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Effexor XR VENLAFAXINE HYDROCHLORIDE 150 mg Capsule, Extended Release, 30-count — NDC 0008-0836-21 (Billing 00008-0836-21)

by Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc. · 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

This is a package of 30 capsules of Effexor XR VENLAFAXINE HYDROCHLORIDE 150 mg Capsule, Extended Release from Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., no longer marketed (first marketed Nov 1997), no longer in the FDA NDC Directory, this package's marketing ended Jun 2026; retail pharmacies pay about $21.63 per capsule (NADAC). It is the main listing for this product, which comes in 2 package sizes.

NDC 00008-0836-21
🏷️ FDA NDC (as labeled) 0008-0836-21 billing pads the labeler segment with a zero
This package
Contains30-count Cost per ea$21.63 NADAC Per package$648.76 / 30 capsules Pack sizes2 compare ↓
Also priced by: Medicaid pays $18.86/unit — full pricing hub ↓
Main listing for product 0008-0836 · Also comes in: 90 capsules 0008-0836-22
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 2, 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 0008-0836-21 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
0008 labeler · 0836 product · 21 package
Package marketed since
Nov 1, 1997
Package marketing ended
Jun 30, 2026
Sample package
No — commercial package
Billing quantity
30 EA per package
Barcode (UPC-A, from the NDC)
3 0008083621 7
Medicaid fills, this package
383 prescriptions in the last four reported quarters
FDA record last changed
Jul 2, 2026
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Jun 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0008-0836-21
Product NDC 0008-0836
11-digit billing NDC 00008083621
NCPDP billing unit EA — each (per item)
RxCUI 313581, 313583, 313585, 729929, 729931, 729932
UNII 7D7RX5A8MO
Application # NDA020699
SPL Set ID 53c3e7ac-1852-4d70-d2b6-4fca819acf26
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 Discontinued
FDA listing status Discontinued by firm (certified through Jun 2026)
Marketing start 1997-11-01
Marketing end 2026-06-30
Route ORAL
Dosage form CAPSULE, EXTENDED RELEASE
Substance VENLAFAXINE HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS

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

GPI-14 58180090107050
GPI class Effexor XR
GCN Seq No 046405
GCN 16818
HICL code 008847
Ingredient (HICL) Venlafaxine Hcl
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 EFFEXOR XR 150 MG CAPSULE
FDB brand name Effexor Xr
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 046405
  • GCN: 16818
  • GPI-14 (Medi-Span): 58180090107050
  • HICL (First Databank): 008847
  • AHFS class code: 28:16.04.16
  • RxCUI (RxNorm): 313581
Why two NDCs? The FDA registers this code as 0008-0836-21 — a 4-4-2 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 labeler segment → 00008-0836-21. 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 EFFEXOR XR 150 MG CAPSULE Ingredient Venlafaxine Hcl
📖 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 →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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 $21.625 $648.76 / 30 capsules
Medicaid paysCMS SDUD · 12 mo $18.86 $565.79 / 30 capsules
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
NADAC price history (per ea) — tap or hover for the price & month
Oct 2021 Oct 2023 May 2026 Aug 2026 $21.625 $16.990
▲ Up 27% over the last 9 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 Per unit Per pack Marketing startMarketing endStatus
00008-0836-21 You're viewing this Main listing 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE $21.63 / ea $648.76 1997-11-01 Jun 30, 2026 Discontinued by firm
00008-0836-22 0008-0836-22 90 CAPSULE, EXTENDED RELEASE in 1 BOTTLE $20.01 / ea $1,801.07 1997-11-01 — Discontinued by firm

You're viewing the smallest of 2 pack sizes for this product.

Per ea, this pack runs about 8% above the cheapest pack (90-count, $20.01 vs $21.63 NADAC).

