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Duloxetine 30 mg Capsule, Delayed Release, 30-count — NDC 71205-0445-30 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Duloxetine 30 mg Capsule, Delayed Release, 30-count — NDC 71205-445-30 (Billing 71205-0445-30)

by Proficient Rx LP · 30 CAPSULE, DELAYED RELEASE in 1 BOTTLE

This is a package of 30 capsules of Duloxetine 30 mg Capsule, Delayed Release from Proficient Rx LP, marketed since May 2012 and currently FDA-listed. It is the main listing for this product, which comes in 3 package sizes.

NDC 71205-0445-30
🏷️ FDA NDC (as labeled) 71205-445-30 billing pads the product segment with a zero
This package
Contains30-count Pack sizes3 compare ↓
Also priced by: Part D plans $0.3495/unit — full pricing hub ↓
Main listing for product 71205-445 · Also comes in: 60 capsules 71205-445-60 90 capsules 71205-445-90
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

⚠️
Other active recalls for Duloxetine (different manufacturers) — 4 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · May 14, 2026 — CGMP Deviations; presence of Nitrosamine Drug Substance Related Impurity (NDSRI), N-nitroso-duloxetine, above the FDA acceptable intake limit. (Asclemed USA Inc.) · FDA recall D-0555-2026
Class II · Apr 29, 2026 — CGMP Deviations: Presence of N-nitroso-Duloxetine impurity above FDA recommended limit of 0.83 ppm, identified at the 12-month and 18-month long-term stability intervals. (Ajanta Pharma Ltd.) · FDA recall D-0514-2026
Class II · Apr 29, 2026 — CGMP Deviations: Presence of N-nitroso-Duloxetine impurity above FDA recommended limit of 0.83 ppm, identified at the 12-month and 18-month long-term stability intervals. (Ajanta Pharma Ltd.) · FDA recall D-0516-2026
Class II · Apr 29, 2026 — CGMP Deviations: Presence of N-nitroso-Duloxetine impurity above FDA recommended limit of 0.83 ppm, identified at the 12-month and 18-month long-term stability intervals. (Ajanta Pharma Ltd.) · FDA recall D-0515-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 71205-445-30
Product NDC 71205-445
11-digit billing NDC 71205044530
NCPDP billing unit EA — each (per item)
RxCUI 596930
UNII 9044SC542W
Application # ANDA203197
SPL Set ID d0a48dfd-af34-470b-9e1f-7678203e9ae5
Established class (EPC) Serotonin and Norepinephrine Reuptake Inhibitor
Mechanism of action Norepinephrine Uptake Inhibitors; Serotonin Uptake Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2012-05-01
Route ORAL
Dosage form CAPSULE, DELAYED RELEASE
Substance DULOXETINE HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS

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

GPI-14 58180025106730
GPI class DULoxetine HCl
GCN Seq No 057892
GCN 23162
HICL code 026521
Ingredient (HICL) Duloxetine 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 DULOXETINE HCL DR 30 MG CAP
FDB brand name Duloxetine Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 057892
  • GCN: 23162
  • GPI-14 (Medi-Span): 58180025106730
  • HICL (First Databank): 026521
  • AHFS class code: 28:16.04.16
  • RxCUI (RxNorm): 596930
Why two NDCs? The FDA registers this code as 71205-445-30 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 71205-0445-30. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Serotonin and Norepinephrine Reuptake Inhibitor class.

Pharmacologic class Serotonin and Norepinephrine Reuptake Inhibitor
Drug family (ATC) Other antidepressants
How it works Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name DULOXETINE HCL DR 30 MG CAP Ingredient Duloxetine Hcl
📖 What it is MedlinePlus · NLM

Duloxetine is used to treat depression and generalized anxiety disorder (GAD; excessive worry and tension that disrupts daily life). Duloxetine is also used to pain associated with diabetic neuropathy (damage to nerves that can develop in people who have diabetes) and fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep). It is also used to treat ongoing bone or muscle pain. Duloxetine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It work...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats major depressive disorder and generalized anxiety disorder. It is also used for diabetic nerve pain, fibromyalgia, and chronic musculoskeletal pain such as low back or os...
  • Take it by mouth, usually once a day, with or without food. Swallow the capsule whole and don’t crush, chew, or open it, unless you have Drizalma Sprinkle, which can be opened over...
  • Nausea, dry mouth, sleepiness, constipation, less appetite, and sweating are the most common. Headache and dizziness also occur. Call your doctor for yellow skin or eyes, a blister...
  • Please don’t stop suddenly. Stopping abruptly can cause discontinuation symptoms, so your prescriber will lower the dose gradually. Check in with them before making any change.
📖 Read our full Duloxetine guide →
1
Nutrient depletion considerations

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

🧪 Full Duloxetine 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $0.3495 $10.49 / 30 capsules
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
71205-0445-30 You're viewing this Main listing 30 CAPSULE, DELAYED RELEASE in 1 BOTTLE 2020-05-19 — Active
71205-0445-60 71205-445-60 60 CAPSULE, DELAYED RELEASE in 1 BOTTLE 2020-05-19 — Active
71205-0445-90 71205-445-90 90 CAPSULE, DELAYED RELEASE in 1 BOTTLE 2020-05-19 — Active

You're viewing the smallest of 3 pack sizes for this product.

