.0

0.2Common Adverse Reactions in Placebo-controlled Studies Common adverse reactions (those that occurred in ≥ 2% of venlafaxine extended-release capsules treated patients [357 MDD patients, 1,381 GAD patients, and 1,820 patients for other indications] and more frequently than placebo) in venlafaxine extended-re… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Alcohol: Increases the release rate of Venlafaxine Extended-Release Tablets. Avoid concomitant use ( 7.1 ).

7.1Drugs Having Clinically Important Interactions with Venlafaxine Extended-Release Tablets Table 13: Clinically Significant Drug Interactions with Venlafaxine Extended-Release Tablets Monoamine Oxidase Inhibitors (MAOI) Clinical Impact Concomitant use of SNRIs, including Venlafaxine Extended-Release Tablets, with MAOIs increases the risk of serotonin syndrome. Intervention Concomitant use of Venlafaxine Extended-Release Tablets is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.9 ), Contraindications ( 4 ), and Warnings and Precautions ( 5.2 )] .

Other Serotonergic Drugs Clinical Impact Concomitant use of Venlafaxine Extended-Release Tablets with other serotonergic drugs (including other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) increases the risk of serotonin syndrome. Intervention Monitor for symptoms of serotonin syndrome when Venlafaxine Extended-Release Tablets is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems.

If serotonin syndrome occurs, consider discontinuation of Venlafaxine Extended-Release Tablets and/or concomitant serotonergic drugs [see Dosage and Administration ( 2.8 ), Warnings and Precautions ( 5.2 )] . Alcohol Clinical Impact Based on an in vitro study, alcohol increases the release rate of Venlafaxine Extended-Release Tablets [see Clinical Pharmacology ( 12.3 )] . Intervention Avoid concomitant use of alcohol during treatment with Venlafaxine Extended-Release Tablets.

Drugs that Interfere with Hemostasis Clinical Impact Concomitant use of Venlafaxine Extended-Release Tablets with an antiplatelet or anticoagulant drug may potentiate the risk of bleeding. This may be due to the effect of venlafaxine on the release of serotonin by platelets. Intervention Closely monitor patients receiving an antiplatelet or anticoagulant drug for bleeding when Venlafaxine Extended-Release Tablets is initiated or discontinued [see Warnings and Precautions ( 5.4 )] .

CYP3A Inhibitors Clinical Impact Concomitant use of Venlafaxine Extended-Release Tablets with a CYP3A inhibitor increases the C max and AUC of venlafaxine and O-desmethylvenlafaxine (ODV) [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of toxicity of venlafaxine. Intervention Consider reducing the dose of Venlafaxine Extended-Release Tablets. CYP2D6 Substrates Clinical Impact Concomitant use of Venlafaxine Extended-Release Tablets with a CYP2D6 substrate increases C max and AUC of the CYP2D6 substrate, which may increase the risk of toxicity of the CYP2D6 substrate [see Clinical Pharmacology ( 12.3 )] .

Intervention Consider reduction in dose of concomitant CYP2D6 substrates.

7.2Other Drug Interactions with Venlafaxine Extended-Release Tablets Weight Loss Agents The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Coadministration of Venlafaxine Extended-Release Tablets and weight loss agents is not recommended. Venlafaxine Extended-Release Tablets are not indicated for weight loss alone or in combination with other products.

Laboratory Test Interference False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of venlafaxine therapy.

Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish venlafaxine from PCP and amphetamine.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: Third trimester use may increase risk for symptoms of poor neonatal adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate ( 8.1 ).

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including Venlafaxine Extended-Release Tablets, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants. Risk Summary Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.4 ) and Clinical Considerations] .

Available data from published epidemiologic studies on venlafaxine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse fetal outcomes (see Data) . Available data from observational studies with venlafaxine have identified a potential increased risk for preeclampsia when used during mid to late pregnancy; exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage (see Clinical Considerations) . There are risks associated with untreated depression in pregnancy and poor neonatal adaptation in newborns exposure to SNRIs, including Venlafaxine Extended-Release Tablets, during pregnancy (see Clinical Considerations) .

In animal studies, there was no evidence of malformations or fetotoxicity following administration of venlafaxine during organogenesis at doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m 2 basis. Postnatal mortality and decreased pup weights were observed following venlafaxine administration to pregnant rats during gestation and lactation at 2.5 times (mg/m 2 ) the maximum human daily dose. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants.

This finding is from a prospective, longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Exposure to Venlafaxine Extended-Release Tablets in mid to late pregnancy may increase the risk for preeclampsia, and exposure to Venlafaxine Extended-Release Tablets in the month before near delivery may be associated with an increased the risk for of postpartum hemorrhage [see Warnings and Precautions ( 5.4 )] .

