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Morphine sulfate 30 mg Tablet, Film Coated, Extended Release, 100-count — NDC 0228-4271-11 (Billing 00228-4271-11)

by Actavis Pharma, Inc. · 100 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE

This is a package of 100 tablets of Morphine sulfate 30 mg Tablet, Film Coated, Extended Release from Actavis Pharma, Inc., no longer marketed (first marketed Oct 2015), no longer in the FDA NDC Directory, this package's marketing ended Jul 2026; retail pharmacies pay about $0.4334 per tablet (NADAC). It is this product's only package size.

NDC 00228-4271-11
🏷️ FDA NDC (as labeled) 0228-4271-11 billing pads the labeler segment with a zero
Rx only Generic Discontinued CII 🛡 REMS ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 30, 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 ↗
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Jul 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0228-4271-11
Product NDC 0228-4271
11-digit billing NDC 00228427111
NCPDP billing unit EA — each (per item)
UNII X3P646A2J0
Application # ANDA203849
SPL Set ID 75fb4282-0bbd-4d63-a7d1-5142780a4fae
Established class (EPC) Opioid Agonist
Mechanism of action Full Opioid Agonists
DEA schedule CII
Marketing category ANDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Jul 2026)
Marketing start 2015-10-26
Marketing end 2026-07-31
Route ORAL
Dosage form TABLET, FILM COATED, EXTENDED RELEASE
Substance MORPHINE SULFATE
TE code (Orange Book) AB · RLD · RS

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

GCN Seq No 004096
GCN 16640
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 SULF ER 30 MG TABLET
FDB brand name Morphine Sulfate Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 004096
  • GCN: 16640
  • HICL (First Databank): 001694
  • AHFS class code: 28:08.08.00
Why two NDCs? The FDA registers this code as 0228-4271-11 — 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 → 00228-4271-11. 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.

Clinical

Label name MORPHINE SULF ER 30 MG TABLET Ingredient Morphine Sulfate
📖 What it is MedlinePlus · NLM

Morphine is used to relieve severe pain. Morphine is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.

Read the full MedlinePlus article ↗
📗 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 eaPer package
Retail pharmacies payNADAC · weekly $0.433 $43.34 / 100 tablets
Medicaid paysCMS SDUD · 12 mo $0.4175 $41.75 / 100 tablets
Medicare drug plans payPart D · Q2 2026 $0.3829 $38.29 / 100 tablets
NADAC price history (per ea) — tap or hover for the price & month
Dec 2021 Jul 2022 Feb 2024 Jul 2026 $0.434 $0.298
▲ Up 30% over the last 23 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
00228-4271-11 You're viewing this Main listing 100 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE 2015-10-26 Jul 31, 2026 Discontinued by firm

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Morphine Sulfate 30 mg 43386-0541-01 Lupin 100 tablets $0.346 — FDA listed save 20%
Morphine sulfate 30 mgthis 00228-4271-11 Actavis 100 tablets $0.433 AB Discontinued —
Morphine Sulfate 30 mg 00406-8330-01 SpecGx 100 tablets $0.441 AB Availability likely +2%
Morphine Sulfate Extended Release 30 mg 00904-6558-61 Major 1 tablet $0.441 AB Availability likely +2%
Morphine Sulfate Extended Release 30 mg 42858-0802-01 Rhodes 100 tablets $0.441 AB Availability likely +2%
Morphine sulfate 30 mg 63304-0451-01 Sun 100 tablets $0.441 AB Availability likely +2%
Morphine Sulfate Extended Release 30 mg 68084-0158-01 American 1 tablet $0.441 AB Availability likely +2%
MS Contin 30 mg 42858-0631-01 Rhodes 100 tablets $8.948 AB Availability likely +1965%
Morphine sulfate 30 mg 63629-1088-01 Bryant 100 tablets — AB Discontinued —
Morphine Sulfate 30 mg 63629-4484-00 Bryant 40 tablets — AB FDA listed —
Morphine sulfate 30 mg 71335-0676-00 Bryant 40 tablets — AB FDA listed —
Morphine sulfate 30 mg 72162-1790-01 Bryant 100 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2015
On the market since
Oct 2015
📍
2026
Currently FDA-listed
11 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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