Pack size FAQ

What quantity is in this package?
This is a 30-count package — 30 capsule, delayed release in 1 bottle.
How does this package differ from NDC 71205-0445-60?
Both are Duloxetine 30 mg Capsule, Delayed Release — the drug itself is identical. This page's package is the 30-count one, while NDC 71205-0445-60 is the 60 capsules package.
What NDC number is used to bill for this package of Duloxetine 30 mg Capsule, Delayed 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.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Duloxetine 30 mg 00228-2891-03 Actavis 30 capsules $0.102 AB Availability likely —
Duloxetine 30 mg 27241-0098-03 Ajanta 30 capsules $0.102 AB Availability likely —
Duloxetine 30 mg 43547-0380-03 Solco 30 capsules $0.102 AB Availability likely —
Duloxetine Delayed-Release 30 mg 51991-0747-10 Breckenridge 1000 capsules $0.102 AB Availability likely —
Duloxetine 30 mg 68001-0595-04 BluePoint 30 capsules $0.102 AB Availability likely —
Duloxetine 30 mg 68180-0295-03 Lupin 1000 capsules $0.102 AB Availability likely —
Duloxetine 30 mg 82009-0030-10 Quallent 1000 capsules $0.102 AB Availability likely —
Duloxetine 30 mg 82009-0171-10 Quallent 1000 capsules $0.102 AB Availability likely —
Duloxetine 30 mg 00615-8495-05 NCS 15 capsules — AB FDA listed —
Duloxetine 30 mg 25000-0609-03 MARKSANS 30 capsules — — FDA listed —
Duloxetine 30 mg 31722-0169-01 Camber 100 capsules — AB FDA listed —
Duloxetine Hydrochloride 30 mg 33342-0161-07 Macleods 30 capsules — AB FDA listed —
Duloxetine Hydrochloride 30 mg 46708-0279-10 Alembic 100 capsules — AB FDA listed —
Duloxetine 30 mg 47335-0382-08 Sun 100 capsules — — FDA listed —
duloxetine 30 mg 49252-0008-10 Inventia 30 capsules — AB FDA listed —
Duloxetine Delayed-Release 30 mg 50090-3205-00 A-S 30 capsules — AB Discontinued —
Duloxetine 30 mg 50090-6281-00 A-S 30 capsules — AB FDA listed —
Duloxetine 30 mg 50090-6899-00 A-S 30 capsules — AB FDA listed —
Duloxetine 30 mg 50090-6900-00 A-S 90 capsules — AB FDA listed —
Duloxetine 30 mg 50090-7784-00 A-S 90 capsules — AB FDA listed —
Duloxetine Hydrochloride 30 mg 50771-0202-01 Yaopharma 90 capsules — — FDA listed —
Duloxetine Delayed-Release 30 mg 51407-0818-30 Golden 30 capsules — AB FDA listed —
Duloxetine Hydrochloride 30 mg 59651-0280-30 Aurobindo 30 capsules — — FDA listed —
Duloxetine 30 mg 60760-0461-30 St. 30 capsules — AB FDA listed —
Duloxetine Hydrochloride 30 mg 62332-0279-30 Alembic 30 capsules — AB FDA listed —
Duloxetine 30 mg 63187-0612-30 Proficient 30 capsules — AB FDA listed —
Duloxetine Delayed-Release 30 mg 63187-0702-30 Proficient 30 capsules — AB FDA listed —
Duloxetine Delayed-Release 30 mg 63629-1991-01 Bryant 90 capsules — AB FDA listed —
Duloxetine 30 mg 65841-0800-06 Zydus 30 capsules — AB FDA listed —
Duloxetine 30 mg 67046-1451-03 Coupler 30 capsules — AB FDA listed —
Duloxetine 30 mg 67046-1585-03 Coupler 30 capsules — AB FDA listed —
Duloxetine 30 mg 67877-0264-01 Ascend 100 capsules — AB FDA listed —
Duloxetine 30 mg 68071-3766-09 NuCare 90 capsules — AB FDA listed —
Duloxetine 30 mg 68071-3779-03 NuCare 30 capsules — AB FDA listed —
Duloxetine 30 mg 68788-4025-03 Preferred 30 capsules — AB FDA listed —
Duloxetine 30 mg 68788-7935-03 Preferred 30 capsules — AB FDA listed —
Duloxetine 30 mg 68788-8608-03 Preferred 30 capsules — AB FDA listed —
duloxetine 30 mg 70247-0013-03 Qingdao 30 capsules — AB FDA listed —
Duloxetine 30 mg 70518-1054-06 REMEDYREPACK 30 capsules — AB FDA listed —
Duloxetine 30 mg 70518-1765-00 REMEDYREPACK 30 capsules — AB Discontinued —
Duloxetine 30 mg 70518-3287-00 REMEDYREPACK 60 capsules — AB FDA listed —
Duloxetine 30 mgthis 71205-0445-30 Proficient 30 capsules — AB FDA listed —
Duloxetine 30 mg 71205-0602-30 Proficient 30 capsules — AB FDA listed —
Duloxetine Delayed-Release 30 mg 71335-0392-01 Bryant 30 capsules — AB Discontinued —
Duloxetine 30 mg 71335-1672-01 Bryant 30 capsules — AB FDA listed —
Duloxetine 30 mg 71335-2017-01 Bryant 30 capsules — AB FDA listed —
Duloxetine 30 mg 71335-2537-01 Bryant 30 capsules — AB FDA listed —
Duloxetine Delayed-Release 30 mg 71610-0218-30 Aphena 30 capsules — AB FDA listed —
Duloxetine 30 mg 71610-0402-60 Aphena 90 capsules — AB FDA listed —
Duloxetine Delayed-Release 30 mg 71610-0736-42 Aphena 1800 capsules — AB FDA listed —
Duloxetine 30 mg 71610-0954-30 Aphena 30 capsules — AB FDA listed —
Duloxetine Delayed-Release 30 mg 72162-1598-09 Bryant 90 capsules — AB FDA listed —
Duloxetine D/R 30 mg 72189-0615-30 Direct_Rx 30 capsules — AB FDA listed —
Duloxetine D/R 30 mg 72189-0661-30 Direct_Rx 30 capsules — AB FDA listed —
Duloxetine 30 mg 76420-0236-30 Asclemed 30 capsules — AB FDA listed —
Duloxetine 30 mg 76420-0634-01 Asclemed 100 capsules — AB FDA listed —
Duloxetine HCL DR 30 mg 80425-0012-01 Advanced 30 capsules — AB FDA listed —
Duloxetine HCL DR 30 mg 80425-0014-01 Advanced 30 capsules — AB FDA listed —
Duloxetine HCL DR 30 mg 80425-0086-01 Advanced 30 capsules — AB FDA listed —
Duloxetine HCL DR 30 mg 80425-0146-01 Advanced 30 capsules — AB FDA listed —
Duloxetine 30 mg 80425-0441-01 Advanced 30 capsules — AB FDA listed —
Drizalma Sprinkle 30 mg 47335-0617-10 SUN 1000 capsules — — FDA listed —
Duloxetine 30 mg 85534-0017-00 HAWAII 30 capsules — AB FDA listed —
Duloxetine 30 mg 87063-0703-12 ASCLEMED 120 capsules — AB FDA listed —
Duloxetine 30 mg 85534-0052-00 HAWAII 30 capsules — AB FDA listed —
Duloxetine 30 mg 70954-0861-20 ANI 90 capsules — AB FDA listed —
Duloxetine 30 mg 51407-0808-10 Golden 1000 capsules — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2012
On the market since
May 2012
📍
2026
Currently FDA-listed
14 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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

