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Morphine (Systemic)

Pronunciation

(MOR feen)

Index Terms

  • Arymo ER
  • MorphaBond
  • MS (error-prone abbreviation and should not be used)
  • MSO4 (error-prone abbreviation and should not be used)
  • Oramorph SR
  • Roxanol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 24 Hour, Oral, as sulfate:

AVINza: 30 mg [DSC] [contains fd&c yellow #10 (quinoline yellow), fumaric acid]

AVINza: 45 mg [DSC] [contains fd&c blue #2 (indigotine)]

AVINza: 60 mg [DSC] [contains fumaric acid]

AVINza: 75 mg [DSC]

AVINza: 90 mg [DSC] [contains fd&c red #40, fumaric acid]

AVINza: 120 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fumaric acid]

Kadian: 10 mg [contains brilliant blue fcf (fd&c blue #1)]

Kadian: 20 mg [contains fd&c yellow #10 (quinoline yellow)]

Kadian: 30 mg [contains brilliant blue fcf (fd&c blue #1)]

Kadian: 40 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Kadian: 50 mg, 60 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]

Kadian: 70 mg [DSC] [contains brilliant blue fcf (fd&c blue #1)]

Kadian: 80 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Kadian: 100 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Kadian: 130 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Kadian: 150 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Kadian: 200 mg

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

Device, Intramuscular, as sulfate:

Generic: 10 mg/0.7 mL (0.7 mL)

Solution, Injection, as sulfate:

Generic: 2 mg/mL (1 mL [DSC]); 5 mg/mL (1 mL [DSC]); 8 mg/mL (1 mL [DSC]); 10 mg/mL (1 mL [DSC], 10 mL [DSC]); 15 mg/mL (1 mL [DSC], 20 mL [DSC])

Solution, Injection, as sulfate [preservative free]:

Duramorph: 0.5 mg/mL (10 mL); 1 mg/mL (10 mL) [antioxidant free]

Infumorph 200: 200 mg/20 mL (10 mg/mL) (20 mL) [antioxidant free]

Infumorph 500: 500 mg/20 mL (25 mg/mL) (20 mL) [antioxidant free]

Generic: 0.5 mg/mL (10 mL); 1 mg/mL (10 mL); 2 mg/mL (1 mL); 4 mg/mL (1 mL); 5 mg/mL (1 mL); 8 mg/mL (1 mL); 10 mg/mL (1 mL)

Solution, Intravenous, as sulfate:

Generic: 1 mg/mL (10 mL [DSC], 30 mL); 25 mg/mL (4 mL [DSC], 10 mL [DSC]); 50 mg/mL (20 mL, 50 mL); 1000 mg/100 mL (100 mL); 2,500 mg/250 mL in NaCl 0.9% (250 mL); 250 mg/250 mL in Dextrose 5% (250 mL); 250 mg/250 mL in NaCl 0.9% (250 mL); 500 mg/250 mL in NaCl 0.9% (250 mL [DSC])

Solution, Intravenous, as sulfate [preservative free]:

Generic: 1 mg/mL (30 mL); 2 mg/mL (1 mL); 4 mg/mL (1 mL); 150 mg/30 mL (30 mL); 8 mg/mL (1 mL); 10 mg/mL (1 mL); 15 mg/mL (1 mL); 25 mg/mL (10 mL)

Solution, Oral, as sulfate:

Generic: 10 mg/5 mL (5 mL, 15 mL, 100 mL, 500 mL); 20 mg/5 mL (5 mL, 100 mL, 500 mL); 100 mg/5 mL (15 mL, 30 mL, 120 mL, 240 mL)

Solution Prefilled Syringe, Intravenous, as sulfate:

Generic: 50 mg/50 mL (50 mL)

Suppository, Rectal, as sulfate:

Generic: 5 mg (12 ea); 10 mg (12 ea); 20 mg (12 ea); 30 mg (12 ea)

Tablet, Oral, as sulfate:

Generic: 15 mg, 30 mg

Tablet ER 12 Hour Abuse-Deterrent, Oral, as sulfate:

MorphaBond ER: 15 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #6 (sunset yellow)]

MorphaBond ER: 30 mg [contains fd&c blue #2 (indigotine), fd&c red #40]

MorphaBond ER: 60 mg [contains fd&c red #40, fd&c yellow #6 (sunset yellow)]

MorphaBond ER: 100 mg [contains fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #6 (sunset yellow)]

Tablet Extended Release, Oral, as sulfate:

MS Contin: 15 mg [contains fd&c blue #2 (indigotine)]

MS Contin: 30 mg [contains brilliant blue fcf (fd&c blue #1)]

MS Contin: 60 mg [contains fd&c yellow #10 (quinoline yellow)]

MS Contin: 100 mg

MS Contin: 200 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Generic: 15 mg, 30 mg, 60 mg, 100 mg, 200 mg

Tablet Extended Release Abuse-Deterrent, Oral, as sulfate:

Arymo ER: 15 mg (100 ea); 30 mg (100 ea) [contains fd&c blue #2 (indigotine)]

Arymo ER: 60 mg (100 ea)

Brand Names: U.S.

  • Arymo ER
  • AVINza [DSC]
  • Duramorph
  • Infumorph 200
  • Infumorph 500
  • Kadian
  • MorphaBond ER
  • MS Contin

Pharmacologic Category

  • Analgesic, Opioid

Pharmacology

Binds to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression

Absorption

Oral: Variable

Distribution

Distributes to skeletal muscle, liver, kidneys, lungs, intestinal tract, spleen and brain; Vd:

Cancer patients (Children age 1.7 to 18.7 years): Median: 5.2 L/kg; a significantly higher Vd was observed in children <11 years (median: 7.1 L/kg) versus >11 years (median: 4.7 L/kg) (Hunt 1999)

Adults: 1 to 6 L/kg; binds to opioid receptors in the CNS and periphery (eg, GI tract)

Metabolism

Hepatic via conjugation with glucuronic acid primarily to morphine-6-glucuronide (M6G) (active analgesic) and morphine-3-glucuronide (M3G) (inactive as analgesic; may contribute to CNS stimulation [Lugo 2002]); minor metabolites include morphine-3-6-diglucuronide; other minor metabolites include normorphine (active) and morphine 3-ethereal sulfate

Excretion

Urine (primarily as morphine-3-glucuronide, neonates: 3% to 15%; adults: ~2% to 12% excreted unchanged); feces (~7% to 10%). It has been suggested that accumulation of morphine-6-glucuronide might cause toxicity with renal insufficiency. All of the metabolites (ie, morphine-3-glucuronide, morphine-6-glucuronide, and normorphine) have been suggested as possible causes of neurotoxicity (eg, myoclonus).

