Home › NDC Lookup › Ingredients › Morphine Sulfate › 00115-1281-01
Morphine Sulfate 80 mg Capsule, Extended Release, 100-count — NDC 00115-1281-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Morphine Sulfate 80 mg Capsule, Extended Release, 100-count — NDC 0115-1281-01 (Billing 00115-1281-01)

by Amneal Pharmaceuticals of New York LLC · 100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

This is a package of 100 capsules of Morphine Sulfate 80 mg Capsule, Extended Release from Amneal Pharmaceuticals of New York LLC, marketed since Apr 2016 and currently FDA-listed. It is the main listing for this product, which comes in 3 package sizes.

NDC 00115-1281-01
🏷️ FDA NDC (as labeled) 0115-1281-01 billing pads the labeler segment with a zero
This package
Contains100-count Pack sizes3 compare ↓
Also priced by: Part D plans $3.77/unit — full pricing hub ↓
Main listing for product 0115-1281 · Also comes in: 30 capsules 0115-1281-08 1000 capsules 0115-1281-03
Rx only Generic On market CII 🛡 REMS ⇄ 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 Morphine Sulfate (different manufacturers) — 4 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class I · Aug 4, 2026 — Labeling: Label Mixup: MicroVault labeled as Morphine 2 mg/1 mL, contains a Prefilled Syringe of Dilaudid 0.5 mg/0.5 mL. (Fresenius Kabi USA, LLC) · FDA recall D-0788-2026
Class III · Nov 26, 2025 — Correct Labeled Product Mispack-Size stated on carton label did not match the size of the bottle in the carton. (Winder Laboratories, LLC) · FDA recall D-0223-2026
Class II · Feb 6, 2025 — Failed Dissolution Specifications (SUN PHARMACEUTICAL INDUSTRIES INC) · FDA recall D-0249-2025
Class II · Mar 12, 2024 — The filter included in the carton has an expiration date that has expired prior to the expiration date of the actual product lot. (Hikma Pharmaceuticals USA Inc.) · FDA recall D-0392-2024
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) 0115-1281-01
Product NDC 0115-1281
11-digit billing NDC 00115128101
NCPDP billing unit EA — each (per item)
RxCUI 892345, 892352, 892554, 892596, 894801, 894814, 1303736
UNII X3P646A2J0
UPC 0301151281011, 0301151280014
Application # ANDA200411
SPL Set ID f7e9a4b3-a2ee-4f0a-becd-6ef90867332b
Established class (EPC) Opioid Agonist
Mechanism of action Full Opioid Agonists
DEA schedule CII
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-04-12
Route ORAL
Dosage form CAPSULE, EXTENDED RELEASE
Substance MORPHINE SULFATE

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

GPI-14 65100055107050
GPI class Morphine Sulfate ER
GCN Seq No 061722
GCN 97508
HICL code 001694
Ingredient (HICL) Morphine Sulfate
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H3
Therapeutic class — intermediate (HIC2) Analgesics
HIC3 code H3A
Therapeutic class — specific (HIC3) Opioid Analgesics
AHFS code 28:08.08.00
AHFS class Opioid Agonists (28:08)
FDB label name MORPHINE SULFATE ER 80 MG CAP
FDB brand name Morphine Sulfate Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 061722
  • GCN: 97508
  • GPI-14 (Medi-Span): 65100055107050
  • HICL (First Databank): 001694
  • AHFS class code: 28:08.08.00
  • RxCUI (RxNorm): 892345
Why two NDCs? The FDA registers this code as 0115-1281-01 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00115-1281-01. 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 Opioid Agonist class.

Pharmacologic class Opioid Agonist
Drug family (ATC) Natural opium alkaloids
How it works Full Opioid Agonists
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 MORPHINE SULFATE ER 80 MG CAP Ingredient Morphine Sulfate
📗 Our plain-language guide HelloPharmacist
  • Morphine treats severe pain when other treatments haven't worked or aren't suitable. Some forms are short-acting, and others are long-acting for around-the-clock pain. Your prescri...
  • Follow your label exactly. Extended-release capsules and tablets must be swallowed whole, never crushed or chewed, because that can release a dangerous dose at once. For liquid, us...
  • No. Alcohol can raise morphine levels and cause a fatal overdose. Avoid products containing alcohol, and check with me before taking other sedating medicines like sleep aids or anx...
  • Constipation, nausea, drowsiness, and dizziness are most common. Call for help right away if you have slow or shallow breathing, extreme sleepiness, fainting, or an allergic reacti...
📖 Read our full Morphine guide →
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 $3.77 $377.22 / 100 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
00115-1281-01 You're viewing this Main listing 100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE 2016-04-12 — Active
00115-1281-03 0115-1281-03 1000 CAPSULE, EXTENDED RELEASE in 1 BOTTLE 2016-04-12 — Active
00115-1281-08 0115-1281-08 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE 2016-04-12 — Active

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

Pack size FAQ

What quantity is in this package?
This is a 100-count package — 100 capsule, extended release in 1 bottle.
How does this package differ from NDC 00115-1281-08?
Both are Morphine Sulfate 80 mg Capsule, Extended Release — the drug itself is identical. This page's package is the 100-count one, while NDC 00115-1281-08 is the 30 capsules package.
What NDC number is used to bill for this package of Morphine Sulfate 80 mg Capsule, Extended Release?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Morphine Sulfate 80 mgthis 00115-1281-01 Amneal 100 capsules — — FDA listed —
Morphine Sulfate 80 mg 00832-0230-00 Upsher-Smith 100 capsules — — FDA listed —
Morphine Sulfate 80 mg 42689-0009-01 Nortec 100 capsules — — 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

