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Duloxetine Delayed-Release Duloxetine Hydrochloride 30 mg Capsule, Delayed Release Pellets, 90-count — NDC 63187-0702-90 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Duloxetine Delayed-Release Duloxetine Hydrochloride 30 mg Capsule, Delayed Release Pellets, 90-count — NDC 63187-702-90 (Billing 63187-0702-90)

by Proficient Rx LP · 90 CAPSULE, DELAYED RELEASE PELLETS in 1 BOTTLE

This is a package of 90 capsules of Duloxetine Delayed-Release Duloxetine Hydrochloride 30 mg Capsule, Delayed Release Pellets from Proficient Rx LP, marketed since Jun 2014 and currently FDA-listed.

NDC 63187-0702-90
🏷️ FDA NDC (as labeled) 63187-702-90 billing pads the product segment with a zero
This package
Contains90-count Pack sizes3 compare ↓
Also priced by: Part D plans $0.3495/unit — full pricing hub ↓
Product page 63187-0702-30 Also comes in: 30 capsules 63187-702-30 60 capsules 63187-702-60
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 Hydrochloride (different manufacturers) — 6 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Jun 4, 2026 — CGMP Deviations: Presence of N-nitroso-duloxetine impurity above FDA recommended interim limit (Breckenridge Pharmaceutical, Inc.) · FDA recall D-0583-2026
Class II · Jun 4, 2026 — CGMP Deviations: Presence of N-nitroso-duloxetine impurity above FDA recommended interim limit (Breckenridge Pharmaceutical, Inc.) · FDA recall D-0582-2026
Class II · Apr 21, 2026 — CGMP Deviations; presence of N-nitroso-duloxetine impurity above the FDA recommended limit (Breckenridge Pharmaceutical, Inc.) · FDA recall D-0522-2026
Class II · Nov 24, 2025 — CGMP Deviations; presence of N-nitroso-duloxetine impurity above the FDA recommended limit (Breckenridge Pharmaceutical, Inc.) · FDA recall D-0216-2026
Class II · Nov 24, 2025 — CGMP Deviations; presence of N-nitroso-duloxetine impurity above the FDA recommended limit (Breckenridge Pharmaceutical, Inc.) · FDA recall D-0215-2026
Class II · Oct 9, 2025 — CGMP Deviations: N-nitroso-duloxetine impurity above the safety assessment limit of 12.5ppm. (Breckenridge Pharmaceutical, Inc.) · FDA recall D-0100-2026
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) 63187-702-90
Product NDC 63187-702
11-digit billing NDC 63187070290
NCPDP billing unit EA — each (per item)
RxCUI 596930
UNII 9044SC542W
UPC 0363187702304
Application # ANDA203088
SPL Set ID 41c86c02-68c0-4db5-af1a-941b0d2ffe11
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 2014-06-11
Route ORAL
Dosage form CAPSULE, DELAYED RELEASE PELLETS
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 63187-702-90 — 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 → 63187-0702-90. 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 →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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 $31.46 / 90 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
63187-0702-30 63187-702-30 Main listing 30 CAPSULE, DELAYED RELEASE PELLETS in 1 BOTTLE 2016-05-02 — Active
63187-0702-60 63187-702-60 60 CAPSULE, DELAYED RELEASE PELLETS in 1 BOTTLE 2016-05-02 — Active
63187-0702-90 You're viewing this 90 CAPSULE, DELAYED RELEASE PELLETS in 1 BOTTLE 2016-05-02 — Active

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

Pack size FAQ

What quantity is in this package?
This is a 90-count package — 90 capsule, delayed release pellets in 1 bottle.
How does this package differ from NDC 63187-0702-30?
Both are Duloxetine Delayed-Release Duloxetine Hydrochloride 30 mg Capsule, Delayed Release Pellets — the drug itself is identical. This page's package is the 90-count one, while NDC 63187-0702-30 is the 30 capsules package.
What NDC number is used to bill for this package of Duloxetine Delayed-Release Duloxetine Hydrochloride 30 mg Capsule, Delayed Release Pellets?
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 —
Cymbalta 30 mg 00002-3240-30 Eli 30 capsules $8.967 — Discontinued —
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 mgthis 63187-0702-90 Proficient 90 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 mg 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 —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2014
On the market since
Jun 2014
📍
2026
Currently FDA-listed
12 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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

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

Inactive Ingredients / Excipients

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

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

  • UNII 5138Q19F1X
    Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
  • UNII 35SW5USQ3G
    A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
  • UNII H3R47K3TBD
    FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
  • UNII H77VEI93A8
    A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
  • UNII 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 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII NX76LV5T8J
    A synthetic plastic polymer made from methacrylic acid and ethyl acrylate. It's used as a coating or binder to control how and where the medicine dissolves in your digestive system.
  • UNII 6OZP39ZG8H
    Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
  • 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 O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • UNII 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.