Clearance: Note: In pediatric patients, adult values are reached by 6 months to 2.5 years of age (McRorie 1992)

Preterm: 0.5 to 3 mL/minute/kg

Neonates 1 to 7 days: Median: 5.5 mL/minute/kg (range: 3.2 to 8.4 mL/minute/kg) (McRorie 1992)

Neonates 8 to 30 days: Median: 7.4 mL/minute/kg (range: 3.4 to 13.8 mL/minute/kg) (McRorie 1992)

Infants 1 to 3 months: Median: 10.5 mL/minute/kg (range: 9.8 to 20.1 mL/minute/kg) (McRorie 1992)

Infants 3 to 6 months: Median: 13.9 mL/minute/kg (range: 8.3 to 24.1 mL/minute/kg) (McRorie 1992)

Infants 6 months to Children 2.5 years: Median: 21.7 mL/minute/kg (range: 5.8 to 28.6 mL/minute/kg) (McRorie 1992)

Preschool Children: 20 to 40 mL/minute/kg

Cancer patients (Children age: 1.7 to 18.7 years): Median: 23.1 mL/minute/kg; a significantly higher clearance was observed in children <11 years (median: 37.4 mL/minute/kg) versus >11 years (median: 21.9 mL/minute/kg) (Hunt 1999)

Children with sickle cell disease (age: 6 to 19 years): ~36 mL/minute/kg (range: 6 to 59 mL/minute/kg) (Dampier 1995)

Adults: 20 to 30 mL/minute/kg

Onset of Action

Patient dependent; dosing must be individualized: Oral (immediate release): ~30 minutes; IV: 5 to 10 minutes

Time to Peak

Plasma:

Tablets, oral solution, epidural: 1 hour

Extended release tablets: 3 to 4 hours; Avinza: 30 minutes (maintained for 24 hours); Kadian: ~10 hours

Suppository: 20 to 60 minutes

SubQ: 50 to 90 minutes

IM: 30 to 60 minutes

IV: 20 minutes

Cerebrospinal fluid: After an oral dose of controlled release morphine concentrations peak at 8 hours for both normal and reduced renal function; morphine-6-glucuronide (active analgesic) and morphine-3-glucuronide distribution into the CNS may be delayed peaking at 12 hours in patients with normal renal function or up to 24 hours in patients with ESRD (peak level of morphine-6-glucuronide is ~15 times higher than patients with normal renal function) (D'Honneur 1994).

Duration of Action

Patient dependent; dosing must be individualized: Pain relief:

Immediate-release formulations (tablet, oral solution, injection): 3 to 5 hours

Extended-release capsule and tablet: 8 to 24 hours (formulation dependent)

Epidural or intrathecal: Single dose: Up to 24 hours (Bujedo 2012)

Suppository: 3 to 7 hours

Half-Life Elimination

Preterm: 10 to 20 hours

Neonates: 7.6 hours (range: 4.5 to 13.3 hours)

Infants 1 to 3 months: Median: 6.2 hours (range: 5 to 10 hours) (McRorie 1992)

Infants 3 to 6 months: Median: 4.5 hours (range: 3.8 to 7.3 hours) (McRorie 1992)

Infants 6 months to Children 2.5 years: Median: 2.9 hours (range: 1.4 to 7.8 hours) (McRorie 1992)

Preschool Children: 1 to 2 hours

Children with sickle cell disease (age: 6 to 19 years): ~1.3 hours (Dampier 1995)

Adults: Immediate-release forms: 2 to 4 hours; Avinza: ~24 hours; Kadian: 11 to 13 hours

Protein Binding

Premature Infants: <20%; Adults: 20% to 35%

Use: Labeled Indications

Pain management:

Injection: Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Preservative-free solutions only:

Duramorph: Epidural or intrathecal management of pain without attendant loss of motor, sensory, or sympathetic function. Note: Not for use in continuous microinfusion devices.

Infumorph: Used in continuous microinfusion devices for intrathecal or epidural administration in management of intractable chronic pain severe enough to require an opioid analgesic and for which less invasive means of controlling pain are inadequate. Note: Not for single-dose IV, IM, or subcutaneous administration or single-dose neuraxial injection.

Oral:

Extended-release: Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Immediate-release: Management of acute and chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Oral solution 100 mg per 5 mL (20 mg/mL) is for opioid-tolerant patients.

Limitations of use: Reserve morphine for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. ER formulations are not indicated as as-needed analgesics.

Severe pain: Rectal: Relief of severe chronic and acute pain.

Contraindications

Hypersensitivity (eg, anaphylaxis) to morphine or any component of the formulation; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days; GI obstruction, including paralytic ileus (known or suspected).

Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Additional contraindications:

Epidural/intrathecal: Infection at infusion site; concomitant anticoagulant therapy; uncontrolled bleeding diathesis; presence of any other concomitant therapy or medical condition that would render administration hazardous; upper airway obstruction.

Rectal: Severe CNS depression; cardiac arrhythmias, heart failure due to chronic lung disease; increased intracranial or cerebrospinal pressure, head injuries, brain tumor; acute alcoholism, delirium tremens; seizure disorder; use after biliary tract surgery, suspected surgical abdomen, surgical anastomosis

Canadian labeling: Additional contraindications (not in US labeling):

Contraindications may vary per product labeling; refer also to product labels: Suspected surgical abdomen (eg, acute appendicitis, pancreatitis); disease/condition that affects bowel transit (known or suspected); chronic obstructive airway; status asthmaticus; management of acute pain, including use in outpatient or day surgeries; mild, intermittent, or short-duration pain that can be managed with other pain medications; acute respiratory depression; hypercarbia; cor pulmonale; acute alcoholism; delirium tremens; convulsive disorders; severe CNS depression; increased cerebrospinal; intracranial pressure; brain tumor; head injury; cardiac arrhythmias; pregnancy; use during labor and delivery; breastfeeding; toxic psychosis and severe kyphoscoliosis (Kadian 2015); severe cirrhosis (M-Ediat 2017); hypotension, (M-Eslon 2014), emotional instability and/or suicidal ideation (Statex 2016); surgical anastomosis (morphine sultafe inj Sandoz 2012)

Dosing: Adult

These are guidelines and do not represent the doses that may be required in all patients. Doses and dosage intervals should be titrated to pain relief/prevention.

Pain management:

IM, SubQ: Note: Repeated SubQ administration causes local tissue irritation, pain, and induration. The use of IM injections is no longer recommended especially for repeated administration due to painful administration, variable absorption and lag time to peak effect; other routes are more reliable and less painful (APS, 2008).

