Morphine

Morphine is used to treat severe pain. Morphine belongs to a class of drugs known as opioid (narcotic) analgesics. It works in the brain to change how your body feels and responds to pain. Morphine is a chemical found in the opium plant. It is a narcotic (opioid) pain-reliever similar to hydrocodone, oxycodone, methadone, fentanyl, and other opioids.

• Morphine is available under the following different brand names: MS Contin, Astramorph, Depodur, Duramorph, Infumorph, Kadian, MorphaBond, and Arymo ER.

Dosages of Morphine

Dosage Forms and Strengths

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 (adult and pediatric)

• 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 (adult and pediatric)

• 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

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 oxycodone, 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 oxycodone, 8 mg/day orally hydromorphone, 25 mg/day orally oxymorphone, or an equianalgesic dose of another opioid

Limitations of use

• Because of the 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

Common side effects of morphine include:

• Itching
• Urinary retention (epidural/intrathecal or oral)
• Vomiting
• Constipation
• Headache
• Sleepiness
• Abdominal pain
• Weakness or lack of energy
• Backache
• Depression
• Diarrhea
• Shortness of breath
• Fever
• Insomnia
• Loss of appetite
• Nausea
• Numbness and tingling
• Swelling of extremities
• Rash
• Sweating
• Dry mouth
• Respiratory depression
• Anxiety
• Dizziness
• Abnormal liver function test results
• Amblyopia
• Hiccups
• Dizziness upon standing
• Lightheadedness/fainting

Other side effects of morphine include:

• Cardiac arrest
• Circulatory depression
• Constricted pupils
• Feeling unwell (malaise)
• Ileus
• Jerky muscle movements
• Lightheadedness
• Severe allergic reaction (anaphylaxis, rare)
• Shock
• Spinning sensation (vertigo)
• Thinking disturbances

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

If your doctor has directed you to use this medication for your condition, your doctor or pharmacist may already be aware of any possible drug interactions or side effects and may be monitoring you for them. Do not start, stop, or change the dosage of this medicine or any medicine before getting further information from your doctor, healthcare provider, or pharmacist first.

• Severe Interactions of morphine include:
  • alvimopan
• Morphine has serious interactions with at least 36 different drugs.
• Morphine has moderate interactions with at least 252 different drugs.
• Mild Interactions of morphine include:
  • benazepril
  • brimonidine
  • celandine
  • dextroamphetamine
  • eucalyptus
  • lidocaine
  • naloxone
  • rifabutin
  • rifampin
  • sage
  • ziconotide

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• Infumorph is not recommended for single-dose intravenous, intramuscular or subcutaneous administration due to the associated risk of overdosage.
• Improper or erroneous substitution of Infumorph 200 or 500 (10-25 mg/mL, respectively for regular Duramorph (0.
• 5 or 1 mg/mL) could result in serious overdosage leading to seizures, respiratory depression, and, possibly fatal outcomes.
• Intrathecal dosage is usually 1/10 that of epidural dosage.
• Observe the patient in a fully equipped and staffed environment for at least 24 hours after the initial epidural or intrathecal dose.
• Naloxone injection and resuscitative equipment should be immediately available for administration, when administering Duramorph or Infumorph, to treat life-threatening or intolerable side effects.
• Inspect drug products for the particular matter before opening the amber ampule, and again for color after removing contents from the ampule; after removal do not use unless a solution is a colorless or pale yellow; the 100 mg/5 mL oral solution is indicated for use in opioid-tolerant patients only.

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

Life-threatening respiratory depression:

• Serious, life-threatening, or fatal respiratory depression may occur
• Monitor for respiratory depression, especially during initiation or following a dose increase
• Instruct patients to swallow tablet/capsule whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal dose

Accidental exposure:

• Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose
• Accidental skin exposure to Duramorph, Astramorph/PF, or Infumorph should be rinsed with water; remove contaminated clothing

Neonatal opioid withdrawal syndrome:

• Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
• Syndrome presents as irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremors, vomiting, diarrhea, and failure to gain weight
• 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
• If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

Alcohol interaction:

• Instruct patients not to consume alcoholic beverages or use alcohol-containing drug products while taking morphine due to the risk of additive sedation and respiratory depression
• Co-ingestion of alcohol with opioid analgesics may increase plasma opioid levels and potentially result in a fatal overdose
• Some long-acting products (i.
• e., Kadian) should not be administered with alcoholic beverages or ethanol-containing products as it may alter the characteristics of the extended-release product and cause rapid release and absorption of a potentially fatal dose

Central nervous system (CNS) depressants:

