Morphine: Generic, Pain Uses, Warnings, Side Effects, Dosage

Generic Name: morphine

Brand Names: MS Contin, Duramorph, Infumorph, Mitigo;

Discontinued Brands: Astramorph, Depodur, Kadian, MorphaBond, Arymo ER

Drug Class: Opioid Analgesics

What is morphine, and what is it used for?

Morphine is a pain reliever (analgesic) derived from the opium plant, used to manage moderate-to-severe acute and chronic pain caused by many conditions. Morphine has effects on both the peripheral nervous system (PNS) and the central nervous system (CNS), changing the perception of pain as well as the body’s response to it. Morphine inhibits the transmission of pain signals from the PNS and activates the descending inhibitory pathways in the CNS.

Morphine works by binding to opioid receptors in the nervous system, particularly to a type known as mu opioid receptors, although it can interact with other types of opioid receptors including kappa and delta. Opioid receptors are protein molecules on nerve cells (neurons) that mediate the body’s response to most hormones and some of their functions include modulating pain, stress response, respiration, digestion, mood and emotion.

Opioid drugs, including morphine, have a high risk for addiction, and must be used with great caution. In addition to pain relief, morphine has multiple other effects including the following:

Central nervous system: Induces relaxation and euphoria, causes respiratory depression, depresses cough reflex and causes constriction of pupils (miosis) even in complete darkness
Gastrointestinal system: Decreases digestive secretions and smooth muscle contractions (peristalsis) that move the digestive contents, which can result in constipation. May also cause spasm of the bladder’s sphincter muscle.
Cardiovascular system: Causes dilation of peripheral blood vessels which may result in low blood pressure (hypotension), including from change in position (orthostatic hypotension) and fainting, and histamine release that can cause opioid-induced itching, flushing, sweating and red eyes.
Endocrine system: Has different effects on the secretion of many hormones, including reproductive, thyroid and growth hormones, stimulatory in some and inhibitory in others.
Immune system: Animal studies indicate that morphine has a variety of effects on components of the immune system, however, its clinical significance is not clear.

Morphine is typically used for the management of pain for which alternative options are inadequate, including:

Moderate-to-severe acute pain
Chronic severe pain
Breakthrough pain
Post-surgical pain
Severe pain in conditions such as cancer and sickle-cell disease
Cyanotic Tetralogy of Fallot (congenital heart defects that lead to low oxygen and bluish skin color in premature newborns)

Warnings

Do not administer morphine to patients who have:
- Hypersensitivity to morphine, morphine salts or any of the drug’s components
- Respiratory depression, in the absence of resuscitative equipment
- Acute or severe bronchial asthma, high carbon dioxide levels (hypercarbia) or upper airway obstruction
- Suspected or confirmed gastrointestinal obstruction, or paralysis of the intestinal muscles (paralytic ileus)
- Toxin-mediated diarrhea
Do not administer morphine within 2 weeks of monoamine oxidase inhibitor (MAOI) therapy; MAOIs can enhance opioid effects
Do not administer morphine simultaneously with other central nervous system (CNS) depressants, including other opioids, phenothiazines, sedative/hypnotics and alcohol; may result in profound sedation, respiratory depression, coma, and death
Administer morphine with great caution to patients with CNS depression, toxic psychosis, acute alcoholism and delirium tremens
Morphine has a high risk for addiction, abuse, and misuse that can lead to overdose and death; prescribe after carefully assessing the patient’s risk, and monitor regularly
Concurrent use with alcohol or other drugs of abuse that depress the central nervous system increases the risk for serious respiratory depression, coma and death
Even therapeutic doses of morphine can cause serious, life-threatening, or fatal respiratory depression in elderly and debilitated patients; use with extreme caution
Patients with chronic obstructive pulmonary disease (COPD) or other conditions with reduced lung capacity are at higher risk for serious respiratory depression; use the lowest effective dose with extreme caution, under medical supervision
The risk for fatal or life-threatening respiratory depression is greatest during initiation of therapy and increase of dosage; monitor the patient closely
Morphine can further reduce cardiac output and cause severe low blood pressure (hypotension), positional (orthostatic) hypotension and loss of consciousness (syncope) in patients with already compromised circulation including reduced blood volume (hypovolemia) or circulatory shock; use with caution, particularly IV administrations
Use with caution in patients with irregular heart rhythm (cardiac arrhythmia)
Use with caution in patients with head injury and high intracranial pressure or cerebrospinal pressure; morphine can further increase intracranial pressure
Do not administer morphine injection formulations to patients with heart failure due to chronic lung disease, head injuries, brain tumors, delirium tremens, seizure disorders, during labor when premature birth anticipated
Morphine use may cause constipation; use preventive measures such as stool softeners and increased fiber, especially in patients with unstable angina or myocardial infarction
Use with caution in patients with biliary tract diseases such as acute pancreatitis; morphine may cause sphincter of Oddi spasms and reduce bile/pancreatic secretions;
Avoid use of morphine after biliary tract surgery and surgical anastomosis
Use morphine with caution in patients with severe liver or kidney impairment, Addison's disease, hypothyroidism, enlarged prostate or urethral stricture
All opioids may aggravate convulsions in patients with seizure disorders; use with caution
Opioids (dose-dependent) can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; taper and reduce if required
Do not use morphine concurrently with drugs that can increase serotonin levels; can lead to serotonin syndrome, a potentially life-threatening condition
Morphine use can cause adrenal insufficiency, more often after one month of use; monitor the patient and treat appropriately
Prolonged opioid use during pregnancy can cause opioid withdrawal syndrome in the newborn, which may be life-threatening if not recognized and treated
Accidental consumption, especially in children, can result in fatal overdose
Some formulations may contain sodium benzoate/benzoic acid, which have been associated with potentially fatal toxicity (gasping syndrome) in newborns
Some formulations contain sulfites, which may cause allergic reactions in sulfite sensitive patients
When discontinuing morphine therapy in physically-dependent patients, gradually taper dosage; do not abruptly discontinue
Healthcare workers are strongly encouraged to complete opioid analgesic risk evaluation and mitigation strategy (REMS) education program to be able to counsel patients and caregivers appropriately on safe use and disposal of opioid analgesics