🏛️
2016
On the market since
Apr 2016
📍
2026
Currently FDA-listed
10 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 yellow / purple / blue / red / orange / green
ShapeCapsule
ImprintJ69
Size16 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

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

Manufacturer & labeler

LabelerAmneal Pharmaceuticals of New York LLC
Application holderIMPAX LABORATORIES INC
FDA applicationANDA200411 (ANDA)
Labeler code00115
First marketedApr 2016
DEA scheduleCII
Product typeHuman Prescription Drug
Portfolio228 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 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📖 Instructions for Use 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~3 min read ▾

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF MORPHINE SULFATE EXTENDED-RELEASE CAPSULES Addiction, Abuse, and Misuse Because the use of morphine sulfate extended-release capsules exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1) ] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of morphine sulfate extended-release capsules, especially during initiation or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of morphine sulfate extended-release capsules are essential [see Warnings and Precautions (5.2) ] . Instruct patients to swallow morphine sulfate extended-release capsules whole or to sprinkle the contents of the capsule on applesauce and swallow immediately without chewing. Crushing, chewing, or dissolving the pellets in morphine sulfate extended-release capsules can cause rapid release and absorption of a fatal dose of morphine [see Warnings and Precautions (5.2) ].

Accidental Ingestion Accidental ingestion of even one dose of morphine sulfate extended-release capsules, especially by children, can result in a fatal overdose of morphine [see Warnings and Precautions (5.2) ] . Interaction with Alcohol Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking morphine sulfate extended-release capsules. The co-ingestion of alcohol with morphine sulfate extended-release capsules may result in increased plasma levels and a potentially fatal overdose of morphine [see Warnings and Precautions (5.3) ] .

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of morphine sulfate injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3) , Drug Interactions (7) ]. Neonatal Opioid Withdrawal Syndrome (NOWS) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated.

Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions (5.4) ] . Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings and Precautions (5.5) ] . WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF MORPHINE SULFATE EXTENDED-RELEASE CAPSULES See full prescribing information for complete boxed warning.

Morphine sulfate extended-release capsules expose users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for these behaviors and conditions. (5.1) Serious, life-threatening, or fatal respiratory depression may occur, especially upon initiation or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of morphine sulfate extended-release capsules are essential. Instruct patients to swallow morphine sulfate extended-release capsules whole to avoid exposure to a potentially fatal dose of morphine . (5.2) Accidental ingestion of morphine sulfate extended-release capsules, especially by children, can result in fatal overdos… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Morphine sulfate extended-release capsules are indicated for the management of severe and persistent pain, that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use: Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions (5.1) ], reserve opioid analgesics, including morphine sulfate extended-release capsules for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Morphine sulfate extended-release capsules are not indicated as an as-needed (prn) analgesic. Morphine sulfate extended-release capsules are indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. (1) Limitations of Use: Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including morphine sulfate extended-release capsules, for use in patients for whom alternative treatment options are ineffective, not tolerated or would be otherwise inadequate to provide sufficient management of pain.

(1 , 5.1) Morphine sulfate extended-release capsules are not indicated as an as-needed (prn) analgesic. (1)

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Morphine sulfate extended-release capsules should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. ( 2.1 ) Morphine sulfate extended-release 100 mg capsules, a single dose greater than 60 mg, or a total daily dose greater than 120 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established. ( 2.1 ) Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg of morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg of oral oxycodone per day, 8 mg of oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.

( 2.1 ) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of morphine sulfate extended-release capsules for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5.1) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse.

(5.1) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with morphine sulfate extended-release capsules. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Instruct patients to swallow morphine sulfate extended-release capsules intact, or to sprinkle the capsule contents on applesauce and immediately swallow without chewing.

( 2.1 , 2.6 ) Instruct patients not to cut, break, chew, crush, or dissolve the pellets in morphine sulfate extended-release capsules to avoid the risk of release and absorption of potentially fatal dose of morphine. ( 2.1 , 2.6 , 5.1 ) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with morphine sulfate extended-release capsules, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose.

( 2.2 , 5.1 , 5.2 , 5.3 ) Morphine sulfate extended-release capsules are administered orally at a frequency of either once daily (every 24 hours) or twice daily (every 12 hours). (2.3) For opioid patients who are not opioid tolerant, initiate with a 30 mg capsule orally every 24 hours. Dosage adjustments may be made every one to two days.

(2.3 , 2.4) Periodically reassess patients receiving morphine sulfate extended-release capsules to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. (2.4) Do not rapidly reduce or abruptly discontinue morphine sulfate extended-release capsules in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

(2.3 , 5.14)

2.1Important Dosage and Administration Instructions Morphine sulfate extended-release capsules should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. Morphine sulfate extended-release capsules 100 mg, a single dose greater than 60 mg, or a total daily dose greater than 120 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 3… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 220 words ▾

3 DOSAGE FORMS AND STRENGTHS Morphine sulfate extended-release capsules, USP contains white to off-white polymer-coated extended-release pellets of morphine sulfate, USP, have an outer opaque capsule with colors and imprints as identified below and are available in seven dose strengths. Morphine Sulfate Extended-Release Capsules USP, 20 mg, has a yellow opaque body and cap, imprinted with “J62” in black ink on cap. Morphine Sulfate Extended-Release Capsules USP, 30 mg, has a violet opaque body and cap, imprinted with “J63” in black ink on cap.

Morphine Sulfate Extended-Release Capsules USP, 40 mg, has a blue violet opaque body and rich yellow opaque cap, imprinted with “J69” in black ink on cap. Morphine Sulfate Extended-Release Capsules USP, 50 mg, has a light blue opaque body and cap, imprinted with “J64” in black ink on cap. Morphine Sulfate Extended-Release Capsules USP, 60 mg, has a red opaque body and cap, imprinted with “J65” in black ink on cap.

