INFUMORPH 500 morphine sulfate 25 mg/mL Injection, Solution, 20 mL — NDC 0641-6040-01 (Billing 00641-6040-01)
This is a package of 20 mL of INFUMORPH 500 morphine sulfate 25 mg/mL Injection, Solution from Hikma Pharmaceuticals USA Inc., marketed since Sep 1984 and currently FDA-listed. It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 0641-6040-01 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 0641 labeler · 6040 product · 01 package
- Package marketed since
- Sep 18, 1984
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Billing quantity
- 20 mL per package
- Barcode (UPC-A, from the NDC)
- 3 0641604001 3
- Medicaid fills, this package
- 14 prescriptions in the last four reported quarters
- FDA record last changed
- Jul 24, 2026
Other active recalls for Morphine Sulfate (different manufacturers) — 3 · tap to view
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 052258
- GCN: 19843
- GPI-14 (Medi-Span): 65100055302040
- HICL (First Databank): 025277
- AHFS class code: 28:08.08.00
- RxCUI (RxNorm): 892652
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 6, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Opioid Agonist class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- 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...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Morphine Sulfate — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 6, 2026
Ask a licensed pharmacist directly — free, answered by our team.
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 system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $9.15 | $182.91 / 20 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J2274 | $18.914 / J2274 unit | — |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Billing & reimbursement
Where does this data come from?
- CMS ASP NDC-HCPCS crosswalk · refreshed Sep 22, 2026
- DMEPDAC NDC-HCPCS crosswalk
- openFDA NSDE billing units · refreshed Sep 7, 2026
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 00641-6040-01 You're viewing this Main listing | 20 mL in 1 AMPULE | 1984-09-18 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Infumorph 500 25 mg/mLthis 00641-6040-01 | Hikma | 20 ml | — | AP | FDA listed | — |
| Mitigo 500 mg/20mL 66794-0162-02 | Piramal | 1 ml | — | AP | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file
Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
🧪 Avoiding an ingredient? See Morphine inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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6.25 mg / 1 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII O40UQP6WCF
A strong acid used in small amounts to adjust and maintain the pH balance of a medicine, helping ensure stability and proper dissolution of the active ingredients.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
4 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 6, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Hikma Pharmaceuticals USA Inc. labeler code 00641
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- INFUMORPH 200 morphine sulfate 10 mg/mL Injection, Solution NDC 0641-6039-01
- Ketorolac Tromethamine 15 mg/mL Injection NDC 0641-6041-25
- Ketorolac Tromethamine 30 mg/mL Injection NDC 0641-6042-25
- Ketorolac Tromethamine 30 mg/mL Injection NDC 0641-6043-25
- Lorazepam 2 mg/mL Injection NDC 0641-6044-25
- Lorazepam 4 mg/mL Injection NDC 0641-6045-25
- Lorazepam 2 mg/mL Injection NDC 0641-6046-10
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF INFUMORPH Risks with Neuraxial Administration Single-dose neuraxial administration may result in acute or delayed respiratory depression up to 24 hours. Because of the risk of severe adverse reactions when INFUMORPH is administered by the epidural or intrathecal route of administration, patients must be observed in a fully equipped and staffed environment for at least 24 hours after the initial dose [ see Warnings and Precautions ( 5.1 ) ]. Addiction, Abuse, and Misuse Because the use of INFUMORPH 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 ( 5.2 ) ].
Life-Threatening Respiratory Depression S erious, life-threatening, or fatal respiratory depression may occur with use of INFUMORPH, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of INFUMORPH are essential [ 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 INFUMORPH and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [ see Warnings and Precautions ( 5.4 ) , 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 ( 5.5 ) ].
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF INFUMORPH See full prescribing information for complete boxed warning. Single-dose neuraxial administration may result in acute or delayed respiratory depression up to 24 hours. Because of the risk of severe adverse reactions when INFUMORPH is administered by the epidural or intrathecal route of administration, patients must be observed in a fully equipped and staffed environment for at least 24 hours after the initial dose.
