Mitigo

Last updated on RxList: 7/22/2021
Mitigo Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Mitigo?

Mitigo (morphine sulfate injection) 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. Morphine sulfate injection is available as a generic.

What Are Side Effects of Mitigo?

Side effects of Mitigo include:

Mitigo can be abused and is subject to misuse, addiction, and criminal diversion. Both tolerance and physical dependence can develop during chronic opioid therapy. Withdrawal symptoms may occur if you suddenly stop taking Mitigo.

Dosage for Mitigo

The initial dosage of Mitigo for epidural administration ranges from 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.

The initial dosage of Mitigo for intrathecal administration ranges from 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.

Mitigo In Children

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.

What Drugs, Substances, or Supplements Interact with Mitigo?

Mitigo may interact with other medicines such as:

  • 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,
  • monoamine oxidase (MAO) inhibitors,
  • mixed agonist/antagonist and partial agonist opioid analgesics
  • alcohol,
  • benzodiazepines and other sedatives/hypnotics,
  • anxiolytics,
  • tranquilizers,
  • muscle relaxants,
  • general anesthetics,
  • antipsychotics,
  • psychotropic drugs,
  • antihistamines,
  • neuroleptics,
  • other opioids,
  • diuretics, and
  • anticholinergics.

Tell your doctor all medications and supplements you use.

Mitigo During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Mitigo; it can harm a fetus. Prolonged use of opioid analgesics such as Mitigo during pregnancy can cause neonatal opioid withdrawal syndrome. Mitigo passes into breast milk but its effects on nursing infants are unknown. Consult your doctor before breastfeeding.

Additional Information

Our Mitigo (morphine sulfate injection) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Source: https://mitigomorphine.com/wp-content/uploads/2019/05/Morphine-US-PI-JUL-2018.pdf

Edited by John Cunha, DO

5-10-21

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Medically speaking, the term "myalgia" refers to what type of pain? See Answer
Mitigo Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Opioid medicine can slow or stop your breathing, and death may occur. A person caring for you should give naloxone and/or seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.

Call your doctor at once if you have:

  • slow heart rate, sighing, shallow breathing, breathing that stops;
  • extreme drowsiness, feeling like you might pass out;
  • flushing (sudden warmth, redness, or tingly feeling);
  • a seizure;
  • high levels of serotonin in the body--agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea; or
  • low cortisol levels-- nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness.

Serious breathing problems may be more likely in older adults and people who are debilitated or have wasting syndrome or chronic breathing disorders.

Common side effects may include:

  • breathing problems;
  • drowsiness, dizziness;
  • constipation, nausea, vomiting;
  • sweating; or
  • numbness, tingling, or cold feeling in your hands and feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Mitigo (Morphine Sulfate Injection)

SLIDESHOW

Back Pain: 16 Back Pain Truths and Myths See Slideshow
Mitigo Professional Information

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]
  • Life-Threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS]
  • Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS]
  • Interactions with CNS Benzodiazepines or Other Depressants [see WARNINGS AND PRECAUTIONS]
  • Inflammatory Masses [see WARNINGS AND PRECAUTIONS]
  • Myoclonic Activity [see WARNINGS AND PRECAUTIONS]
  • Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]
  • Severe Hypotension [see WARNINGS AND PRECAUTIONS]
  • Gastrointestinal Adverse Reactions [see WARNINGS AND PRECAUTIONS]
  • Seizures [see WARNINGS AND PRECAUTIONS]
  • Withdrawal [see WARNINGS AND PRECAUTIONS]
  • Urinary Retention [see WARNINGS AND PRECAUTIONS]
  • Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]

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 Morphine Sulfate Injection USP - Preservative-free 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.

Genitourinary 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 Morphine Sulfate Injection USP - Preservative-free.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].

DRUG INTERACTIONS

Table 1 includes clinically significant drug interactions with Morphine Sulfate Injection USP - Preservative-free.

Table 1: Clinically Significant Drug Interactions with Morphine Sulfate Injection USP - Preservative-free

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.
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. Follow patients closely for signs of respiratory depression and sedation [see WARNINGS AND PRECAUTIONS].
Examples Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, psychotropic drugs, antihistamines, neuroleptics, 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 Morphine Sulfate Injection USP - Preservative-free 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), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine Oxidase Inhibitors (MAOIs)
Clinical Impact MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS AND PRECAUTIONS].
Intervention Do not use Morphine Sulfate Injection USP - Preservative-free 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, hydrocodone, 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 Morphine Sulfate Injection USP -Preservative-free 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 Morphine Sulfate Injection USP - Preservative-free and/or the muscle relaxant as necessary.
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 Morphine Sulfate Injection USP - Preservative-free is used concomitantly with anticholinergic drugs.

Drug Abuse And Dependence

Controlled Substance

Morphine Sulfate Injection USP - Preservative-free contains morphine, a Schedule II controlled drug substance.

Abuse

Morphine Sulfate Injection USP - Preservative-free contains morphine, a substance with a high potential for abuse similar to other opioids. Morphine Sulfate Injection USP - Preservative-free can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS AND PRECAUTIONS].

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

Morphine Sulfate Injection USP - Preservative-free, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Morphine Sulfate Injection USP - Preservative-free should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION]. If Morphine Sulfate Injection USP - Preservative-free is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use In Specific Populations].

Read the entire FDA prescribing information for Mitigo (Morphine Sulfate Injection)

© Mitigo Patient Information is supplied by Cerner Multum, Inc. and Mitigo Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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