Morphine Sulfate Extended-Release Capsules USP, 80 mg, has an orange opaque body and cap, imprinted with “J66” in black ink on cap. Morphine Sulfate Extended-Release Capsules USP, 100 mg, has a light green opaque body and cap, imprinted with “J67” in black ink on cap. Extended-release capsules: 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 80 mg and 100 mg.

( 3 )

⛔ Contraindications 153 words ▾

4 CONTRAINDICATIONS Morphine sulfate extended-release capsules are contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.2) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.7) ] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Warnings and Precautions (5.8) , Drug Interactions (7) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12) ] Hypersensitivity (e.g., anaphylaxis) to morphine [see Adverse Reactions (6.2) ] Significant respiratory depression.

( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. ( 4 ) Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days. ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus.

( 4 ) Hypersensitivity to morphine. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. ( 5.6 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Regularly evaluate closely, particularly during initiation and titration.

( 5.7 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off the opioid. ( 5.9 ) Severe Hypotension : Regularly evaluate during dosage initiation and titration Avoid use of morphine sulfate extended-release capsules in patients with circulatory shock. ( 5.10 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression.

Avoid use of morphine sulfate extended-release capsules in patients with impaired consciousness or coma. ( 5.11 )

5.1Addiction, Abuse, and Misuse Morphine sulfate extended-release capsules contains morphine, a Schedule II controlled substance. As an opioid, morphine sulfate extended-release capsules expose users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed morphine sulfate extended-release capsules.

Addiction can occur at recommended doses and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions (6.2) ] .

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing morphine sulfate extended-release capsules, and reassess all patients receiving morphine sulfate extended-release capsules for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient.

Patients at increased risk may be prescribed opioids such as morphine sulfate extended-release capsules, but use in such patients necessitates intensive counseling about the risks and proper use of morphine sulfate extended-release capsules along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration (2.2) , Warnings and Precautions (5.2) ] . Abuse or misuse of morphine sulfate extended-release capsules by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of morphine and can result in overdose and death [see Overdosage (10) ] .

Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing morphine sulfate extended-release capsules. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and proper disposal of unused drug.

Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

5.2Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Resp… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ] Life Threatening Respiratory Depression [see Warnings and Precautions (5.2) ] Risks from Concomitant Use with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions (5.3) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4) ] Opioid-Induced Hyperalgesia and Allodynia [See Warnings and Precautions (5.6 )] Adrenal Insufficiency [see Warnings and Precautions (5.9) ] Severe Hypotension [see Warnings and Precautions (5.10) ] Risks of Use in Patients with Gastrointestinal Conditions [see Warnings and Precautions (5.12) ] Increased Risk of Seizures in Patients with Seizure Disorders [see Warnings and Precautions (5.13) ] Withdrawal [see Warnings and Precautions (5.14)] Most common adverse reactions (> 10%): constipation, nausea, and somnolence.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. In the randomized study, the most common adverse reactions with morphine sulfate extended-release capsules therapy were drowsiness, constipation, nausea, dizziness, and anxiety. The most common adverse reactions leading to study discontinuation were nausea, constipation (may be severe), vomiting, fatigue, dizziness, pruritus, and somnolence.

Clinical trial patients with chronic cancer pain (n=227) (AE by Body System as seen in 2% or more of patients) Percentage % CENTRAL NERVOUS SYSTEM 28 Drowsiness 9 Dizziness 6 Anxiety 5 Confusion 4 Dry mouth 3 Tremor 2 GASTROINTESTINAL 26 Constipation 9 Nausea 7 Diarrhea 3 Anorexia 3 Abdominal pain 3 Vomiting 2 BODY AS A WHOLE 16 Pain 3 Disease progression 3 Chest pain 2 Diaphoresis 2 Fever 2 Asthenia 2 Accidental injury 2 RESPIRATORY 3 Dyspnea 3 SKIN & APPENDAGES 3 Rash 3 METABOLIC & NUTRITIONAL 3 Peripheral edema 3 HEMIC & LYMPHATIC 4 Anemia 2 Leukopenia 2 In clinical trials in patients with chronic cancer pain, the most common adverse events reported by patients at least once during therapy were drowsiness (9%), constipation (9%), nausea (7%), dizziness (6%), and anxiety (6%).

Other less common side effects expected from morphine sulfate extended-release capsules or seen in less than 2% of patients in the clinical trials were: Body as a Whole: Headache, chills, flu syndrome, back pain, malaise, withdrawal syndrome Cardiovascular: Tachycardia, atrial fibrillation, hypotension, hypertension, pallor, facial flushing, palpitations, bradycardia, syncope Central Nervous System: Confusion, anxiety, abnormal thinking, abnormal dreams, lethargy, depression, loss of concentration, insomnia, amnesia, paresthesia, agitation, vertigo, foot drop, ataxia, hypesthesia, slurred speech, hallucinations, vasodilation, euphoria, apathy, seizures, myoclonus Endocrine: Hyponatremia due to inappropriate ADH secretion, gynecomastia Gastrointestinal: Dysphagia, dyspepsia, stomach atony disorder, gastro-esophageal reflux, delayed gastric emptying, biliary colic Hemic and Lymphatic: Thrombocytopenia Metabolic and Nutritional: Hyponatremia, edema Musculoskeletal: Back pain, bone pain, arthralgia Respiratory: Hiccup, rhinitis, atelectasis, asthma, hypoxia, respiratory insufficiency, voice alteration, depressed cough reflex, non-cardiogenic pulmonary edema Skin and Appendages: Decubitus ulcer, pruritus, skin flush Special Senses: Amblyopia, conjunctivitis, miosis, blurred vision, nystagmus, diplopia Urogenital: Urinary abnormality, amenorrhea, urinary retention, urinary hesitancy, reduced libido, reduced potency, prolonged lab… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with morphine sulfate extended-release capsules. Table 1: Clinically Significant Drug Interactions with Morphine Sulfate Extended-Release Capsules Alcohol Clinical Impact: Concomitant use of alcohol with morphine sulfate extended-release capsules can result in an increase of morphine plasma levels and potentially fatal overdose of morphine. Intervention: Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on morphine sulfate extended-release capsules therapy [see Warnings and Precautions (5.3) ].

Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required.

Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation) . If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration (2.1 , 2.2) , Warnings and Precautions (5.1 , 5.2 , 5.3) ] . Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol.

Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue morphine sulfate extended-release capsules if serotonin syndrome is suspected.

Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.8) ] .

Intervention: Do not use morphine sulfate extended-release capsules in patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of morphine sulfate extended-release capsules and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use.

Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Morphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Because respiratory depression may be greater than otherwise expected, decrease the dosage of morphine sulfate extended-release capsules and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of muscle relaxants and opioids, consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration (2.2) , Warnings and Precautions (5.2 , 5.3) ] .

Examples: cyclobenzaprine, metaxalone Cimetidine Clinical Impact: The concomi… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy : May cause fetal harm. ( 8.1 ) Lactation : Not recommended. ( 8.2 )

8.1Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4) ]. There are no available data with morphine sulfate extended-release capsules in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see Human Data] .

In published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (HDD) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the HDD in the rabbit, growth retardation at 6 times the HDD in the rat, and axial skeletal fusion and cryptorchidism at 16 times the HDD in the mouse.

Administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3 to 4 times the HDD; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the HDD [see Animal Data] . Based on animal data, advise pregnant women of the potential risk to a fetus.

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 Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.

Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.4) ]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate.

Morphine sulfate extended-release capsules are not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including morphine sulfate extended-release capsules, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor.

Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Human Data The results from a population-based prospective cohort, including 70 women exposed to morphine during the first trimester of pregnancy and 448 women exposed to morphine… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4) ]. There are no available data with morphine sulfate extended-release capsules in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see Human Data] .

In published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (HDD) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the HDD in the rabbit, growth retardation at 6 times the HDD in the rat, and axial skeletal fusion and cryptorchidism at 16 times the HDD in the mouse.

Administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3 to 4 times the HDD; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the HDD [see Animal Data] . Based on animal data, advise pregnant women of the potential risk to a fetus.

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 Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.

Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.4) ]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate.

Morphine sulfate extended-release capsules are not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including morphine sulfate extended-release capsules, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor.

Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Human Data The results from a population-based prospective cohort, including 70 women exposed to morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. However, these studie… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 22 words ▾

8.4Pediatric Use The safety and efficacy of morphine sulfate extended-release capsules in patients less than 18 years have not been established.

🧓 Geriatric Use 212 words ▾

8.5Geriatric Use Clinical studies of morphine sulfate extended-release capsules did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients (aged 65 years or older) may have increased sensitivity to morphine. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of morphine sulfate extended-release capsules slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.7) ] . This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Clinical Presentation Acute overdosage with morphine can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2) ] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication.

Treatment of Overdose In cases of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures.

For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. Because the duration of reversal would be expected to be less than the duration of action of morphine in morphine sulfate extended-release capsules, carefully monitor the patient until spontaneous respiration is reliably re-established. Morphine sulfate extended-release capsules will continue to release morphine add to the morphine load for 24 to 48 hours or longer following ingestion, necessitating prolonged monitoring.

If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered.

If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of the reversal agent.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of morphine is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine.

Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

12.2Pharmacodynamics CNS Depressant/Alcohol Interaction Additive pharmacodynamic effects may be expected when morphine sulfate extended-release capsules are used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression. Effects on the Central Nervous System Morphine produces respiratory depression by direct action on brainstem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brainstem respiratory centers to both increases in carbon dioxide tension and to electrical stimulation.

Morphine causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Effects on the Gastrointestinal Tract and Other Smooth Muscle Morphine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation.

Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED). Effects on the Cardiovascular System Morphine produces peripheral vasodilation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.

Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions (6.2) ] . They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility.

The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions (6.2) ] . Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.

Overall, the effects of opioids appear to be modestly immunosuppressive. Concentration-Efficacy Relationships The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonists. The minimum effective analgesic concentration of morphine for any individual patient may increase over time due to an increase in pain, th… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 114 words ▾

12.1Mechanism of Action Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of morphine is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine.

Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

📦 How Supplied / Storage and Handling ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Morphine sulfate extended-release capsules, USP contain white to off-white polymer-coated extended-release pellets of morphine sulfate and are available in seven dose strengths. Morphine Sulfate Extended-Release Capsules USP, 20 mg are size 4 capsule, yellow opaque body and cap, imprinted with “J62” in black ink on cap. Capsules are supplied as follows: Bottles of 30: NDC 0115-1277-08 Bottles of 60: NDC 0115-1277-13 Bottles of 100: NDC 0115-1277-01 Bottles of 1000: NDC 0115-1277-03 Morphine Sulfate Extended-Release Capsules USP, 30 mg are size 4 capsule, violet opaque body and cap, imprinted with “J63” in black ink on cap.