Fetal/Neonatal Adverse Reactions Neonates exposed to SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying.

These findings are consistent with either a direct toxic effect of SNRIs or possibly a drug discontinuation syndro… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including Venlafaxine Extended-Release Tablets, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants. Risk Summary Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.4 ) and Clinical Considerations] .

Available data from published epidemiologic studies on venlafaxine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse fetal outcomes (see Data) . Available data from observational studies with venlafaxine have identified a potential increased risk for preeclampsia when used during mid to late pregnancy; exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage (see Clinical Considerations) . There are risks associated with untreated depression in pregnancy and poor neonatal adaptation in newborns exposure to SNRIs, including Venlafaxine Extended-Release Tablets, during pregnancy (see Clinical Considerations) .

In animal studies, there was no evidence of malformations or fetotoxicity following administration of venlafaxine during organogenesis at doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m 2 basis. Postnatal mortality and decreased pup weights were observed following venlafaxine administration to pregnant rats during gestation and lactation at 2.5 times (mg/m 2 ) the maximum human daily dose. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants.

This finding is from a prospective, longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Exposure to Venlafaxine Extended-Release Tablets in mid to late pregnancy may increase the risk for preeclampsia, and exposure to Venlafaxine Extended-Release Tablets in the month before near delivery may be associated with an increased the risk for of postpartum hemorrhage [see Warnings and Precautions ( 5.4 )] .

Fetal/Neonatal Adverse Reactions Neonates exposed to SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying.

These findings are consistent with either a direct toxic effect of SNRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5.2 )] . Monitor neonates who were exposed to Venlafaxine Extended-Release Tablets in the third trimester of p… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use Safety and effectiveness of Venlafaxine Extended-Release Tablets in pediatric patients have not been established. Two placebo-controlled trials in 766 pediatric patients with MDD and two placebo-controlled trials in 793 pediatric patients with GAD have been conducted with venlafaxine extended-release capsules, and the data were not sufficient to support use in pediatric patients. In the studies conducted in pediatric patients ages 6 to 17 years, the occurrence of blood pressure and cholesterol increases was considered to be clinically relevant in pediatric patients and was similar to that observed in adult patients [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 )] .

The following adverse reactions were also observed in pediatric patients: abdominal pain, agitation, dyspepsia, ecchymosis, epistaxis, and myalgia. Although no studies have been designed to primarily assess Venlafaxine Extended-Release Tablet’s impact on the growth, development, and maturation of children and adolescents, the studies that have been done suggest that venlafaxine extended-release capsules may adversely affect weight and height [see Warnings and Precautions ( 5.10 )] . Decreased appetite and weight loss were observed in placebo-controlled studies of pediatric patients 6 to 17 years [see Warnings and Precautions (5.10, 5.11 )] .

In pediatric clinical studies, the adverse reaction, suicidal ideation, was observed. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions ( 5.1 )] .

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use The percentage of patients in clinical studies for venlafaxine extended-release capsules for MDD and GAD who were 65 years of age or older are shown in Table 14. Table 14: Percentage (and Number of Patients Studied) of Patients 65 Years of Age and Older by Indication* Indication Venlafaxine Extended-Release Capsules * In addition, in the premarketing assessment of venlafaxine tablets, 12% (357/2,897) of patients were ≥ 65 years of age. MDD 4 (14/357) GAD 6 (77/1,381) No overall differences in effectiveness or safety were observed between geriatric patients and younger patients, and other reported clinical experience generally has not identified differences in response between the elderly and younger patients.

However, greater sensitivity of some older individuals cannot be ruled out. SSRIs and SNRIs, including Venlafaxine Extended-Release Tablets, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see Warnings and Precautions ( 5.9 )] . The pharmacokinetics of venlafaxine and ODV are not substantially altered in the elderly [see Clinical Pharmacology ( 12.3 )] .

No dose adjustment is recommended for the elderly on the basis of age alone, although other clinical circumstances, some of which may be more common in the elderly, such as renal or hepatic impairment, may warrant a dose reduction [see Dosage and Administration ( 2.6 , 2.7 )] .

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Human Experience During the premarketing evaluations of venlafaxine extended-release capsules and immediate-release venlafaxine tablets (for MDD), there were twenty reports of acute overdosage with immediate-release venlafaxine tablets (6 and 14 reports in venlafaxine extended-release capsules and immediate-release venlafaxine tablets patients, respectively), either alone or in combination with other drugs and/or alcohol. Somnolence was the most commonly reported symptom. Among the other reported symptoms were paresthesia of all four limbs, moderate dizziness, nausea, numb hands and feet, and hot-cold spells 5 days after the overdose.