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

What it looks like

Color White / Blue
ShapeCapsule
ImprintDulox;30mg
Size18 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

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

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

  • UNII 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII 5138Q19F1X
    Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
  • UNII 8PJ61P6TS3
    Butyl alcohol is a clear liquid organic solvent derived from petroleum or natural sources. In medicines, it helps dissolve active ingredients and serves as a solvent in liquid formulations and some topical products.
  • UNII 68401960MK
    Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
  • UNII L06K8R7DQK
    A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
  • UNII XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • UNII 2G86QN327L
    Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
  • UNII RFW2ET671P
    Hydroxypropyl cellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and as a film-former to coat tablets or control how fast the medicine releases.
  • UNII 87Y6436BKR
    Hypromellose phthalate is a plant-derived polymer that forms a protective coating around pills and capsules. It dissolves in the intestines rather than the stomach, helping deliver the medicine to the right place for absorption.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII ND2M416302
    Isopropyl alcohol is a clear liquid solvent derived from petroleum. In medicines, it dissolves active ingredients and other components, helps the product flow smoothly, and aids in sterilization during manufacturing.
  • UNII 588X2YUY0A
    Methylene chloride is a volatile organic solvent used in pharmaceutical manufacturing to dissolve and process active ingredients and other substances. It evaporates during production, helping create tablets, capsules, or coatings with uniform quality.
  • UNII WZH3C48M4T
    Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 46N107B71O
    Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
  • UNII 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
  • UNII C151H8M554
    A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
  • UNII 8Z96QXD6UM
    Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.

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

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

Inactive ingredient FAQ

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

Manufacturer & labeler

LabelerProficient Rx LP
Application holderALKEM LABORATORIES LTD
FDA applicationANDA203197 (ANDA)
Labeler code71205
First marketedMay 2012
Product typeHuman Prescription Drug
Portfolio1,729 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 112 words ▾

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions (5.1) ] . In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors.

Advise families and caregivers of the need for close observation and communication with the prescriber [see Warnings and Precautions (5.1) ].

🎯 Indications and Usage 83 words ▾

1 INDICATIONS AND USAGE Duloxetine is indicated for the treatment of: • Major Depressive Disorder [see Clinical Studies (14.1 )] • Generalized Anxiety Disorder [see Clinical Studies (14.2 )] • Diabetic Peripheral Neuropathy [see Clinical Studies (14.3 )] • Chronic Musculoskeletal Pain [see Clinical Studies (14.5) ] Duloxetine Hydrochloride is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for: • Major Depressive Disorder (MDD) (1) • Generalized Anxiety Disorder (GAD) (1) • Diabetic Peripheral Neuropathic Pain (DPNP) (1) • Chronic Musculoskeletal Pain (1)

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Swallow Duloxetine Delayed-Release Capsules USP whole. Do not chew or crush. Do not open the capsule and sprinkle its contents on food or mix with liquids.

All of these might affect the enteric coating. Duloxetine Delayed-Release Capsules USP can be given without regard to meals. If a dose of Duloxetine Delayed-Release Capsules USP is missed, take the missed dose as soon as it is remembered.

If it is almost time for the next dose, skip the missed dose and take the next dose at the regular time. Do not take two doses of Duloxetine Delayed-Release Capsules USP at the same time. • Take Duloxetine Delayed-Release Capsules USP once daily, with or without food. Swallow Duloxetine Delayed-Release Capsules USP whole; do not crush or chew, do not open capsule.

Take a missed dose as soon as it is remembered. Do not take two doses of Duloxetine Delayed-Release Capsules USP at the same time. (2) Indication Starting Dose Target Dose Maximum Dose MDD (2.1) 40 mg/day to 60 mg/day Acute Treatment: 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or as 30 mg twice daily); Maintenance Treatment: 60 mg/day 120 mg/day GAD (2.2) Adults 60 mg/day 60 mg/day (once daily) 120 mg/day DPNP (2.3) 60 mg/day 60 mg/day (once daily) 60 mg/day Chronic Musculoskeletal Pain (2.5) 30 mg/day 60 mg/day (once daily) 60 mg/day • Some patients may benefit from starting at 30 mg once daily (2) • There is no evidence that doses greater than 60 mg/day confers additional benefit, while some adverse reactions were observed to be dose-dependent (2) • Discontinuing Duloxetine Delayed-Release Capsules USP: Gradually reduce dosage to avoid discontinuation symptoms ( 2.7 , 5.7 ) • Hepatic Impairment: Avoid use in patients with chronic liver disease or cirrhosis ( 5.14 ) • Renal Impairment: Avoid use in patients with severe renal impairment, GFR < 30 mL/min ( 5.14 )

2.1Dosage for Treatment of Major Depressive Disorder Administer duloxetine at a total dose of 40 mg/day (given as 20 mg twice daily) to 60 mg/day (given either once daily or as 30 mg twice daily). For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer any additional benefits.

The safety of doses above 120 mg/day has not been adequately evaluated. Periodically reassess to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.1) ] .

2.2Dosage for Treatment of Generalized Anxiety Disorder Adults- For most patients, initiate duloxetine 60 mg once daily. For some patients, it may be desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg once daily. While a 120 mg once daily dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit.

Nevertheless, if a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The safety of doses above 120 mg once daily has not been adequately evaluated. Periodically reassess to determine the continued need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2) ] .

Pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules. However, due to Eli Lilly and Company, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.3Dosage for Treatment of Diabetic Peripheral Neuropathic Pain Administer duloxetine 60 mg once daily. There is no evidence that doses higher than 60 mg confer additional significant benefit and the higher dose is clearly less well tolerated [see Clinical Studies (14.3) ] . For patients for whom tolerability is a conce… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 75 words ▾

3 DOSAGE FORMS AND STRENGTHS Duloxetine is available as delayed release capsules: 20 mg opaque green capsules printed “Dulox” on cap and “20 mg” on body in black ink. 30 mg white and blue capsules printed “Dulox” on cap and “30 mg” on body in black ink. 60 mg green and blue capsules printed “Dulox” on cap and “60 mg” on body in white ink. 20 mg, 30 mg, and 60 mg delayed-release capsules (3)

⛔ Contraindications 170 words ▾

4 CONTRAINDICATIONS Monoamine Oxidase Inhibitors (MAOIs) — The use of MAOIs intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated because of an increased risk of serotonin syndrome. The use of duloxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.8) and Warnings and Precautions (5.4) ] . Starting duloxetine in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.9) and Warnings and Precautions (5.4) ] . • Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine.

Do not use duloxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start duloxetine in a patient who is being treated with linezolid or intravenous methylene blue (4)

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported in patients treated with duloxetine. Duloxetine should be discontinued in patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be established. Duloxetine should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease (5.2) • Orthostatic Hypotension, Falls and Syncope: Cases have been reported with duloxetine therapy (5.3) • 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 duloxetine and initiate supportive treatment ( 5.4 ) • Increased Risk of Bleeding: Duloxetine may increase the risk of bleeding events. Concomitant use of NSAIDs, aspirin, other antiplatelet drugs, warfarin, and anticoagulants may increase this risk ( 5.5 , 7.4 , 8.1 ) • Severe Skin Reactions: Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS), can occur with duloxetine. Duloxetine should be discontinued at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified.

(5.6) • Discontinuation: Taper dose when possible and monitor for discontinuation symptoms (5.7) • Activation of mania or hypomania has occurred (5.8) • Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. (5.9) • Seizures: Prescribe with care in patients with a history of seizure disorder (5.10) • Blood Pressure: Monitor blood pressure prior to initiating treatment and periodically throughout treatment (5.11) • Inhibitors of CYP1A2 or Thioridazine: Should not administer with duloxetine (5.12) • Hyponatremia: Can occur in association with SIADH.

Cases of hyponatremia have been reported (5.13) • Glucose Control in Diabetes: In diabetic peripheral neuropathic pain patients, small increases in fasting blood glucose, and HbA 1c , have been observed (5.14) • Conditions that Slow Gastric Emptying: Use cautiously in these patients (5.14)

5.1Suicidal Thoughts and Behaviors in Children, Adolescents and Young Adults Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders.

Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 a… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Suicidal Thoughts and Behaviors in Children, Adolescents and Young Adults [see Boxed Warning and Warnings and Precautions (5.1)] • Hepatotoxicity [see Warnings and Precautions (5.2)] • Orthostatic Hypotension, Falls and Syncope [see Warnings and Precautions (5.3)] • Serotonin Syndrome [see Warnings and Precautions (5.4)] • Abnormal Bleeding [see Warnings and Precautions (5.5)] • Severe Skin Reactions [see Warnings and Precautions (5.6)] • Discontinuation of Treatment with duloxetine [see Warnings and Precautions (5.7)] • Activation of Mania/Hypomania [see Warnings and Precautions (5.8)] • Angle-Closure Glaucoma [see Warnings and Precautions (5.9)] • Seizures [see Warnings and Precautions (5.10)] • Effect on Blood Pressure [see Warnings and Precautions (5.11)] • Clinically Important Drug Interactions [see Warnings and Precautions (5.12)] • Hyponatremia [see Warnings and Precautions (5.13)] • Urinary Hesitation and Retention [see Warnings and Precautions (5.15)] • Most common adverse reactions (≥5% and at least twice the incidence of placebo patients): nausea, dry mouth, somnolence, constipation, decreased appetite, and hyperhidrosis (6.3).

To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) 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 trials of another drug and may not reflect the rates observed in practice. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Reactions reported during the studies were not necessarily caused by the therapy, and the frequencies do not reflect investigator impression (assessment) of causality. Adults — The data described below reflect exposure to duloxetine in placebo-controlled trials for MDD (N=3779), GAD (N=1018), OA (N=503), CLBP (N=600), DPNP (N=906), and another indication (N=1294). The population studied was 17 to 89 years of age; 65.7%, 60.8% , 60.6%, 42.9%, and 94.4% female; and 81.8%, 72.6%, 85.3%, 74.0%, and 85.7% Caucasian for MDD, GAD, OA and CLBP, DPNP, and another indication, respectively.

Most patients received doses of a total of 60 to 120 mg per day [see Clinical Studies (14 )] . Information describing two additional clinical studies in which efficacy was not demonstrated in patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules. Other pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules.

However, due to Eli Lilly and Company, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Adverse Reactions Reported as Reasons for Discontinuation of Treatment in Adult Placebo-Controlled Trials Major Depressive Disorder — Approximately 8.4% (319/3779) of the patients who received duloxetine in placebo-controlled trials for MDD discontinued treatment due to an adverse reaction, compared with 4.6% (117/2536) of the patients receiving placebo. Nausea (duloxetine 1.1%, placebo 0.4%) was the only common adverse reaction reported as a reason for discontinuation and considered to be drug-related (i.e., discontinuation occurring in at least 1% of the duloxetine-treated patients and at a rate of at least twice that of placebo).

Generalized Anxiety Disorder — Approximately 13.7% (139/1018) of the patients who received duloxetine in placebo-controlled trials for GAD d… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism. • Potent inhibitors of CYP1A2 should be avoided ( 7.1 ) • Potent inhibitors of CYP2D6 may increase duloxetine concentrations ( 7.2 ) • Duloxetine is a moderate inhibitor of CYP2D6 ( 7.9 )

7.1Inhibitors of CYP1A2 When duloxetine 60 mg was co-administered with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to male subjects (n=14) duloxetine AUC was increased approximately 6-fold, the C max was increased about 2.5-fold, and duloxetine t 1/2 was increased approximately 3-fold. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin [see Warnings and Precautions (5.12) ] .

7.2Inhibitors of CYP2D6 Concomitant use of duloxetine (40 mg once daily) with paroxetine (20 mg once daily) increased the concentration of duloxetine AUC by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) [see Warnings and Precautions (5.12) ] .

7.3Dual Inhibition of CYP1A2 and CYP2D6 Concomitant administration of duloxetine 40 mg twice daily with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to CYP2D6 poor metabolizer subjects (n=14) resulted in a 6-fold increase in duloxetine AUC and C max .