Capsules are supplied as follows: Bottles of 30: NDC 0115-1278-08 Bottles of 60: NDC 0115-1278-13 Bottles of 100: NDC 0115-1278-01 Bottles of 1000: NDC 0115-1278-03 Morphine Sulfate Extended-Release Capsules USP, 40 mg are size 2 capsule, blue violet opaque body and rich yellow opaque cap, imprinted with “J69” in black ink on cap. Capsules are supplied as follows: Bottles of 100: NDC 0115-1479-01 Morphine Sulfate Extended-Release Capsules USP, 50 mg are size 2 capsule, light blue opaque body and cap, imprinted with “J64” in black ink on cap.

Capsules are supplied as follows: Bottles of 30: NDC 0115-1279-08 Bottles of 60: NDC 0115-1279-13 Bottles of 100: NDC 0115-1279-01 Bottles of 1000: NDC 0115-1279-03 Morphine Sulfate Extended-Release Capsules USP, 60 mg are size 1 capsule, red opaque body and cap, imprinted with “J65” in black ink on cap. Capsules are supplied as follows: Bottles of 30: NDC 0115-1280-08 Bottles of 60: NDC 0115-1280-13 Bottles of 100: NDC 0115-1280-01 Bottles of 1000: NDC 0115-1280-03 Morphine Sulfate Extended-Release Capsules USP, 80 mg are size 0 capsule, orange opaque body and cap, imprinted with “J66” in black ink on cap.

Capsules are supplied as follows: Bottles of 30: NDC 0115-1281-08 Bottles of 60: NDC 0115-1281-13 Bottles of 100: NDC 0115-1281-01 Bottles of 1000: NDC 0115-1281-03 Morphine Sulfate Extended-Release Capsules USP, 100 mg are size 0 capsule, light green opaque body and cap, imprinted with “J67” in black ink on cap. Capsules are supplied as follows: Bottles of 30: NDC 0115-1282-08 Bottles of 60: NDC 0115-1282-13 Bottles of 100: NDC 0115-1282-01 Bottles of 1000: NDC 0115-1282-03 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Protect from light and moisture. Dispense in a tightly-closed, light-resistant container as defined in the USP, with a child-resistant closure, as required. Store morphine sulfate extended-release capsules securely and dispose of properly [see Patient Counseling Information (17) ] .

📋 Description ~1 min read ▾

11 DESCRIPTION Morphine Sulfate Extended-Release Capsules, USP, an opioid agonist, are for oral use and contain pellets of morphine sulfate. Each morphine sulfate extended-release capsule, USP contains either 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 80 mg, or 100 mg of morphine sulfate, USP and the following inactive ingredients common to all strengths: hypromellose, ethylcellulose, methacrylic acid copolymer, polyethylene glycol, diethyl phthalate, talc, corn starch, and sucrose. The capsule shells contain gelatin and titanium dioxide.

In addition, the 20 mg and 40 mg capsule shells contain yellow iron oxide; the 30 mg and 40 mg capsule shells contain FD&C Blue No. 1 and FD&C Red No. 3; the 50 mg capsule shell contains FD&C Blue No.

1; the 60 mg capsule shell contains FD&C Red No. 40; the 80 mg capsule shell contains D&C Red No. 28, D&C Yellow No.

10, and FD&C Red No. 40; and the 100 mg capsule shell contains D&C Yellow No. 10 and FD&C Green No.

3. The black ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide, potassium hydroxide, and purified water. The chemical name of morphine sulfate is 7,8-didehydro-4,5α-epoxy-17-methylmorphinan-3,6α-diol sulfate (2:1) (salt) pentahydrate.

The molecular formula is (C 17 H 19 NO 3 )2∙H 2 SO 4 ∙5H 2 O and its molecular weight is 758.85. Morphine sulfate, USP is an odorless, white, crystalline powder with a bitter taste. It has a solubility of 1 in 21 parts of water and 1 in 1000 parts of alcohol, but is practically insoluble in chloroform or ether.

The octanol: water partition coefficient of morphine is 1.42 at physiologic pH and the pK b is 7.9 for the tertiary nitrogen (mostly ionized at pH 7.4). Its structural formula is: Chemical Structure USP dissolution test pending.

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store morphine sulfate extended-release capsules securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home . Inform patients that leaving morphine sulfate extended-release capsules unsecured can pose a deadly risk to others in the home [see Warnings and Precautions ( 5.1 , 5.2 , 5.5 ) , Drug Abuse and Dependence (9.2) ].

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused morphine sulfate extended-release capsules should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.

Addiction, Abuse, and Misuse Inform patients that the use of morphine sulfate extended-release capsules, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1) ] . Instruct patients not to share morphine sulfate extended-release capsules with others and to take steps to protect morphine sulfate extended-release capsules from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting morphine sulfate extended-release capsules or when the dosage is increased, and that it can occur even at recommended dosages.

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Warnings and Precautions ( 5.2 ) ] . Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.2) ] . Interactions with Alcohol Instruct patients not to consume alcoholic beverages, or prescription and over-the-counter products that contain alcohol, during treatment with morphine sulfate extended-release capsules.

The co-ingestion of alcohol with morphine sulfate extended-release capsules may result in increased plasma levels and a potentially fatal overdose of morphine [see Warnings and Precautions (5.3) and Drug Interactions (7) ] . Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if morphine sulfate extended-release capsules are used with benzodiazepines or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.3) and Drug Interactions (7) ] .

Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.

Discuss with the patient the options for obtaining an opioid overdose reversal agen… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

Medication Guide Morphine Sulfate (mor’ feen sul’ fate) Extended-Release Capsules, USP, CII Morphine sulfate extended-release capsules are: A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine when other pain medicines do not treat your pain well enough or you cannot tolerate them. A long-acting (extended-release) opioid pain medicine that can put you at risk for overdose and death.

Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death. Not to be taken on an “as needed” basis. Important information about morphine sulfate extended-release capsules: Get emergency help or call 911 right away if you take too much morphine sulfate extended-release capsules (overdose).

When you first start taking morphine sulfate extended-release capsules, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse an opioid overdose. Taking morphine sulfate extended-release capsules with other opioid medicines, benzodiazepines, gabapentinoids (gabapentin or pregabalin), alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.

Never give anyone else your morphine sulfate extended-release capsules. They could die from taking it. Selling or giving away morphine sulfate extended-release capsules is against the law.

Store morphine sulfate extended-release capsules securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Do not take morphine sulfate extended-release capsules if you have: severe asthma, trouble breathing, or other lung problems. a bowel blockage or have narrowing of the stomach or intestines. Before taking morphine sulfate extended-release capsules, tell your healthcare provider if you have a history of: head injury, seizures liver, kidney, thyroid problems problems urinating pancreas or gallbladder problems abuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental health problems.

Tell your healthcare provider if you are: noticing your pain getting worse. If your pain gets worse after you take morphine sulfate extended-release capsules, do not take more of morphine sulfate extended-release capsules without first talking to your healthcare provider. Talk to your healthcare provider if the pain that you have increases, if you feel more sensitive to pain, or if you have new pain after taking morphine sulfate extended-release capsules. pregnant or planning to become pregnant.

Use of morphine sulfate extended-release capsules for an extended period of time during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. breastfeeding. Not recommended during treatment with morphine sulfate extended-release capsules. It may harm your baby. living in a household where there are small children or someone who has abused street or prescription drugs. taking prescription or over-the-counter medicines, vitamins, or herbal supplements.

Taking morphine sulfate extended-release capsules with certain other medicines can cause serious side effects. When taking morphine sulfate extended-release capsules: Do not change your dose. Take morphine sulfate extended-release capsules exactly as prescribed by your healthcare provider.

Use the lowest dose possible for the shortest time needed. Take your prescribed dose every 12 or 24 hours at the same time every day. Do not take more than your prescribed dose in 24 hours.

If you miss a dose, take your next dose at your usual time. Swallow morp… [Excerpted — this section continues on DailyMed.]

🍼 Nursing Mothers 76 words ▾

8.3Females and Males of Reproductive Potential Infertility Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2) , Clinical Pharmacology (12.2) ]. In published animal studies, morphine administration adversely effected fertility and reproductive endpoints in male rats and prolonged estrus cycle in female rats [see Nonclinical Toxicology (13) ] .

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Morphine sulfate extended-release capsules contain polymer coated extended-release pellets of morphine sulfate that release morphine significantly more slowly than oral morphine solution. Following the administration of oral morphine solution, approximately 50% of the morphine absorbed reaches the systemic circulation within 30 minutes compared to 8 hours with an equal amount of morphine sulfate extended-release capsules. Because of pre-systemic elimination, only about 20% to 40% of the administered dose reaches the systemic circulation.

Both dose-normalized C max and dose-normalized AUC 0-48hr values of morphine after a single dose administration of morphine sulfate extended-release capsules in healthy volunteers are less than those for morphine oral solution or an extended-release tablet formulation (Table 2). When morphine sulfate extended-release capsules were given twice daily to 24 patients with chronic pain due to malignancy, steady-state was achieved in about two days. At steady-state, morphine sulfate extended-release capsules have a significantly lower C max and a higher C min than equivalent doses of oral morphine solution given every 4 hours and an extended-release tablet given twice daily.

When given once daily to 24 patients with malignancy, morphine sulfate extended-release capsules had a similar C max and higher C min at steady-state when compared to extended-release morphine tablets, given twice daily at an equivalent total daily dosage (see Table 2). The single-dose pharmacokinetics of morphine sulfate extended-release capsules is linear over the dosage range of 30 to 100 mg. Table 2: Mean pharmacokinetic parameters (% coefficient variation) resulting from a fasting single dose study in normal volunteers and a multiple-dose study in patients with cancer pain Regimen/Dosage Form AUC #, + (ng∙h/mL) C max + (ng/mL) T max (h) C min + (ng/mL) Fluctuation * Single Dose (n=24) Morphine Sulfate Extended-Release Capsule 271.0 (19.4) 15.6 (24.4) 8.6 (41.1) N/A N/A Extended-Release Tablet 304.3 (19.1) 30.5 (32.1) 2.5 (52.6) N/A N/A Morphine Solution 362.4 (42.6) 64.4 (38.2) 0.9 (55.8) N/A N/A Multiple Dose (n=24) Morphine Sulfate Extended-Release Capsule Once Daily 500.9 (38.6) 37.3 (37.7) 10.3 (32.2) 9.9 (52.3) 3.0 (45.5) Extended-Release Tablet Twice Daily 457.3 (40.2) 36.9 (42.0) 4.4 (53.0) 7.6 (60.3) 4.1 (51.5) # For single dose AUC = AUC 0-48h , for multiple dose AUC = AUC 0-24h at steady-state + For single dose parameter normalized to 100 mg, for multiple dose parameter normalized to 100 mg per 24 hours * Steady-state fluctuation in plasma concentrations = C max -C min /C min Food Effect: While concurrent administration of food slows the rate of absorption of morphine sulfate extended-release capsules, the extent of absorption is not affected and morphine sulfate extended-release capsules can be administered without regard to meals.

Distribution Once absorbed, morphine is distributed to skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen and brain. The volume of distribution of morphine is approximately 3 to 4 L/kg. Morphine is 30% to 35% reversibly bound to plasma proteins.