( 5.1 ) INFUMORPH exposes users to the risks of opioid 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. ( 5.2 ) Serious, life-threatening, or fatal respiratory depression may occur with use of INFUMORPH, especially during initiation or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of INFUMORPH are essential. ( 5.3 ) 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.
( 5.4 , 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 available at delivery. ( 5.5 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE INFUMORPH is for use in continuous microinfusion devices and indicated only for intrathecal or epidural infusion in the management of intractable chronic pain severe enough to require an opioid analgesic and for which less invasive means of controlling pain are inadequate. Limitations of Use Not for single-dose intravenous, intramuscular, or subcutaneous administration due to the risk of overdose. Not for single-dose neuraxial injection because INFUMORPH is too concentrated for accurate delivery of the smaller doses used in this setting.
INFUMORPH is an opioid agonist, for use in continuous microinfusion devices and indicated only for intrathecal or epidural infusion in the management of intractable chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. ( 1 ) Limitations of Use: Not for single-dose intravenous, intramuscular, or subcutaneous administration due to the risk of overdose. Not for single-dose neuraxial injection because INFUMORPH is too concentrated for accurate delivery of the smaller doses used in this setting.
( 1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION INFUMORPH should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) Should be administered by or under the direction of a physician experienced in the techniques of epidural or intrathecal administration. ( 2.1 ) Patients should be observed in a fully equipped and staffed environmentforatleast24hoursaftereachtestdoseand,as indicated, for the first several days after surgery.
(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 INFUMORPH 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 , 5.2 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with INFUMORPH. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.3 ) Initial Dosage: Must be individualized, based upon in-hospital evaluation of the response to serial single dose epidural bolus injections of regular DURAMORPH (morphine sulfate injection, USP) 0.5 mg/mL or 1 mg/mL, with close observation for analgesic efficacy and adverse effects prior to surgery involving the continuous microinfusion device.
( 2.2 ) Dosage for Epidural Administration: Initial dose range of 3.5 to 7.5 mg/day for patients with no tolerance to opioids. The usual starting dose for continuous epidural infusion in patients with some degree of opioid tolerance is 4.5 to 10 mg/day and may increase significantly during treatment to 20-30 mg/day. ( 2.3 ) Dosage for Intrathecal Administration: Initial dose range of 0.2 to 1 mg/day for patients with no tolerance to opioids.
The range of doses for patients with some degree of opioid tolerance varies from 1 to 10 mg/day. Doses above 20 mg/day should be employed with caution. ( 2.4 ) Periodically reassess patients receiving INFUMORPH to evaluate the continued need for opioid analgesics to maintain pain control, for signs or symptoms of adverse reactions, and for the development of addiction, abuse or misuse.
( 2.5 ) Do not rapidly reduce or abruptly discontinue INFUMORPH in a physically-dependent patient. ( 2.6 , 5.16 )
2.1Important Dosage and Administration Instructions INFUMORPH should be administered by or under the direction of a physician experienced in the techniques of epidural or intrathecal administration and familiar with the patient management problems associated with epidural or intrathecal drug administration. INFUMORPH should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Because of the risk of delayed respiratory depression, patients should be observed in a fully equipped and staffed environment for at least 24 hours after each test dose and, as indicated, for the first several days after surgery.
Because epidural administration has been associated with less potential for immediate or late adverse effects than intrathecal administration, the epidural route should be used whenever possible. For safety reasons, it is recommended that administration of INFUMORPH 200 and 500 (10 and 25 mg/mL, respectively) by the intrathecal route be limited to the lumbar area. INFUMORPH 200 and 500 (10 and 25 mg/mL, respectively) should not be used for single-dose neuraxial injection because lower doses can be more reliably administered with the standard preparation of DURAMORPH (0.5 and 1 mg/mL).