7.4Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin) Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are co-administered with warfarin.

Concomitant administration of warfarin (2-9 mg once daily) under steady state conditions with duloxetine 60 or 120 mg once daily for up to 14 days in healthy subjects (n=15) did not significantly change INR from baseline (mean INR changes ranged from 0.05 to +0.07). The total warfarin (protein bound plus free drug) pharmacokinetics (AUCτ,ss, C max ,ss or t max ,ss) for both R- and S-warfarin were not altered by duloxetine. Because of the potential effect of duloxetine on platelets, patients receiving warfarin therapy should be carefully monitored when duloxetine is initiated or discontinued [see Warnings and Precautions (5.5) ] .

7.5Lorazepam Under steady-state conditions for duloxetine (60 mg Q 12 hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of duloxetine were not affected by co-administration.

7.6Temazepam Under steady-state conditions for duloxetine (20 mg qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not affected by co-administration.

7.7Drugs that Affect Gastric Acidity Duloxetine has an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely acidic conditions, duloxetine, unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using duloxetine in patients with conditions that may slow gastric emptying (e.g., some diabetics).

Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine. However, co-administration of duloxetine with aluminum- and magnesium-containing antacids (51 mEq) or duloxetine with famotidine, had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose. It is unknown whether the concomitant administration of proton pump inhibitors affects duloxetine absorption [see Warnings and Precautions (5.14) ] .

7.8Drugs Metabolized by CYP1A2 In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS · Pregnancy: Third trimester use may increase risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate ( 8.1 ) Pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules. However, due to Eli Lilly and Company, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

8.1Pregnancy Risk Summary Data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. Data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see Data). There are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to SNRIs and SSRIs, including duloxetine, during pregnancy (see Clinical Considerations).

In rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (MRHD) of 120 mg/day given to adolescents on a mg/m2 basis. When duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD given to adolescents on a mg/m2 basis.

At this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. Post-weaning growth was not adversely affected. The estimated background risk of major birth defects and miscarriage for the indicated population 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 depressive disorder 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. Pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis.

It is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. Maternal Adverse Reactions Use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 )]. Fetal/Neonatal Adverse Reaction Neonates exposed to duloxetine and other SNRIs or SSRIs 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, tremor, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. Data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see Data). There are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to SNRIs and SSRIs, including duloxetine, during pregnancy (see Clinical Considerations).

In rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (MRHD) of 120 mg/day given to adolescents on a mg/m2 basis. When duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD given to adolescents on a mg/m2 basis.

At this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. Post-weaning growth was not adversely affected. The estimated background risk of major birth defects and miscarriage for the indicated population 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 depressive disorder 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. Pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis.

It is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. Maternal Adverse Reactions Use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.5 )]. Fetal/Neonatal Adverse Reaction Neonates exposed to duloxetine and other SNRIs or SSRIs 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, tremor, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of the SNRIs or SSRIs, 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 ( 5.4 )]. Data Human Data Data from a postmarketing retrospective claims-based cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% CI: 1.08-2.1… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use The safety and effectiveness in pediatric patients less than 7 years of age have not been established. Safety and effectiveness of duloxetine have not been established in pediatric patients less than 18 years of age with MDD. Decreased appetite and weight loss have been observed in association with the use of SSRIs and SNRIs.

Perform regular monitoring of weight and growth in children and adolescents treated with an SNRI such as duloxetine [see Adverse Reactions ( 6.11 )] . Information describing two additional clinical studies in which efficacy was not demonstrated in patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules. Other pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules.

However, due to Eli Lilly and Company, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Animal Data — Duloxetine administration to young rats from post-natal day 21 (weaning) through post-natal day 90 (adult) resulted in decreased body weights that persisted into adulthood, but recovered when drug treatment was discontinued; slightly delayed (~1.5 days) sexual maturation in females, without any effect on fertility; and a delay in learning a complex task in adulthood, which was not observed after drug treatment was discontinued.

These effects were observed at the high dose of 45 mg/kg/day (2 times the MRHD, for a child); the no-effect-level was 20 mg/kg/day (≈1 times the MRHD, for a child).

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Of the 2,418 patients in premarketing clinical studies of duloxetine for MDD, 5.9% (143) were 65 years of age or over. Of the 1041 patients in CLBP premarketing studies, 21.2% (221) were 65 years of age or over. Of the 487 patients in OA premarketing studies, 40.5% (197) were 65 years of age or over.

Of the 1,074 patients in the DPNP premarketing studies, 33% (357) were 65 years of age or over. In the MDD, DPNP, OA, CLBP and other studies, no overall differences in safety or effectiveness were generally observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. SSRIs and SNRIs, including duloxetine 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 (5.13) ] .

In an analysis of data from all placebo-controlled-trials, patients treated with duloxetine reported a higher rate of falls compared to patients treated with placebo. The increased risk appears to be proportional to a patient’s underlying risk for falls. Underlying risk appears to increase steadily with age.

As elderly patients tend to have a higher prevalence of risk factors for falls such as medications, medical comorbidities and gait disturbances, the impact of increasing age by itself on falls during treatment with duloxetine is unclear. Falls with serious consequences including bone fractures and hospitalizations have been reported [see Warnings and Precautions (5.3) and Adverse Reactions ( 6.10 )].

🆘 Overdosage ~1 min read ▾

10 OVERDOSAGE

10.1Signs and Symptoms In postmarketing experience, fatal outcomes have been reported for acute overdoses, primarily with mixed overdoses, but also with duloxetine only, at doses as low as 1000 mg. Signs and symptoms of overdose (duloxetine alone or with mixed drugs) included somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting.

10.2Management of Overdose There is no specific antidote to duloxetine, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. In case of acute overdose, treatment should consist of those general measures employed in the management of overdose with any drug. An adequate airway, oxygenation, and ventilation should be assured, and cardiac rhythm and vital signs should be monitored.

Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption of duloxetine from the gastrointestinal tract.

Administration of activated charcoal has been shown to decrease AUC and C max by an average of one-third, although some subjects had a limited effect of activated charcoal. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be beneficial. In managing overdose, the possibility of multiple drug involvement should be considered.