Initial: Opioid naive: 5 to 10 mg every 4 hours as needed; usual dosage range: 5 to 15 mg every 4 hours as needed. Patients with prior opioid exposure may require higher initial doses.

IV: Initial: Opioid naive: 2.5 to 5 mg every 3 to 4 hours; patients with prior opioid exposure may require higher initial doses. Note: Administration of 2 to 3 mg every 5 minutes until pain relief or if associated sedation, oxygen saturation <95%, or serious adverse event occurs may be appropriate in treating acute moderate to severe pain in settings such as the immediate postoperative period or the emergency department (Aubrun, 2012; Lvovschi, 2008); dose reduction in the immediate postoperative period (postanesthesia care unit) in the elderly is usually not necessary (Aubrun, 2002). A maximum cumulative dose (eg, 10 mg) prompting reevaluation of continued morphine use and/or dose should be included as part of any medication order intended for short-term use (eg, PACU orders). Refer to institution-specific protocols as appropriate.

Acute myocardial infarction, analgesia (off-label dose): Initial management: 4 to 8 mg (lower doses in elderly patients); subsequently may give 2 to 8 mg every 5 to 15 minutes as needed (O'Gara, 2012)

Critically ill patients, analgesia (off-label dose): 2 to 4 mg every 1 to 2 hours or 4 to 8 mg every 3 to 4 hours as needed (Barr, 2013)

IV, SubQ continuous infusion: Opioid tolerant: 0.8 to 10 mg/hour; usual range: 20 to 50 mg/hour (higher doses have been reported) (Citron 1984). Note: May administer a loading dose (amount administered should depend on severity of pain) prior to initiating the infusion. A continuous (basal) infusion is not recommended in an opioid-naive patient (ISMP 2009)

Continuous infusion for critically ill patients: Usual dosage range: 2 to 30 mg/hour (Barr, 2013)

Patient-controlled analgesia (PCA) (APS, 2008): Note: In opioid-naive patients, consider lower end of dosing range:

Usual concentration: 1 mg/mL

Demand dose: Usual: 1 mg; range: 0.5 to 2.5 mg

Lockout interval: 5 to 10 minutes

Epidural: Note: Must use preservative-free (PF) formulation indicated for epidural use. Administer with extreme caution and in reduced dosage to geriatric or debilitated patients. Vigilant monitoring is particularly important in these patients.

Single dose (using 0.5 or 1 mg/mL PF solution): Lumbar region: 30 to 100 mcg/kg (optimal range: 2.5 to 3.75 mg; may depend upon patient comorbidities) (Bujedo 2012; Sultan 2011)

Continuous infusion (using 0.5 or 1 mg/mL PF solution; may be combined with bupivacaine): 0.2 to 0.4 mg/hour (Bujedo 2012; Mahoney 1990).

Continuous microinfusion (using 10 mg/mL or 25 mg/mL PF solution; may require dilution):

Opioid naive: Initial: 3.5 to 7.5 mg over 24 hours

Opioid tolerant: Initial: 4.5 to 10 mg over 24 hours, titrate to effect; usual maximum is ~30 mg per 24 hours

Intrathecal: Note: Must use preservative-free (PF) formulation indicated for intrathecal use. Administer with extreme caution and in reduced dosage to geriatric or debilitated patients. Intrathecal dose is usually 1/10 (one-tenth) that of epidural dosage.

Opioid naive:

Single dose (using 0.5 or 1 mg/mL PF solution): Lumbar region:

Manufacturer's labeling: 0.2 to 1 mg may provide satisfactory pain relief for up to 24 hours. (Caution: This is only 0.4 to 2 mL of the 0.5 mg/mL potency or 0.2 to 1 mL of the 1 mg/mL potency.) Do not inject intrathecally more than 2 mL of the 0.5 mg/mL potency or 1 mL of the 1 mg/mL potency; repeat doses are not recommended.

Alternative recommendations: 0.1 to 0.3 mg (may provide adequate relief for up to 24 hours; APS, 2008); repeat doses are not recommended. If pain recurs within 24 hours of administration, use of an alternate route of administration is recommended. Note: Although product labeling recommends doses up to 1 mg, an analgesic ceiling exists with doses >0.3 mg and the risk of respiratory depression is higher with doses >0.3 mg (Rathmell 2005).

Continuous microinfusion (using 10 mg/mL or 25 mg/mL PF solution; may require dilution): Lumbar region: Initial: 0.2 to 1 mg over 24 hours only after initial in-hospital evaluation of response to single-dose injections using morphine 0.5 or 1 mg/mL PF solution.

Opioid tolerant: Continuous microinfusion (using 10 mg/mL or 25 mg/mL PF solution; may require dilution]): Lumbar region: Dosage range: 1 to 10 mg over 24 hours, titrate to effect; usual maximum is ~20 mg over 24 hours

Note: Limited experience with continuous intrathecal infusion of morphine has shown that the daily doses have to be increased over time. Employ doses >20 mg/day with caution.

Oral (immediate-release formulations): Opioid naive: Initial: Note: Usual dosage range: 10 to 30 mg every 4 hours as needed. Patients with prior opioid exposure may require higher initial doses.

Solution: 10 to 20 mg every 4 hours as needed.

Tablet: 15 to 30 mg every 4 hours as needed.

Oral (extended-release formulations): Note: Patients taking opioids chronically may become tolerant and require doses higher than the usual dosage range to maintain the desired effect. Tolerance can be managed by appropriate dose titration. There is no optimal or maximal dose for morphine in chronic pain. The appropriate dose is one that relieves pain throughout its dosing interval without causing unmanageable side effects. Consider total daily dose, potency, prior opioid use, degree of opioid experience and tolerance, conversion from previous opioid (including opioid formulation), patient’s general condition, concurrent medications, and type and severity of pain during prescribing process. Opioid tolerance is defined as: Patients already taking at least 60 mg of oral morphine daily, 25 mcg transdermal fentanyl per hour, 30 mg of oral oxycodone daily, 8 mg oral hydromorphone daily, 25 mg of oral oxymorphone daily, 60 mg oral hydrocodone, or an equivalent dose of another opioid for at least 1 week.

A patient's morphine requirement should be established using immediate-release formulations. Conversion to long-acting products may be considered when chronic, continuous treatment is required. Higher dosages should be reserved for use only in opioid-tolerant patients.

Capsules, extended release (Avinza): Daily dose administered once daily (for best results, administer at same time each day). Note: Avinza 90 mg and 120 mg are only indicated for use in opioid-tolerant patents.