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

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

Inactive ingredient FAQ

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

Manufacturer & labeler

LabelerProficient Rx LP
Application holderBRECKENRIDGE PHARMACEUTICAL INC
FDA applicationANDA203088 (ANDA)
Labeler code63187
First marketedJun 2014
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 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🍼 Nursing Mothers 🧬 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 191 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) ]. Duloxetine Delayed-release Capsules are not approved for use in pediatric patients [see Use in Specific Populations (8.4) ]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. • Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants ( 5.1 ) • Monitor for worsening and emergence of suicidal thoughts and behaviors ( 5.1 ) • Duloxetine Delayed-release Capsules are not approved for use in pediatric patients ( 8.4 )

🎯 Indications and Usage ~2 min read ▾

1. INDICATIONS AND USAGE Duloxetine Delayed-release Capsules is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for: • Major Depressive Disorder (MDD) ( 1.1 ) • Generalized Anxiety Disorder (GAD) ( 1.2 ) • Diabetic Peripheral Neuropathic Pain (DPNP) ( 1.3 ) • Chronic Musculoskeletal Pain ( 1.5 )

1.1Major Depressive Disorder Duloxetine Delayed-release Capsules are indicated for the treatment of major depressive disorder (MDD). The efficacy of Duloxetine Delayed-release Capsules was established in four short-term and one maintenance trial in adults [see Clinical Studies (14.1) ] . A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or a suicide attempt or suicidal ideation.

1.2Generalized Anxiety Disorder Duloxetine Delayed-release Capsules are indicated for the treatment of generalized anxiety disorder (GAD). The efficacy of Duloxetine Delayed-release Capsules was established in three short-term trials and one maintenance trial in adults [see Clinical Studies (14.2) ] . Generalized anxiety disorder is defined by the DSM-IV as excessive anxiety and worry, present more days than not, for at least 6 months.

The excessive anxiety and worry must be difficult to control and must cause significant distress or impairment in normal functioning. It must be associated with at least 3 of the following 6 symptoms: restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, and/or sleep disturbance.

1.3Diabetic Peripheral Neuropathic Pain Duloxetine Delayed-release Capsules are indicated for the management of neuropathic pain (DPNP) associated with diabetic peripheral neuropathy [see Clinical Studies (14.3) ] .

1.5Chronic Musculoskeletal Pain Duloxetine Delayed-release Capsules are indicated for the management of chronic musculoskeletal pain. This has been established in studies in patients with chronic low back pain (CLBP) and chronic pain due to osteoarthritis [see Clinical Studies (14.5) ] .

⏱️ Dosage and Administration ~3 min read ▾

2. DOSAGE AND ADMINISTRATION Duloxetine Delayed-release Capsules should be swallowed whole and should not be chewed or crushed, nor should the capsule be opened and its contents sprinkled on food or mixed with liquids. All of these might affect the enteric coating.

Duloxetine Delayed-release Capsules can be given without regard to meals. • Duloxetine Delayed-release Capsules should generally be administered once daily without regard to meals. Duloxetine Delayed-release 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 ( 2 ) Indication Starting Dose Target Dose Maximum Dose MDD ( 2.1 , 2.2 ) 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 ( 2.1 ) 60 mg/day 60 mg/day (once daily) 120 mg/day DPNP ( 2.1 ) 60 mg/day 60 mg/day (once daily) 60 mg/day Chronic Musculoskeletal Pain ( 2.1 ) 30 mg/day 60 mg/day (once daily) 60 mg/day • Some patients may benefit from starting at 30 mg once daily ( 2.1 ) • There is no evidence that doses greater than 60 mg/day confers additional benefit, while some adverse reactions were observed to be dose-dependent ( 2.1 ) • Discontinuing Duloxetine Delayed-release Capsules: A gradual dose reduction is recommended to avoid discontinuation symptoms ( 2.4 , 5.7 )

2.1Initial Treatment Major Depressive Disorder — Duloxetine Delayed-release Capsules should be administered 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 [see Clinical Studies (14.1) ] . Generalized Anxiety Disorder — For most patients, the recommended starting dose for Duloxetine Delayed-release Capsules is 60 mg administered 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, dose increases should be in increments of 30 mg once daily. The safety of doses above 120 mg once daily has not been adequately evaluated [see Clinical Studies (14.2) ] .