In most cases, no signs or symptoms were associated with overdose. The majority of the reports involved ingestion in which the total dose of venlafaxine taken was estimated to be no more than several-fold higher than the usual therapeutic dose. One patient who ingested 2.75 g of venlafaxine was observed to have two generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline.

Mild sinus tachycardia was reported in two of the other patients. Actions taken to treat the overdose included no treatment, hospitalization and symptomatic treatment, and hospitalization plus treatment with activated charcoal. All patients recovered.

In postmarketing experience, overdose with venlafaxine has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported.

Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher preexisting burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage, as opposed to some characteristic(s) of venlafaxine-treated patients, is not clear.

Prescriptions for Venlafaxine Extended-Release Tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. Management of Overdosage No specific antidotes for Venlafaxine Extended-Release Tablets are known. In managing overdosage, consider the possibility of multiple drug involvement.

Consider contacting a Poison Center (1-800-222-1222) or a medical toxicologist for overdosage management recommendations for Venlafaxine Extended-Release Tablets.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action of venlafaxine in treatment of MDD and GAD is unclear, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of reuptake of serotonin and norepinephrine.

12.2Pharmacodynamics In-Vitro studies have demonstrated that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent and selective inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant affinity for muscarinic-cholinergic, H 1 -histaminergic, or α 1 -adrenergic receptors in vitro . Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs.

Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity. Cardiac Electrophysiology The effect of venlafaxine on the QT interval was evaluated in a randomized, double-blind, placebo- and positive-controlled three-period crossover thorough QT study in 54 healthy adult subjects. No significant QT prolongation effect of venlafaxine 450 mg (2 times the maximum recommended dosage) was detected.

12.3Pharmacokinetics Following single doses of Venlafaxine Extended-Release Tablets under fed conditions, the dose-normalized geometric mean area under curve (AUC) of venlafaxine and ODV were 93.21% and 93.14%, respectively, and the dose-normalized geometric mean peak concentration (C max ) of venlafaxine and ODV were 93.27% and 106.3%, respectively, compared to those following venlafaxine extended-release capsules under fed conditions. Steady-state plasma concentrations of venlafaxine and ODV are attained within 3 days of oral multiple-dose therapy.

Absorption The absolute bioavailability of venlafaxine extended-release capsule is approximately 45%. Following a 112.5 mg Venlafaxine Extended-Release Tablets under fed conditions, the median time to attain C max (T max ) was 10 hours (range 5-18 hours) for venlafaxine and 18 hours (range 5-28 hours) for ODV. Effect of Food Ingestion of a high-fat meal with Venlafaxine Extended-Release Tablets increases mean AUC of venlafaxine and ODV by 18% and 17%, respectively; increases mean C max of venlafaxine and ODV by 35% and 22%, respectively.

Median T max was altered by food (median T max was 24 hours for both venlafaxine and ODV under fasted conditions). Distribution At therapeutic concentrations, venlafaxine and ODV are minimally bound to plasma proteins (27% and 30%, respectively). Administration of Venlafaxine Extended-Release Tablets to a patient taking another drug that is highly protein-bound should not cause increased free concentrations of the other drug.

Following a single 112.5 mg dose of Venlafaxine Extended-Release Tablets, the mean apparent volume of distribution (V z /F) of venlafaxine is 1375 L. Elimination Following a single 112.5 mg dose of Venlafaxine Extended-Release Tablets, the mean apparent clearance (CL/F) of venlafaxine is 170 L/hour and the mean elimination half-life (t 1/2 ) of venlafaxine and ODV are 6.8 ± 1.6 hours and 11.3 ± 2.3 hours, respectively. Metabolism Following absorption, venlafaxine undergoes extensive pre-systemic metabolism in the liver, primarily to ODV, but also to N-desmethylvenlafaxine, N,O-didesmethylvenlafaxine, and other minor metabolites.

In vitro studies indicate that the formation of ODV is catalyzed by CYP2D6; this has been confirmed in a clinical study showing that poor metabolizers of CYP2D6 had increased levels of venlafaxine and reduced levels of ODV compared to extensive metabolizers (Figure 1). Excretion Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%). Renal elimination of venlafaxine and its metabolite… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 44 words ▾

12.1Mechanism of Action The mechanism of action of venlafaxine in treatment of MDD and GAD is unclear, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of reuptake of serotonin and norepinephrine.