Candidates for neuraxial administration of INFUMORPH in a continuous microinfusion device shoul… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 200 mg per 20 mL (10 mg/mL) Preservative-free amber glass ampuls Injection: 500 mg per 20 mL (25 mg/mL) Preservative-free amber glass ampuls Injection: 200 mg/20 mL (10 mg/mL) Preservative-free amber glass ampuls Injection: 500 mg/20 mL (25 mg/mL) Preservative-free amber glass ampuls ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS INFUMORPH 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 (5.9) ] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Warnings and Precautions (5.10) , Drug Interactions (7) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.14) ] Hypersensitivity to morphine (e.g., anaphylaxis) [see Adverse Reactions (6) ] Neuraxial administration of INFUMORPH is contraindicated in patients with: Infection at the injection microinfusion site [see Warnings and Precautions (5.1) ] Concomitant anticoagulant therapy [see Warnings and Precautions (5.1)] Uncontrolled bleeding diathesis [see Warnings and Precautions (5.1) ] The presence of any other concomitant therapy or medical condition which would render epidural or intrathecal administration of medication especially hazardous.
Significant respiratory depression ( 4 ) Acute or severe bronchial asthma in an unmonitored setting in 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 or intolerance to morphine ( 4 ) Neuraxial administration of INFUMORPH is contraindicated in patients with: Infection at the injection microinfusion site ( 4 ) Concomitant anticoagulant therapy ( 4 ) Uncontrolled bleeding diathesis ( 4 ) The presence of any other concomitant therapy or medical condition which would render epidural or intrathecal administration of medication especially hazardous.
( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Risk of Inflammatory Masses: Monitor patients receiving continuous infusion of INFUMORPH via indwelling intrathecal catheter for new signs or symptoms of neurologic impairment. ( 5.6 ) Risk of Tolerance and Myoclonic Activity: Monitor patients for unusual acceleration of neuraxial morphine, which may cause myoclonic-like spasm of lower extremities. Detoxification may be required.
( 5.7 ) 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. ( 5.8 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration.
( 5.9 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.11 ) Severe Hypotension: Monitor during dosage initiation and titration. Avoid use of INFUMORPH in patients with circulatory shock.
( 5.12 ) 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 INFUMORPH in patients with impaired consciousness or coma. ( 5.13 )
5.1Risks with Neuraxial Administration Control of pain by neuraxial opiate delivery, using a continuous microinfusion device, is always accompanied by considerable risk to the patients and requires a high level of skill to be successfully accomplished. The task of treating these patients must be undertaken by experienced clinical teams, well-versed in patient selection, evolving technology and emerging standards of care. INFUMORPH should be administered by or under the direction of a physician experienced in the techniques of epidural or intrathecal administration and familiar with the patient management problems associated with epidural or intrathecal drug administration.
The physician should be familiar with patient conditions (such as infection at the injection site, bleeding diathesis, anticoagulant therapy, etc.) which call for special evaluation of the benefit versus risk potential. Because of the risk of severe adverse effects when the epidural or intrathecal route of administration is employed, patients must be observed in a fully equipped and staffed environment for at least 24 hours after the initial dose. The facility must be equipped to resuscitate patients with severe opioid overdosage, and the personnel must be familiar with the use and limitations of specific narcotic antagonists (naloxone, naltrexone) in such cases.
For safety reasons, it is recommended that administration of INFUMORPH 200 and 500 (10 and 25 mg/mL, respectively) by the intrathecal route be limited to the lumbar area.
5.2Addiction, Abuse, and Misuse INFUMORPH contains morphine, a Schedule II controlled substance. As an opioid, INFUMORPH exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9) ] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed INFUMORPH.
Addiction can occur at recommended dosages 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 INFUMORPH, and monitor all patients receiving INFUMORPH for the development of these behaviors and conditions. Risks are increased in patients with a personal or family… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
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 (5.2) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3) ] Interactions with CNS Benzodiazepines or Other Depressants [see Warnings and Precautions (5.4) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.5) ] Inflammatory Masses [see Warnings and Precautions (5.6) ] Myoclonic Activity [see Warnings and Precautions (5.7) ] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.8) ] Adrenal Insufficiency [see Warnings and Precautions (5.11) ] Severe Hypotension [see Warnings and Precautions (5.12) ] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.14) ] Seizures [see Warnings and Precautions (5.15) ] Withdrawal [see Warnings and Precautions (5.16) ] Urinary Retention [see Warnings and Precautions (5.18) ] Orthostatic Hypotension [see Warnings and Precautions (5.19) ] The following adverse reactions associated with the use of morphine were identified in clinical studies or postmarketing reports.