Use as the first opioid analgesic or use in patients who are not opioid tolerant: Initial: 30 mg once daily

Titration and maintenance: Adjust in increments ≤30 mg daily every 3 to 4 days. Maximum: 1600 mg daily due to fumaric acid content.

Capsules, extended release (Kadian): Note: Kadian 100 and 200 mg and a total daily dose >120 mg are only for use in opioid-tolerant patients.

Use as the first opioid analgesic: Has not been evaluated. Use an immediate-release morphine formulation and then convert patients to Kadian in the same fashion as initiating therapy in a nonopioid-tolerant patient.

Use in patients who are not opioid tolerant: Initial: 30 mg once daily.

Titration and maintenance: Dose adjustments may be done every 1 to 2 days.

Tablets, extended release (Arymo ER):

Use as the first opioid analgesic or in patients who are not opioid tolerant: Initial: 15 mg every 8 to 12 hours.

Titration and maintenance: Dose adjustments may be done every 1 to 2 days.

Tablets, extended release (MorphaBond ER):

Use as the first opioid analgesic or who are not opioid tolerant: Initial: 15 mg every 12 hours.

Titration and maintenance: Dose adjustments may be done every 1 to 2 days.

Tablets, extended release (MS Contin): Note: MS Contin 100 mg and 200 mg tablets are only for use in opioid-tolerant patients.

Use as the first opioid analgesic: Initial: 15 mg every 8 to 12 hours

Use in patients who are not opioid tolerant: Initial: 15 mg every 12 hours.

Titration and maintenance: Dose adjustments may be done every 1 to 2 days.

Rectal: 10 to 20 mg every 4 hours

Conversion from other oral morphine formulations to extended-release formulations:

Arymo ER, MS Contin: Total daily oral morphine dose may be administered either in 2 divided doses daily (every 12 hours) or in 3 divided doses (every 8 hours).

Avinza: Total daily morphine dose administered once daily. The first dose of Avinza may be taken with the last dose of the immediate-release morphine. Maximum: 1,600 mg daily due to fumaric acid content.

Kadian: Total daily oral morphine dose may be either administered once daily or in 2 divided doses daily (every 12 hours).

MorphaBond ER: Total daily oral morphine dose administered in 2 divided doses (every 12 hours).

Conversion from parenteral morphine or other opioids to extended-release formulations: Substantial interpatient variability exists in relative potency. Therefore, it is safer to underestimate a patient's daily oral morphine requirement and provide breakthrough pain relief with immediate-release morphine than to overestimate requirements. Consider the parenteral to oral morphine ratio or other oral or parenteral opioids to oral morphine conversions.

Parenteral to oral morphine ratio: Between 2 to 6 mg of oral morphine may be required for analgesia equivalent to 1 mg of parenteral morphine. An oral dose 3 times the daily parenteral dose may be sufficient in chronic pain settings.

Other parenteral or oral nonmorphine opioids to oral morphine: Specific recommendations are not available; refer to published relative potency data realizing that such ratios are only approximations. In general, it is safest to administer 50% of the estimated daily morphine requirement as the initial dose, and to manage inadequate analgesia by supplementation with immediate-release morphine.

Conversion from methadone to extended-release formulations: Close monitoring is required when converting methadone to another opioid. Ratio between methadone and other opioid agonists varies widely according to previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

Discontinuation of oral formulations: Decrease dose by 25% to 50% every 2 to 4 days; monitor carefully for signs/symptoms of withdrawal. If patient displays withdrawal symptoms, increase dose to previous dose and then reduce dose more slowly by increasing interval between dose reductions, decreasing amount of daily dose reduction, or both.

Dosing: Geriatric

Refer to adult dosing. Use with caution; may require reduced dosage.

Dosing: Pediatric

These are guidelines and do not represent the doses that may be required in all patients. Doses and dosage intervals should be titrated to pain relief/prevention.

Acute pain (moderate to severe): Note: The use of IM injections is no longer recommended, especially for repeated administration due to painful administration, variable absorption, and lag time to peak effect; other routes are more reliable and less painful (American Pain Society 2008).

Infants ≤6 months, nonventilated: Note: Infants <3 months of age are more susceptible to respiratory depression; lower doses are recommended (American Pain Society 2008):

Oral: Oral solution (2 mg/mL or 4 mg/mL): 0.08 to 0.1 mg/kg/dose every 3 to 4 hours (American Pain Society 2008; Berde 2002)

IV or SubQ: 0.025 to 0.03 mg/kg/dose every 2 to 4 hours as needed (American Pain Society 2008; Berde 2002).

Infants >6 months, Children, and Adolescents:

Oral: Immediate-release tablets, oral solution (2 mg/mL or 4 mg/mL):

Patient weight <50 kg: 0.2 to 0.5 mg/kg/dose every 3 to 4 hours as needed; some experts have recommended an initial dose of 0.3 mg/kg for severe pain; usual initial maximum dose: 15 to 20 mg (American Pain Society 2008; APA 2012; Berde 2002)

Patient weight ≥50 kg: 15 to 20 mg every 3 to 4 hours as needed (American Pain Society 2008; Berde 2002)

IM, IV, or SubQ; intermittent dosing:

Patient weight <50 kg: Initial: 0.05 mg/kg/dose; usual range: 0.1 to 0.2 mg/kg/dose every 2 to 4 hours as needed; usual maximum dose: Infants: 2 mg/dose; Children 1 to 6 years: 4 mg/dose; Children 7 to 12 years: 8 mg/dose; Adolescents: 10 mg/dose

Patient weight ≥50 kg: Initial: 2 to 5 mg every 2 to 4 hours as needed; higher doses have been recommended (5 to 8 mg every 2 to 4 hours as needed) and may be needed in tolerant patients (Berde 2002; Kliegman 2011)

Continuous IV infusion, SubQ continuous infusion:

Patient weight <50 kg: Initial: 0.01 mg/kg/hour (10 mcg/kg/hour); titrate carefully to effect; dosage range: 0.01 to 0.04 mg/kg/hour (10 to 40 mcg/kg/hour) (APA 2012; Friedrichsdorf 2007; Golianu 2000)

Patient weight ≥50 kg: 1.5 mg/hour (Berde 2002)

Conversion from intermittent IV morphine: Administer the patient's total daily IV morphine dose over 24 hours as a continuous infusion; titrate dose to appropriate effect

Analgesia for minor procedures/sedation: Infants, Children, and Adolescents: IV: 0.05 to 0.1 mg/kg/dose; administer 5 minutes before the procedure; maximum dose: 4 mg; may repeat dose in 5 minutes if necessary (Cramton 2012; Zeltzer 1990)

Patient-controlled analgesia (PCA), opioid-naive: Note: All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting PCA for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naïve. Assess patient and pain control at regular intervals and adjust settings if needed (American Pain Society 2008): IV:

Children ≥5 years and Adolescents, weighing <50 kg: Note: PCA has been used in children as young as 5 years of age; however, clinicians need to assess children 5 to 8 years of age to determine if they are able to use the PCA device correctly (American Pain Society 2008).

Usual concentration: 1 mg/mL

Demand dose: Usual initial: 0.02 mg/kg/dose; usual range: 0.01 to 0.03 mg/kg/dose

Lockout: Usual initial: 5 doses/hour

Lockout interval: Range: 6 to 8 minutes

Usual basal rate: 0 to 0.03 mg/kg/hour

Children ≥5 years and Adolescents, weighing ≥50 kg:

Usual concentration: 1 mg/mL

Demand dose: Usual initial: 1 mg; usual range: 0.5 to 2.5 mg

Lockout interval: Usual initial: 6 minutes; usual range: 5 to 10 minutes

Pain management: Tablets, extended release (MS Contin) (off-label use): Note: Patients taking chronic opioids may become tolerant and require higher-than-usual doses to maintain the desired effect. Tolerance can be managed by appropriate dose titration. There is no optimal/maximal dose for morphine in chronic pain. An appropriate dose relieves pain throughout the dosing interval while avoiding unmanageable side effects. Consider total daily dose, potency, prior opioid use, degree of opioid experience and tolerance, conversion from previous opioid (including opioid formulation), patient's general condition, concurrent medications, and type/severity of pain during prescribing process. For extended-/controlled-release preparations, morphine requirement should be established using immediate-release formulations; conversion to long acting products may be considered when chronic, continuous treatment is required. Higher dosages should be reserved for use only in opioid-tolerant patients. Do not discontinue abruptly; gradually titrate dose downward (eg, every 2 to 4 days). Due to more rapid clearance, a sustained-release morphine formulation dosed every 12 hours in adults may require every-8-hour dosing in children (Berde 2002).

Analgesia: Children and Adolescents able to swallow tablets whole: Oral:

20 to <35 kg: Suggested initial dose: 15 mg every 8 to 12 hours (Berde 2002)

35 to <50 kg: Suggested initial dose: 15 to 30 mg every 8 to 12 hours (Berde 2002)

≥50 kg: Suggested initial dose: 30 to 45 mg every 8 to 12 hours (Berde 2002)

Cancer-related pain: Children and Adolescents able to swallow tablets whole: Oral: 0.3 to 0.6 mg/kg/dose every 12 hours (Berde 1990)

Dosing: Renal Impairment

According to the manufacturer's labeling, no specific dosage adjustments are provided (all formulations). In general, the manufacturers recommend starting cautiously with lower doses; titrating slowly while carefully monitoring for side effects. However, the choice of an alternate opioid may be prudent in patients with baseline renal impairment or rapidly changing renal function especially since other analgesics may be safer and reduced initial morphine dosing may result in suboptimal analgesia. Although clearance of morphine is similar to patients with normal renal function, glucuronide metabolites (M3G [inactive as an analgesic; may contribute to CNS stimulation] and M6G [active analgesic]) accumulate in renal impairment resulting in increased sensitivity; patients may experience severe and prolonged respiratory depression which may even be delayed (Lugo 2002; Niscola 2010).

Dosing: Hepatic Impairment

There are no dosage adjustment provided in the manufacturer's labeling. Pharmacokinetics unchanged in mild liver disease; substantial extrahepatic metabolism may occur. In cirrhosis, increases in half-life and AUC suggest dosage adjustment required.

Reconstitution

Parenteral:

IV push/intermittent infusion: May dilute to a final concentration of 0.5 to 5 mg/mL

Continuous IV infusion: Dilute in D5W, D10W, or NS to a usual final concentration of 0.1 to 1 mg/mL; more concentrated solutions may be used in patients requiring fluid restriction or high doses (Murray 2014; Sinclair-Pingel 2006); concentrations >5 mg/mL are rarely needed (Gahart 2014). ISMP and Vermont Oxford Network recommend a standard concentration of 0.1 mg/mL for neonates (ISMP 2011).

Epidural and intrathecal: Use only preservative-free injections indicated for epidural/intrathecal use. Dilution may be required (preservative-free NS recommended); determined by the individual dosage requirements and the characteristics of the continuous microinfusion device; filter through ≤5 micron microfilter before injecting into microinfusion device.

Extemporaneously Prepared

A 0.4 mg/mL oral solution may be made using the 2 mg/mL oral morphine solution. Measure 10 mL (20 mg) of the 2 mg/mL oral morphine solution and transfer to a plastic amber bottle. Measure 40 mL of sterile water for irrigation and add to bottle containing the morphine. Shake to mix. Store at room temperature. Stable for 60 days.

Sauberan J, Rossi S, Kim JH. Stability of dilute oral morphine solution for neonatal abstinence syndrome. J Addict Med. 2013;7(2):113-115.23370932

Administration

Oral: Do not crush, chew, or dissolve extended release (ER) formulations; swallow whole. Cutting, breaking, crushing, chewing, or dissolving ER formulations may result in uncontrolled delivery of morphine, leading to overdose and death.

Avinza, Kadian: Capsules may be opened and sprinkled on applesauce and eaten immediately without chewing; do not crush, dissolve, or chew the beads, as it can result in a rapid release of a potentially fatal dose of morphine. Ensure all pellets have been swallowed by rinsing mouth. Contents of Kadian capsules may be opened and sprinkled over 10 mL water and flushed through prewetted 16F gastrostomy tube; do not administer Kadian through gastric/nasogastric tubes.

Arymo ER: Swallow tablets whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth; do not pre-soak, lick, or wet tablets prior to placing in the mouth.

IV: Administer single-use prefilled syringes/cartridges via slow IV push over 4 to 5 minutes (rapid administration may result in chest wall rigidity). Concentrated vials are available for preparation of continuous IV infusion or PCA; refer to indication-specific infusion rates in dosing for detailed recommendations.

Epidural, intrathecal: Use only preservative-free solutions indicated for intrathecal or epidural use; refer to indication-specific infusion rates in dosing for detailed recommendations.

Dietary Considerations

Morphine may cause GI upset; take with food if GI upset occurs. Be consistent when taking morphine with or without meals.

Storage

Parenteral: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Store in carton until use. Protect from light. Degradation depends on pH and presence of oxygen; relatively stable in pH ≤4. Darkening of solutions indicate degradation. Do not heat-sterilize.

Oral:

Extended release: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect capsules from light and moisture.

