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

Dosage Considerations – Should be Given as Follows:

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