📦 How Supplied / Storage and Handling 68 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Venlafaxine Extended-Release Tablets are suppled as: 112.5 mg, white, round, biconvex tablet, with “ALM” over “632” printed in black ink on one side, and plain on the other side. NDC 52427-632-30 Bottle of 30 tablets Storage and Handling Store at controlled room temperature 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 173 words ▾

11 DESCRIPTION Venlafaxine Extended-Release Tablets contains venlafaxine, an SNRI, present as venlafaxine besylate monohydrate salt. Venlafaxine besylate monohydrate is designated (R/S)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol benzene sulfonate monohydrate or Cyclohexanol, 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-, benzenesulfonate, monohydrate and has the molecular formula of C 23 H 33 NO 5 S⸱H 2 O. Its molecular weight is 453.59.

The structural formula is shown as follows: Venlafaxine besylate is a white to almost white crystalline powder, with a solubility of about 32 mg/ml in water. Its octanol:water partition coefficient is 0.154. Drug release is controlled by a combination of diffusion through the extended-release coating and erosion of the core tablets.

The modified drug release is pH independent. Venlafaxine Extended-Release Tablets are intended for oral administration and contains 183.95 mg of venlafaxine besylate monohydrate equivalent to 112.5 mg of venlafaxine. Inactive ingredients: ammonio methacrylate copolymer, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, silicon dioxide, simethicone, talc, titanium dioxide, and triacetin.

The tablet printing ink is composed of ammonium hydroxide, black iron oxide, n-butyl alcohol, isopropyl alcohol, propylene glycol, and shellac.

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients, and caregivers to look for the emergence of suicidality especially early during treatment and when the dose is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [see Boxed Warning and Warnings and Precautions ( 5.1 )] . Concomitant Medication Instruct patients not to take Venlafaxine Extended-Release Tablets with an MAOI or within 14 days of stopping an MAOI [see Contraindications ( 4 )] .

Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of Venlafaxine Extended-Release Tablets with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, amphetamines, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.1 )] .

Elevated Blood Pressure Advise patients that they should have regular monitoring of blood pressure when taking Venlafaxine Extended-Release Tablets [see Warnings and Precautions ( 5.3 )] . Increased Risk of Bleeding Inform patients about the concomitant use of Venlafaxine Extended-Release Tablets with NSAIDs, aspirin, other antiplatelet drugs, warfarin, or other drugs that affect coagulation because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the-counter medications that increase the risk of bleeding [see Warnings and Precautions ( 5.4 )] .

Activation of Mania/Hypomania Advise patients, their families and caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions ( 5.6 )] . Discontinuation Syndrome Advise patients not to abruptly stop taking Venlafaxine Extended-Release Tablets without talking first with their healthcare provider. Patients should be aware that discontinuation effects may occur when stopping Venlafaxine Extended-Release Tablets and they should monitor for discontinuation symptoms [see Warnings and Precautions ( 5.7 ) and Adverse Reactions ( 6.1 )] .

Sexual Dysfunction Advise patients that use of Venlafaxine Extended-Release Tablets may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions ( 5.13 )] . Cardiovascular/Cerebrovascular Disease Caution is advised in administering Venlafaxine Extended-Release Tablets to patients with cardiovascular, cerebrovascular, or lipid metabolism disorders [see Adverse Reactions ( 6.1 )] .

Serum Cholesterol and Triglyceride Elevation Advise patients that elevations in total cholesterol, LDL and triglycerides may occur and that measurement of serum lipids may be considered [see Warnings and Precautions ( 6.1 )] . Interference with Cognitive and Motor Performance Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that Venlafaxine Extended-Release Tablets therapy does not adversely affect their ability to engage in such activities. Alcohol Advise patients to avoid alcohol while taking Venlafaxine Extended-Release Tablets [see Drug Interactions ( 7.1 )] .

Allergic Reactions Advise patients to notify their healthcare provider if they develop allergic phenomena such as rash, hives, swelling, or difficulty breathing [see Contraindications ( 4 )… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. MEDICATION GUIDE Venlafaxine Extended-Release Tablets (ven'' la fax' een) for oral use What is the most important information I should know about Venlafaxine Extended-Release Tablets?

Venlafaxine Extended-Release Tablets may cause serious side effects, including: Increased risk of suicidal thoughts and actions. Venlafaxine Extended-Release Tablets and other antidepressant medicines may increase suicidal thoughts and actions in some children, adolescents, and young adults, especially within the first few months of treatment or when the dose is changed. Venlafaxine Extended-Release Tablets is not for use in children.

Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member? Pay close attention to any changes, especially sudden changes, in mood, behavior, actions, thoughts, or feelings.

This is very important when an antidepressant medicine is started or when the dose is changed. Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider or get emergency help right away if you or a family member have any of the following symptoms, especially if they are new, worse, or worry you: attempts to commit suicide acting aggressive, being angry, or violent new or worse depression panic attacks new or worse irritability an extreme increase in activity or talking (mania) thoughts about suicide or dying acting on dangerous impulses new or worse anxiety feeling very agitated or restless trouble sleeping other unusual changes in behavior or mood What is Venlafaxine Extended-Release Tablets?