Because some of these reactions were 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. The most serious adverse reactions encountered during continuous intrathecal or epidural infusion of INFUMORPH were respiratory depression, myoclonus, and formation of inflammatory masses. Cardiovascular System: While low doses of intravenously administered morphine have little effect on cardiovascular stability, high doses are excitatory, resulting from sympathetic hyperactivity and increase in circulating catecholamines.
Excitation of the central nervous system, resulting in convulsions, may accompany high doses of morphine given intravenously. Central Nervous System: myoclonus, seizures, dysphoric reactions, toxic psychosis, dizziness, euphoria, anxiety, confusion, headache. Lumbar puncture-type headache is encountered in a significant minority of cases for several days following intrathecal catheter implantation and generally responds to bed rest and/or other conventional therapy.
Gastrointestinal System: Nausea, vomiting, constipation Skin: Pruritus, urticaria, wheals, and/or local tissue irritation. Genito-Urinary System: Urinary retention, oliguria, unexplained genital swelling in male patients, following infusion-device implant surgery. Other: Other adverse experiences reported following morphine therapy include depression of cough reflex, interference with thermal regulation, peripheral edema.
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 following greater than one month of use. Anaphylaxis: Anaphylaxis has been reported with ingredients contained in INFUMORPH.
Androgen deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time. [see Clinical Pharmacology (12.2)] . Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions (5.8)] Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).
Opioid-induced esophageal dysfunction (OIED): Cases of OIED have been reported in patients taking opioids and may occur more frequently in patients taking higher doses of opioids, and/or in patients taking opioids longer term [see Warnings and Precautions (5.14)] . Adverse Reactions from Observational Studies A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with INFUMORPH. Table 1. Clinically Significant Drug Interactions with INFUMORPH 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.
The depressant effects of morphine are potentiated by the presence of other CNS depressants. Use of neuroleptics in conjunction with neuraxial morphine may increase the risk of respiratory depression [see Warnings and Precautions (5.4) ] . 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. Monitor patients closely for signs of respiratory depression and sedation [see Warnings and Precautions (5.4) ] . Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, psychotropic drugs, antihistamines, neuroleptics, 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, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue INFUMORPH 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 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 (5.10)].
Intervention: Do not use INFUMORPH in patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydromorphone, oxymorphone, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of INFUMORPH 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: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of INFUMORPH and/or the muscle relaxant as necessary. Examples: Cyclobenzaprine, metaxalone. Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced ga… [Excerpted — this section continues on DailyMed.]
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy : May cause fetal harm. (8.1) Hepatic and Renal Impairment : May affect the metabolism and excretion of INFUMORPH. (8.6)
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 (5.5) ] . Available data with INFUMORPH in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are adverse outcomes reported with fetal exposure to opioid analgesics (see Clinical Considerations) .
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 3-4 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 (5.5) ] . Labor or Delivery INFUMORPH 200 and 500 (10 and 25 mg/mL, respectively) are too highly concentrated for routine use in obstetric neuraxial analgesia. Opioids, including intravenously, epidurally, and intrathecally administered morphine, readily cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.
An opioid antagonist, such as naloxone, and resuscitative equipment must be available for reversal of opioid-induced respiratory depression in the neonate. INFUMORPH is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including INFUMORPH, 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… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
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 (5.5) ] . Available data with INFUMORPH in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are adverse outcomes reported with fetal exposure to opioid analgesics (see Clinical Considerations) .
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 3-4 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 (5.5) ] . Labor or Delivery INFUMORPH 200 and 500 (10 and 25 mg/mL, respectively) are too highly concentrated for routine use in obstetric neuraxial analgesia. Opioids, including intravenously, epidurally, and intrathecally administered morphine, readily cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.
An opioid antagonist, such as naloxone, and resuscitative equipment must be available for reversal of opioid-induced respiratory depression in the neonate. INFUMORPH is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including INFUMORPH, 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 morph… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Adequate studies to establish the safety and effectiveness of spinal morphine in pediatric patients have not been performed, and usage in this population is not recommended.