Diabetic Peripheral Neuropathic Pain — The recommended dose for Duloxetine Delayed-release Capsules is 60 mg administered 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 concern, a lower starting dose may be considered.

Since diabetes is frequently complicated by renal disease, a lower starting dose and gradual increase in dose should be considered for patients with renal impairment [see Dosage and Administration (2.3) , Use in Specific Populations (8.10) , and Clinical Pharmacology (12.3) ]. Chronic Musculoskeletal Pain — The recommended dose for Duloxetine Delayed-release Capsules is 60 mg once daily. Dosing may be started at 30 mg for one week, to allow patients to adjust to the medication before increasing to 60 mg once daily.

There is no evidence that higher doses confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher doses are associated with a higher rate of adverse reactions [see Clinical Studies (14.5) ] .

2.2Maintenance/Continuation/Extended Treatment Major Depressive Disord… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 78 words ▾

3. DOSAGE FORMS AND STRENGTHS Duloxetine Delayed-release Capsules are available as: 20 mg opaque ochre capsules imprinted with "B" on the cap and "746" on the body. 30 mg opaque green (cap) /opaque white (body) capsules imprinted with "B" on the cap and "747" on the body. 60 mg opaque green (cap) /opaque ochre (body) capsules imprinted with "B" on the cap and "748" on the body. 20 mg, 30 mg, and 60 mg capsules ( 3 )

⛔ Contraindications ~1 min read ▾

4. CONTRAINDICATIONS • Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with Duloxetine Delayed-release Capsules or within 5 days of stopping treatment with Duloxetine Delayed-release Capsules. Do not use Duloxetine Delayed-release Capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders.

In addition, do not start Duloxetine Delayed-release Capsules in a patient who is treated with linezolid or intravenous methylene blue ( 4.1 ) • Use in patients with uncontrolled narrow-angle glaucoma ( 4.2 )

4.1Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with Duloxetine Delayed-release Capsules or within 5 days of stopping treatment with Duloxetine Delayed-release Capsules is contraindicated because of an increased risk of serotonin syndrome. The use of Duloxetine Delayed-release Capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.5) and Warnings and Precautions (5.4) ]. Starting Duloxetine Delayed-release Capsules 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 (2.6) and Warnings and Precautions (5.4) ].

4.2Uncontrolled Narrow-Angle Glaucoma In clinical trials, Duloxetine Delayed-release Capsule use was associated with an increased risk of mydriasis; therefore, its use should be avoided in patients with uncontrolled narrow-angle glaucoma [see Warnings and Precautions (5.13) ] .

⚠️ Warnings and Cautions ~3 min read ▾

5. WARNINGS AND PRECAUTIONS • Suicidality: Monitor for clinical worsening and suicide risk ( 5.1 ) • Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported in patients treated with Duloxetine Delayed-release Capsules. Duloxetine Delayed-release Capsules 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 Delayed-release Capsules should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease ( 5.2 ) • Orthostatic Hypotension and Syncope: Cases have been reported with duloxetine therapy ( 5.3 ) • Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including with Duloxetine Delayed-release Capsules, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone and St.

John's Wort). If such symptoms occur, discontinue Duloxetine Delayed-release Capsules and initiate supportive treatment. If concomitant use of Duloxetine Delayed-release Capsules with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases ( 5.4 ) • Abnormal Bleeding: Duloxetine Delayed-release Capsules may increase the risk of bleeding events.