Although the primary site of action of morphine is in the CNS, only small quantities pass the blood-brain barrier. Morphine also crosses the placental membranes [see Use in Specific Populations (8.1) ] and has been found in breast milk [see Use in Specific Populations (8.2) ] . Elimination Metabolism Major pathways of morphine metabolism include glucuronidation in the liver to produce metabolites including morphine-3-glucuronide, M3G (about 50%) and morphine-6-glucuronide, M6G (about 5% to 15%) and sulfation in the liver to produce morphine-3-etheral sulfate.

A small fraction (less than 5%) of morphine is demethylated. M3G has no significant contribution to the analgesic activity. Although M6G does not readily cross the blood-brain barrier, it has been shown to have opioid agonist and analgesic act… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~2 min read ▾

12.2Pharmacodynamics CNS Depressant/Alcohol Interaction Additive pharmacodynamic effects may be expected when morphine sulfate extended-release capsules are used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression. Effects on the Central Nervous System Morphine produces respiratory depression by direct action on brainstem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brainstem respiratory centers to both increases in carbon dioxide tension and to electrical stimulation.

Morphine causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Effects on the Gastrointestinal Tract and Other Smooth Muscle Morphine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation.

Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED). Effects on the Cardiovascular System Morphine produces peripheral vasodilation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.

Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions (6.2) ] . They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility.

The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions (6.2) ] . Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.

Overall, the effects of opioids appear to be modestly immunosuppressive. Concentration-Efficacy Relationships The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonists. The minimum effective analgesic concentration of morphine for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome, and/or the development of analgesic tolerance [see Dosage and Administration (2.1, 2.3) ] .

Concentration–Adverse Reaction Relationships There is a relationship between increasing morphine plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see Dosage and Administration (2.1, 2.3, 2.4) ].

🔒 Drug Abuse and Dependence ~3 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Morphine sulfate extended-release capsules contain morphine, a Schedule II controlled substance.

9.2Abuse Morphine sulfate extended-release capsules contains morphine, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1) ] . Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of morphine sulfate extended-release capsules increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death.

The risk is increased with concurrent abuse of morphine sulfate extended-release capsules with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of morphine sulfate extended-release capsules abuse include those with a history of prolonged use of any opioid, including products containing morphine, those with a history of drug or alcohol abuse, or those who use morphine sulfate extended-release capsules in combination with other abused drugs. “Drug-seeking” behavior is very common in persons with substance use disorders.

Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Morphine sulfate extended-release capsules, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Morphine sulfate extended-release capsules Abuse of morphine sulfate extended-release capsules poses a risk of overdose and death. This risk is increased with concurrent use of morphine sulfate extended-release capsules with alcohol and/or other CNS depressants. Taking cut, broken chewed, crushed, or dissolved morphine sulfate extended-release capsules enhances drug release and increases the risk of overdose and death.

Morphine sulfate extended-release capsules are approved for oral use only. Inappropriate intravenous, intramuscular, or subcutaneous use of morphine sulfate extended-release capsules can result in death, local tissue necrosis, i… [Excerpted — this section continues on DailyMed.]

🔒 Controlled Substance 14 words ▾

9.1Controlled Substance Morphine sulfate extended-release capsules contain morphine, a Schedule II controlled substance.

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals to evaluate the carcinogenic potential of morphine have not been conducted. Mutagenesis No formal studies to assess the mutagenic potential of morphine have been conducted. In the published literature, morphine was found to be mutagenic in vitro increasing DNA fragmentation in human T-cells.

Morphine was reported to be mutagenic in the in vivo mouse micronucleus assay and positive for the induction of chromosomal aberrations in mouse spermatids and murine lymphocytes. Mechanistic studies suggest that the in vivo clastogenic effects reported with morphine in mice may be related to increases in glucocorticoid levels produced by morphine in this species. In contrast to the above positive findings, in vitro studies in the literature have also shown that morphine did not induce chromosomal aberrations in human leukocytes or translocations or lethal mutations in Drosophila .

Impairment of Fertility No formal nonclinical studies to assess the potential of morphine to impair fertility have been conducted. Several nonclinical studies from the literature have demonstrated adverse effects on male fertility in the rat from exposure to morphine. One study in which male rats were administered morphine sulfate subcutaneously prior to mating (up to 30 mg/kg twice daily) and during mating (20 mg/kg twice daily) with untreated females, a number of adverse reproductive effects including reduction in total pregnancies and higher incidence of pseudo pregnancies at 20 mg/kg/day (3.2 times the HDD) were reported.

Studies from the literature have also reported changes in hormonal levels in male rats (i.e. testosterone, luteinizing hormone) following treatment with morphine at 10 mg/kg/day or greater (1.6 times the HDD). Female rats that were administered morphine sulfate intraperitoneally prior to mating exhibited prolonged estrous cycles at 10 mg/kg/day (1.6 times the HDD). Exposure of adolescent male rats to morphine has been associated with delayed sexual maturation and following mating to untreated females, smaller litters, increased pup mortality, and/or changes in reproductive endocrine status in adult male offspring have been reported (estimated 5 times the plasma levels at the HDD).

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

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals to evaluate the carcinogenic potential of morphine have not been conducted. Mutagenesis No formal studies to assess the mutagenic potential of morphine have been conducted. In the published literature, morphine was found to be mutagenic in vitro increasing DNA fragmentation in human T-cells.

Morphine was reported to be mutagenic in the in vivo mouse micronucleus assay and positive for the induction of chromosomal aberrations in mouse spermatids and murine lymphocytes. Mechanistic studies suggest that the in vivo clastogenic effects reported with morphine in mice may be related to increases in glucocorticoid levels produced by morphine in this species. In contrast to the above positive findings, in vitro studies in the literature have also shown that morphine did not induce chromosomal aberrations in human leukocytes or translocations or lethal mutations in Drosophila .

Impairment of Fertility No formal nonclinical studies to assess the potential of morphine to impair fertility have been conducted. Several nonclinical studies from the literature have demonstrated adverse effects on male fertility in the rat from exposure to morphine. One study in which male rats were administered morphine sulfate subcutaneously prior to mating (up to 30 mg/kg twice daily) and during mating (20 mg/kg twice daily) with untreated females, a number of adverse reproductive effects including reduction in total pregnancies and higher incidence of pseudo pregnancies at 20 mg/kg/day (3.2 times the HDD) were reported.

Studies from the literature have also reported changes in hormonal levels in male rats (i.e. testosterone, luteinizing hormone) following treatment with morphine at 10 mg/kg/day or greater (1.6 times the HDD). Female rats that were administered morphine sulfate intraperitoneally prior to mating exhibited prolonged estrous cycles at 10 mg/kg/day (1.6 times the HDD). Exposure of adolescent male rats to morphine has been associated with delayed sexual maturation and following mating to untreated females, smaller litters, increased pup mortality, and/or changes in reproductive endocrine status in adult male offspring have been reported (estimated 5 times the plasma levels at the HDD).

📖 Instructions for Use ~1 min read ▾

Instructions For Use Morphine Sulfate (mor’ feen sul’ fate) Extended-Release Capsules, USP, CII If you cannot swallow morphine sulfate extended-release capsules, tell your healthcare provider. There may be another way to take morphine sulfate extended-release capsules that may be right for you. If your healthcare provider tells you that you can take morphine sulfate extended-release capsules using this other way, follow these steps: Morphine sulfate extended-release capsules can be opened and the pellets inside the capsule can be sprinkled over applesauce, as follows: Figure 1 Open the morphine sulfate extended-release capsule and sprinkle the pellets over about one tablespoon of applesauce.

(see Figure 1) Figure 2 Swallow all of the applesauce and pellets right away. Do not save any of the applesauce and pellets for another dose. (see Figure 2) Figure 3 Rinse your mouth to make sure you have swallowed all of the pellets.

Do not chew the pellets. (see Figure 3) Figure 4 Flush the empty capsule down the toilet right away. (see Figure 4) You should not receive morphine sulfate extended-release capsules through a nasogastric tube.

This Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured by: Amneal Pharmaceuticals of NY, LLC Brookhaven, NY 11719 Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev.

12-2021-03 Figure 1 Figure 2 Figure 3 Figure 4

📄 Recent Major Changes 33 words ▾

RECENT MAJOR CHANGES Boxed Warning 10/2025 Indications and Usage (1) 10/2025 Dosage and Administration (2.2 , 2.3 , 2.5) 10/2025 Warnings and Precautions (5.1 , 5.2 , 5.3 , 5.12 , 5.14) 10/2025

📄 Package Label / Principal Display Panel 182 words ▾

PRINCIPAL DISPLAY PANEL - 20 mg Capsule Bottle Label NDC 0115-1277-01 Morphine Sulfate Extended-Release Capsules USP, 20 mg Rx only 100 Capsules Amneal Pharmaceuticals LLC 1

PRINCIPAL DISPLAY PANEL - 30 mg Capsule Bottle Label NDC 0115-1278-01 Morphine Sulfate Extended-Release Capsules USP, 30 mg Rx only 100 Capsules Amneal Pharmaceuticals LLC 2

PRINCIPAL DISPLAY PANEL - 40 mg Capsule Bottle Label NDC 0115-1479-01 Morphine Sulfate Extended-Release Capsules USP, 40 mg Rx only 100 Capsules Amneal Pharmaceuticals LLC 3

PRINCIPAL DISPLAY PANEL - 50 mg Capsule Bottle Label NDC 0115-1279-01 Morphine Sulfate Extended-Release Capsules USP, 50 mg Rx only 100 Capsules Amneal Pharmaceuticals LLC 4

PRINCIPAL DISPLAY PANEL - 60 mg Capsule Bottle Label NDC 0115-1280-01 Morphine Sulfate Extended-Release Capsules USP, 60 mg Rx only 100 Capsules Amneal Pharmaceuticals LLC 5

PRINCIPAL DISPLAY PANEL - 80 mg Capsule Bottle Label NDC 0115-1281-01 Morphine Sulfate Extended-Release Capsules USP, 80 mg Rx only 100 Capsules Amneal Pharmaceuticals LLC 6

PRINCIPAL DISPLAY PANEL - 100 mg Capsule Bottle Label NDC 0115-1282-01 Morphine Sulfate Extended-Release Capsules USP, 100 mg Rx only 100 Capsules Amneal Pharmaceuticals LLC 7

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

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

Medicare Part D (outpatient prescription) spending for Morphine Sulfate — the program that covers self-administered drugs. 9 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Morphine Sulfate. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$3.7M
Claims incl. refills
161.4K
Beneficiaries
87.6K
Spend / beneficiary
$42.30
Spend / claim
$22.95
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.
🛡
This drug has a REMS. A Risk Evaluation & Mitigation Strategy is an FDA-required safety program. It may require enrollment, counseling, or monitoring to manage a serious risk. See the boxed warning & full label below, and REMS@FDA ↗.

About this NDC listing & data coverage

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

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Amneal Pharmaceuticals of New York LLC. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 30 capsules (00115-1281-08), 1000 capsules (00115-1281-03). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Amneal Pharmaceuticals of New York LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 00115-1280-01 · Amneal 00115-1282-01 · Amneal →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.