Immediate release: Store at 20°C to 25°C (68°F to 77°F). Protect from moisture.

Suppositories: Store below 25°C (77°F).

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alvimopan: Opioid Analgesics may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Opioid Analgesics. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Analgesics. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Antiplatelet Agents (P2Y12 Inhibitors): Morphine (Systemic) may diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Morphine (Systemic) may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Management: Consider alternative anti-ischemic/analgesic therapies (eg, beta-blockers, nitroglycerin) in patients with acute coronary syndromes treated with a P2Y12 inhibitor when possible. The risks associated with other opioids are unknown. Exceptions: Cangrelor. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Opioid Analgesics. Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Desmopressin: Opioid Analgesics may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Opioid Analgesics may enhance the adverse/toxic effect of Diuretics. Opioid Analgesics may diminish the therapeutic effect of Diuretics. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Eluxadoline: Opioid Analgesics may enhance the constipating effect of Eluxadoline. Avoid combination

Esmolol: Morphine (Systemic) may increase the serum concentration of Esmolol. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Gabapentin: May enhance the CNS depressant effect of Morphine (Systemic). Morphine (Systemic) may increase the serum concentration of Gabapentin. Monitor therapy

Gastrointestinal Agents (Prokinetic): Opioid Analgesics may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Morphine (Systemic). Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Opioid Analgesics. Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Opioid Analgesics. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Opioid Analgesics: CNS Depressants may enhance the CNS depressant effect of Opioid Analgesics. Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Analgesics. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pegvisomant: Opioid Analgesics may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ramosetron: Opioid Analgesics may enhance the constipating effect of Ramosetron. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

RifAMPin: May decrease the serum concentration of Morphine (Systemic). Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: Opioid Analgesics may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Succinylcholine: May enhance the bradycardic effect of Opioid Analgesics. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

Some quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered.

Adverse Reactions

>10%

Central nervous system: Drowsiness (oral: 9% to >10%), headache (<2% to >10%)

Gastrointestinal: Constipation (9% to >10%), nausea (7% to >10%), vomiting (2% to >10%)

Genitourinary: Urinary retention (<2%)

1% to 10%:

Cardiovascular: Peripheral edema (3% to 10%), chest pain (oral: 2%), atrial fibrillation (oral: <2%), bradycardia (oral, rectal: <2%), edema (oral, rectal: <2%), facial flushing (oral, rectal: <2%), flushing (oral: <2%), hypertension (oral: <2%), hypotension (oral: <2%), palpitations (oral, rectal: <2%), syncope (oral, rectal: <2%), tachycardia (oral: <2%), vasodilatation (oral: <2%)

Central nervous system: Depression (oral: <2% to 10%), insomnia (oral, rectal: <2% to 10%), paresthesia (oral: <2% to 10%), dizziness (6%), anxiety (≤6%), abnormality in thinking (oral: <5%), confusion (<5%), seizure (<5%), pain (oral: 3%), abnormal dreams (oral: <2%), agitation (oral, rectal: <2%), amnesia (oral: <2%), apathy (oral: <2%), ataxia (oral: <2%), chills (oral: <2%), decreased cough reflex (<2%), euphoria (<2%), hallucination (oral: <2%), hypoesthesia (oral: <2%), lack of concentration (oral: <2%), lethargy (oral: <2%), malaise (oral: <2%), myoclonus (<2%), slurred speech (oral: <2%), vertigo (oral: <2%), voice disorder (oral: <2%), withdrawal syndrome (oral: <2%)

Dermatologic: Skin rash (oral, rectal: 3% to 10%), diaphoresis (oral, rectal: 2% to 10%), decubitus ulcer (oral: <2%), pallor (oral: <2%), pruritus (<2%)

Endocrine & metabolic: Amenorrhea (oral: <2%), decreased libido (oral, rectal: <2%), gynecomastia (oral: <2%), hyponatremia (oral: <2%), SIADH (oral: <2%)

Gastrointestinal: Abdominal pain (oral: 3% to 10%), anorexia (oral, rectal: 3% to 10%), diarrhea (3% to 10%), xerostomia (oral, rectal: 3% to 10%), biliary colic (oral: <2%), delayed gastric emptying (oral: <2%), dyspepsia (oral: <2%), dysphagia (oral: <2%), gastric atony (oral: <2%), gastroesophageal reflux disease (oral: <2%), hiccups (oral: <2%)

Genitourinary: Impotence (oral: <2%), urinary hesitancy (oral, rectal: <2%), urine abnormality (oral: <2%)

Hematologic & oncologic: Anemia (oral: 2% to <5%), thrombocytopenia (oral: <5%), leukopenia (oral: 2%)

Neuromuscular & skeletal: Back pain (oral: <2% to 10%), tremor (oral: 2%), weakness (oral, rectal: ≤2%), arthralgia (oral: <2%), bone pain (oral: <2%), foot-drop (oral: <2%)

Ophthalmic: Amblyopia (oral: <2%), blurred vision (oral: <2%), conjunctivitis (oral: <2%), diplopia (oral: <2%), miosis (oral, IV: <2%), nystagmus (oral: <2%)

Respiratory: Dyspnea (3% to 10%), flu-like symptoms (oral: <2% to 10%), hypoventilation (<5%), asthma (oral: <2%), atelectasis (oral: <2%), hypoxia (oral: <2%), pulmonary edema (oral: <2%; includes noncardiogenic), respiratory depression (IV, epidural, intrathecal: <2%), respiratory insufficiency (oral: <2%), rhinitis (oral: <2%)

Miscellaneous: Accidental injury (oral: 2% to 10%), fever (oral: 2% to 10%), increased severity of condition (oral: 3%)

Frequency not defined:

Cardiovascular: Circulatory depression (oral, IV), orthostatic hypotension (IM, IV), peripheral vascular insufficiency (IV), phlebitis (IV), presyncope (oral, rectal), shock

Central nervous system: Abnormal gait (oral), altered mental status (IV), coma (oral), delirium (oral), disorientation (oral, rectal), disruption of body temperature regulation (IV, epidural, intrathecal), dysphoria, dyssynergia (oral), fear (IV), feeling abnormal (oral), increased catecholamines (IV, epidural, intrathecal), increased intracranial pressure (oral), mood changes (oral), nervousness (oral), paradoxical central nervous system stimulation (IV, epidural, intrathecal), sedation (oral, rectal), toxic psychosis (IM, IV, epidural, intrathecal)

Dermatologic: Hemorrhagic urticaria (IV, rectal), urticaria, xeroderma (oral)

Endocrine & metabolic: Antidiuretic effect (oral, rectal), increased thirst (oral), weight loss (oral)