Patients should be cautioned about the risk of bleeding associated with the concomitant use of duloxetine and NSAIDs, aspirin, or other drugs that affect coagulation ( 5.5 , 7.4 ) • Severe Skin Reactions: Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS), can occur with Duloxetine Delayed-release Capsules. Duloxetine Delayed-release Capsules 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: May result in symptoms, including dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue ( 5.7 ) • Activation of mania or hypomania has occurred ( 5.8 ) • Seizures: Prescribe with care in patients with a history of seizure disorder ( 5.9 ) • Blood Pressure: Monitor blood pressure prior to initiating treatment and periodically throughout treatment ( 5.10 ) • Inhibitors of CYP1A2 or Thioridazine: Should not administer with Duloxetine Delayed-release Capsules ( 5.11 ) • Hyponatremia: Cases of hyponatremia have been reported ( 5.12 ) • Hepatic Insufficiency and Severe Renal Impairment: Should ordinarily not be administered to these patients ( 5.13 ) • Controlled Narrow-Angle Glaucoma: Use cautiously in these patients ( 5.13 ) • Glucose Control in Diabetes: In diabetic peripheral neuropathic pain patients, small increases in fasting blood glucose, and HbA1c have been observed ( 5.13 ) • Conditions that Slow Gastric Emptying: Use cautiously in these patients ( 5.13 ) • Urinary Hesitation and Retention ( 5.14 )

5.1Suicidal Thoughts and Behaviors in 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 tri… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6. ADVERSE REACTIONS • 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 Breckenridge Pharmaceutical, Inc. at 1-800-367-3395 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial Data Sources The data described below reflect exposure to duloxetine in placebo-controlled trials for MDD (N=2489), GAD (N=910), OA (N=239), CLBP (N=600), and DPNP (N=906). The population studied was 17 to 91 years of age; 65.5%, 62.5%, 61.5%, and 42.9% female; and 86.5%, 81.2%, 86.2%, and 74.0% Caucasian for MDD, GAD, OA and CLBP, DPNP, respectively. Most patients received doses of a total of 60 to 120 mg per day [see Clinical Studies (14) ] .

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.

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.

6.2Adverse Reactions Reported as Reasons for Discontinuation of Treatment in Placebo-Controlled Trials Major Depressive Disorder — Approximately 9% (209/2327) of the patients who received duloxetine in placebo-controlled trials for MDD discontinued treatment due to an adverse reaction, compared with 4.7% (68/1460) of the patients receiving placebo. Nausea (duloxetine 1.3%, placebo 0.5%) 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 15.3% (102/668) of the patients who received duloxetine in placebo-controlled trials for GAD discontinued treatment due to an adverse reaction, compared with 4.0% (20/495) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 3.7%, placebo 0.2%), and vomiting (duloxetine 1.3%, placebo 0.0%), and dizziness (duloxetine 1.0%, placebo 0.2%). Diabetic Peripheral Neuropathic Pain — Approximately 12.9% (117/906) of the patients who received duloxetine in placebo-controlled trials for DPNP discontinued treatment due to an adverse reaction, compared with 5.1% (23/448) for placebo.

Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 3.5%, placebo 0.7%), dizziness (duloxetine 1.2%, placebo 0.4%), and somnolence (duloxetine 1.1%, placebo 0.0%). Chronic Pain due to Osteoarthritis — Approximately 16.3% (39/239) of the patients who received duloxetine in 13-week, placebo-controlled trials for chronic pain due to OA discontinued treatment due to an adverse reaction, compared with 5.6% (14/248) for placebo.

Common adverse reactions reported as a reason for discontinuation and considered to be drug-related (as defined above) included nausea (duloxetine 2.9%, placebo 0.8%) and asthenia (duloxetine 1.3%, placebo 0.0%). Chronic Low Back Pain — Approximately 16.5% (99/600) of the patients who received duloxetine in 13-week, placebo-controlled trials for CLBP discontinued treatment due to an adverse reaction, compared with 6.3% (28/441) for placebo. Common adverse reactions reported as a reason for discontinuation and considered to be drug-r… [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 (5.11) ] .

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 (5.11) ] .

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 (AUC T,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 Delayed-release Capsules have 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 Delayed-release Capsules, unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using Duloxetine Delayed-release Capsules 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 Delayed-release Capsules with aluminum- and magnesium-containing antacids (51 mEq) or Duloxetine Delayed-release Capsules 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 Precau… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8. USE IN SPECIFIC POPULATIONS • Pregnancy and Nursing Mothers: Use only if the potential benefit justifies the potential risk to the fetus or child ( 2.3 , 8.1 , 8.3 ).