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

Inactive Ingredients / Excipients

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

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

LabelerActavis Pharma, Inc.
Application holderACTAVIS ELIZABETH LLC AN INDIRECT WHOLLY OWNED SUB OF TEVA PHARMACEUTICALS USA INC
FDA applicationANDA203849 (ANDA)
Labeler code00228
First marketedOct 2015
DEA scheduleCII
Product typeHuman Prescription Drug
Portfolio324 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 🆘 Overdosage 🧬 Clinical Pharmacology 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🔒 Drug Abuse and Dependence 🧪 Nonclinical Toxicology 📄 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 TABLETS Addiction, Abuse, and Misuse Because the use of morphine sulfate extended-release 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, especially during initiation or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of morphine sulfate extended-release tablets are essential. Instruct patients to swallow morphine sulfate extended-release tablets whole; crushing, chewing, or dissolving morphine sulfate extended-release tablets can cause rapid release and absorption of a potentially fatal dose of morphine [see Warnings and Precautions ( 5.2 )] . Accidental Ingestion Accidental ingestion of even one dose of morphine sulfate extended-release tablets, especially by children, can result in a fatal overdose of morphine [see Warnings and Precautions ( 5.2 )] .

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 extended-release 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 TABLETS See full prescribing information for complete boxed warning.

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

To reduce the risk of respiratory depression, proper dosing and titration of morphine sulfate extended-release are essential. Instruct patients to swallow morphine sulfate extended-release tablets whole to avoid exposure to a potentially fatal dose of morphine. (5.2 ) Accidental ingestion of morphine sulfate extended-release tablets, especially by children, can result in a fatal overdose of morphine.

(5.2 ) 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 for use in patients for whom alternative treatment options are inadequate. ( 5.3 , 7 ) 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… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Morphine sulfate extended-release tablets 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 (5.2)] , reserve opioid analgesics, including morphine sulfate extended-release, 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 tablets are not indicated as an as-needed (prn) analgesic. Morphine sulfate extended-release is an opioid agonist 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, 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 tablets are not indicated as an as-needed (prn) analgesic. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Morphine sulfate extended-release tablets should be prescribed only by healthcare providers 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 and 200 mg tablets, 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 tablets 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 ) 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.

( 2.1 , 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with morphine sulfate extended-release tablets. 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 tablets intact and not to cut, break, chew, crush, or dissolve morphine sulfate extended-release tablets (risk of potentially fatal dose) ( 2.1 , 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 tablets, 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 tablets are administered orally once every 8 or 12 hours. ( 2.3 ) For patients who are not opioid tolerant, initiate with 15 mg tablets orally every 8 to 12 hours. ( 2.3 ) Periodically reassess patients receiving morphine sulfate extended-release tablets 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 tablets in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.5 , 5.14 )

2.1Important Dosage and Administration Instructions Morphine sulfate extended-release should be prescribed 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 100 mg and 200 mg tablets, 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 morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone daily, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautio… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 158 words ▾

3 DOSAGE FORMS AND STRENGTHS 15 mg – Each round, white to off white, film-coated tablet debossed with on one side and 270 on the other side contains 15 mg of morphine sulfate, USP. 30 mg – Each round, yellow, film-coated tablet debossed with on one side and 271 on the other side contains 30 mg of morphine sulfate, USP. 60 mg – Each round, pink, film-coated tablet debossed with on one side and 311 on the other side contains 60 mg of morphine sulfate, USP.

