morphine (Rx)

Brand and Other Names:MS Contin, Astramorph, more...Depodur, Duramorph, Infumorph, Kadian, MorphaBond, Arymo ER
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

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

  • 15mg, 30mg, 60mg, 100mg, 200mg

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

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

capsule, morphine sulfate extended-release: Schedule II

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

capsule, extended-release (Kadian): Schedule II

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

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

  • 10mg/mL

injectable solution (Duramorph): Schedule II

  • 0.5mg/mL
  • 1mg/mL

injectable solution, high potency (Infumorph): Schedule II

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

morphine sulfate, injectable solution: Schedule II

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

tablet, morphine sulfate immediate release : Schedule II

  • 15mg, 30mg

morphine sulfate, suppository: Schedule II

  • 5mg, 10mg, 20mg, 30mg

morphine sulfate, oral solution: Schedule II

  • 10mg/5mL; 20mg/5mL

morphine sulfate, intramuscular device

  • 10mg/0.7mL
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Acute Pain

Immediate-release tablet

  • Opioid-naïve patients: 15-30 mg PO q4hr PRN

Oral solution

  • Opioid-naïve patients: 10-20 mg PO q4hr PRN

Suppository

  • 10-20 mg PR q4hr

Parenteral solution

  • SC/IM (opioid-naïve patients): 5-10 mg q4hr PRN; dose range, 5-20 mg
  • IV (opioid-naïve patients): 2.5-5 mg q3-4hr PRN, infused over 4-5 minutes; dose range, 4-10 mg

Preservative-free parenteral solution

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

Extended-release liposomal injection

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

Dosing considerations

  • Injection formulation not for IV administration unless opioid antagonist immediately available
  • Usual dosage of IV morphine in adults, regardless of indication, is 2-10 mg/70 kg body weight
  • Consider 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 PO of morphine, 30 mg/day PO of oxycodone, 12 mg/day PO of hydromorphone, or equianalgesic dose of another opioid for >1 week
  • PO solution: 100 mg/5 mL concentration is appropriate only for opioid-tolerant patients
  • Parenteral solution: IM injection is painful and has variable onset of analgesia because of delayed onset of action and erratic absorption; repeated SC administration may cause local tissue damage, as well as induration, irritation, and pain at injection site
  • Preservative-free parenteral solution: American Pain Society describes "ceiling" for analgesic effect with dosages >0.3 mg/day and increase in adverse effects (eg, respiratory depression); extreme caution is warranted with epidural or intrathecal 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 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

Extended-release tablet (MS Contin)

  • Opioid-naïve patients (as first opioid dose): Initiate with 15 mg PO q8-12hr; use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
  • Opioid-tolerant patients: Dose depends on daily dose of previous opioid analgesic (individualization required for conversion)
  • MS Contin dose equivalent to one-half of patient's calculated 24-hr PO morphine requirement q12hr; alternatively, dose equivalent to one-third of patient's calculated 24-hr PO morphine requirement q8hr
  • Tablet must be swallowed whole and not broken, chewed, dissolved, or crushed; sudden release of morphine content increases risk of respiratory depression and death

Extended-release capsule (Kadian)

  • Opioid-naive patients: Not indicated for use as initial opioid analgesic; initiate with IR formulation, then convert to Kadian
  • Nonopioid-tolerant patients: 30 mg PO qDay
  • Opioid-tolerant patients: Dose depends on daily dose of previous opioid analgesic (individualization required for conversion)
  • Kadian dose equivalent to one half of patient’s 24-hr PO morphine requirement q12hr; alternatively, dose equivalent to patient’s 24-hr PO morphine requirement once daily
  • 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 risk of respiratory depression and death

Extended-release tablet, abuse deterrent (MorphaBond)

  • Opioid-naïve patients (as first opioid dose): 15 mg PO q12hr
  • Opioid-tolerant patients: Dose depends on daily dose of previous opioid analgesic (individualization required for conversion)
  • MorphaBond dose equivalent to one-half of patient's calculated 24-hr PO morphine requirement administered q12hr
  • Tablet must be swallowed whole and not broken, chewed, dissolved, or crushed; sudden release of morphine content increases 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 PO q8-12hr
  • Conversion to Arymo ER
    • Morphine recipients: Administer one-half of 24-hr morphine requirement as Arymo ER PO q12hr, or one-third of 24-hr morphine requirement as Arymo ER PO q8hr
    • Patients receiving other opioids: Discontinue all around-the-clock opioid drugs, then initiate Arymo ER 15mg PO q8-12 hours
    • Arymo ER dose when converted from other opioids or parenteral morphine: Calculate 24-hr PO morphine equivalent requirement and administer one-half of that daily equivalent as Arymo ER q12hr; alternatively, may give one-third of patient's calculated 24-hour PO morphine requirement q8hr
    • Methadone to morphine sulfate ER conversion: Methadone has 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 IT administration must be individualized on basis of in-hospital evaluation of response to serial single-dose bolus injections using 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 hr
  • IT (opioid-tolerant patients): 1-10 mg over 24 hr; caution warranted with dosages >20 mg/24 hr
  • Epidural (opioid-naïve patients): 3.5-7.5 mg over 24 hr
  • Epidural (opioid-tolerant patients) 4.5-10 mg over 24 hr