8.1Pregnancy Teratogenic Effects, Pregnancy Category C — In animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. When duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of teratogenicity at doses up to 45 mg/kg/day (7 times the maximum recommended human dose [MRHD, 60 mg/day] and 4 times the human dose of 120 mg/day on a mg/m 2 basis, in rat; 15 times the MRHD and 7 times the human dose of 120 mg/day on a mg/m 2 basis in rabbit).

However, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (2 times the MRHD and ≈1 times the human dose of 120 mg/day on a mg/m 2 basis in rat; 3 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis in rabbits). When duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (5 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis); the no-effect dose was 10 mg/kg/day.

Furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. Post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. There are no adequate and well-controlled studies in pregnant women; therefore, duloxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects — Neonates exposed to SSRIs or serotonin and norepinephrine reuptake inhibitors (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, tremor, jitteriness, irritability, and constant crying.

These features are consistent with either a direct toxic effect of SSRIs and 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 (5.4) ] . When treating pregnant women with Duloxetine Delayed-release Capsules during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

The physician may consider tapering Duloxetine Delayed-release Capsules in the third trimester [see Dosage and Administration (2.3) ] .

8.2Labor and Delivery The effect of duloxetine on labor and delivery in humans is unknown. Duloxetine should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

8.3Nursing Mothers Duloxetine is excreted into the milk of lactating women. The estimated daily infant dose on a mg/kg basis is approximately 0.14% of the maternal dose. Because the safety of duloxetine in infants is not known, nursing while on Duloxetine Delayed-release Capsules is not recommended.

However, if the physician determines that the benefit of duloxetine therapy for the mother outweighs any potential risk to the infant, no dosage adjustment is required as lactation did not influence duloxetine pharmacokinetics. The disposition of duloxetine was studied in 6 lactating women who were at least 12 weeks postpartum. Duloxetine 40 mg twice daily was given for 3.5 days.

Like many other drugs, duloxetine is detected in… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Teratogenic Effects, Pregnancy Category C — In animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. When duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of teratogenicity at doses up to 45 mg/kg/day (7 times the maximum recommended human dose [MRHD, 60 mg/day] and 4 times the human dose of 120 mg/day on a mg/m 2 basis, in rat; 15 times the MRHD and 7 times the human dose of 120 mg/day on a mg/m 2 basis in rabbit).

However, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (2 times the MRHD and ≈1 times the human dose of 120 mg/day on a mg/m 2 basis in rat; 3 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis in rabbits). When duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (5 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis); the no-effect dose was 10 mg/kg/day.

Furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. Post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. There are no adequate and well-controlled studies in pregnant women; therefore, duloxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects — Neonates exposed to SSRIs or serotonin and norepinephrine reuptake inhibitors (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, tremor, jitteriness, irritability, and constant crying.

These features are consistent with either a direct toxic effect of SSRIs and 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 (5.4) ] . When treating pregnant women with Duloxetine Delayed-release Capsules during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

The physician may consider tapering Duloxetine Delayed-release Capsules in the third trimester [see Dosage and Administration (2.3) ] .

🧒 Pediatric Use 188 words ▾

8.4Pediatric Use Safety and effectiveness in the pediatric population has not been established [see Boxed Warning and Warnings and Precautions (5.1) ] . 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 Delayed-release Capsules.

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; the no-effect-level was 20 mg/kg/day.

Information describing two additional clinical studies performed by Eli Lilly and Company that failed to demonstrate pediatric efficacy is approved for Eli Lilly and Company's Duloxetine Delayed-release Capsules. However, due to Eli Lilly and Company's marketing exclusivity rights, this drug product is not labeled with that pediatric information.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Of the 2,418 patients in premarketing clinical studies of Duloxetine Delayed-release Capsules 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. Premarketing clinical studies of GAD did not include sufficient numbers of subjects age 65 or over to determine whether they respond differently from younger subjects. In the MDD, DPNP, OA, and CLBP studies, no overall differences in safety or effectiveness were 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 Delayed-release Capsules 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 (5.12) ] . The pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females (65 to 77 years) and healthy middle-age females (32 to 50 years). There was no difference in the C max , but the AUC of duloxetine was somewhat (about 25%) higher and the half-life about 4 hours longer in the elderly females.

Population pharmacokinetic analyses suggest that the typical values for clearance decrease by approximately 1% for each year of age between 25 to 75 years of age; but age as a predictive factor only accounts for a small percentage of between-patient variability. Dosage adjustment based on the age of the patient is not necessary [see Dosage and Administration (2.3) ] .

🆘 Overdosage ~2 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 Delayed-release Capsules, 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 Delayed-release Capsules 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 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 Delayed-release Capsules is in a class of drugs known to affect urethral resistance. If symptoms of urinary hesitation develop during treatment with Duloxetine Delayed-release Capsules, 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 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 α 1 -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.

🧬 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 74 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Duloxetine Delayed-release Capsules are available as delayed release capsules in the following strengths, colors, imprints, and presentations: Features 30 mg equivalent to duloxetine base Body color Opaque white Cap color Opaque green Cap imprint B Body imprint 747 Bottles of 30 63187-702-30 Bottles of 60 63187-702-60 Bottles of 90 63187-702-90

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

📦 Storage and Handling 16 words ▾

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

📋 Description 209 words ▾

11 DESCRIPTION Duloxetine Delayed-release Capsules (duloxetine hydrochloride) are a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) 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 slightly brownish white solid, 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 ammonium hydroxide, black iron oxide, hypromellose, methacrylic acid copolymer dispersion (methacrylic acid-ethyl acrylate copolymer, polysorbate 80, sodium lauryl sulfate), potassium hydroxide, propylene glycol, shellac, sucrose, sugar spheres (maize starch, sucrose), talc, titanium dioxide, triethylcitrate, and hard gelatin capsules (gelatin, titanium dioxide). The 20 mg hard gelatin capsule colorant is yellow iron oxide. The 30 mg hard gelatin capsule colorants are FD&C Blue No.

1, FD&C Yellow No. 6, and FD&C Yellow No. 10.

The 60 mg hard gelatin capsule colorants are FD&C Blue No. 1, FD&C Yellow No. 6, FD&C Yellow No.10, and yellow iron oxide.

Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling ( Medication Guide ).

17.1Information on Medication Guide Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Duloxetine Delayed-release Capsules and should counsel them in its appropriate use. A patient Medication Guide is available for Duloxetine Delayed-release Capsules. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide before starting Duloxetine Delayed-release Capsules and each time their prescription is renewed, and should assist them in understanding its contents.

Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Duloxetine Delayed-release Capsules.

17.2Suicidal Thoughts and Behaviors Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt.

Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [see Boxed Warning , and Warnings and Precautions (5.1) ] .

17.3Medication Administration Duloxetine Delayed-release 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.

17.4Continuing the Therapy Prescribed While patients may notice improvement with Duloxetine Delayed-release Capsules therapy in 1 to 4 weeks, they should be advised to continue therapy as directed.

17.5Hepatotoxicity Patients should be informed that severe liver problems, sometimes fatal, have been reported in patients treated with Duloxetine Delayed-release Capsules. Patients should be instructed to talk to their healthcare provider if they develop itching, right upper belly pain, dark urine, or yellow skin/eyes while taking Duloxetine Delayed-release Capsules, which may be signs of liver problems. Patients should talk to their healthcare provider about their alcohol consumption.

Use of Duloxetine Delayed-release Capsules with heavy alcohol intake may be associated with severe liver injury [see Warnings and Precautions (5.2) ] .

17.6Alcohol Although Duloxetine Delayed-release Capsules do not increase the impairment of mental and motor skills caused by alcohol, use of Duloxetine Delayed-release Capsules concomitantly with heavy alcohol intake may be associated with severe liver injury. For this reason, Duloxetine Delayed-release Capsules should not be prescribed for patients with substantial alcohol use [see Warnings and Precautions (5.2) and Drug Interactions (7.15) ] .

17.7Orthostatic Hypotension and Syncope Patients should be advised of the risk of orthostatic hypotension and syncope, especially during the period of initial use and subsequent dose escalation, and in association with the use of concomitant drugs that might potentiat… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

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

Talk with your healthcare provider if there is something you do not understand or want to learn more about. What is the most important information I should know about Duloxetine Delayed-release Capsules? Duloxetine Delayed-release Capsules and other antidepressant medicines may cause serious side effects, including: 1.

Suicidal thoughts or actions: • Duloxetine Delayed-release Capsules 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. • Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. • Watch for these changes and call your healthcare provider right away if you notice: o New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. o Pay particular attention to such changes when Duloxetine Delayed-release Capsules are started or when the dose is changed.

Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: • attempts to commit suicide • acting on dangerous impulses • acting aggressive or violent • thoughts about suicide or dying • new or worse depression • new or worse anxiety or panic attacks • feeling agitated, restless, angry or irritable • trouble sleeping • an increase in activity or talking more than what is normal for you • other unusual changes in behavior or mood Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency.

Duloxetine Delayed-release Capsules may be associated with these serious side effects: 2. Liver damage- symptoms may include: • itching • right upper abdominal pain • dark urine • hepatitis with yellow skin or eyes • enlarged liver • increased liver enzymes 3. Serotonin Syndrome -This condition can be life-threatening and may include: • agitation, hallucinations, coma or other changes in mental status • coordination problems or muscle twitching (overactive reflexes) • racing heartbeat, high or low blood pressure • sweating or fever • nausea, vomiting, or diarrhea • muscle rigidity • dizziness • flushing • tremor • seizures 4.

Abnormal bleeding: Duloxetine Delayed-release Capsules and other antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin ® , Jantoven ® ), a non-steroidal anti-inflammatory drug (NSAIDs, like ibuprofen or naproxen), or aspirin. 5. Severe skin reactions: Duloxetine Delayed-release Capsules may cause serious skin reactions that may require stopping its use.

This may need to be treated in a hospital and may be life-threatening. Call your doctor right away or get emergency help if you have skin blisters, peeling rash, sores in the mouth, hives or any other allergic reactions. 6.

Manic episodes: • greatly increased energy • severe trouble sleeping • racing thoughts • reckless behavior • unusually grand ideas • excessive happiness or irritability • talking more or faster than usual 7. Seizures or convulsions 8. Changes in blood pressure.

Monitor your blood pressure before starting and throughout treatment. Duloxetine Delayed-release Capsules may: • increase your blood pressure. • decrease your blood pressure when standing and cause dizziness or fainting, mostly when first starting Duloxetine Delayed-release Capsules or when increasing th… [Excerpted — this section continues on DailyMed.]

🍼 Nursing Mothers 184 words ▾

8.3Nursing Mothers Duloxetine is excreted into the milk of lactating women. The estimated daily infant dose on a mg/kg basis is approximately 0.14% of the maternal dose. Because the safety of duloxetine in infants is not known, nursing while on Duloxetine Delayed-release Capsules is not recommended.

However, if the physician determines that the benefit of duloxetine therapy for the mother outweighs any potential risk to the infant, no dosage adjustment is required as lactation did not influence duloxetine pharmacokinetics. The disposition of duloxetine was studied in 6 lactating women who were at least 12 weeks postpartum. Duloxetine 40 mg twice daily was given for 3.5 days.

Like many other drugs, duloxetine is detected in breast milk, and steady state concentrations in breast milk are about one-fourth those in plasma. The amount of duloxetine in breast milk is approximately 7 µg/day while on 40 mg BID dosing. The excretion of duloxetine metabolites into breast milk was not examined.

Because the safety of duloxetine in infants is not known, nursing while on Duloxetine Delayed-release Capsules is not recommended [see Dosage and Administration (2.3) ] .

🧬 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 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 α 1 -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.

🧬 Pharmacodynamics 89 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 Delayed-release Capsules is in a class of drugs known to affect urethral resistance. If symptoms of urinary hesitation develop during treatment with Duloxetine Delayed-release Capsules, consideration should be given to the possibility that they might be drug-related.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Major Depressive Disorder The efficacy of Duloxetine Delayed-release Capsules 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 Delayed-release Capsules 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 Delayed-release Capsules 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 Delayed-release Capsules 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 Delayed-release Capsules demonstrated superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score. 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.

In another study, 533 patients meeting DSM-IV criteria for MDD received Duloxetine Delayed-release Capsules 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 Delayed-release Capsules at the same dose (N=136) or to placebo (N=142) for 6 months.

Patients on Duloxetine Delayed-release Capsules experienced a statistically significantly longer time to relapse of depression than did patients on placebo. Relapse was defined as an increase in the CGI-S score of ≥2 points compared with that obtained at week 12, as well as meeting the DSM-IV criteria for MDD at 2 consecutive visits at least 2 weeks apart, where the 2-week temporal criterion had to be satisfied at only the second visit. The effectiveness of Duloxetine Delayed-release Capsules in hospitalized patients with major depressive disorder has not been studied.