100 mg – Each round, red, film-coated tablet debossed with on one side and 323 on the other side contains 100 mg of morphine sulfate, USP. 200 mg – Each capsule-shaped, red, film-coated tablet debossed with on one side and 347 on the other side contains 200 mg of morphine sulfate, USP. Extended-release tablets: 15 mg, 30 mg, 60 mg, 100 mg, 200 mg ( 3 ) logo logo logo logo logo

⛔ Contraindications 154 words ▾

4 CONTRAINDICATIONS Morphine sulfate extended-release is 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, particularly during initiation and titration.

( 5.7 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.9 ) Severe Hypotension : Regularly evaluate during dosage initiation and titration. Avoid use 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 in patients with impaired consciousness or coma. ( 5.11 )

5.1Addiction, Abuse, and Misuse Morphine sulfate extended-release contains morphine, a Schedule II controlled substance. As an opioid, morphine sulfate extended-release exposes its 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.

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, and reassess all patients receiving morphine sulfate extended-release for 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, but use in such patients necessitates intensive counseling about the risks of proper use of morphine sulfate extended-release 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 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. 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. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depres… [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 )] Interactions 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 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.12 )] Seizures [see Warnings and Precautions ( 5.13 )] Withdrawal [see Warnings and Precautions ( 5.14 )] Most common adverse reactions (>10%): constipation, nausea, and sedation.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Morphine sulfate extended-release may increase the risk of serious adverse reactions such as those observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, or shock [see Overdosage ( 10 )] .

Most Frequently Observed Reactions In clinical trials, the most common adverse reactions with morphine sulfate extended-release were constipation, dizziness, sedation, nausea, vomiting, sweating, dysphoria, and euphoric mood. Some of these effects seem to be more prominent in ambulatory patients and in those not experiencing severe pain. Less Frequently Observed Reactions Cardiovascular disorders: tachycardia, bradycardia, palpitations Eye disorders: visual impairment, vision blurred, diplopia, miosis Gastrointestinal disorders: dry mouth, diarrhea, abdominal pain, constipation, dyspepsia General disorders and administration site conditions: chills, feeling abnormal, edema, edema peripheral, weakness Hepatobiliary disorders: biliary colic Metabolism and nutrition disorders: anorexia Musculoskeletal and connective tissue disorders: muscle rigidity, muscle twitching Nervous system disorders: presyncope, syncope, headache, tremor, uncoordinated muscle movements, convulsion, intracranial pressure increased, taste alteration, paresthesia, nystagmus Psychiatric disorders: agitation, mood altered, anxiety, depression, abnormal dreams, hallucination, disorientation, insomnia Renal and urinary disorders: urinary retention, urinary hesitation, antidiuretic effects Reproductive system and breast disorders: reduced libido and/or potency Respiratory, thoracic, and mediastinal disorders: laryngospasm Skin and subcutaneous tissue disorders: pruritus, urticaria, rash Vascular disorders: flushing, hypotension, hypertension

6.2Post-Marketing Experience The following adverse reactions have been identified during post-approval use of morphine sulfate extended-release. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Amenorrhea, asthenia, bronchospasm, confusional state, drug hypersensitivity, fatigue, hyperalgesia, hypertonia, ileus, increased hepatic enzymes, intestinal obstruction, lethargy, malaise, pulmonary edema, thinking disturbances, somnolence, and vertigo.

Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often follo… [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. Table 1: Clinically Significant Drug Interactions with Morphine Sulfate Extended-Release 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 [see Warnings and Precautions ( 5.3 )].

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 and 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 ( 2.2 , 2.5 ), Warnings and Precautions ( 5.1 , 5.2 , 5.3 )]. Examples: Benzodiazepines and other sedative 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 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 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 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 and/or the muscle relaxant as necessary.

Due to the risk of respiratory depression with concomitant use of skeletal 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 concomitant use of cimetidine can potentiate morphine effects and increase risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Evaluate patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of morphine sulfate extended-release and/or cimetidine as necessary.

Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by indu… [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 withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . There are no available data with morphine sulfate extended-release 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 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 is 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, 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… [Excerpted — this section continues on DailyMed.]