Opioid-tolerant definition

  • Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO 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 (eg, nonopioid 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 a PRN analgesic

Dosage Forms & Strengths

injectable solution: Schedule II

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

tablet, immediate release: Schedule II

  • 15mg, 30mg
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Analgesia/Cyanotic Tetralogy of Fallot

Neonates (<30 days): 0.3-1.2 mg/kg/day IM/SC divided q4hr; 0.005-0.03 mg/kg/hr slow IV  

Infants and children (PO solution): 0.2-0.5 mg/kg PO q4-6hr PRN

Infants and children (IM/SC): 0.05-0.2 mg/kg q2-4hr PRN; not to exceed 15 mg/dose

Pain

Continuous infusion: 0.025-2.6 mg/kg/hr IV; average, 0.06 mg/kg/hr 

Neonates (<30 days): 0.01-0.02 mg/kg/hr by IV infusion

Postoperative pain: 0.01-0.04 mg/kg/hr by IV infusion

Sickle-cell disease, cancer: 0.04-0.07 mg/kg/hr by IV infusion

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Interactions

Interaction Checker

and morphine

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            Adverse Effects

            >10%

            Pruritus (≤80%)

            Urinary retention (epidural/IT) (15-70%)

            Vomiting (7-70%)

            Constipation (>10%)

            Headache (>10%)

            Somnolence (>10%)

            1-10%

            Abdominal pain (5-10%)

            Asthenia (5-10%)

            Backache (5-10%)

            Depression (5-10%)

            Diarrhea (5-10%)

            Dyspnea (5-10%)

            Fever (5-10%)

            Insomnia (5 -10% )

            Loss of appetite (5-10%)

            Nausea (5-10%)

            Paresthesia (5-10%)

            Peripheral edema (5-10%)

            Rash (5-10%)

            Sweating (5-10%)

            Xerostomia (5-10%)

            Respiratory depression (IT) (4-7%)

            Anxiety (6%)

            Dizziness (6%)

            Abnormal liver function test results (<5%)

            Amblyopia (<5%)

            Hiccups (<5%)

            Orthostatic hypotension (<5%)

            Syncope (<5%)

            Urinary retention (PO) (<5%)

            <1%

            Respiratory depression (epidural) (0.25-0.4% )

            Frequency Not Defined

            Anaphylaxis (rare )

            Cardiac arrest

            Circulatory depression

            Finding of intracranial pressure

            Ileus

            Lightheadedness

            Malaise

            Miosis

            Myoclonus

            Shock

            Thinking disturbances

            Vertigo

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            Warnings

            Black Box Warnings

            Infumorph not recommended for single-dose intravenous, intramuscular or subcutaneous administration due to 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 outcome

            Intrathecal dosage is usually 1/10 that of epidural dosage

            Observe patient in a fully equipped and staffed environment for at least 24 hr after 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 particular matter before opening amber ampule, and again for color after removing contents from ampule; after removal do not use unless solution is 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 prior to 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 espoxure 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 and 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

            Alcohol interaction

            • Instruct patients not to consume alcoholic beverages or use alcohol-containing drug products while taking morphine due to risk of additive sedation and respiratory depression
            • Coingestion of alcohol with opioid analgesics may increase plasma opioid levels and potentially result in fatal overdose
            • Some long-acting products (ie, 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

            • Coadministration 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 risk of additive sedation and respiratory depression

            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, deliriums tremens, seizure disorders, during labor when premature birth anticipated (injectable formulation)

            Cardiac arrhythmia, increased intracranial or cerebrospinal pressure, acute alcoholism, use after biliary tract surgery, surgical anastomosis (suppository formulcation)

            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 (eg, stool softener, increased fiber) to reduce potential for constipation, especially in patients with unstable angina and patients with myocardial infarction

            Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected

            Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists

            Use with caution in patients with adrenal insufficiency, including addison's disease; chronic opioid use may cause secondary hypogonadism, which may lead to mood disorders, osteoporosis, sexual dysfunction, and infertility

            Warn patients not to drive or operate dangerous machinery unless they are tolerant to effects of drug and know how they will react to medication

            Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; use may cause constriction of sphincter of Oddi diminishing biliary and pancreatic secretion

            Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

            Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

            In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma

            Some formulations may contain sodium benzoate/benzoic acid, which have been associated with potentially fatal toxicity (gasping syndrome) in neonates

            Use in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages

            While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, risk is greatest during initiation of therapy or following dosage increase; monitor patients closely for respiratory depression, especially within first 24 to 72 hr of initiating therapy with and following dosage increases; accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to overdose of opioid

            Avoid use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or precipitate withdrawal symptoms; when discontinuing therapy in physically-dependent patient, gradually taper dosage; do not abruptly discontinue therapy in these patients

            Monoamine oxidase inhibitors (MAOIs) may potentiate effects of opioid, opioid’s active metabolite, including respiratory depression, coma, and confusion; therapy should not be administered within 14 days of initiating or stopping MAOIs

            Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency

            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 ability to operate heavy machinery

            All formulations are capable of producing respiratory depression

            Use with caution, particularlyl with IV administration, in patients with hypovolemia, cardiovascular disease, circulatory shock or drugs that may exagerate hypotensive effects, including general anesthetics and phenothiazines; may cause orthostatic hypotension and syncope in ambulatory patients

            After chronic maternal exposure to opioids, neonatal withdrawal syndrome may occur in the newborn

            Opioid pharmacokinetics may be altered in patients with renal failure; clearance may be decreased and metabolites may accumulate much higher plasma levels in patients with renal failure as compared to patients with normal renal function; start with a lower than normal dosage or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension

            Use caution when selecting dosage for an elderly patient, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function

            Use in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages

            Therapy may increase frequency of seizures in patients with seizure disorders and in other clinical settings associated with seizures; monitor patients for worsened seizure control during therapy

            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 opioid present (see Black Box Warnings)
            • Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, 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 (see Black Box Warnings)
            • Serious, life-threatening, or fatal respiratory depression reported (see Black Box Warnings)
            • Accidental exposure reported, including fatalities (see Black Box Warnings)
            • Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black Box Warnings)
            • Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate 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 PRN use
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            Pregnancy & Lactation

            Pregnancy

            Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Labor and delivery

            • Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

            Infertility

            • Due to effects of androgen deficiency, chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible

            Lactation

            Morphine is present in breast milk; published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine AUC ratio of 2.5:1 measured in one lactation study; however, there is insufficient information to determine effects of morphine on breastfed infant and effects of morphine on milk production; no information is available on effects of drug on breastfed infant or effects of drug on milk production

            The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

            Monitor infants exposed to therapy through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of morphine is stopped, or when breastfeeding is stopped

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways, thus altering response to pain; produces analgesia, respiratory depression, and sedation; suppresses cough by acting centrally in medulla

            Absorption

            Onset: PO, 15-30 min; IV, <5 min

            Duration: 4 hr (immediate-release)

            Peak plasma time: PO, <60 min; PR, 20-60 min; SC, 50-90 min; IM, 30-60 min; IV, 20 min

            Peak plasma concentration: PO, 20-40 ng/mL

            Distribution

            Protein bound: IV, 36%

            Vd: IV, 1-4.7 L/kg

            Metabolism

            Metabolized in liver via conjugation with glucuronic acid

            Metabolites: 6-Glucuronide, 3,6-diglucuronide, 3-glucuronide

            Elimination

            Half-life: 2-4 hr (immediate release); 11-13 hr (Kadian)

            Excretion: Urine (2-12%), feces (7-10%)

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            Administration

            IV Incompatibilities

            Additive: Aminophylline, amobarbital, chlorothiazide, floxacillin, fluorouracil, heparin, meperidine, midazolam(?), phenobarbital, phenytoin, sodium bicarbonate, thiopental

            Syringe: Haloperidol, meperidine, pentobarbital(?), prochlorperazine(?), promethazine(?), thiopental

            Y-site: Acyclovir (concentration-dependent?), alatrofloxacin, amphotericin B cholesteryl sulfate, azithromycin, cefepime, doxorubicin liposomal, furosemide(?), minocycline, phenytoin, propofol (concentration-dependent?), sargramostim, thiopental (concentration-dependent?)

            IV Compatibilities

            Solution: Most common solvents

            Additive (partial list): Alteplase, atracurium, baclofen, dobutamine, fluconazole, furosemide, metoclopramide, ondansetron, succinylcholine, verapamil

            Syringe (partial list): Atropine, chlorpromazine, cimetidine, clonidine, dimenhydrinate, diphenhydramine, fentanyl, glycopyrrolate, heparin(?), hydroxyzine, ketamine, metoclopramide, midazolam, milrinone, ondansetron, ranitidine

            Y-site (partial list): Allopurinol, amikacin, amiodarone, ampicillin, atenolol, atracurium, atropine, aztreonam, calcium chloride, cefazolin, cisplatin, clindamycin, cytarabine, diazepam, diltiazem, diphenhydramine, dobutamine, dopamine, doxorubicin, erythromycin, esmolol, fentanyl, fluconazole, granisetron, haloperidol, heparin, hydroxyzine, labetalol, linezolid, lorazepam, magnesium sulfate, metoclopramide, metronidazole, midazolam, milrinone, nitroglycerin, penicillin G, phenobabital, potassium chloride, propranolol, sodium bicarbonate, sodium nitroprusside, tirofiban, tobramycin, trimethoprim-sulfamethoxazole, vancomycin, vecuronium, vitamins B and C, warfarin, zidovudine

            IV Preparation

            IV push: Dilute 2.5-15 mg in 4-5 mL of SWI

            Infusion: Dilute in D5W to 0.1-1 mg/mL

            Solution should be colorless; if it is discolored, do not administer

            IV Administration

            IV push: Administer over 4-5 minutes

            Continuous infusion: Administer via controlled infusion device

            Intrathecal & Epidural Administration

            High-potency injectable solution (Infumorph): To be administered only IT or epidurally; not to be administered SC, IM, or IV, because of overdose risk; may require dilution before use, depending based on administration device and patient dose

            Oral Administration

            Extended-release tablet (MS Contin)

            • Coingestion of alcohol with long-acting morphine products is known to disrupt slow-release delivery properties and lead to rapid release of drug, which may result in toxicity and potential overdose
            • Swallow tablet whole; crushing, dissolving, or chewing the tablet can cause rapid release and absorption of a potentially fatal dose of morphine

            Extended-release capsule (Kadian)

            • 100-, 130-, 150-, and 200-mg capsules are appropriate only for patients tolerant of comparably potent opioid
            • Kadian is not bioequivalent to other ER morphine products, and same total daily doses may result in excess sedation or inadequate pain relief
            • Consumption of alcohol or alcohol-containing medications should be avoided during use, in that coingestion of alcohol may result in increased levels of morphine and potentially fatal overdose
            • Swallow capsule whole; dissolving, or chewing the tablet can cause rapid release and absorption of a potentially fatal dose of morphine
            • Alternatively, the contents of the Kadian capsules (pellets) may be sprinkled over applesauce and then swallowed; this method is appropriate only for patients able to reliably swallow the applesauce without chewing (rinse mouth following to be sure all pellets are swallowed)
            • Do not administer through a nasogastric-tube
            • Administered through a 16-Fr gastronomy-tube
              • Contents of the Kadian capsules (pellets) may be administered through a 16 French gastrostomy tube
              • Flush the gastrostomy tube with water to ensure that it is wet
              • Sprinkle the pellets into 10 mL of water
              • Use a swirling motion to pour the pellets and water into the gastrostomy tube through a funnel
              • Rinse the beaker with a further 10 mL of water and pour this into the funnel
              • Repeat rinsing until no pellets remain in the beaker

            Extended-release tablet, abuse deterrent (MorphaBond)

            • 100-mg tablets, a single dose >60 mg, or a total daily dose >120 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established
            • Swallow tablet whole; crushing, dissolving, or chewing the tablet can cause rapid release and absorption of a potentially fatal dose of morphine

            Extended-release tablet, abuse deterrent (Arymo ER)

            • A single dose >60 mg or a total daily dose >120 mg are only for use in patients who are opioid-tolerant
            • Swallow tablet whole with sufficient water; do not crush, chew, or dissolve
            • Do not lick or wet tablet prior to swallowing tablet

            General principles for opioid administration

            • Titration and maintenance
              • Breakthrough pain may be managed with PRN morphine sulfate IR
              • Subsequent dose increases may be made every 1-2 days combining morphine sulfate ER dose and morphine sulfate IR dose
              • Titrate dose according to response  
            • Discontinuation
              • Taper dose gradually by 25-50% every 2 to 4 days, monitoring for symptoms of withdrawal
              • If symptoms occur, increase dose to previous dose and titrate more slowly
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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