Venlafaxine Extended-Release Tablets is a prescription medicine used to treat adults with: a certain type of depression called Major Depressive Disorder (MDD) Generalized Anxiety Disorder (GAD) It is not known if Venlafaxine Extended-Release Tablets is safe and effective for use in children. Do not take Venlafaxine Extended-Release Tablets if you: are allergic to venlafaxine besylate, venlafaxine hydrochloride, desvenlafaxine succinate, or any of the ingredients in Venlafaxine Extended-Release Tablets. See the end of this Medication Guide for a complete list of ingredients in Venlafaxine Extended-Release Tablets. take a Monoamine Oxidase Inhibitor (MAOI) have stopped taking an MAOI in the last 14 days are being treated with the antibiotic linezolid or intravenous methylene blue Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including MAOIs such as linezolid or intravenous methylene blue.

Do not start taking an MAOI for at least 7 days after you stop treatment with Venlafaxine Extended-Release Tablets. Before taking Venlafaxine Extended-Release Tablets tell your healthcare provider about all your medical conditions, including if you : have, or have a family history of suicide, bipolar disorder, depression, mania or hypomania have high blood pressure have heart problems have cerebrovascular problems or had a stroke have or have had bleeding problems have high pressure in the eye (glaucoma) have high cholesterol or high triglycerides have kidney or liver problems have or have had seizures or convulsions have low sodium levels in your blood have lung problems drink alcohol are pregnant or plan to become pregnant.

Venlafaxine Extended-Release Tablets may harm your unborn baby. Talk to your healthcare provider about the risk to you and your unborn baby if you take Venlafaxine Extended-Release Tablets during pregnancy. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with Venlafaxine Exten… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Following single doses of Venlafaxine Extended-Release Tablets under fed conditions, the dose-normalized geometric mean area under curve (AUC) of venlafaxine and ODV were 93.21% and 93.14%, respectively, and the dose-normalized geometric mean peak concentration (C max ) of venlafaxine and ODV were 93.27% and 106.3%, respectively, compared to those following venlafaxine extended-release capsules under fed conditions. Steady-state plasma concentrations of venlafaxine and ODV are attained within 3 days of oral multiple-dose therapy.

Absorption The absolute bioavailability of venlafaxine extended-release capsule is approximately 45%. Following a 112.5 mg Venlafaxine Extended-Release Tablets under fed conditions, the median time to attain C max (T max ) was 10 hours (range 5-18 hours) for venlafaxine and 18 hours (range 5-28 hours) for ODV. Effect of Food Ingestion of a high-fat meal with Venlafaxine Extended-Release Tablets increases mean AUC of venlafaxine and ODV by 18% and 17%, respectively; increases mean C max of venlafaxine and ODV by 35% and 22%, respectively.

Median T max was altered by food (median T max was 24 hours for both venlafaxine and ODV under fasted conditions). Distribution At therapeutic concentrations, venlafaxine and ODV are minimally bound to plasma proteins (27% and 30%, respectively). Administration of Venlafaxine Extended-Release Tablets to a patient taking another drug that is highly protein-bound should not cause increased free concentrations of the other drug.

Following a single 112.5 mg dose of Venlafaxine Extended-Release Tablets, the mean apparent volume of distribution (V z /F) of venlafaxine is 1375 L. Elimination Following a single 112.5 mg dose of Venlafaxine Extended-Release Tablets, the mean apparent clearance (CL/F) of venlafaxine is 170 L/hour and the mean elimination half-life (t 1/2 ) of venlafaxine and ODV are 6.8 ± 1.6 hours and 11.3 ± 2.3 hours, respectively. Metabolism Following absorption, venlafaxine undergoes extensive pre-systemic metabolism in the liver, primarily to ODV, but also to N-desmethylvenlafaxine, N,O-didesmethylvenlafaxine, and other minor metabolites.

In vitro studies indicate that the formation of ODV is catalyzed by CYP2D6; this has been confirmed in a clinical study showing that poor metabolizers of CYP2D6 had increased levels of venlafaxine and reduced levels of ODV compared to extensive metabolizers (Figure 1). Excretion Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%). Renal elimination of venlafaxine and its metabolites is the primary route of excretion.

Specific Population A population pharmacokinetic analysis of patients from two studies receiving immediate-release venlafaxine tablets involving both twice daily and three times daily regimens showed that dose-normalized trough plasma levels of either venlafaxine or ODV were unaltered by age or gender differences. Exposures of venlafaxine and ODV in specific populations are summarized in Figure 1. Figure 1: Pharmacokinetics of Venlafaxine and Active Metabolite O-Desmethylvenlafaxine (ODV) in Special Populations.