Gastrointestinal: Biliary tract spasm (rectal), decreased appetite (IV), dysgeusia (oral), gastroenteritis (oral), gastrointestinal hypermotility (IV; in patients with chronic ulcerative colitis), rectal disease (oral), toxic megacolon (IV; patients with chronic ulcerative colitis)

Genitourinary: Dysuria (oral), ejaculatory disorder (oral), erectile dysfunction (IV), hypogonadism (oral), oliguria, ureteral spasm (IV)

Hematologic & oncologic: Granuloma (IV, epidural, intrathecal)

Hepatic: Increased liver enzymes (oral)

Hypersensitivity: Anaphylactoid reaction (IM)

Local: Erythema at injection site (IV), induration at injection site (SC), local irritation (IV, epidural, intrathecal), local swelling (IV, intrathecal, epidural; genital swelling in males following infusion device implant surgery), pain at injection site (SC), residual mass at injection site (inflammatory; IV, epidural, intrathecal)

Neuromuscular & skeletal: Decreased bone mineral density (oral), laryngospasm (oral), muscle rigidity (oral), muscle spasm (IV, epidural, intrathecal; myoclonic spasm of lower extremities), muscle twitching (oral), vesicle sphincter spasm (IV)

Ophthalmic: Eye pain (oral), visual disturbance (oral, rectal)

Respiratory: Apnea (oral, IV)

Miscellaneous: Impaired physical performance (IV)

<1%, postmarketing, and/or case reports: Anaphylaxis, bronchospasm, dehydration, difficulty thinking, fatigue, hyperalgesia, hypersensitivity reaction, hypertonia, increased serum prolactin (Molitch 2008; Vuong 2010), intestinal obstruction, sepsis

ALERT: U.S. Boxed Warning

Risks with neuroaxial administration (Infumorph, Duramorph):

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. Single-dose Duramorph neuraxial administration may result in acute or delayed respiratory depression for up to 24 hours. Monitor patients receiving Infumorph, as appropriate, for the first several days after catheter implantation.

Ethanol use (extended-release capsules):

Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking morphine extended-release (ER) capsules. The coingestion of alcohol with morphine ER may result in increased plasma levels and a potentially fatal overdose of morphine.

Addiction, abuse, and misuse:

Morphine 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 morphine and monitor all patients regularly for the development of these behaviors and conditions.

Life-threatening respiratory depression:

Serious, life-threatening, or fatal respiratory depression may occur with use of morphine. Monitor for respiratory depression, especially during initiation of morphine or following a dose increase. Swallow morphine ER formulations whole. ER capsule contents may be sprinkled on applesauce and swallowed immediately without chewing. Crushing, chewing, or dissolving the tablets or contents within the capsule can cause rapid release and absorption of a potentially fatal dose of morphine. Because of delay in maximum CNS effect with IV administration (30 minutes), rapid IV administration may result in overdosing. Observe patients in a fully equipped and staffed environment for at least 24 hours after each test dose of Infumorph and, as indicated, for the first several days after surgery.

Neonatal opioid withdrawal syndrome:

Prolonged use of morphine 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. 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.

Accidental ingestion (oral formulations):

Accidental ingestion of even one dose of morphine, especially by children, can result in a fatal overdose of morphine.

Risk of medication errors (oral solution):

Ensure accuracy when prescribing, dispensing, and administering morphine oral solution. Dosing errors due to confusion between mg and mL, and other morphine solutions of different concentrations, can result in accidental overdose and death

Risks from concomitant use with benzodiazepines or other CNS depressants:

Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of morphine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Some dosage forms may be contraindicated in patients with severe CNS depression.

• Constipation: May cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.

• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), circulatory shock, or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock. Some dosage forms may be contraindicated in patients with cardiac arrhythmias or heart failure due to chronic lung disease.

• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).

• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Swallow morphine ER formulations whole (or may sprinkle the contents of the capsule on applesauce and swallow without chewing); crushing, chewing, or dissolving the ER formulations can cause rapid release and absorption of a potentially fatal dose of morphine. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction or acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

• CNS depression/coma: Avoid use in patients with impaired consciousness or coma, as these patients are susceptible to intracranial effects of CO2 retention.

• Delirium tremens: Use with caution in patients with delirium tremens. Some dosage forms may be contraindicated in patients with delirium tremens.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur. Some dosage forms may be contraindicated in patients with increased intracranial or cerebrospinal pressure, head injuries, or brain tumor.

• Hepatic impairment: Use with caution in patients with severe hepatic impairment.

• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).

• Obesity: Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis: Use with caution in patients with toxic psychosis.

• Renal impairment: Use with caution in patients with renal impairment.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or preexisting respiratory depression, particularly when initiating therapy and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Sleep-disordered breathing: Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).

• Seizure disorders: Use with caution in patients with seizure disorders; may cause or exacerbate preexisting seizures. Some dosage forms may be contraindicated in patients with seizure disorder.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: [US Boxed Warning]: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of morphine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation. Some dosage forms may be contraindicated in patients with acute alcoholism.

• Ethanol use: Extended-release capsules: [US Boxed Warning]: Patients should not consume alcoholic beverages or medication containing ethanol while taking ER capsules; ethanol may increase morphine plasma levels, resulting in a potentially fatal overdose.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Elderly: Use with caution in elderly patients; may be more sensitive to adverse effects, including life-threatening respiratory depression. Decrease initial dose. In the setting of chronic pain, monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). Consider the use of alternative nonopioid analgesics in these patients.

• Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged maternal use of opioids during pregnancy can cause neonatal withdrawal syndrome in the newborn, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If prolonged opioid therapy is required in a pregnant woman, ensure treatment is available and warn patient of risk to the neonate. Signs and symptoms include irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

• Pediatric: Infants <3 months of age, especially if premature, are more susceptible to respiratory depression and/or apnea; use with caution and generally in reduced doses in this age group (APS 2008).

Dosage form specific issues:

• Infumorph, Duramorph: Neuroaxial administration: [US Boxed Warning]: 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. Single-dose Duramorph neuraxial administration may result in acute or delayed respiratory depression for up to 24 hours. Monitor patients receiving Infumorph for the first several days after catheter implantation. Naloxone injection should be immediately available. Thoracic epidural administration has been shown to dramatically increase the risk of early and late respiratory depression. High doses (> 20 mg/day) of neuraxial morphine may produce myoclonic events. Patients with reduced circulating blood volume or impaired myocardial function, or on concomitant sympatholytic drugs should be monitored for orthostatic hypotension, a frequent complication in single-dose neuraxial morphine.