What are the side effects of morphine?

Common side effects of morphine include:

Itching (pruritus)
Urinary retention
Vomiting
Headache
Drowsiness (somnolence)
Constipation

Less common side effects of morphine include:

Fever
Weakness (asthenia)
Backache
Abdominal pain
Nausea
Diarrhea
Loss of appetite (anorexia)
Dry mouth (xerostomia)
Sweating
Swelling of extremities (peripheral edema)
Rash
Shortness of breath (dyspnea)
Respiratory depression
Dizziness
Abnormal skin sensations (paresthesia)
Sleeplessness (insomnia)
Depression
Anxiety
Thinking disturbances
Hiccups
Lazy eye (amblyopia)
Constriction of pupils (miosis)
Abnormal liver function test results
Feeling unwell (malaise)
Drop in blood pressure when standing up from sitting or lying down (orthostatic hypotension)
Fainting (syncope)
Lightheadedness
Vertigo
Brief muscle spasms or convulsions (myoclonus)

Serious side effects of morphine include:

Respiratory depression
Cardiac arrest
Circulatory depression
Shock
Increase in intracranial pressure
Temporary paralysis of intestinal muscles (ileus)
Severe allergic reaction (anaphylaxis), rare

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

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What are the dosages of morphine?

Adult:

Tablet, extended-release (MS Contin): Schedule II

15mg, 30mg, 60mg, 100mg, 200mg

Tablet, extended release (abuse-deterrent): Schedule II

15 mg, 30 mg, 60 mg (Arymo ER)
15 mg, 30 mg, 60 mg, 100 mg (MorphaBond)

Capsule, morphine sulfate extended-release: Schedule II

10 mg, 20 mg, 30 mg, 45 mg, 50 mg, 60 mg
75 mg, 80 mg, 90 mg, 100 mg, 120 mg

Capsule, extended-release (Kadian): Schedule II

10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg
70 mg, 80 mg, 100 mg, 130 mg, 150 mg, 200 mg

Injectable suspension, extended-release, liposomal (DepoDur): Schedule II

10 mg/mL

Injectable solution (Duramorph): Schedule II

0.5 mg/mL
1 mg/mL

Injectable solution, high potency (Infumorph): Schedule II

10 mg/mL (200 mg/20mL ampule)
25 mg/mL (500 mg/20mL ampule)

Morphine sulfate, injectable solution: Schedule II

0.5 mg/mL, 1 mg/mL, 2 mg/mL, 4 mg/mL, 5 mg/mL
8 mg/mL, 10 mg/mL, 15 mg/mL, 25 mg/mL, 50 mg/mL