🧓 Geriatric Use ▾
8.5Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to INFUMORPH. 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 INFUMORPH slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.8) ] . The pharmacodynamic effects of neuraxial morphine in the elderly are more variable than in the younger population. Patients will vary widely in the effective initial dose, rate of development of tolerance and the frequency and magnitude of associated adverse effects as the dose is increased.
Initial doses should be based on careful clinical observation following “test doses”, after making due allowances for the effects of the patient’s age and infirmity on his/her ability to clear the drug, particularly in patients receiving epidural morphine. Morphine 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 monitor renal function.
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation Acute overdose with INFUMORPH 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 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 morphine overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. As the duration of effect of naloxone is considerably shorter than that of epidural or intrathecal morphine, repeated administration may be necessary. Patients should be closely observed for evidence of renarcotization.
Because the duration of opioid reversal is expected to be less than the duration of action of morphine in INFUMORPH, particularly with epidural or intrathecal morphine, carefully monitor the patient until spontaneous respiration is reliably re-established. 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 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 begun with care and by titration with smaller than usual doses of the reversal agent.
🧬 Clinical Pharmacology ▾
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 Effects on the Central Nervous System Morphine produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem 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 opioid overdose but are not pathognomic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Both early and late respiratory depression (up to 24 hours post dosing) have been reported following neuraxial administration.
Circulation of the spinal fluid may also result in high concentrations of morphine reaching the brain stem directly. 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 and/or peripheral vasodilation may include pruritis, flushing, red eyes and sweating and/or orthostatic hypotension. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and lutenizing hormone (LH) in humans [see Adverse Reactions (6) ] . 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) ] .
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 d… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
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 ▾
16 HOW SUPPLIED/STORAGE AND HANDLING INFUMORPH (preservative-free morphine sulfate sterile solution), is, a preservative-free solution, supplied in amber ampuls for epidural or intrathecal administration via a continuous microinfusion device as follows: NDC 0641-6039-01 INFUMORPH 200 200 mg/20 mL (10 mg/mL) Single Use amber ampuls packaged individually NDC 0641-6040-01 INFUMORPH 500 500 mg/20 mL (25 mg/mL) Single Use amber ampuls packaged individually INFUMORPH is supplied in sealed ampuls. Accidental dermal exposure should be treated by the removal of any contaminated clothing and rinsing the affected area with water.
PROTECT FROM LIGHT. Keep stored in carton until time of use. Store at 20˚‑25˚C (68˚‑77˚F), excursions permitted to 15˚‑30˚C (59˚‑86˚F) [See USP Controlled Room Temperature].
DO NOT FREEZE. INFUMORPH contains no preservative or antioxidant. Each 20 mL ampul of INFUMORPH is intended for SINGLE USE ONLY.
Discard any unused portion. Do not heat-sterilize. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
For Product Inquiry call 1-877-845-0689.
📋 Description ▾
11 DESCRIPTION INFUMORPH (preservative-free morphine sulfate sterile solution) is an opioid agonist, available as a sterile, nonpyrogenic, isobaric, high potency solution of morphine sulfate in strengths of 10 mg or 25 mg morphine sulfate per mL, free of antioxidants, preservatives or other potentially neurotoxic additives. INFUMORPH is intended for use in continuous microinfusion devices for intraspinal administration in the management of pain. Morphine is the most important alkaloid of opium and is a phenanthrene derivative.
It is available as the sulfate salt, chemically identified as 7,8-Didehydro-4,5- epoxy-17- methyl-(5α,6α)-morphinan-3,6-diol sulfate (2:1) (salt), pentahydrate, with the following structural formula: (C 17 H 19 NO 3 ) 2 • H 2 SO 4 • 5H 2 O Molecular Weight is 758.83 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 pKa is 7.9 for the tertiary nitrogen (the majority is ionized at pH 7.4).
Each mL of INFUMORPH 200 contains morphine sulfate, USP 10 mg (200 mg/20 mL) and sodium chloride 8 mg in Water for Injection, USP. Each mL of INFUMORPH 500 contains morphine sulfate, USP 25 mg (500 mg/20 mL) and sodium chloride 6.25 mg in Water for Injection, USP. If needed, sodium hydroxide and/or sulfuric acid are added for pH adjustment to 4.5.