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Clinical Presentation Acute overdose 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 case of overdose, priorities are the re-establishment 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, carefully monitor the patient until spontaneous respiration is reliably reestablished. Morphine sulfate extended-release will continue to release morphine and 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 is 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 electrical stimulation.

Morphine causes miosis, even in total darkness. Pinpoint pupils are a sign of narcotic 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 in the 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 reduction in biliary and pancreatic secretions, spasm of the sphincter of Oddi, 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 and/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… [Excerpted — this section continues on DailyMed.]

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Morphine sulfate extended-release tablets are available as follows: 15 mg Each round, white to off white, film-coated tablet debossed with on one side and 270 on the other side contains 15 mg of morphine sulfate, USP. Tablets are supplied in bottles of 100 (NDC 0228-4270-11). 30 mg Each round, yellow, film-coated tablet debossed with on one side and 271 on the other side contains 30 mg of morphine sulfate, USP.

Tablets are supplied in bottles of 100 (NDC 0228-4271-11). 60 mg Each round, pink, film-coated tablet debossed with on one side and 311 on the other side contains 60 mg of morphine sulfate, USP. Tablets are supplied in bottles of 100 (NDC 0228-4311-11).

100 mg Each round, red, film-coated tablet debossed with on one side and 323 on the other side contains 100 mg of morphine sulfate, USP. Tablets are supplied in bottles of 100 (NDC 0228-4323-11). 200 mg Each capsule-shaped, red, film-coated tablet debossed with on one side and 347 on the other side contains 200 mg of morphine sulfate, USP.

Tablets are supplied in bottles of 100 (NDC 0228-4347-11). Store at 25°C (77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Store morphine sulfate extended-release tablets securely and dispose of properly [see Patient Counseling Information ( 17 )] .

Dispense in a tight, light-resistant container as defined in the USP. logo logo logo logo logo

📋 Description 191 words ▾

11 DESCRIPTION Morphine sulfate extended-release tablets are for oral use and contain morphine sulfate, USP an opioid agonist. Each tablet contains the following inactive ingredients common to all strengths: anhydrous lactose, cetostearyl alcohol, hydroxyethyl cellulose, magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide. The 30 mg tablets also contain yellow iron oxide.

The 60 mg tablets also contain red iron oxide. The 100 mg and 200 mg tablets also contain red iron oxide and yellow iron oxide. The tablet strengths, 15 mg, 30 mg, 60 mg, 100 mg, and 200 mg, describe the amount of morphine per tablet as the pentahydrated sulfate salt (morphine sulfate).

Morphine sulfate, USP is an odorless, white, crystalline powder with a bitter taste. Morphine sulfate, USP is soluble in water and ethanol. 1 g dissolves in 15.5 mL of water at 25°C and 1 g dissolves in 565 mL of ethanol at 25°C.

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 molecular weight is 758.83 and its structural formula is: T:\Maryland\Published\Solids\Morphine Sulfate Extended-Release tablets\6-14\struct.jpg

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store morphine sulfate extended-release tablets 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 tablets unsecured can pose a deadly risk to others in the home [see Warnings and Precautions ( 5.1 ), 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 tablets 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 tablets, 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 tablets with others and to take steps to protect morphine sulfate extended-release tablets 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 tablets 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 ), Overdosage ( 10 ) ]. 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 Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if morphine sulfate extended-release tablets 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 ( 5.2 ) , 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 agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.3 )]. Educate patients and caregivers on how to recognize the signs and symptoms of an overdose. Explain to patients and caregivers that effects of opioid overdose reversal agents like naloxone and nalmefene are temporary, and that they must call 911 or get emergency medical help right away in all cases of kno… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

Medication Guide Morphine Sulfate (mor' feen sul' fate) Extended-Release Tablets, CII M orphine sulfate extended-release tablets are: A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage severe and persistent pain that required 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 m orphine sulfate extended-release tablets: Get emergency help or call 911 right away if you take too much morphine sulfate extended-release tablets (overdose).