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 30-count package — 30 capsule, extended release in 1 bottle.
How does this package differ from NDC 00008-0836-22?
Both are Effexor XR VENLAFAXINE HYDROCHLORIDE 150 mg Capsule, Extended Release — the drug itself is identical. This page's package is the 30-count one, while NDC 00008-0836-22 is the 90 capsules package. Per-ea NADAC also differs: $21.63 here vs $20.01 for the 90 capsules pack.
What NDC number is used to bill for this package of Effexor XR VENLAFAXINE HYDROCHLORIDE 150 mg Capsule, Extended Release?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Venlafaxine Hydrochloride 150 mg 00093-7386-05 Teva 500 capsules $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 00904-7489-61 Major 1 capsule $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 42806-0603-05 Epic 500 capsules $0.119 AB Availability likely save 99%
venlafaxine hydrochloride 150 mg 43598-0002-05 Dr.Reddys 500 capsules $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 50268-0875-15 AvPAK 1 capsule $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 65862-0697-01 Aurobindo 100 capsules $0.119 — Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 68084-0713-01 American 1 capsule $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 70010-0186-03 Granules 30 capsules $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 70710-1700-00 Zydus 1000 capsules $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 72603-0749-01 NorthStar 90 capsules $0.119 AB Availability likely save 99%
Venlafaxine Hydrochloride 150 mg 82009-0058-05 QUALLENT 500 capsules $0.119 AB Availability likely save 99%
Venlafaxine hydrochloride 150 mg 33342-0196-07 Macleods 30 capsules $0.139 AB FDA listed save 99%
Effexor XR 150 mg 58151-0127-77 Viatris 90 capsules $21.622 AB Availability likely +0%
Effexor XR 150 mgthis 00008-0836-21 Wyeth 30 capsules $21.625 AB Discontinued —
Venlafaxine Hydrochloride 150 mg 00615-8510-39 NCS 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 10135-0827-10 Marlex 1000 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 31722-0004-01 Camber 10 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 42291-0899-30 AvKARE 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 46708-0794-30 Alembic 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 50090-2519-00 A-S 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 50090-5890-00 A-S 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 50090-6896-00 A-S 90 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 50090-7323-00 A-S 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 50090-7324-00 A-S 90 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 50090-7942-00 A-S 30 capsules — AB FDA listed —
venlafaxine hydrochloride 150 mg 55111-0455-01 Dr.Reddy's 100 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 62332-0794-30 Alembic 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 63187-0420-30 Proficient 30 capsules — AB FDA listed —
venlafaxine hydrochloride 150 mg 65841-0753-06 Zydus 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 67046-1656-03 Coupler 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 68071-3727-09 NuCare 90 capsules — AB FDA listed —
venlafaxine hydrochloride 150 mg 68071-4442-09 NuCare 90 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 68071-5020-09 NuCare 90 capsules — AB FDA listed —
venlafaxine hydrochloride 150 mg 68382-0036-06 Zydus 30 capsules — AB FDA listed —
venlafaxine hydrochloride 150 mg 68788-6806-01 Preferred 100 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 68788-8072-03 Preferred 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 68788-8752-03 Preferred 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 68788-8774-01 Preferred 100 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 70518-2259-00 REMEDYREPACK 90 capsules — AB Discontinued —
Venlafaxine Hydrochloride 150 mg 70518-4154-00 REMEDYREPACK 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 70771-1838-00 Zydus 1000 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 71335-1642-01 Bryant 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 71335-1812-01 Bryant 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 71335-2495-01 Bryant 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 71335-2992-01 Bryant 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 71785-1008-00 Annora 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 72888-0181-30 Advagen 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 76420-0632-01 Asclemed 100 capsules — AB FDA listed —
Venlafaxine HCL ER 150 mg 80425-0194-02 Advanced 60 capsules — AB FDA listed —
Venlafaxine hydrochloride ER 150 mg 80425-0297-01 Advanced 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 82804-0038-30 Proficient 30 capsules — AB FDA listed —
Venlafaxine Hydrochloride 150 mg 24658-0127-05 PURACAP 500 capsules — AB FDA listed —
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

🏛️
1997
On the market since
Nov 1997
📍
2026
Currently FDA-listed
29 years listed
🔓
·
Generic versions listed
see equivalents
✅Generic appears available

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

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.

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.

We could not link this NDC to a current FDA Structured Product Label. An inactive-ingredient list is therefore not available from this source.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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

LabelerWyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
Application holderUPJOHN US 2 LLC
FDA applicationNDA020699 (NDA)
Labeler code00008
First marketedNov 1997
Product typeHuman Prescription Drug
Portfolio31 products on file

More NDCs from Wyeth Pharmaceuticals LLC, a subsidiary of Pfize... labeler code 00008

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 📦 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 122 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) ]. Effexor XR is 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 thoughts and behavior in pediatric patients and young adults taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors ( 5.1 ). • Effexor XR is not approved for use in pediatric patients ( 8.4 ).

🎯 Indications and Usage 101 words ▾

1 INDICATIONS AND USAGE Effexor XR is indicated in adults for the treatment of: • Major Depressive Disorder (MDD) [see Clinical Studies (14.1) ] • Generalized Anxiety Disorder (GAD) [see Clinical Studies (14.2) ] • Social Anxiety Disorder (SAD) [see Clinical Studies (14.3) ] • Panic Disorder (PD) [see Clinical Studies (14.4) ] Effexor XR is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of adults with: • Major Depressive Disorder (MDD) ( 1 ) • Generalized Anxiety Disorder (GAD) ( 1 ) • Social Anxiety Disorder (SAD) ( 1 ) • Panic Disorder (PD) ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Indication Starting Dose Target Dose Maximum Dose MDD ( 2.2 ) 37.5 –75 mg/day 75 mg/day 225 mg/day GAD ( 2.3 ) 37.5 –75 mg/day 75 mg/day 225 mg/day SAD ( 2.4 ) 75 mg/day 75 mg/day 75 mg/day PD ( 2.5 ) 37.5 mg/day 75 mg/day 225 mg/day • Take once daily with food. Capsules should be taken whole; do not divide, crush, chew, or dissolve ( 2.1 ). • When discontinuing treatment, reduce the dose gradually ( 2.10 , 5.7 ). • Renal impairment: reduce the total daily dose by 25% to 50% in patients with renal impairment.