Contains no preservative. Each 20 mL ampul of INFUMORPH is intended for SINGLE USE ONLY. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Addiction, Abuse, and Misuse Inform patients that the use of INFUMORPH, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.2) ] . Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting INFUMORPH or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.3) ] .
Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop. Hyperalgesia and Allodynia Advise patients to inform their healthcare provider if they experience symptoms of hyperalgesia, including worsening pain, increased sensitivity to pain, or new pain [see Warnings and Precautions (5.8) ; Adverse Reactions (6.2) ] . Serotonin Syndrome Inform patients that INFUMORPH could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs.
Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop after discharge from the hospital. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see Drug Interactions (7) ] . MAOI Interaction Inform patients not to take INFUMORPH while using any drugs that inhibit monoamine oxidase.
Patients should not start MAOIs while taking INFUMORPH [see Warnings and Precautions (5.10) , Drug Interactions (7) ] . Driving or Operating Heavy Machinery Inform patients that INFUMORPH may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.17) ].
Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6)] . Hypotension Inform patients that INFUMORPH may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.12) ] .
Anaphylaxis Inform patients that anaphylaxis have been reported with ingredients contained in INFUMORPH. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4) , Adverse Reactions (6) ]. Pregnancy Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that use of INFUMORPH for an extended period of time during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see Warnings and Precautions (5.5) , Use in Specific Populations (8.1) ].
Embryo-Fetal Toxicity Inform female patients of reproductive potential that INFUMORPH can cause fetal harm and to inform the healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.3) ] . Lactation Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see Use in Specific Populations (8.2)] .
Infertility Inform patients that use of opioids for an extended period of time may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6)] .
🍼 Nursing Mothers ▾
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) , 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 ▾
12.3Pharmacokinetics Epidural Administration Absorption Morphine, injected into the epidural space , is rapidly absorbed into the general circulation. Absorption is so rapid that the plasma concentration-time profiles closely resemble those obtained after intravenous or intramuscular administration. Peak plasma concentrations averaging 33–40 ng/mL (range 5–62 ng/mL) are achieved within 10 to 15 minutes after administration of 3 mg of morphine.
Distribution Plasma concentrations decline in a multiexponential fashion. CSF concentrations of morphine, after epidural doses of 2 to 6 mg in postoperative patients, have been reported to be 50 to 250 times higher than corresponding plasma concentrations. The CSF levels of morphine exceed those in plasma after only 15 minutes and are detectable for as long as 20 hours after the injection of 2 mg of epidural morphine.
Approximately 4% of the dose injected epidurally reaches the CSF. This corresponds to the relative minimum effective epidural and intrathecal doses of 5 mg and 0.25 mg, respectively. The disposition of morphine in the CSF follows a biphasic pattern, with an early half-life of 1.5h and a late phase half-life of about 6 h.
Morphine crosses the dura slowly, with an absorption half-life across the dura averaging 22 minutes. Maximum CSF concentrations are seen 60–90 minutes after injection. Minimum effective CSF concentrations for postoperative analgesia average 150 ng/mL (range < 1-380 ng/mL).
Elimination The terminal half-life is reported to range from 39 to 249 minutes (mean of 90 ± 34.3 min) for epidural administration. Metabolism The major pathway of clearance is hepatic glucuronidation to morphine-3-glucuronide, which is pharmacologically inactive. Excretion The major excretion path of the morphine-3-glucuronide conjugate is through the kidneys, with about 10% in the feces.
Morphine is also eliminated by the kidneys, 2 to 12% being excreted unchanged in the urine. Intrathecal Administration Absorption Time-to-peak plasma concentrations, however, are similar (5-10 min) after either epidural or intrathecal bolus administration of morphine. Maximum plasma morphine concentrations after 0.3 mg intrathecal morphine have been reported from < 1 to 7.8 ng/mL.