14.2Generalized Anxiety Disorder The efficacy of Duloxetine Delayed-release Capsules in the treatment of generalized anxiety disorder (GAD) was established in 1 fixed-dose randomized, double-blind, placebo-controlled trial and 2 flexible-dose randomized, double-blind, placebo-controlled trials in adult outpatients between 18 and 83 years of age meeting the DSM-IV criteria for GAD. In 1 flexible-dose study and in the fixed-dose study, the starting dose was 60 mg once daily where down titration to 30 mg once daily was allowed for tolerability reasons before increasing it to 60 mg once daily.

Fifteen percent of patients were down titrated. One flexible-dose study had a starting dose of 30 mg once daily for 1 week before increasing it to 60 mg once daily. The 2 flexible-dose studies involved dose titration with Duloxetine Delayed-release Capsules doses ranging from 60 mg once daily to 120 mg once daily (N=168 and N=162) compared to placebo (N=159 and N=161) over a 10-week treatment period.

The mean dose for completers at endpoint in the flexible-dose studies was 104.75 mg/day. The fixed-dose study evaluated Duloxetine Delayed-release Capsules doses of 60 mg once daily (N=168) and 120 mg once daily (N=170) compared to placebo (N=175) over a 9-week treatment period. While a 120 mg/day dose was shown to be effective, there is no evidence that doses greater than 60 mg/day confer additional benefit.

In all 3 studies, Duloxetine Delayed-release Capsules demonstrated superiority over placebo as measured by greater impro… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence 126 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.2Abuse In animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. While Duloxetine Delayed-release Capsules have 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 Delayed-release Capsules (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 (11 times the maximum recommended human dose [MRHD, 60 mg/day] and 6 times the human dose of 120 mg/day on a mg/m 2 basis), there was an increased incidence of hepatocellular adenomas and carcinomas. The no-effect dose was 50 mg/kg/day (4 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis).

Tumor incidence was not increased in male mice receiving duloxetine at doses up to 100 mg/kg/day (8 times the MRHD and 4 times the human dose of 120 mg/day on a mg/m 2 basis). In rats, dietary doses of duloxetine up to 27 mg/kg/day in females (4 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis) and up to 36 mg/kg/day in males (6 times the MRHD and 3 times the human dose of 120 mg/day on a mg/m 2 basis) 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 (7 times the maximum recommended human dose of 60 mg/day and 4 times the human dose of 120 mg/day on a mg/m 2 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 (11 times the maximum recommended human dose [MRHD, 60 mg/day] and 6 times the human dose of 120 mg/day on a mg/m 2 basis), there was an increased incidence of hepatocellular adenomas and carcinomas. The no-effect dose was 50 mg/kg/day (4 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis).

Tumor incidence was not increased in male mice receiving duloxetine at doses up to 100 mg/kg/day (8 times the MRHD and 4 times the human dose of 120 mg/day on a mg/m 2 basis). In rats, dietary doses of duloxetine up to 27 mg/kg/day in females (4 times the MRHD and 2 times the human dose of 120 mg/day on a mg/m 2 basis) and up to 36 mg/kg/day in males (6 times the MRHD and 3 times the human dose of 120 mg/day on a mg/m 2 basis) 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 (7 times the maximum recommended human dose of 60 mg/day and 4 times the human dose of 120 mg/day on a mg/m 2 basis) did not alter mating or fertility.

📄 Recent Major Changes 70 words ▾

Dosage and Administration: Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders ( 2.5 ) 10/2012 Use of Duloxetine Delayed-release Capsules with Other MAOIs such as Linezolid or Methylene Blue ( 2.6 ) 10/2012 Contraindications – Monoamine Oxidase Inhibitors ( 4.1 ) 10/2012 Warnings and Precautions: Serotonin Syndrome ( 5.4 ) 10/2012 Discontinuation of Treatment with Duloxetine Delayed-release Capsules ( 5.7 ) 08/2012

📄 Package Label / Principal Display Panel 22 words ▾

PRINCIPAL DISPLAY PANEL - 30 mg Capsule Bottle Label NDC 63187-702-30 Duloxetine Delayed-release Capsules, USP 30 mg 30 Capsules Rx Only 63187-702-30

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

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