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• Extended-release formulations: Therapy should only be prescribed by health care professionals familiar with the use of potent opioids for chronic pain. Extended-release products are not interchangeable. When determining a generic equivalent or switching from one extended-release product to another, a thorough understanding of the pharmacokinetic properties is important in determining the proper generic equivalent or proper dose of the other extended-release product (review of the manufacturer's label may be necessary).

- Arymo ER: Moistened tablets may become sticky, leading to difficulty in swallowing the tablets; choking, gagging, regurgitation, and tablets getting stuck in the throat may occur. Tablet stickiness and swelling may also predispose patients to intestinal obstruction and exacerbation of diverticulitis. Do not to pre-soak, lick, or otherwise wet tablets prior to placing in the mouth; take one tablet at a time with enough water to ensure complete swallowing. Consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying GI disorders resulting in a small GI lumen (eg, esophageal cancer, colon cancer).

- Avinza capsules: Dosage form contains fumaric acid; dangerous quantities of fumaric acid may be ingested when >1,600 mg/day is used. Serious renal toxicity may occur above the maximum dose.

• Oral solution: Risk of medication errors: [US Boxed Warning]: Ensure accuracy when prescribing, dispensing, and administering morphine oral solution. Dosing errors due to confusion between mg and mL, and other morphine solutions of different concentrations, can result in accidental overdose and death. The 100 mg per 5 mL (20 mg/mL) is for use in opioid-tolerant patients only.

• Injections: [US Boxed Warning]: Because of delay in maximum CNS effect with IV administration (30 minutes), rapid IV administration may result in overdosing. Observe patients in a fully equipped and staffed environment for at least 24 hours after each test dose of Infumorph and, as indicated, for the first several days after surgery. Products are designed for administration by specific routes (ie, IV, intrathecal, epidural). Use caution when prescribing, dispensing, or administering to use formulations only by intended route(s). Rapid IV administration may result in chest wall rigidity. Use with caution when injecting IM into chilled areas or in patients with hypotension or shock (impaired perfusion may prevent complete absorption); if repeated injections are administered, an excessive amount may be suddenly absorbed if normal circulation is re-established.

• Infumorph: Should only be used in microinfusion devices; not for IV, IM, or SubQ administration or for single-dose administration. Administer intrathecal doses of 10 and 25 mg/mL to the lumbar area. Monitor closely, especially in the first 24 hours. Inflammatory masses (eg, granulomas), some resulting in severe neurologic impairment, have occurred when receiving Infumorph via indwelling intrathecal catheter; monitor carefully for new neurologic signs/symptoms.

• Product interchange: Improper or erroneous substitution of Infumorph for regular Duramorph is likely to result in serious overdosage, leading to seizures, respiratory depression, and possibly a fatal outcome.

• Sulfites: Some dosage forms may contain sulfites that may cause allergic reactions in sulfite sensitive patients.

Other warnings/precautions:

• Abuse/misuse/diversion: [US Boxed Warning]: Morphine exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient’s risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).

• Accidental exposure: Oral: formulations: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of morphine.

• Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, NSAIDS, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and nonopioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).

• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.

• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics. Some dosage forms may be contraindicated after biliary tract surgery, suspected surgical abdomen, or surgical anastomosis.

• Withdrawal: Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Taper dose gradually when discontinuing.

Monitoring Parameters

Pain control, respiratory and mental status; blood pressure; signs of misuse, abuse, and addiction; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)

Alternate recommendations: Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and with consideration for re-checking at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (Dowell [CDC 2016]).

Epidural/intrathecal: Patients should be observed in a fully equipped and staffed environment for at least 24 hours following initiation, and as appropriate for the first several days after catheter implantation. Naloxone injection should be immediately available. Patient should remain in this environment for at least 24 hours following the initial dose. For patients receiving Infumorph via microinfusion device, patient may be observed, as appropriate, for the first several days after catheter implantation.

Alternative monitoring recommendations (Bujedo 2012): Epidural: Note: All patients receiving neuraxial opioids should be monitored for adequate ventilation (eg, respiratory rate, depth of respiration [without disturbing patient]), oxygenation (eg, pulse oximetry when appropriate), and level of consciousness.

Single dose: Monitor patient for a minimum of 24 hours after administration with a frequency of at least once per hour for the first 12 hours after administration, followed by at least once every 2 hours for the next 12 hours (ie, from 12 to 24 hours after administration). After 24 hours, frequency dictated by overall clinical condition and concurrent medications.

Continuous infusion or patient controlled epidural analgesia (PCEA): Monitor patient during the entire duration of the infusion with a frequency of at least once per hour for the first 12 hours, followed by at least once every 2 hours for the next 12 hours (ie, from 12 to 24 hours after administration). After 24 hours, monitor at least once every 4 hours. After discontinuation of infusion or PCEA, frequency dictated by overall clinical condition and concurrent medications.

Note: Also refer to institution specific protocols as appropriate.

Pregnancy Considerations

[US Boxed Warning]: Prolonged maternal use of opioids during pregnancy can cause neonatal withdrawal syndrome in the newborn, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If prolonged opioid therapy is required in a pregnant woman, ensure treatment is available and warn patient of risk to the neonate.

Morphine crosses the placenta. Maternal use of opioids may be associated with birth defects, poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2016]). If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur (Chou 2009). Symptoms of neonatal abstinence syndrome (NAS) following opioid exposure may be autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, hyperactivity, increased muscle tone, increased wakefulness/abnormal sleep pattern, irritability, sneezing, seizure, tremor, yawning) (Dow 2012; Hudak 2012). Mothers who are physically dependent on opioids may give birth to Infants who are also physically dependent. Opioids may cause respiratory depression and psycho-physiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.

Morphine is commonly used for the treatment of pain during labor and immediately postpartum (ACOG 177 2017). Not all preparations are recommended for use and morphine should not be used when other analgesic techniques are more appropriate. Agents other than morphine are used to treat chronic non-cancer pain in pregnant women or those who may become pregnant (CDC [Dowell 2016]; Chou 2009; Kahan 2011).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dry mouth, nausea, vomiting, headache, anxiety, abdominal pain, sweating a lot, diarrhea, lack of appetite, or tablet shell in stool. Have patient report immediately to prescriber difficulty breathing, slow breathing, shallow breathing, noisy breathing, severe dizziness, passing out, angina, tachycardia, confusion, seizures, severe constipation, swelling of arms or legs, chills, pharyngitis, painful urination, depression, burning or numbness feeling, signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), sexual dysfunction (males), decreased libido, amenorrhea, infertility, severe loss of strength and energy, mood changes, or severe fatigue (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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