Reduce the total daily dose by 50% or more in patients undergoing dialysis or with severe renal impairment ( 2.9 ). • Hepatic impairment: reduce the daily dose by 50% in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment or hepatic cirrhosis, it may be necessary to reduce the dose by more than 50% ( 2.8 ).

2.1General Administration Information Administer Effexor XR as a single dose with food, either in the morning or in the evening at approximately the same time each day [see Clinical Pharmacology (12.3) ] . Swallow capsules whole with fluid. Do not divide, crush, chew, or place in water.

The capsule may also be administered by carefully opening the capsule and sprinkling the entire contents on a spoonful of applesauce. This drug/food mixture should be swallowed immediately without chewing and followed with a glass of water to ensure complete swallowing of the pellets (spheroids).

2.2Major Depressive Disorder For most patients, the recommended starting dose for Effexor XR is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day.

Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 4 days. In the clinical studies establishing efficacy, upward titration was permitted at intervals of 2 weeks or more.

2.3Generalized Anxiety Disorder For most patients, the recommended starting dose for Effexor XR is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day.

Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 4 days.

2.4Social Anxiety Disorder (Social Phobia) The recommended dose is 75 mg per day, administered in a single dose. There was no evidence that higher doses confer any additional benefit.

2.5Panic Disorder The recommended starting dose is 37.5 mg per day of Effexor XR for 7 days. Patients not responding to 75 mg per day may benefit from dose increases to a maximum of approximately 225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 7 days.

2.6Screen for Bipolar Disorder Prior to Starting Effexor XR Prior to initiating treatment with Effexor XR, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6) ].

2.7Switching Patients from Effexor Tablets Patients with depression who are currently being treated with Effexor may be switched to Effexor XR at the nearest equivalent dose (mg per day), e.g., 37.5 mg venlafaxine twice a day to 75 mg Effexor XR once daily. However, individual dosage adjustments may be necessary.

2.8Dosage Recommendations for Patients with Hepatic Impairment Reduce the Effexor XR total daily dose by 50% in patients with mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 96 words ▾

3 DOSAGE FORMS AND STRENGTHS Effexor XR ® is available in the following strengths: • 37.5 mg extended-release capsule: grey cap and peach body with "W" and "Effexor XR" on the cap and "37.5" on the body • 75 mg extended-release capsule: peach cap and body with "W" and "Effexor XR" on the cap and "75" on the body • 150 mg extended-release capsule: dark orange cap and body with "W" and "Effexor XR" on the cap and "150" on the body • Ÿ Extended-release capsules: 37.5 mg, 75 mg, and 150 mg ( 3 ).

⛔ Contraindications 111 words ▾

4 CONTRAINDICATIONS Effexor XR is contraindicated in patients: • with known hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate or to any excipients in the formulation [see Adverse Reactions (6.2) ] . • taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of the risk of serotonin syndrome [see Dosage and Administration (2.11) , Warnings and Precautions (5.2) , and Drug Interactions (7.1) ] . • ŸHypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate, or any excipients in the Effexor XR formulation ( 4 ). • Concomitant use of monoaminoxidase 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 • Ÿ Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also when taken alone. If it occurs, discontinue Effexor XR and initiate supportive treatment ( 4 , 5.2 , 7.1 ). • Ÿ 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 or Hypomania : Screen patients for bipolar disorder ( 5.6 ). • Ÿ Discontinuation Syndrome : Taper dose and monitor for discontinuation symptoms ( 5.7 ). • Ÿ Seizures : Can occur.

Use cautiously in patients with seizure disorder ( 5.8 ). • Ÿ Hyponatremia : Can occur in association with SIADH ( 5.9 ). • Interstitial Lung Disease and Eosinophilic Pneumonia : Can occur ( 5.12 ). • Sexual Dysfunction : Effexor XR 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 Effexor XR is not approved in pediatric patients. and Adult 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 Effexor XR, 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 Effexor XR, 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, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort) and with drugs that impair me… [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) ] • Seizure [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 Wyeth Pharmaceuticals Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Most Common Adverse Reactions The most commonly observed adverse reactions in the clinical study database in Effexor XR treated patients in MDD, GAD, SAD, and PD (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 all indications, 12% of the 3,558 patients who received Effexor XR (37.5–225 mg) discontinued treatment due to an adverse experience, compared with 4% of the 2,197 placebo-treated patients in those studies. The most common adverse reactions leading to discontinuation in ≥1% of the Effexor XR treated patients in the short-term studies (up to 12 weeks) across indications are shown in Table 7.