• Co-administration with benzodiazepines or other 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; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation
• Instruct patients not to consume alcoholic beverages or use alcohol-containing drug products while taking morphine due to the risk of additive sedation and respiratory depression
• This medication contains morphine.
• Do not take MS Contin, Astramorph, Depodur, Duramorph, Infumorph, Kadian, MorphaBond, or Arymo ER if you are allergic to morphine or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• Paralytic ileus
• Toxin-mediated diarrhea
• Respiratory depression, acute or severe bronchial asthma, upper airway obstruction
• Within 2 weeks of monoamine oxidase inhibitor (MAOI) therapy
• GI obstruction (extended-release)
• Hypercarbia (immediate-release tablets/solution)
• Upper airway obstruction (epidural/intrathecal)
• Heart failure due to chronic lung disease, head injuries, brain tumors, delirium tremens, seizure disorders, during labor when premature birth is anticipated (injectable formulation)
• Cardiac arrhythmia, increased intracranial or cerebrospinal pressure, acute alcoholism, use after biliary tract surgery, surgical anastomosis (suppository formulation)

Effects of Drug Abuse

Addiction, abuse, and misuse:

• Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioids present
• Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (e.g., major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary
• Assess each patient’s risk before prescribing and monitor all patients regularly for the development of these behaviors or conditions

Short-Term Effects

• May cause CNS depression and impair the ability to operate heavy machinery.
• See "What Are Side Effects Associated with Using Morphine?"

Long-Term Effects

• Prolonged use may result in fungal or bacterial superinfection.
• Tetracycline use during tooth development (last half of pregnancy through age 8 years) can cause tooth enamel hypoplasia or permanent teeth discoloration; more common with long-term use and with repeated, short courses.
• See "What Are Side Effects Associated with Using Morphine?"

Cautions

Use with caution in acute pancreatitis, Addison disease, benign prostatic hyperplasia, cardiac arrhythmias, central nervous system (CNS) depression, drug abuse or dependence, emotional lability, gallbladder disease, gastrointestinal (GI) disorder, morbidly obese patients, patients with urinary stricture, pseudomembranous colitis, GI surgery, head injury, hypothyroidism or untreated myxedema, intracranial hypertension, brain tumor, toxic psychosis, urethral stricture, urinary tract surgery, seizures, acute alcoholism, delirium tremens, shock, cor pulmonale, chronic pulmonary disease, emphysema, hypercapnia, kyphoscoliosis, severe obesity, renal or hepatic impairment, elderly or debilitated patients, neonates.

• May cause constipation; consider preventive measures (e.g., stool softener, increased fiber) to reduce the potential for constipation, especially in patients with unstable angina and patients with myocardial infarction.
• Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists.
• Use caution in patients with adrenal insufficiency, including Addison’s disease; chronic opioid use may cause secondary hypogonadism, leading to mood disorders, osteoporosis, sexual dysfunction, and infertility.
• Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; use may cause constriction of the sphincter of Oddi diminishing biliary and pancreatic secretion.
• Avoid the use of morphine in patients with CNS depression or coma who may be susceptible to intracranial effects of CO2 retention.
• Some formulations may contain sodium benzoate/benzoic acid, which has been associated with potentially fatal toxicity (gasping syndrome) in neonates.
• Products are designed for specific routes; use caution when prescribing, dispensing, or administering to use formulations only by intended routes.
• Some formulations contain sulfites, which may cause allergic reactions in sulfite-sensitive patients.
• Kadian: Avoid concurrent consumption of alcohol or alcohol-containing foods or medications; co-ingestion results in increased plasma levels and potentially fatal overdose.
• May cause CNS depression and impair the ability to operate heavy machinery.
• All formulations are capable of producing respiratory depression.
• Use with caution, particularly with IV administration, in patients with hypovolemia, cardiovascular disease, circulatory shock, or drugs that may exaggerate hypotensive effects, including general anesthetics and phenothiazines; may cause orthostatic hypotension and syncope in ambulatory patients.
• After chronic maternal exposure to opioids, a neonatal withdrawal syndrome may occur in the newborn.
• May obscure diagnosis or clinical course of patients with acute abdominal conditions.

Long-acting opioids:

• Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioids present
• Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (e.g., major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary
• Serious, life-threatening, or fatal respiratory depression reported
• Accidental exposure was reported, including fatalities
• Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy
• Interactions with central nervous system (CNS) depressants (e.g., alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, and other opioids) can cause additive effects and increase the risk for respiratory depression, profound sedation, and hypotension
• Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients
• Not indicated for as-needed use

Pregnancy and Lactation

Use morphine with caution during pregnancy if the benefits outweigh the risks. Animal studies show risk and human studies are not available or neither animal nor human studies were done. According to some authorities, if used near term, only use morphine in LIFE-THREATENING emergencies when no safer drug is available. There is positive evidence of human fetal risk.

Neonatal opioid withdrawal syndrome:

• Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
• Syndrome presents as irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight
• 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
• If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

Morphine is excreted in breast milk (the American Academy of Pediatrics committee states that the drug is compatible with nursing).