Tablet, morphine sulfate immediate release: Schedule II

15 mg, 30 mg

Morphine sulfate, suppository: Schedule II

5 mg, 10 mg, 20 mg, 30 mg

Morphine sulfate, oral solution: Schedule II

10 mg/5mL; 20 mg/5mL

Morphine sulfate, intramuscular device

10 mg/0.7mL

Pediatric:

Morphine sulfate, injectable solution: Schedule II

0.5 mg/mL, 1 mg/mL, 2 mg/mL, 4 mg/mL, 5 mg/mL
8 mg/mL, 10 mg/mL, 15 mg/mL, 25 mg/mL, 50 mg/mL

Tablet, morphine sulfate immediate release: Schedule II

15 mg, 30 mg

Adult:

Addiction, abuse, and misuse:

Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death

Assess each patient’s risk before prescribing and monitor all patients regularly for the development of these behaviors or conditions

Acute Pain

Immediate-release tablet

Opioid-naïve patients: 15-30 mg orally every 4 hours as needed

Oral solution

Opioid-naïve patients: 10-20 mg orally every 4 hours as needed

Suppository

10-20 mg PR every 4 hours

Parenteral solution

Subcutaneously/intramuscularly (SC/IM) (opioid-naïve patients): 5-10 mg every 4 hours as needed; dose range, 5-20 mg
Intravenously (IV) (opioid-naïve patients): 2.5-5 mg every 3-4 hours as needed, infused over 4-5 minutes; dose range, 4-10 mg

Preservative-free parenteral solution

Epidural injection
- Single-dose: 5-10 mg once daily in the lumbar region
- Continuous infusion: 2-4 mg IV infused over 24 hours
Intrathecal (IT)
- Single-dose (opioid-naive patients): 0.1-0.3 mg single dose, plus an available infusion of naloxone; dosage range per manufacturer, is 0.2-1 mg/day; because repeated IT injections are not recommended, the alternative route should be used if pain recurs within 24 hours
- Continuous infusion (opioid naive patients): 0.2-1 mg on lumbar region over 24 hours
- Continuous infusion (opioid tolerant): 1-10 mg over 24 hours microinfusion on the lumbar region; not to exceed 20 mg over 24 hours

Extended-release liposomal injection

DepoDur treatment of pain after major surgical procedures
After cesarean section: 10 mg as a single lumbar epidural injection after the umbilical cord is clamped
Major orthopedic surgery of lower extremity: 10-15 mg as a single lumbar epidural injection before the procedure
Lower abdominal or pelvic surgery: 10-15 mg as a single lumbar epidural injection before the procedure; may benefit from 20 mg dose

Dosing considerations

Injection formulation not for intravenous (IV) administration unless opioid antagonist immediately available
The usual dosage of IV morphine in adults, regardless of indication, is 2-10 mg/70 kg body weight
Consider the lowest end of dosing range and monitor for side effects in elderly patients and those with renal or hepatic impairment
Opioid-tolerant patients may require higher initial doses; patients are considered opioid-tolerant if they take at least 60 mg/day orally of morphine, 30 mg/day orally of morphine, 12 mg/day orally of hydromorphone, or an equianalgesic dose of another opioid for more than 1 week
Oral solution: 100 mg/5 mL concentration is appropriate only for opioid-tolerant patients
Parenteral solution: Intramuscular (IM) injection is painful and has a variable onset of analgesia because of delayed onset of action and erratic absorption; repeated subcutaneous (SC) administration may cause local tissue damage, as well as induration, irritation, and pain at the injection site
Preservative-free parenteral solution: American Pain Society describes "ceiling" for analgesic effect with dosages greater than 0.3 mg/day and increase in adverse effects (e.g., respiratory depression); extreme caution is warranted with epidural or intrathecal (IT) administration in aged or debilitated patients, and lower dosages are usually adequate
Extended-release liposomal injectable suspension: To be administered only in a single dose via lumbar epidural route; not recommended for administration into thoracic or higher epidural spaces; not to be administered IT, IV, or IM

Chronic Severe Pain

Extended-release (ER)/long-acting (LA) formulations are indicated for the management of severe pain requiring daily, around-the-clock, long-term opioid treatment for which alternative options are inadequate
Immediate-release (IR): May also be used for management of chronic pain but require more frequent dosing; may also be used in combination with ER/LA products for breakthrough pain