Table 7: Incidence (%) of Patients Reporting Adverse Reactions Leading to Discontinuation in Placebo-controlled Clinical Studies (up to 12 Weeks Duration) Body System Adverse Reaction Effexor XR 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 The number of patients receiving multiple doses of Effexor XR during the premarketing assessment for each approved indication is shown in Table 8. The conditions and duration of exposure to venlafaxine in all development programs varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient (Effexor only) and outpatient studies, fixed-dose, and titration studies. Table 8: Patients Receiving Effexor XR in Premarketing Clinical Studies Indication Effexor XR MDD 705 In addition, in the premarketing assessment of Effexor, multiple doses were administered to 2,897 patients in studies for MDD.

GAD 1,381 SAD 819 PD 1,314 The incidences of common adverse reactions (those that occurred in ≥2% of Effexor XR treated patients [357 MDD patients, 1,381 GAD pati… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS

7.1Drugs Having Clinically Important Interactions with Effexor XR Table 15: Clinically Important Drug Interactions with Effexor XR Monoamine Oxidase Inhibitors (MAOI) Clinical Impact The concomitant use of SNRIs, including Effexor XR, with MAOIs increases the risk of serotonin syndrome. Intervention Concomitant use of Effexor XR is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.11) , Contraindications (4) and Warnings and Precautions (5.2) ].

Other Serotonergic Drugs Clinical Impact Concomitant use of Effexor XR with other serotonergic drugs increases the risk of serotonin syndrome. Intervention Monitor for symptoms of serotonin syndrome when Effexor XR is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of Effexor XR and/or concomitant serotonergic drugs [see Dosage and Administration (2.11) and Warnings and Precautions (5.2) ].

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

Effect of CYP3A Inhibitors Clinical Impact Concomitant use of 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 Effexor XR. Intervention Consider reducing the dose of Effexor XR. CYP2D6 Substrates Clinical Impact Concomitant use of Effexor XR increases C max and AUC of a 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 Effexor XR Central Nervous System (CNS)-Active Drugs The risk of using venlafaxine concomitantly with other CNS-active drugs (including alcohol) has not been systematically evaluated. Consequently, caution is advised when Effexor XR is taken concomitantly in combination with other CNS-active drugs. Weight Loss Agents Concomitant use of Effexor XR and weight loss agents is not recommended.

The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Effexor XR is 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 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 ~3 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 Effexor XR, 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/clinical-and-research-programs/pregnancyregistry/antidepressants/ . Risk Summary 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 with exposure to SNRIs, including Effexor XR, 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 that followed 201 pregnant women with a history of major depression who were euthymic and taking antidepressants 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 in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage. 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 Effexor XR in the third trimester of pregnancy for drug discontinuation syndrome (see Data ). Data Human Data Published epidemiological studies of pregnant women exposed to venlafaxine have not established an inc… [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 Effexor XR, 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/clinical-and-research-programs/pregnancyregistry/antidepressants/ . Risk Summary 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 with exposure to SNRIs, including Effexor XR, 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 that followed 201 pregnant women with a history of major depression who were euthymic and taking antidepressants 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 in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage. 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 Effexor XR in the third trimester of pregnancy for drug discontinuation syndrome (see Data ). Data Human Data Published epidemiological studies of pregnant women exposed to venlafaxine have not established an increased risk of major birth defects, miscarriage or other adverse developmental outcomes.

Methodological limitations may both fail to identify true findings and also identify findings that are not true. Retrospective cohort studies based on claim… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 215 words ▾

8.4Pediatric Use Safety and effectiveness of Effexor XR 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 Effexor XR, and the data were not sufficient to support use in pediatric patients. In the studies conducted in pediatric patients ages 6 to17 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 Effexor XR's impact on the growth, development, and maturation of children and adolescents, the studies that have been done suggest that Effexor XR may adversely affect weight and height [see Warnings and Precautions (5.10 , 5.11) ]. Decreased appetite and weight loss were observed in placebo-controlled studies of pediatric patients 6 to 17 years.

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 Effexor XR for MDD, GAD, SAD, and PD who were 65 years of age or older are shown in Table 16. Table 16: Percentage (and Number of Patients Studied) of Patients 65 Years of Age and Older by Indication In addition, in the premarketing assessment of Effexor (immediate-release), 12% (357/2,897) of patients were ≥ 65 years of age. Indication Effexor XR MDD 4 (14/357) GAD 6 (77/1,381) SAD 1 (10/819) PD 2 (16/1,001) 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 Effexor XR, 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) ] (see Figure 1 ).

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 (2.8 , 2.9) ] .

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Human Experience During the premarketing evaluations of Effexor XR (for MDD, GAD, SAD, and PD) and Effexor (for MDD), there were twenty reports of acute overdosage with Effexor (6 and 14 reports in Effexor XR and Effexor 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 Effexor XR should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. Management of Overdosage No specific antidotes for Effexor XR 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 Effexor XR.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

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

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 at 450 mg (2 times the maximum recommended dosage) was detected.

