MITIGO Morphine Sulfate 200 mg/20mL Injection, 1 mL
Other active recalls for Morphine Sulfate (different manufacturers) — 4 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Opioid Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Morphine injection is used to relieve severe pain. Morphine is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.
Read the full MedlinePlus article ↗- Morphine is typically prescribed only when your pain is severe enough that other options — like non-opioid medicines or weaker opioid combinations — haven't worked or aren't expect...
- Why is my doctor prescribing morphine instead of something milder?
- No — and this is one of the most important rules with morphine. Alcohol combined with morphine can push your morphine blood levels to life-threatening highs. This means no wine, be...
- Can I drink alcohol while taking morphine?
Patient education
Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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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.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $10.54 | $10.54 / 1 vial |
| 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 | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Infumorph 200 10 mg/mL 00641-6039-01 | Hikma | 20 ml | — | AP | FDA listed | — |
| Mitigo 200 mg/20mLthis 66794-0160-02 | Piramal | 1 ml | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ 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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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 66794-0160-02 You're viewing this | 1 mL in 1 VIAL, SINGLE-USE (66794-160-02) | 2019-02-25 | Active |
🧭 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 |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF MITIGO ® WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF MITIGO ® 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 MITIGO ® 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 MITIGO ® 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 Serious, life-threatening, or fatal respiratory depression may occur with use of MITIGO ® , especially during initiation or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of MITIGO ® 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 MITIGO ® 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 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 MITIGO ® 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 MITIGO ® 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 ) MITIGO ® 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 MITIGO ® , especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of MITIGO ® 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 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 & USAGE MITIGO ® 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 MITIGO ® is too concentrated for accurate delivery of the smaller doses used in this setting.
MITIGO ® 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 : ( 1 ) Not for single-dose intravenous, intramuscular, or subcutaneous administration due to the risk of overdose. Not for single-dose neuraxial injection because MITIGO ® is too concentrated for accurate delivery of the smaller doses used in this setting.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION
2.1Important Dosage and Administration Instructions MITIGO ® 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. MITIGO ® 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 MITIGO ® 200 mg/20 mL and 500 mg/20mL (10 and 25 mg/mL, respectively) by the intrathecal route be limited to the lumbar area. MITIGO ® 200 mg/20 mL and 500 mg/20 mL (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 MITIGO ® 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.
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. Injecting the solution into the tissue around the device or (in the case of devices that have more than one port) attempting to inject the refill dose into the direct injection port will result in a large, clinically significant, overdosage to the patient.
Safety and Handling Instructions: MITIGO ® is supplied in sealed vials. Accidental dermal exposure should be treated by the removal of any contaminated clothing and rinsing the affected area with water. Inspect parenteral drug products for particulate matter before opening the amber vials and again for color after removing contents from the vial.
Do not use if the solution in the unopened vial contains a precipitate which does not disappear upon shaking. After removal, do not use unless the solution is colorless or pale yellow. MITIGO ® is intended for single-use only.
Protect from light, discard any unused portion. Do not heat-sterilize.
2.2 Initial Dosage The starting dose of MITIGO ® must be individualized, based upo…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 200 mg per 20 mL (10 mg/mL) Preservative-free amber glass single-dose vials Injection: 500 mg per 20 mL (25 mg/mL) Preservative-free amber glass single-dose vials Injection: 200 mg/20 mL (10 mg/mL) Preservative-free amber glass single-dose vials Injection: 500 mg/20 mL (25 mg/mL) Preservative-free amber glass single-dose vials ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS MITIGO ® 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 MITIGO ® 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 MITIGO ® 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
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. MITIGO ® 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 MITIGO ® 200 mg/20 mL and 500 mg/20 mL (10 and 25 mg/mL, respectively) by the intrathecal route be limited to the lumbar area.
5.2Addiction, Abuse, and Misuse MITIGO ® contains morphine, a Schedule II controlled substance. As an opioid, MITIGO ® 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 MITIGO ® .
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 MITIGO ® , and monitor all patients receiving MITIGO ® 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 MITIGO ® but use in such patients necessitates intensive counseling about the risks and proper use of MITIGO ® 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 MITIGO ® .
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 vial of MITIGO ® 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. MITIGO ® should be subject to rigid accounting, rigorous control of wastage, and restricted access.
5.3 Life-Threatening Respiratory Depression S…
🤒 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 MITIGO ® 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 MITIGO ® .
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…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with MITIGO ® . Table 1. Clinically Significant Drug Interactions with MITIGO ® 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 MITIGO ® 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 MITIGO ® 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 MITIGO ® 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 MITIGO ® 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 gastr…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
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 MITIGO ® 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 MITIGO ® 200 mg/20 mL and 500 mg/20 mL (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 overdose reversal agent, such as naloxone or nalmefene, and resuscitative equipment must be available for reversal of opioid-induced respiratory depression in the neonate. MITIGO ® is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including MITIGO ® , 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…
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation Acute overdose with MITIGO ® 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 MITIGO ®, 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…
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING MITIGO ® (morphine sulfate injection, USP), is a preservative-free solution, supplied in amber vials for epidural or intrathecal administration via a continuous microinfusion device as follows: MITIGO ® 200 mg/20 mL (10 mg/mL) – NDC 66794-160-02: Single-Dose amber vials packaged individually MITIGO ® 500 mg/20 mL (25 mg/mL) – NDC 66794-162-02: Single-Dose amber vials packaged individually MITIGO ® is supplied in sealed vials. 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. MITIGO ® contains no preservative or antioxidant. Each 20 mL vial of MITIGO ® is intended for SINGLE DOSE ONLY.
Discard any unused portion. Do not heat-sterilize. To report SUSPECTED ADVERSE REACTIONS, contact Piramal Critical Care, Inc. at 1-888-822-8431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For Product Inquiry call 1-888-822-8431.
📋 Description ▾
11 DESCRIPTION MITIGO ® (morphine sulfate injection, USP – Preservative-free) 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. MITIGO ® 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 MITIGO ® 200 mg/20 mL contains morphine sulfate, USP 10 mg and sodium chloride 8 mg in Water for Injection, USP. Each mL of MITIGO ® 500 mg/20 mL contains morphine sulfate, USP 25 mg 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 vial of MITIGO ® is intended for SINGLE USE ONLY. mitigo-structure