When you first start taking morphine sulfate extended-release tablets, 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 tablets 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 tablets. They could die from taking it. Selling or giving away morphine sulfate extended-release tablets is against the law.

Store morphine sulfate extended-release tablets 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 tablets 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 tablets, 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 tablets, do not take more of morphine sulfate extended-release tablets without first talking to your healthcare provider. Talk to your healthcare provider if the pain you have increases, if you feel more sensitive to pain, or if you have new pain after taking morphine sulfate extended-release tablets.

Pregnant or planning to become pregnant. Use of morphine sulfate extended-release tablets 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 tablets. 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 tablets with certain other medicines can cause serious side effects. When taking morphine sulfate extended-release tablets: Do not change your dose.

Take morphine sulfate extended-release tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest duration. Take your prescribed dose every 8 to 12 hours, as directed by your healthcare provider.

Do not take more than your prescribed dose. If you miss a dose, take your next dose at the usual time. Swallow morphine sulfate extended-re… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence ~3 min read ▾

9 DRUG ABUSE AND DEPENDENCE

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

9.2Abuse Morphine sulfate extended-release contains morphine, a substance with a 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 health care 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 to other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of morphine sulfate extended-release 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 with alcohol and/or 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 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 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 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 poor pain control.

Morphine sulfate extended-release, 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 M orphine Sulfate Extended-Release Abuse of morphine sulfate extended-release poses a risk of overdose and death. This risk is increased with concurrent use of morphine sulfate extended-release with alcohol and/or other CNS depressants [see Warnings and Precautions ( 5.1 , 5.3 ), Drug Interactions ( 7) ] . Taking cut, broken, chewed, crushed, or dissolved morphine sulfate extended-release enhances drug release and increases the risk of overdose and death.

Morphine sulfate extended-release is approved for oral use only. Due to the presence of talc as one of the excipients in morphine sulfate extended-release, parenteral abuse can be expected to result in local tissue necrosis, infection, pulmonary granulomas, e… [Excerpted — this section continues on DailyMed.]

🧪 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 pseudopregnancies 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).

📄 Recent Major Changes 36 words ▾

Boxed Warning 12/2025 Indications and Usage ( 1 ) 12/2025 Dosage and Administration ( 2.2 , 2.3 , 2.6 ) 12/2025 Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.12 , 5.14 ) 12/2025

📄 Package Label / Principal Display Panel 152 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0228- 4270 -11 Morphine Sulfate Extended-Release Tablets 15 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 100 Tablets 1

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0228- 4271 -11 Morphine Sulfate Extended-Release Tablets 30 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 100 Tablets 2

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0228- 4311 -11 Morphine Sulfate Extended-Release Tablets 60 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. Rx only 100 Tablets 3

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0228- 4323 -11 Morphine Sulfate Extended-Release Tablets 100 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. FOR USE IN OPIOID-TOLERANT PATIENTS ONLY Rx only 100 Tablets 4

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 0228- 4347 -11 Morphine Sulfate Extended-Release Tablets 200 mg PHARMACIST: Dispense the accompanying Medication Guide to each patient. FOR USE IN OPIOID-TOLERANT PATIENTS ONLY Rx only 100 Tablets 5

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

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
45
Units reimbursed last 4 qtrs
2.7K
Gross reimbursed last 4 qtrs
$1.1K
Avg / prescription
$25.49
Avg / unit
$0.4175
Latest quarter Q1 2026
0Rx
Medicaid pays / ea
$0.4175
gross reimbursed
vs
NADAC / ea
$0.4334
acquisition cost
=
Spread
−$0.0159
-4% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
36% FFS 64% MCO
Fee-for-service · 16 Rx Managed care · 29 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 1,787 units · 17.8 per 100k residents MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 960 units · 2.5 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
2.517.8
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Michigan 17.8 /100k
2 California 2.5 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

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

Questions about this listing

What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Who lists this product with the FDA?
Actavis Pharma, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 00228-4241-06 · Actavis 00234-0575-40 · Molnlycke →
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.