12.3Pharmacokinetics Venlafaxine and ODV steady-state concentrations are reached within 3 days. Venlafaxine and ODV exhibited linear kinetics over the dosage range of 75 to 450 mg per day (0.33 to 2 times the maximum recommended dosage). Time of administration (AM versus PM) did not affect the pharmacokinetics of venlafaxine and ODV from the 75 mg Effexor XR capsule.

Absorption Venlafaxine is well absorbed. On the basis of mass balance studies, at least 92% of a single oral dose of venlafaxine is absorbed. The absolute bioavailability of venlafaxine is approximately 45%.

Administration of Effexor XR (150 mg once daily) generally resulted in lower C max and later T max values than for Effexor administered twice daily (Table 17). When equal daily doses of venlafaxine were administered as either an immediate-release tablet or the extended-release capsule, the exposure to both venlafaxine and ODV was similar for the two treatments, and the fluctuation in plasma concentrations was slightly lower with the Effexor XR capsule. Therefore, Effexor XR provides a slower rate of absorption, but the same extent of absorption compared with the immediate-release tablet.

Table 17: Comparison of C max and T max Values for Venlafaxine and ODV Following Oral Administration of Effexor XR and Effexor (Immediate-Release) Venlafaxine ODV C max (ng/mL) T max (h) C max (ng/mL) T max (h) Effexor XR (150 mg once daily) 150 5.5 260 9 Effexor (75 mg twice daily) 225 2 290 3 Effect of Food Food did not affect the bioavailability of venlafaxine or its active metabolite, ODV. Distribution Venlafaxine is 27% and ODV is 30% bound to plasma proteins. The apparent volume of distribution at steady-state is 7.5 ±

3.7L/kg for venlafaxine and 5.7 ±

1.8L/kg for ODV. Elimination Mean ± SD plasma apparent clearance at steady-state is 1.3 ±

0.6L/h/kg for venlafaxine and 0.4 ±

0.2L/h/kg for ODV. The apparent elimination half-life is 5 ± 2 hours for venlafaxine and 11 ± 2 hours for ODV. Metabolism Following absorption, venlafaxine undergoes extensive presystemic 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 patients with low CYP2D6 levels (poor metabolizers) had increased levels of venlafaxine and reduced levels of ODV compared to people with normal CYP2D6 levels (extensive metabolizers) (see 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… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 44 words ▾

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

📦 How Supplied / Storage and Handling 202 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Effexor XR ® is available as: • 37.5 mg, grey cap/peach body with "W" and "Effexor XR" on the cap and "37.5" on the body. NDC 0008-0837-20, bottle of 15 capsules in unit-of-use package. NDC 0008-0837-21, bottle of 30 capsules in unit-of-use package.

NDC 0008-0837-22, bottle of 90 capsules in unit-of-use package. NDC 0008-0837-03, carton of 10 Redipak ® blister strips of 10 capsules each. • 75 mg, peach cap and body with "W" and "Effexor XR" on the cap and "75" on the body. NDC 0008-0833-20, bottle of 15 capsules in unit-of-use package.

NDC 0008-0833-21, bottle of 30 capsules in unit-of-use package. NDC 0008-0833-22, bottle of 90 capsules in unit-of-use package. NDC 0008-0833-03, carton of 10 Redipak ® blister strips of 10 capsules each. • 150 mg, dark orange cap and body with "W" and "Effexor XR" on the cap and "150" on the body.

NDC 0008-0836-20, bottle of 15 capsules in unit-of-use package. NDC 0008-0836-21, bottle of 30 capsules in unit-of-use package. NDC 0008-0836-22, bottle of 90 capsules in unit-of-use package.

NDC 0008-0836-03, carton of 10 Redipak ® blister strips of 10 capsules each. Store at controlled room temperature, 20° to 25°C (68° to 77°F).

📦 Storage and Handling 11 words ▾

Store at controlled room temperature, 20° to 25°C (68° to 77°F).

📋 Description 142 words ▾

11 DESCRIPTION Effexor XR is an extended-release capsule for once-a-day oral administration that contains venlafaxine hydrochloride, a serotonin and norepinephrine reuptake inhibitor (SNRI). Venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[α- [(dimethylamino)methyl]-p-methoxybenzyl] cyclohexanol hydrochloride and has the empirical formula of C 17 H 27 NO 2 HCl. Its molecular weight is 313.86.