The extended-release tablet (MS Contin)

Opioid-naïve patients (as first opioid dose): Initiate with 15 mg orally every 8-12 hours; use of higher starting doses in patients who are not opioid-tolerant may cause fatal respiratory depression
Opioid-tolerant patients: Dose depends on a daily dose of previous opioid analgesic (individualization required for conversion)
MS Contin dose equivalent to one-half of patient's calculated 24-hr orally morphine requirement every 12 hours; alternatively, dose equivalent to one-third of the patient's calculated 24-hr orally morphine requirement every 8 hours
The tablet must be swallowed whole and not broken, chewed, dissolved, or crushed; sudden release of morphine content increases the risk of respiratory depression and death

The extended-release capsule (Kadian)

Opioid-naive patients: Not indicated for use as an initial opioid analgesic; initiate with immediate-release (IR) formulation, then convert to Kadian
Nonopioid-tolerant patients: 30 mg orally once/day
Opioid-tolerant patients: Dose depends on a daily dose of previous opioid analgesic (individualization required for conversion)
Kadian dose equivalent to one half of patient’s 24-hr orally morphine requirement every 12 hours; alternatively, dose equivalent to patient's 24-hr orally morphine requirement once daily
The capsule must be swallowed whole, or contents must be sprinkled on applesauce and immediately swallowed; must not be chewed, crushed, or dissolved; sudden release of morphine content increases the risk of respiratory depression and death

Extended-release tablet, abuse-deterrent (MorphaBond)

Opioid-naïve patients (as first opioid dose): 15 mg orally every 12 hours
Opioid-tolerant patients: Dose depends on a daily dose of previous opioid analgesic (individualization required for conversion)
MorphaBond dose equivalent to one-half of patient's calculated 24-hr orally morphine requirement administered every 12 hours
The tablet must be swallowed whole and not broken, chewed, dissolved, or crushed; sudden release of morphine content increases the risk of respiratory depression and death

Extended-release tablet, abuse-deterrent (Arymo ER)

Initial dosing
- Opioid naïve patients and opioid non-tolerant patients: 15 mg orally every 8-12 hours
Conversion to Arymo ER
- Morphine recipients: Administer one-half of 24-hr morphine requirement as Arymo ER orally every 12 hours, or one-third of 24-hr morphine requirement as Arymo ER orally every 8 hours
- Patients receiving other opioids: Discontinue all around-the-clock opioid drugs, then initiate Arymo ER 15mg orally every 8 hours Arymo ER dose when converted from other opioids or parenteral morphine: Calculate 24-hr orally
- Morphine equivalent requirement and administer one-half of that daily equivalent as Arymo ER every 12 hours; alternatively, may give one-third of the patient's calculated 24-hour oral morphine requirement every 8 hours
- Methadone to morphine sulfate ER conversion: Methadone has a long half-life and may accumulate in plasma; conversion dose may vary widely; judicious dosing and close monitoring is warranted

High-potency injectable solution (Infumorph)

Treatment of intractable chronic pain
Starting dose for epidural or intrathecal (IT) administration must be individualized on basis of the in-hospital evaluation of response to serial single-dose bolus injections using a lower concentration of preservative-free morphine solution, with close observation of analgesic efficacy and adverse effects before surgery involving continuous microinfusion device
IT (opioid-naïve patients): 0.2-1 mg over 24 hours
IT (opioid-tolerant patients): 1-10 mg over 24 hours; caution warranted with dosages greater than 20 mg/24 hours
Epidural (opioid-naïve patients): 3.5-7.5 mg over 24 hours
Epidural (opioid-tolerant patients) 4.5-10 mg over 24 hours

Opioid-tolerant definition

Patients who are opioid-tolerant are those receiving, for 1 week or longer, at least 60 mg/day orally morphine, 25 mcg/hour transdermal fentanyl, 30 mg/day orally morphine, 8 mg/day orally hydromorphone, 25 mg/day orally oxymorphone, or an equianalgesic dose of another opioid

Dosing Considerations

Access to naloxone for opioid overdose

Assess need for naloxone upon initiating and renewing treatment
Consider prescribing naloxone
- Based on patient’s risk factors for overdose (eg, concomitant use of central nervous system (CNS) depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
- Household members (including children) or other close contacts at risk for accidental ingestion or overdose
Consult patients and caregivers on the following:
- Availability of naloxone for emergency treatment of opioid overdose
- Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, as part of a community-based program)

Limitations of use

Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
Not indicated for acute pain or as an as-needed analgesic

Pediatric:

Analgesia/Cyanotic Tetralogy of Fallot

Neonates (less than 30 days): 0.3-1.2 mg/kg/day intramuscular/subcutaneous (IM/SC) divided every 4 hours; 0.005-0.03 mg/kg/hour slow intravenous (IV)
Infants and children (oral solution): 0.2-0.5 mg/kg orally every 4-6 hours as needed
Infants and children (IM/SC): 0.05-0.2 mg/kg every 2-4 hours as needed; not to exceed 15 mg/dose

Pain

Continuous infusion: 0.025-2.6 mg/kg/hour intravenously (IV); average, 0.06 mg/kg/hour
Neonates (less than 30 days): 0.01-0.02 mg/kg/hour by IV infusion
Postoperative pain: 0.01-0.04 mg/kg/hour by IV infusion
Sickle-cell disease, cancer: 0.04-0.07 mg/kg/hour by IV infusion

Addiction/overdose

Morphine has a high potential for addiction, abuse, and misuse, and can lead to overdose, which can cause respiratory depression with or without central nervous system depression. Severe overdose can cause constricted pupils, and extreme drowsiness leading to respiratory arrest, circulatory collapse, coma, cardiac arrest and death.
Opioid overdose treatment includes:
- Supportive care to maintain respiration with assisted ventilation, oxygen, intravenous fluids and medication to increase arterial pressure.
- Severe overdose may require respiratory resuscitation and cardiac defibrillation.
- Administration of naloxone hydrochloride, the antidote used to reverse opioid effects, if there is significant respiratory and circulatory depression.
- Gastric emptying with induced vomiting and lavage to remove unabsorbed drug, in case of oral overdose, and administration of activated charcoal.

QUESTION

Medically speaking, the term “myalgia” refers to what type of pain?
See Answer

What drugs interact with morphine?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

Severe Interactions of morphine include:
- alvimopan
- safinamide
Morphine has serious interactions with at least 50 different drugs.
Morphine has moderate interactions with at least 259 different drugs.
Mild Interactions of morphine include:
- benazepril
- brimonidine
- celandine
- dextroamphetamine
- eucalyptus
- lidocaine
- rifabutin
- rifampin
- sage
- ziconotide

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

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Pregnancy and breastfeeding

Use morphine in pregnancy only if its benefits clearly outweigh the potential risks and in late term, only in life-threatening emergencies if no alternative is adequate.
Morphine may produce respiratory depression and other effects in the newborn; monitor newborn closely; keep an opioid antagonist, such as naloxone, available for reversal of opioid-induced respiratory depression in the newborn.
Avoid use of morphine during and immediately prior to labor; opioid analgesics may prolong labor by reducing strength, duration, and frequency of uterine contractions; however, this effect is not consistent.
Morphine is present in breast milk, the concentration depending on mother’s morphine levels; because of the potential for respiratory depression, sedation and possible withdrawal symptoms in nursing infants, decide to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Chronic use of opioids may reduce fertility in both men and women of reproductive potential; it is not known whether these effects are reversible.
Chronic opioid use by the mother during pregnancy can result in physical dependence and opioid withdrawal syndrome in the newborn, and increase the risk of sudden infant death syndrome.
Animal studies indicate that prolonged opioid use in the mother during pregnancy can lead to growth and behavioral abnormalities in the offspring, and affect their fertility.

What else should I know about morphine?

Morphine is a Schedule II controlled substance; diversion of Schedule II products is subject to criminal penalty
Morphine exposes users to the risks of addiction, abuse, and misuse, and can lead to fatal overdose
There is a greater risk for overdose and death with extended-release opioids, including morphine, due to the larger amount of active opioid present
Take morphine exactly as prescribed; do not take a higher or more frequent dosage
Swallow tablet/capsule whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal dose
In case of known or suspected overdose, seek medical help immediately
Do not drink alcohol or take alcohol-containing drugs while taking morphine; it increases the risk for sedation and respiratory depression
Store morphine well out of reach of children; accidental consumption, especially in children, can result in a fatal overdose
Morphine can impair mental and physical ability; avoid driving, operating heavy machinery or performing other potentially hazardous tasks while on morphine therapy