A specific caution involves patients who are taking or have recently taken duloxetine and might ingest excessive quantities of a TCA. In such a case, decreased clearance of the parent tricyclic and/or its active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation [see Warnings and Precautions (5.4) and Drug Interactions (7) ] . The physician should consider contacting a poison control center (1-800-222-1222 or www.poison.org) for additional information on the treatment of any overdose.

Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR).

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS.

12.2Pharmacodynamics Preclinical studies have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors in vitro . Duloxetine does not inhibit monoamine oxidase (MAO).

Duloxetine is in a class of drugs known to affect urethral resistance. If symptoms of urinary hesitation develop during treatment with duloxetine, consideration should be given to the possibility that they might be drug-related.

12.3Pharmacokinetics Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range. Steady-state plasma concentrations are typically achieved after 3 days of dosing. Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP1A2 and CYP2D6.

Absorption and Distribution — Orally administered duloxetine hydrochloride is well absorbed. There is a median 2 hour lag until absorption begins (T lag ), with maximal plasma concentrations (C max ) of duloxetine occurring 6 hours post dose. Food does not affect the C max of duloxetine, but delays the time to reach peak concentration from 6 to 10 hours and it marginally decreases the extent of absorption (AUC) by about 10%.

There is a 3 hour delay in absorption and a one-third increase in apparent clearance of duloxetine after an evening dose as compared to a morning dose. The apparent volume of distribution averages about 1640 L. Duloxetine is highly bound (>90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein.

The interaction between duloxetine and other highly protein bound drugs has not been fully evaluated. Plasma protein binding of duloxetine is not affected by renal or hepatic impairment. Metabolism and Elimination — Biotransformation and disposition of duloxetine in humans have been determined following oral administration of 14 C-labeled duloxetine.

Duloxetine comprises about 3% of the total radiolabeled material in the plasma, indicating that it undergoes extensive metabolism to numerous metabolites. The major biotransformation pathways for duloxetine involve oxidation of the naphthyl ring followed by conjugation and further oxidation. Both CYP1A2 and CYP2D6 catalyze the oxidation of the naphthyl ring in vitro .

Metabolites found in plasma include 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. Many additional metabolites have been identified in urine, some representing only minor pathways of elimination. Only trace (<1% of the dose) amounts of unchanged duloxetine are present in the urine.

Most (about 70%) of the duloxetine dose appears in the urine as metabolites of duloxetine; about 20% is excreted in the feces. Duloxetine undergoes extensive metabolism, but the major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine. Pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules.

However, due to Eli Lilly and Company, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

🧬 Mechanism of Action 41 words ▾

12.1Mechanism of Action Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS.

📦 How Supplied / Storage and Handling 86 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Duloxetine Delayed-Release Capsules USP are available as delayed release capsules in the following strengths, colors, imprints, and presentations: Features Strengths 30 mg a Body color White Cap color Blue Cap imprint Dulox Body imprint 30mg Capsule size 2 Presentations and NDC Codes Bottles of 30 71205-445-30 Bottles of 60 71205-445-60 Bottles of 90 71205-445-90 a equivalent to duloxetine base

16.2Storage and Handling Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [ see USP Controlled Room Temperature].

📋 Description 174 words ▾

11 DESCRIPTION Duloxetine Hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) for oral administration. Its chemical designation is (+)-( S )- N -methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride. The empirical formula is C 18 H 19 NOS•HCl, which corresponds to a molecular weight of 333.88.

The structural formula is: Duloxetine hydrochloride is a white to off-white crystalline powder, which is slightly soluble in water. Each capsule contains enteric-coated pellets of 22.4, 33.7, or 67.3 mg of duloxetine hydrochloride equivalent to 20, 30, or 60 mg of duloxetine, respectively. These enteric-coated pellets are designed to prevent degradation of the drug in the acidic environment of the stomach.

Inactive ingredients include FD&C Blue No. 2, gelatin, hypromellose, hydroxypropyl cellulose, sodium lauryl sulfate, crosspovidone, sugar spheres, hypromellose phthalates, talc, titanium dioxide, and triethyl citrate. The 20 and 60 mg capsules also contain iron oxide yellow.

The printing ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, potassium hydroxide, black iron oxide (for 20 mg and 30 mg strengths), titanium dioxide and purified water. duloxetine-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, their families, and their caregivers to look for the emergence of suicidal ideation and behavior, especially during treatment and when the dose is adjusted up or down and instruct them to report such symptoms to their healthcare provider [ see Boxed Warning and Warnings and Precautions ( 5.1 )]. · Duloxetine capsules should be swallowed whole and should not be chewed or crushed, nor should the capsule be opened and its contents be sprinkled on food or mixed with liquids.

All of these might affect the enteric coating. · Hepatotoxicity — Inform patients that severe liver problems, sometimes fatal, have been reported in patients treated with duloxetine. Instruct patients to talk to their healthcare provider if they develop itching, right upper belly pain, dark urine, or yellow skin/eyes while taking duloxetine, which may be signs of liver problems. Instruct patients to talk to their healthcare provider about their alcohol consumption.

Use of duloxetine with heavy alcohol intake may be associated with severe liver injury [see Warnings and Precautions (5.2 )] . · Alcohol — Although duloxetine does not increase the impairment of mental and motor skills caused by alcohol, use of duloxetine concomitantly with heavy alcohol intake may be associated with severe liver injury. For this reason, duloxetine should not be prescribed for patients with substantial alcohol use [see Warnings and Precautions (5.2) and Drug Interactions (7.15)] . · Orthostatic Hypotension, Falls and Syncope — Advise patients of the risk of orthostatic hypotension, falls and syncope, especially during the period of initial use and subsequent dose escalation, and in association with the use of concomitant drugs that might potentiate the orthostatic effect of duloxetine [see Warnings and Precautions (5.3)] . · Serotonin Syndrome — Caution patients about the risk of serotonin syndrome with the concomitant use of duloxetine and other serotonergic agents including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan,amphetamines, and St.

John’s Wort [see Contraindications (4) , Warnings and Precautions (5.4) , and Drug Interactions (7.14) ] . Advise patients of the signs and symptoms associated with serotonin syndrome that may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular changes (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Caution patients to seek medical care immediately if they experience these symptoms. · Abnormal Bleeding — Caution patients about the concomitant use of duloxetine and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding [see Warnings and Precautions (5.5 ) and Use in Specific Populations ( 8.1 )]. · Severe Skin Reactions — Caution patients that duloxetine may cause serious skin reactions.

This may need to be treated in a hospital and may be life-threatening. Counsel patients to call their doctor right away or get emergency help if they have skin blisters, peeling rash, sores in their mouth, hives, or any other allergic reactions [see Warnings and Precautions (5.6)] . ·Discontinuation of Treatment — Instruct patients that discontinuation of duloxetine may be associated with symptoms such as dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue, and should be advised not to alter their dosing regimen, or stop taking duloxetine without consulting their physician… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

Medication Guide Duloxetine Delayed-Release Capsules USP (doo-LOX-e-teen) Read this Medication Guide before you start taking duloxetine and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

Talk to your healthcare provider about: • all risks and benefits of treatment with antidepressant medicines • all treatment choices for depression or other serious mental illness What is the most important information I should know about antidepressant medicines, depression, other serious mental illnesses, and suicidal thoughts or actions? 1. Duloxetine and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults within the first few months of treatment or when the dose is changed.

2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts or actions. Some people may have a particularly high risk of having suicidal thoughts or actions.

These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness). 3. How can I watch for and try to prevent suicidal thoughts and actions? • Pay close attention to any changes in mood, behavior, actions, thoughts, or feelings, especially sudden changes.

This is very important when an antidepressant medicine is started or when the dose is changed. • Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. • Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider right away if you have any of the following symptoms or feelings, especially if they are new, worse, or worry you.

In an emergency, call 911. • attempts to commit suicide • acting on dangerous impulses • acting aggressive, being angry, or violent • thoughts about suicide or dying • new or worse depression • new or worse anxiety • panic attacks • feeling very agitated or restless • new or worse irritability • trouble sleeping • an extreme increase in activity or talking (mania) • other unusual changes in behavior or mood What else do I need to know about antidepressant medicines? • Never stop an antidepressant medicine without first talking to a healthcare provider.

Stopping an antidepressant medicine suddenly can cause other symptoms. • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients should discuss all treatment choices with your healthcare provider, not just the use of antidepressants. • Antidepressant medicines have other side effects.

Talk to your healthcare provider about the side effects of the medicine prescribed for you or your family member. • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show your healthcare provider.

Do not start new medicines without first checking with your healthcare provider. What is duloxetine? Duloxetine is a prescription medicine used to treat a certain type of depression called Major Depressive Disorder (MDD).

Duloxetine belongs to a class of medicines known as SNRIs (or serotonin-norepinephrine reuptake inhibitors). Duloxetine is also used to treat or manage: • Generalized Anxiety Disorder (GAD) • Diabetic Peripheral Neuropathic Pain (DPNP) • Chronic Musculoskeletal Pain Who should not take Duloxetine? Do Not take Duloxetine if you: • take a Monoamine Oxidase Inhibitor (MAOI) .

Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid or intravenous methylene blue. • Do not take an MAOI within 5 days of stopping duloxetine unless di… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Duloxetine has an elimination half-life of about 12 hours (range 8 to 17 hours) and its pharmacokinetics are dose proportional over the therapeutic range. Steady-state plasma concentrations are typically achieved after 3 days of dosing. Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP1A2 and CYP2D6.

Absorption and Distribution — Orally administered duloxetine hydrochloride is well absorbed. There is a median 2 hour lag until absorption begins (T lag ), with maximal plasma concentrations (C max ) of duloxetine occurring 6 hours post dose. Food does not affect the C max of duloxetine, but delays the time to reach peak concentration from 6 to 10 hours and it marginally decreases the extent of absorption (AUC) by about 10%.

There is a 3 hour delay in absorption and a one-third increase in apparent clearance of duloxetine after an evening dose as compared to a morning dose. The apparent volume of distribution averages about 1640 L. Duloxetine is highly bound (>90%) to proteins in human plasma, binding primarily to albumin and α1-acid glycoprotein.

The interaction between duloxetine and other highly protein bound drugs has not been fully evaluated. Plasma protein binding of duloxetine is not affected by renal or hepatic impairment. Metabolism and Elimination — Biotransformation and disposition of duloxetine in humans have been determined following oral administration of 14 C-labeled duloxetine.

Duloxetine comprises about 3% of the total radiolabeled material in the plasma, indicating that it undergoes extensive metabolism to numerous metabolites. The major biotransformation pathways for duloxetine involve oxidation of the naphthyl ring followed by conjugation and further oxidation. Both CYP1A2 and CYP2D6 catalyze the oxidation of the naphthyl ring in vitro .

Metabolites found in plasma include 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. Many additional metabolites have been identified in urine, some representing only minor pathways of elimination. Only trace (<1% of the dose) amounts of unchanged duloxetine are present in the urine.

Most (about 70%) of the duloxetine dose appears in the urine as metabolites of duloxetine; about 20% is excreted in the feces. Duloxetine undergoes extensive metabolism, but the major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine. Pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules.

However, due to Eli Lilly and Company, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

🧬 Pharmacodynamics 85 words ▾

12.2Pharmacodynamics Preclinical studies have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors in vitro . Duloxetine does not inhibit monoamine oxidase (MAO).

Duloxetine is in a class of drugs known to affect urethral resistance. If symptoms of urinary hesitation develop during treatment with duloxetine, consideration should be given to the possibility that they might be drug-related.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of duloxetine has been established in the following adequate and well-controlled trials: • Major Depressive Disorder (MDD): 4 short-term and 1 maintenance trial in adults [see Clinical Studies (14.1) ] . • Generalized Anxiety Disorder (GAD): 3 short-term trials in adults, 1 maintenance trial in adults [see Clinical Studies (14.2 )] . • Diabetic Peripheral Neuropathic Pain (DPNP): Two 12-week trials in adults [see Clinical Studies (14.3) ] . • Chronic Musculoskeletal Pain: Two 12- to 13-week trials in adult patients with chronic low back pain (CLBP) and one 13-week trial in adult patients with chronic pain due to osteoarthritis [see Clinical Studies (14.5)].

Pediatric use information for patients ages 7 to 17 years is approved for Eli Lilly and Company, Inc.’s duloxetine delayed-release capsules. However, due to Eli Lilly and Company, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

14.1Major Depressive Disorder The efficacy of duloxetine as a treatment for depression was established in 4 randomized, double-blind, placebo-controlled, fixed-dose studies in adult outpatients (18 to 83 years) meeting DSM-IV criteria for major depression. In 2 studies, patients were randomized to duloxetine 60 mg once daily (N=123 and N=128, respectively) or placebo (N=122 and N=139, respectively) for 9 weeks; in the third study, patients were randomized to duloxetine 20 or 40 mg twice daily (N=86 and N=91, respectively) or placebo (N=89) for 8 weeks; in the fourth study, patients were randomized to duloxetine 40 or 60 mg twice daily (N=95 and N=93, respectively) or placebo (N=93) for 8 weeks.

There is no evidence that doses greater than 60 mg/day confer additional benefits. In all 4 studies, duloxetine demonstrated superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score (Studies 1-4 in Table 7). In all of these clinical studies, analyses of the relationship between treatment outcome and age, gender, and race did not suggest any differential responsiveness on the basis of these patient characteristics.

Table 7: Summary of the Primary Efficacy Results for Studies in Major Depressive Disorder Study Number Treatment Group Primary Efficacy Measure: HAMD-17 Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Difference a (95% CI) Study 1 Duloxetine (60 mg/day) b Placebo 21.5 (4.10) 21.1 (3.71) -10.9 (0.70) -6.1 (0.69) -4.9 (-6.8, -2.9) - Study 2 Duloxetine (60 mg/day) b Placebo 20.3 (3.32) 20.5 (3.42) -10.5 (0.71) -8.3 (0.67) -2.2 (-4.0, -0.3) - Study 3 Duloxetine (20 mg BID) b Duloxetine (40 mg BID) b Placebo 18.6 (5.85) 18.1 (4.52) 17.2 (5.11) -7.4 (0.80) -8.6 (0.81) -5.0 (0.81) -2.4 (-4.7, -0.2) -3.6 (-5.9, -1.4) -- Study 4 Duloxetine (40 mg BID) b Duloxetine (60 mg BID) b Placebo 19.9 (3.54) 20.2 (3.41) 19.9 (3.58) -11.0 (0.49) -12.1 (0.49) -8.8 (0.50) -2.2 (-3.6, -0.9) -3.3 (-4.7, -1.9) -- SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: confidence interval, not adjusted for multiplicity in trials where multiple dose groups were included. a Difference (drug minus placebo) in least-squares mean change from baseline. b Doses statistically significantly superior to placebo.

In another study, 533 patients meeting DSM-IV criteria for MDD received duloxetine 60 mg once daily during an initial 12-week open-label treatment phase. Two hundred and seventy-eight patients who responded to open label treatment (defined as meeting the following criteria at weeks 10 and 12: a HAMD-17 total score ≤9, Clinical Global Impressions of Severity (CGI-S) ≤2, and not meeting the DSM-IV criteria for MDD) were randomly assigned to continuation of duloxetine at the same dose (N=136) or to placebo (N=142) for 6 months.

Patients on duloxetine experienced a statistically significantly longer time to relapse of depression than did patients on placebo (Study 5 in Figure 1). R… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence 122 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.2Abuse In animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. While duloxetine has not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. 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, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of duloxetine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

9.3Dependence In drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats.

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis — Duloxetine was administered in the diet to mice and rats for 2 years. In female mice receiving duloxetine at 140 mg/kg/day (3 times the maximum recommended human dose (MRHD) of 120 mg/day given to children on a mg/m2 basis), there was an increased incidence of hepatocellular adenomas and carcinomas. The no-effect dose was 50 mg/kg/day (1 time the MRHD given to children).

Tumor incidence was not increased in male mice receiving duloxetine at doses up to 100 mg/kg/day (2 times the MRHD given to children). In rats, dietary doses of duloxetine up to 27 mg/kg/day in females (1 time the MRHD given to children) and up to 36 mg/kg/day in males (1.4 times the MRHD given to children) did not increase the incidence of tumors. Mutagenesis — Duloxetine was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test) and was not clastogenic in an in vivo chromosomal aberration test in mouse bone marrow cells.

Additionally, duloxetine was not genotoxic in an in vitro mammalian forward gene mutation assay in mouse lymphoma cells or in an in vitro unscheduled DNA synthesis (UDS) assay in primary rat hepatocytes, and did not induce sister chromatid exchange in Chinese hamster bone marrow in vivo. Impairment of Fertility — Duloxetine administered orally to either male or female rats prior to and throughout mating at doses up to 45 mg/kg/day (3 times the MRHD given to adolescents on a mg/m2 basis) did not alter mating or fertility.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis — Duloxetine was administered in the diet to mice and rats for 2 years. In female mice receiving duloxetine at 140 mg/kg/day (3 times the maximum recommended human dose (MRHD) of 120 mg/day given to children on a mg/m2 basis), there was an increased incidence of hepatocellular adenomas and carcinomas. The no-effect dose was 50 mg/kg/day (1 time the MRHD given to children).

Tumor incidence was not increased in male mice receiving duloxetine at doses up to 100 mg/kg/day (2 times the MRHD given to children). In rats, dietary doses of duloxetine up to 27 mg/kg/day in females (1 time the MRHD given to children) and up to 36 mg/kg/day in males (1.4 times the MRHD given to children) did not increase the incidence of tumors. Mutagenesis — Duloxetine was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test) and was not clastogenic in an in vivo chromosomal aberration test in mouse bone marrow cells.

Additionally, duloxetine was not genotoxic in an in vitro mammalian forward gene mutation assay in mouse lymphoma cells or in an in vitro unscheduled DNA synthesis (UDS) assay in primary rat hepatocytes, and did not induce sister chromatid exchange in Chinese hamster bone marrow in vivo. Impairment of Fertility — Duloxetine administered orally to either male or female rats prior to and throughout mating at doses up to 45 mg/kg/day (3 times the MRHD given to adolescents on a mg/m2 basis) did not alter mating or fertility.

📄 Recent Major Changes 7 words ▾

Warnings and Precautions ( 5.5 ) 10/2019

📄 Package Label / Principal Display Panel 13 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 71205-445-60 Bottles of 60 capsules Rx Only 71205-445-60

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

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