The structural formula is shown as follows: Venlafaxine hydrochloride is a white to off-white crystalline solid, with a solubility of 572 mg/mL in water (adjusted to ionic strength of

0.2M with sodium chloride). Its octanol:water (0.2 M sodium chloride) partition coefficient is 0.43. Drug release is controlled by diffusion through the coating membrane on the spheroids and is not pH-dependent. Capsules contain venlafaxine hydrochloride equivalent to 37.5 mg, 75 mg, or 150 mg venlafaxine. Inactive ingredients consist of cellulose, ethylcellulose, gelatin, hypromellose, iron oxide, and titanium dioxide. Chemical Structure

💬 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 Effexor XR 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 Effexor XR with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, 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 healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [ s ee 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 Effexor XR [see Warnings and Precautions (5.3) ] . Increased Risk of Bleeding Inform patients about the concomitant use of Effexor XR 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) ] . Cardiovascular/Cerebrovascular Disease Caution is advised in administering Effexor XR 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 Adverse Reactions (6.1) ] .

Discontinuation Syndrome Advise patients not to abruptly stop taking Effexor XR without talking first with their healthcare provider. Patients should be aware that discontinuation effects may occur when stopping Effexor XR 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 Effexor XR 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) ]. Interference with Cognitive and Motor Performance Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that Effexor XR therapy does not adversely affect their ability to engage in such activities. Alcohol Advise patients to avoid alcohol while taking Effexor XR [see Drug Interactions (7.2) ] .

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) and Adverse Reactions (6.2) ] . Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with Effexor XR. Advise patients that Effexor XR use during mid to late pregnancy may lead to an increased r… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

This Medication was approved by the U.S. Food and Drug Administration. Revised: 8/2022 MEDICATION GUIDE EFFEXOR XR (e-fex-or XR) (venlafaxine extended-release) capsules What is the most important information I should know about EFFEXOR XR?

EFFEXOR XR may cause serious side effects, including: • Increased risk of suicidal thoughts and actions. EFFEXOR XR 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. EFFEXOR XR is not for use in children.How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?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: • Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. • Pay close attention to any changes, especially sudden changes, in mood, behaviors, 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. • 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 EFFEXOR XR?

EFFEXOR XR is a prescription medicine used to treat adults with: • a certain type of depression called Major Depressive Disorder (MDD) • Generalized Anxiety Disorder (GAD) • Social Anxiety Disorder (SAD) • Panic Disorder (PD) It is not known if EFFEXOR XR is safe and effective for use in children. Do not take EFFEXOR XR if you: • are allergic to venlafaxine hydrochloride, desvenlafaxine succinate, or any of the ingredients in EFFEXOR XR. See the end of this Medication Guide for a complete list of ingredients in EFFEXOR XR. • 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 EFFEXOR XR. Before taking EFFEXOR XR 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 had seizures or convulsions • have low sodium levels in your blood • have lung problems • drink alcohol • are pregnant or plan to become pregnant.

EFFEXOR XR may harm your unborn baby. Talk to your healthcare provider about the risk to you and your unborn baby if you take EFFEXOR XR during pregnancy. • Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with EFFEXOR XR. • Pregnancy Exposure Registry. There is a pregnancy registry for women who are exposed to EFFEXOR XR during pregnancy.

The purpose of the registry is to collect information about the health of you and your baby. If you become pregnant during treatment with EFFEXOR XR, talk to your healthca… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Venlafaxine and ODV steady-state concentrations are reached within 3 days. Venlafaxine and ODV exhibited linear kinetics over the dosage range of 75 to 450 mg per day (0.33 to 2 times the maximum recommended dosage). Time of administration (AM versus PM) did not affect the pharmacokinetics of venlafaxine and ODV from the 75 mg Effexor XR capsule.

Absorption Venlafaxine is well absorbed. On the basis of mass balance studies, at least 92% of a single oral dose of venlafaxine is absorbed. The absolute bioavailability of venlafaxine is approximately 45%.

Administration of Effexor XR (150 mg once daily) generally resulted in lower C max and later T max values than for Effexor administered twice daily (Table 17). When equal daily doses of venlafaxine were administered as either an immediate-release tablet or the extended-release capsule, the exposure to both venlafaxine and ODV was similar for the two treatments, and the fluctuation in plasma concentrations was slightly lower with the Effexor XR capsule. Therefore, Effexor XR provides a slower rate of absorption, but the same extent of absorption compared with the immediate-release tablet.

Table 17: Comparison of C max and T max Values for Venlafaxine and ODV Following Oral Administration of Effexor XR and Effexor (Immediate-Release) Venlafaxine ODV C max (ng/mL) T max (h) C max (ng/mL) T max (h) Effexor XR (150 mg once daily) 150 5.5 260 9 Effexor (75 mg twice daily) 225 2 290 3 Effect of Food Food did not affect the bioavailability of venlafaxine or its active metabolite, ODV. Distribution Venlafaxine is 27% and ODV is 30% bound to plasma proteins. The apparent volume of distribution at steady-state is 7.5 ±

3.7L/kg for venlafaxine and 5.7 ±

1.8L/kg for ODV. Elimination Mean ± SD plasma apparent clearance at steady-state is 1.3 ±

0.6L/h/kg for venlafaxine and 0.4 ±

0.2L/h/kg for ODV. The apparent elimination half-life is 5 ± 2 hours for venlafaxine and 11 ± 2 hours for ODV. Metabolism Following absorption, venlafaxine undergoes extensive presystemic 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 patients with low CYP2D6 levels (poor metabolizers) had increased levels of venlafaxine and reduced levels of ODV compared to people with normal CYP2D6 levels (extensive metabolizers) (see 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%).

Specific Populations The effect of intrinsic patient factors on the pharmacokinetics of venlafaxine and its active metabolite ODV is presented in Figure 1. Figure 1: Pharmacokinetics of Venlafaxine and Active Metabolite O-desmethylvenlafaxine (ODV) in Special Populations ODV=O-desmethylvenlafaxine; AUC=area under the curve; C max =peak plasma concentrations. * Similar effect is expected with strong CYP2D6 inhibitors. Figure 1 Drug Interaction Studies Clinical Studies Effect of Other Drugs on Effexor XR and active metabolite ODV The effects of other drugs on the exposure of venlafaxine and ODV are summarized in Figure 2.

Figure 2: Effect of Other Drugs on the Pharmacokinetics of Venlafaxine and Active Metabolite O-desmethylvenlafaxine (ODV) ODV=O-desmethylvenlafaxine; AUC=area under the curve; C max =peak plasma concentrations; EM's=extensive metabolizers; PM's=poor metabolizers. Figure 2 Effect of Effexor XR on Other Drugs The effects of Effexor XR on the exposure of other drugs are summarized in Figure 3. Figure 3: Effect of Venlafaxine on the Pharmacokinetics Interacting Drugs and their Active Metabolites AUC=area under the curve; C max= peak plasma concentrations; OH=hydroxyl. * Data for 2-OH desipramine were not plotted to enhance clarit… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 132 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 at 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 Effexor XR (venlafaxine hydrochloride) 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. In moderately depressed outpatients, the initial dose of venlafaxine was 75 mg per day. In both studies, Effexor XR 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, Effexor XR 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. A 4-week study of inpatients meeting DSM-III-R criteria for MDD with melancholia utilizing Effexor in a range of 150 to 375 mg per day (divided in a three-times-a-day schedule) demonstrated superiority of Effexor over placebo based on the HAM-D-21 total score. The mean dose in completers was 350 mg per day (study 3).

In a longer-term study, adult outpatients with MDD who had responded during an 8-week open-label study on Effexor XR (75, 150, or 225 mg, once daily every morning) were randomized to continuation of their same Effexor XR 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 Effexor XR treatment experienced statistically significantly lower relapse rates over the subsequent 26 weeks compared with those receiving placebo (study 4). In a second longer term trial, adult outpatients with MDD, recurrent type, who had responded (HAM-D-21 total score ≤12 at the day 56 evaluation) and continued to be improved [defined as the following criteria being met for days 56 through 180: (1) no HAM-D-21 total score ≥20; (2) no more than 2 HAM-D-21 total scores >10, and (3) no single CGI Severity of Illness item score ≥4 (moderately ill)] during an initial 26 weeks of treatment on Effexor [100 to 200 mg per day, on a twice daily schedule] were randomized to continuation of their same Effexor dose or to placebo.

The follow-up period to observe patients for relapse, defined as a CGI Severity of Illness item score ≥4, was for up to 52 weeks. Patients receiving continued Effexor treatment experienced statistically significantly lower relapse rates over the subsequent 52 weeks compared with those receiving placebo (study 5). Table 18: Primary Efficacy Results for Studies in Major Depressive Disorder in Adults (Studies 1, 2, 3) Study Number Treatment Group Primary Efficacy Measure: HAM-D Score Mean Baseline Score (SD) LS Mean Change from Baseline Placebo Subtracted Difference Difference (drug minus placebo) in least-squares mean change from baseline.

(95%CI) SD=standard deviation; LS Mean=least-squares mean; CI=confidence interval. Study 1 Effexor(XR 75–225 mg/day) Doses statistically significantly superior to placebo. 24.5 -11.7 -4.45(-6.66,-2.25) Placebo 23.6 -7.24 - Study 2 Effexor(XR 75–225 mg/day) 24.5 -15.11 -6.40(-8.45,-4.34) Placebo 24.9 -8.71 Study 3 Effexor(IR 150–375 mg/day) 28.2 (0.5) -14.9 -10.2 (-14.4,-6.0) Placebo 28.6 (0.6) -4.7 -

14.2Generalized Anxiety Disorder The efficacy of E… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence ~1 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Effexor XR 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 (2.10) and Warnings and Precautions (5.7) ] .

🔒 Controlled Substance 13 words ▾

9.1Controlled Substance Effexor XR 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 60 words ▾

Boxed Warning 8/2022 Dosage and Administration ( 2.10 ) 11/2021 Dosage and Administration ( 2.2 , 2.3 , 2.6 , 2.8 , 2.9 , 2.11 ) 8/2022 Warnings and Precautions ( 5.13 ) 9/2021 Warnings and Precautions ( 5.7 ) 11/2021 Warnings and Precautions ( 5.1 , 5.2 , 5.4 , 5.5 , 5.6 , 5.7 , 5.8 ) 8/2022

📄 Package Label / Principal Display Panel ~2 min read ▾

PRINCIPAL DISPLAY PANEL - 37.5 mg Capsule Bottle Label ALWAYS DISPENSE WITH MEDICATION GUIDE Pfizer NDC 0008-0837-21 Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 37.5 mg* 30 Capsules Rx only Principal Display Panel - 37.5 mg Capsule Bottle Label

PRINCIPAL DISPLAY PANEL - 37.5 mg Capsule Blister Pack Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 37.5 mg Wyeth ® Phila. PA 19101 Principal Display Panel - 37.5 mg Capsule Blister Pack

PRINCIPAL DISPLAY PANEL - 37.5 mg Capsule Blister Pack Carton ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0837-03 Pfizer Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 37.5 mg* 10 Redipak ® Blister Strips of 10 Capsules 100 Capsules Rx only Principal Display Panel - 37.5 mg Capsule Blister Pack Carton

PRINCIPAL DISPLAY PANEL - 75 mg Capsule Bottle Label ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0833-21 Pfizer Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 75 mg* 30 Capsules Rx only Principal Display Panel - 75 mg Capsule Bottle Label

PRINCIPAL DISPLAY PANEL - 75 mg Capsule Blister Pack Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 75 mg Wyeth ® Phila. PA 19101 Principal Display Panel - 75 mg Capsule Blister Pack

PRINCIPAL DISPLAY PANEL - 75 mg Capsule Blister Pack Carton ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0833-03 Pfizer Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 75 mg* 10 Redipak ® Blister Strips of 10 Capsules 100 Capsules Rx only Principal Display Panel - 75 mg Capsule Blister Pack Carton

PRINCIPAL DISPLAY PANEL - 150 mg Capsule Bottle Label ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0836-21 Pfizer Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 150 mg* 30 Capsules Rx only Principal Display Panel - 150 mg Capsule Bottle Label

PRINCIPAL DISPLAY PANEL - 150 mg Capsule Blister Pack Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 150 mg Wyeth ® Phila. PA 19101 Principal Display Panel - 150 mg Capsule Blister Pack

PRINCIPAL DISPLAY PANEL - 150 mg Capsule Blister Pack Carton ALWAYS DISPENSE WITH MEDICATION GUIDE NDC 0008-0836-03 Pfizer Effexor XR ® (venlafaxine HCl) Extended-Release Capsules 150 mg* 10 Redipak ® Blister Strips of 10 Capsules 100 Capsules Rx only Principal Display Panel - 150 mg Capsule Blister Pack Carton

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
383
Units reimbursed last 4 qtrs
20.1K
Gross reimbursed last 4 qtrs
$379.8K
Avg / prescription
$991.73
Avg / unit
$18.8597
Latest quarter Q1 2026
0Rx
Medicaid pays / ea
$18.8597
gross reimbursed
vs
NADAC / ea
$21.6254
acquisition cost
=
Spread
−$2.7657
-13% 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 ⓘ
64% FFS 36% MCO
Fee-for-service · 247 Rx Managed care · 136 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 926 units · 16.1 per 100k residents MN Wisconsin: no data reported WI Michigan: 2,100 units · 20.9 per 100k residents MI New York: 5,100 units · 26.1 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 480 units · 11.3 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: 1,650 units · 12.7 per 100k residents PA New Jersey: no data reported NJ Massachusetts: 900 units · 12.9 per 100k residents MA California: 4,730 units · 12.1 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 1,320 units · 15.1 per 100k residents VA Maryland: no data reported MD Connecticut: 960 units · 26.5 per 100k residents 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: 1,974 units · 18.2 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: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
11.326.5
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 Connecticut 26.5 /100k
2 New York 26.1 /100k
3 Michigan 20.9 /100k
4 North Carolina 18.2 /100k
5 Minnesota 16.1 /100k
6 Virginia 15.1 /100k
7 Massachusetts 12.9 /100k
8 Pennsylvania 12.7 /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.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
30 capsules this page00008-0836-21 383 Rx · $379,834
90 capsules00008-0836-22 No Medicaid data
Drug total (last 4 qtrs): 383 Rx · 20,140 units · $379,834 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Effexor XR — the program that covers self-administered drugs. 2 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Effexor XR. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$5.14M
Claims incl. refills
3.7K
Beneficiaries
1.9K
Spend / beneficiary
$2,764.08
Spend / claim
$1,376.85
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) ✓ Available
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 90 capsules (00008-0836-22). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 00008-0423-03 · Wyeth 00008-0841-81 · Wyeth →
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.