Infumorph 500
morphine sulfate · Injection, Solution · Epidural, Intrathecal
Current shortage
Infumorph 500 (Preservative-Free Morphine Sulfate Sterile Solution), Injection, 25 mg/1 mL (NDC 0641-6040-01) – Available (Hikma Pharmaceuticals USA, Inc., updated Sep 18, 2026)
Additional lots are scheduled to be manufactured. Product will be made available as it is released.
Uses
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 ) 2.1 Important 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 should be hospitalized to provide for adequate patient monitoring during assessment of response to single doses of intrathecal or epidural morphine. Hospitalization should be maintained for several days after surgery involving the infusion device for additional monitoring and adjustment of daily dosage. The facility must be equipped with resuscitative equipment, oxygen, opioid overdose reversal agent (e.g., naloxone, nalmefene) and other resuscitative drugs. A period of observation appropriate to the clinical situation should follow each refill or manipulation of the drug reservoir. Before discharge, the patient and attendant(s) should receive instruction in the proper home care of the device and insertion site and in the recognition and practical treatment of an overdose of neuraxial morphine. Familiarization with the continuous microinfusion device is essential. The desired amount of morphine should be withdrawn from the ampul through a microfilter. To minimize risk from glass or other particles, the product must be filtered through a 5 μ (or smaller) microfilter before injecting into the microinfusion device. If dilution is required, 0.9% Sodium Chloride Injection is recommended. Reservoir filling must be performed by fully trained and qualified personnel, following the directions provided by the device manufacturer. Care should be taken in selecting the proper refill frequency to prevent depletion of the reservoir, which would result in exacerbation of severe pain, onset of opioid withdrawal symptoms, and/or reflux of cerebrospinal fluid into some devices. Strict aseptic technique is required to avoid bacterial contamination and serious infection. Extreme care must be taken to ensure that the needle is properly inserted into the filling port of the device before attempting to refill the reservoir.
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 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 ) 5.1 Risks 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. 5.2 Addiction, 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 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 INFUMORPH but use in such patients necessitates intensive counseling about the risks and proper use of INFUMORPH along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing INFUMORPH. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity. 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. Each ampul of INFUMORPH contains a large amount of a potent narcotic which has been associated with abuse and dependence among health care providers. Due to the limited indications for this product, the risk of overdosage and the risk of its diversion and abuse, it is recommended that special measures must be taken to control this product within the hospital or clinic. INFUMORPH should be subject to rigid accounting, rigorous control of wastage, and restricted access. 5.3 Life-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 depression may include close observation, supportive measures, and use of opioid overdose reversal agents (e.g., naloxone, nalmefene), depending on the patient’s clinical status [see Overdosage (10) ]. Carbon dioxide (CO) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Side effects
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 patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90-day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months. Over 12 months: approximately 1% to 6% of participants across the two cohorts newly met criteria for addiction, as assessed with two validated interview-based measures of moderate-to-severe opioid use disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and approximately 9% and 22% of participants across the two cohorts newly met criteria for prescription opioid abuse and misuse [defined in Drug Abuse and Dependence (9.2)] , respectively, as measured with a validated self-reported instrument. A retrospective, observational cohort study estimated the risk of opioid-involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days’ supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database.
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 gastric motility when INFUMORPH is used concomitantly with anticholinergic drugs. Oral P2Y 12 Inhibitors Clinical Impact: The co-administration of oral P2Y 12 inhibitors and intravenous morphine sulfate can decrease the absorption and peak concentration of oral P2Y 12 inhibitors and delay the onset of the antiplatelet effect. Intervention: Consider the use of parenteral antiplatelet agent in the setting of acute coronary syndrome requiring co-administration of intravenous morphine sulfate. Examples: clopidogrel, prasugrel, ticagrelor Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue INFUMORPH if serotonin syndrome is suspected. ( 7 ) Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with INFUMORPH because they may reduce the effect of INFUMORPH or precipitate withdrawal symptoms. ( 7 )
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) 8.1 Pregnancy 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 morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and nonrandomized study design. Animal Data Formal reproductive and developmental toxicology studies for morphine have not been conducted. Exposure margins for the following published study reports are based on human daily dose of 60 mg morphine using a body surface area comparison (HDD). Neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of morphine sulfate (35-322 mg/kg) on Gestation Day 8 to pregnant hamsters (4.7 to 43.5 times the HDD). A no adverse effect level was not defined in this study and the findings cannot be clearly attributed to maternal toxicity. Neural tube defects (exencephaly), axial skeletal fusions, and cryptorchidism were reported following a single subcutaneous (SC) injection of morphine sulfate to pregnant mice (100-500 mg/kg) on Gestation Day 8 or 9 at 200 mg/kg or greater (16 times the HDD) and fetal resorption at 400 mg/kg or higher (32 times the HDD). No adverse effects were noted following 100 mg/kg morphine in this model (8 times the HDD). In one study, following continuous subcutaneous infusion of doses greater than or equal to 2.72 mg/kg to mice (0.2 times the HDD), exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted. The effects were reduced with increasing daily dose; possibly due to rapid induction of tolerance under these infusion conditions. The clinical significance of this report is not clear.
Pregnancy
8.1 Pregnancy 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 morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and nonrandomized study design. Animal Data Formal reproductive and developmental toxicology studies for morphine have not been conducted. Exposure margins for the following published study reports are based on human daily dose of 60 mg morphine using a body surface area comparison (HDD). Neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of morphine sulfate (35-322 mg/kg) on Gestation Day 8 to pregnant hamsters (4.7 to 43.5 times the HDD). A no adverse effect level was not defined in this study and the findings cannot be clearly attributed to maternal toxicity. Neural tube defects (exencephaly), axial skeletal fusions, and cryptorchidism were reported following a single subcutaneous (SC) injection of morphine sulfate to pregnant mice (100-500 mg/kg) on Gestation Day 8 or 9 at 200 mg/kg or greater (16 times the HDD) and fetal resorption at 400 mg/kg or higher (32 times the HDD). No adverse effects were noted following 100 mg/kg morphine in this model (8 times the HDD). In one study, following continuous subcutaneous infusion of doses greater than or equal to 2.72 mg/kg to mice (0.2 times the HDD), exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted. The effects were reduced with increasing daily dose; possibly due to rapid induction of tolerance under these infusion conditions. The clinical significance of this report is not clear. Decreased fetal weights were observed in pregnant rats treated with 20 mg/kg/day morphine sulfate (3.2 times the HDD) from Gestation Day 7 to 9.
Pediatric use
8.4 Pediatric 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
8.5 Geriatric 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
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.
Description
(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
Mechanism of action
12.1 Mechanism 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
(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.
Patient 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)] .
Label text from the FDA structured product label by Hikma Pharmaceuticals USA Inc. (revised Dec 31, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Morphine Sulfate in 1 product
Infumorph 500 NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0641-6040 | Morphine Sulfate 25 mg/mL Injection, Solution | Hikma Pharmaceuticals USA Inc. | NDA · DEA CII |
Frequently asked questions
What is Infumorph 500 used for?
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…
What are the side effects of Infumorph 500?
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… See the full label for the complete list.
Who makes Infumorph 500?
Infumorph 500 is listed by 1 labeler in the FDA NDC directory, including Hikma Pharmaceuticals USA Inc..