Abbreviations: ODV, O-desmethylvenlafaxine; AUC, area under the curve; Cmax, peak plasma concentrations; *Similar effect is expected with strong CYP2D6 inhibitors Drug Interaction Studies Effects of other drugs on the exposure of venlafaxine and ODV are summarized in Figure 2. Figure 2: Effect of Interacting Drugs on the Pharmacokinetics of Venlafaxine and Active Metabolite O-desmethylvenlafaxine (ODV). Abbreviations: ODV, O-desmethylvenlafaxine; AUC, area under the curve; Cmax, peak plasma concentrations; EM's, extensive metabolizers; PM's, poor metabolizers * No dose adjustment on co-administration with CYP2D6 inhibitors.

Effects of venlafaxine on the exposure of other drugs are summarized in Figure 3. Figure 3: Effect of Venlafaxi… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 131 words ▾

12.2Pharmacodynamics In-Vitro studies have demonstrated that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent and selective inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant affinity for muscarinic-cholinergic, H 1 -histaminergic, or α 1 -adrenergic receptors in vitro . Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs.

Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity. Cardiac Electrophysiology The effect of venlafaxine on the QT interval was evaluated in a randomized, double-blind, placebo- and positive-controlled three-period crossover thorough QT study in 54 healthy adult subjects. No significant QT prolongation effect of venlafaxine 450 mg (2 times the maximum recommended dosage) was detected.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Major Depressive Disorder The efficacy of Venlafaxine Extended-Release Tablets for the treatment of major depressive disorder (MDD) in adult patients is based upon adequate and well-controlled studies of venlafaxine extended-release capsules. The results of these adequate and well-controlled studies of venlafaxine extended-release capsules are presented below. The efficacy of venlafaxine extended-release capsules as a treatment for Major Depressive Disorder (MDD) was established in two placebo-controlled, short-term (8 weeks for study 1; 12 weeks for study 2), flexible-dose studies, with doses starting at 75 mg per day and ranging to 225 mg per day in adult outpatients meeting DSM-III-R or DSM-IV criteria for MDD [Venlafaxine Extended-Release Tablets are only available in 112.5 mg dosage strength].

In moderately depressed outpatients, the initial dose of venlafaxine was 75 mg per day. In both studies, venlafaxine extended-release capsules demonstrated superiority over placebo on the primary efficacy measure defined as change from baseline in the HAM-D-21 total score to the endpoint visit. Venlafaxine extended-release capsules also demonstrated superiority over placebo on the key secondary efficacy endpoint, the Clinical Global Impressions (CGI) Severity of Illness scale.

Examination of gender subsets of the population studied did not reveal any differential responsiveness on the basis of gender. In a longer-term study, adult outpatients with MDD who had responded during an 8-week open-label study on venlafaxine extended-release capsules 75 mg, 150 mg, or 225 mg, once daily every morning were randomized to continuation of their same venlafaxine extended-release capsules dose or to placebo, for up to 26 weeks of observation for relapse. Response during the open-label phase was defined as a CGI Severity of Illness item score of ≤3 and a HAM-D-21 total score of ≤10 at the day 56 evaluation.

Relapse during the double-blind phase was defined as follows: (1) a reappearance of major depressive disorder as defined by DSM-IV criteria and a CGI Severity of Illness item score of ≥4 (moderately ill), (2) 2 consecutive CGI Severity of Illness item scores of ≥4, or (3) a final CGI Severity of Illness item score of ≥4 for any patient who withdrew from the study for any reason. Patients receiving continued venlafaxine extended-release capsules treatment experienced statistically significantly lower relapse rates over the subsequent 26 weeks compared with those receiving placebo.

Table 15: Primary Efficacy Results for Studies in Major Depressive Disorder in Adults (Studies 1 and 2) Study number Treatment Group Primary Efficacy Measure: HAM-D Score Mean Baseline Score (SD) LS Mean Change from Baseline Placebo Subtracted Difference b (95%CI) SD: standard deviation; LS Mean: least-squares mean; CI: confidence interval. a Venlafaxine Extended-Release Tablets are only available as 112.5 mg dosage strength. b Difference (drug minus placebo) in least-squares mean change from baseline. * Doses statistically significantly superior to placebo.

Study 1 Venlafaxine extended-release capsules (75 mg a , 150 mg a , 225 mg per day)* 24.5 -11.7 -4.45 (-6.66,-2.25) Placebo 23.6 -7.24 - Study 2 Venlafaxine extended-release capsules (75 mg a , 150 mg a , 225 mg per day)* 24.5 -15.11 -6.40 (-8.45,-4.34) Placebo 24.9 -8.71

14.2Generalized Anxiety Disorder The efficacy of Venlafaxine Extended-Release Tablets for the treatment of Generalized Anxiety Disorder (GAD) in adult patients is based upon adequate and well-controlled studies of venlafaxine extended-release capsules. The results of these adequate and well-controlled studies of venlafaxine extended-release capsules are presented below. The efficacy of venlafaxine extended-release capsules as a treatment for Generalized Anxiety Disorder (GAD) was established in two 8-week, placebo-controlled, fixed-dose studies of 75 mg to 225 mg per day, one 6-month, placebo-controlled, flexible-dose stu… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence ~1 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Venlafaxine Extended-Release Tablets contains venlafaxine which is not a controlled substance.

9.2Abuse Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. While venlafaxine has not been systematically studied in clinical studies for its potential for abuse, there was no indication of drug-seeking behavior in the clinical studies. However, it is not possible to predict on the basis of premarketing experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed.

Consequently, providers should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of venlafaxine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

9.3Dependence Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. In vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine, phencyclidine (PCP), or N-methyl-D-aspartic acid (NMDA) receptors. Venlafaxine was not found to have any significant CNS stimulant activity in rodents.

In primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability. Discontinuation effects have been reported in patients receiving venlafaxine [see Dosage and Administration ( 2.8 ) and Warnings and Precautions ( 5.7 )] .

🔒 Controlled Substance 14 words ▾

9.1Controlled Substance Venlafaxine Extended-Release Tablets contains venlafaxine which is not a controlled substance.

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Tumors were not increased by venlafaxine treatment in mice or rats. Venlafaxine was given by oral gavage to mice for 18 months at doses up to 120 mg/kg per day, which was 1.7 times the maximum recommended human dose on a mg/m 2 basis. Venlafaxine was also given to rats by oral gavage for 24 months at doses up to 120 mg/kg per day.

In rats receiving the 120 mg/kg dose, plasma concentrations of venlafaxine at necropsy were 1 times (male rats) and 6 times (female rats) the plasma concentrations of patients receiving the maximum recommended human dose. Plasma levels of the ODV were lower in rats than in patients receiving the maximum recommended dose. ODV, the major human metabolite of venlafaxine, administered by oral gavage to mice and rats for 2 years did not increase the incidence of tumors in either study.

Mice received ODV at dosages up to 500/300 mg/kg/day (dosage lowered after 45 weeks of dosing). The exposure at the 300 mg/kg/day dose is 9 times that of a human dose of 225 mg/day. Rats received ODV at dosages up to 300 mg/kg/day (males) or 500 mg/kg/day (females).

The exposure at the highest dose is approximately 8 (males) or 11 (females) times that of a human dose of 225 mg/day. Mutagenesis Venlafaxine and the major human metabolite, ODV, were not mutagenic in the Ames reverse mutation assay in Salmonella bacteria or the Chinese hamster ovary/HGPRT mammalian cell forward gene mutation assay. Venlafaxine was also not mutagenic or clastogenic in the in vitro BALB/c-3T3 mouse cell transformation assay, the sister chromatid exchange assay in cultured Chinese hamster ovary cells, or in the in vivo chromosomal aberration assay in rat bone marrow.

ODV was not clastogenic in the in vitro Chinese hamster ovary cell chromosomal aberration assay or in the in vivo chromosomal aberration assay in rats. Impairment of Fertility Reproduction and fertility studies of venlafaxine in rats showed no adverse effects of venlafaxine on male or female fertility at oral doses of up to 2 times the maximum recommended human dose of 225 mg/day on a mg/m 2 basis. However, when desvenlafaxine succinate, the major human metabolite of venlafaxine, was administered orally to male and female rats, fertility was reduced at the high dose of 300 mg/kg/day, which is 10 (males) and 19 (females) times the AUC exposure at an adult human dose of 100 mg per day.

There was no effect on fertility at 100 mg/kg/day, which is 3 (males) or 5 (females) times the AUC exposure at an adult human dose of 100 mg per day. These studies did not address reversibility of the effect on fertility. The relevance of these findings to humans is not known.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Tumors were not increased by venlafaxine treatment in mice or rats. Venlafaxine was given by oral gavage to mice for 18 months at doses up to 120 mg/kg per day, which was 1.7 times the maximum recommended human dose on a mg/m 2 basis. Venlafaxine was also given to rats by oral gavage for 24 months at doses up to 120 mg/kg per day.

In rats receiving the 120 mg/kg dose, plasma concentrations of venlafaxine at necropsy were 1 times (male rats) and 6 times (female rats) the plasma concentrations of patients receiving the maximum recommended human dose. Plasma levels of the ODV were lower in rats than in patients receiving the maximum recommended dose. ODV, the major human metabolite of venlafaxine, administered by oral gavage to mice and rats for 2 years did not increase the incidence of tumors in either study.

Mice received ODV at dosages up to 500/300 mg/kg/day (dosage lowered after 45 weeks of dosing). The exposure at the 300 mg/kg/day dose is 9 times that of a human dose of 225 mg/day. Rats received ODV at dosages up to 300 mg/kg/day (males) or 500 mg/kg/day (females).

The exposure at the highest dose is approximately 8 (males) or 11 (females) times that of a human dose of 225 mg/day. Mutagenesis Venlafaxine and the major human metabolite, ODV, were not mutagenic in the Ames reverse mutation assay in Salmonella bacteria or the Chinese hamster ovary/HGPRT mammalian cell forward gene mutation assay. Venlafaxine was also not mutagenic or clastogenic in the in vitro BALB/c-3T3 mouse cell transformation assay, the sister chromatid exchange assay in cultured Chinese hamster ovary cells, or in the in vivo chromosomal aberration assay in rat bone marrow.

ODV was not clastogenic in the in vitro Chinese hamster ovary cell chromosomal aberration assay or in the in vivo chromosomal aberration assay in rats. Impairment of Fertility Reproduction and fertility studies of venlafaxine in rats showed no adverse effects of venlafaxine on male or female fertility at oral doses of up to 2 times the maximum recommended human dose of 225 mg/day on a mg/m 2 basis. However, when desvenlafaxine succinate, the major human metabolite of venlafaxine, was administered orally to male and female rats, fertility was reduced at the high dose of 300 mg/kg/day, which is 10 (males) and 19 (females) times the AUC exposure at an adult human dose of 100 mg per day.

There was no effect on fertility at 100 mg/kg/day, which is 3 (males) or 5 (females) times the AUC exposure at an adult human dose of 100 mg per day. These studies did not address reversibility of the effect on fertility. The relevance of these findings to humans is not known.

📄 Recent Major Changes 9 words ▾

Warnings and Precautions ( 5.2 , 5.4 ) 8/2023

📄 Package Label / Principal Display Panel 28 words ▾

PACKAGE LABEL PRINCIPAL DISPLAY PANEL SECTION NDC 52427- 632 -30 Venlafaxine Extended-Release Tablets 112.5 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 30 Tablets

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
2.1K
Units reimbursed last 4 qtrs
80.1K
Gross reimbursed last 4 qtrs
$508.5K
Avg / prescription
$245.76
Avg / unit
$6.3501
Latest quarter Q1 2026
498Rx
Medicaid pays / ea
$6.3501
gross reimbursed
vs
NADAC / ea
$6.2298
acquisition cost
=
Spread
+$0.1203
+2% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
60% FFS 40% MCO
Fee-for-service · 1,237 Rx Managed care · 832 Rx
State Medicaid map
Alaska: no data reported AK Maine: 5,255 units · 377 per 100k residents ME Washington: no data reported WA Idaho: no data reported ID Montana: 2,100 units · 186 per 100k residents MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 8,117 units · 80.9 per 100k residents MI New York: 14,075 units · 71.9 per 100k residents NY Vermont: 2,806 units · 434 per 100k residents VT New Hampshire: no data reported NH Oregon: 7,325 units · 173 per 100k residents OR Nevada: 990 units · 31.0 per 100k residents NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: 1,440 units · 44.9 per 100k residents IA Illinois: 11,614 units · 92.5 per 100k residents IL Indiana: 5,850 units · 85.3 per 100k residents IN Ohio: 4,048 units · 34.3 per 100k residents OH Pennsylvania: 310 units · 2.4 per 100k residents PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 4,710 units · 12.1 per 100k residents CA Utah: 2,100 units · 61.5 per 100k residents UT Colorado: 776 units · 13.2 per 100k residents CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: 3,250 units · 71.8 per 100k residents KY West Virginia: no data reported WV Virginia: 1,230 units · 14.1 per 100k residents VA Maryland: 764 units · 12.4 per 100k residents MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 2,955 units · 27.3 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 359 units · 1.2 per 100k residents TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.2434
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Vermont 434 /100k
2 Maine 377 /100k
3 Montana 186 /100k
4 Oregon 173 /100k
5 Illinois 92.5 /100k
6 Indiana 85.3 /100k
7 Michigan 80.9 /100k
8 New York 71.9 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.
← 52427-0437-90 · Almatica 52427-0658-30 · Almatica →
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.