The minimum analgesic morphine plasma concentration during Patient Controlled Analgesia (PCA) has been reported as 20–40 ng/mL, suggesting that any analgesic contribution from systemic redistribution would be minimal after the first 30–60 minutes with epidural administration and virtually absent with intrathecal administration of morphine. Distribution The intrathecal route of administration circumvents meningeal diffusion barriers and, therefore, lower doses of morphine produce comparable analgesia to that induced by the epidural route.
After intrathecal bolus injection of morphine, there is a rapid initial distribution phase lasting 15–30 minutes and a half-life in the CSF of 42–136 min (mean 90 ± 16 min). Derived from limited data, it appears that the disposition of morphine in the CSF, from 15 minutes postintrathecal administration to the end of a six-hour observation period, represents a combination of the distribution and elimination phases. Morphine concentrations in the CSF averaged 332 ± 137 ng/mL at 6 hours, following a bolus dose of 0.3 mg of morphine.
The apparent volume of distribution of morphine in the intrathecal space is about 22 ± 8 mL.
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Effects on the Central Nervous System Morphine produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem 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 opioid overdose but are not pathognomic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Both early and late respiratory depression (up to 24 hours post dosing) have been reported following neuraxial administration.
Circulation of the spinal fluid may also result in high concentrations of morphine reaching the brain stem directly. 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 and/or peripheral vasodilation may include pruritis, flushing, red eyes and sweating and/or orthostatic hypotension. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and lutenizing hormone (LH) in humans [see Adverse Reactions (6) ] . 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) ] .
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 , 2.5) ] . 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 , 2.2 , 2.6) ] .
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance INFUMORPH contains morphine, a Schedule II controlled drug substance.
9.2Abuse INFUMORPH 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 (5.2) ] . 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 INFUMORPH 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 INFUMORPH 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 INFUMORPH 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 INFUMORPH 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. INFUMORPH, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful recordkeeping 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 INFUMORPH Abuse of INFUMORPH poses a risk of overdose and death. The risk is increased with concurrent use of INFUMORPH with alcohol and/or other CNS depressants.
Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
9.3Dependence Both tolerance and physical dependence can develop during use of opioid therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal may be precipitated through the… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
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 maybe 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).
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
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 maybe 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).
📄 Recent Major Changes ▾
RECENT MAJOR CHANGES Boxed Warnings 12/2025 Indications and Usage ( 1 ) 12/2025 Dosage and Administration ( 2.6 ) 12/2025 Warnings and Precautions ( 5.2 , 5.3 , 5.4 , 5.14 , 5.16 ) 12/2025
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL NOT for IV, IM or Subcutaneous Injection NDC 0641- 6039 -01 20 mL Single Dose Ampul INFUMORPH 200 Rx only (Preservative-free Morphine Sulfate Sterile Solution) CII 200 mg per 20 mL (10 mg/mL) For Neuraxial Administration in Continuous Microinfusion Devices NOT for Intravenous, Intramuscular or Subcutaneous Injection NDC 0641- 6039 -01 20 mL Single Dose Ampul Infumorph 200 Rx only (Preservative-free Morphine Sulfate Sterile Solution) CII 200 mg per 20 mL (10 mg/mL) For Neuraxial Administration in Continuous Microinfusion Devices amp carton 200 mg
PRINCIPAL DISPLAY PANEL NOT for IV, IM or Subcutaneous Injection NDC 0641- 6040 -01 20 mL Single Dose Ampul INFUMORPH 500 Rx only (Preservative-free Morphine Sulfate Sterile Solution) CII 500 mg per 20 mL (25 mg/mL) For Neuraxial Administration in Continuous Microinfusion Devices NOT FOR IV, IM, or SC INJECTION NDC 0641-6040-01 20 mL Single Dose Ampul INFUMORPH 500 (Preservative-free Morphine Sulfate Sterile Solution) CII 500 mg per 20 mL (25 mg/mL) FOR NEURAXIAL ADMINISTRATION IN CONTINUOUS MICROINFUSION DEVICES amp carton 500 mg
Medicaid utilization & spend
Medicare Part D spend CMS · PART D · 2026 (Q1)
Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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About this NDC listing & data coverage
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) | ✓ 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 | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |