morphine (Rx)

Brand and Other Names:MS Contin, Astramorph, more...Depodur, Duramorph, Infumorph, Kadian, MorphaBond, Mitigo
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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, Mitigo): 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; 20mg/mL

morphine sulfate, intramuscular device

  • 10mg/0.7mL

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

  • Oral formulation of 20 mg/mL is for use only in opioid tolerant adult patients
  • 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, Mitigo)

  • 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

Dosing Considerations

Access to naloxone for opioid overdose

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

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

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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            Contraindicated (2)

            • alvimopan

              alvimopan, morphine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

            • safinamide

              morphine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            Serious - Use Alternative (49)

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • bremelanotide

              bremelanotide will decrease the level or effect of morphine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • buprenorphine

              buprenorphine, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • buprenorphine buccal

              buprenorphine buccal, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • butorphanol

              butorphanol, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • calcium/magnesium/potassium/sodium oxybates

              morphine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cimetidine

              cimetidine increases effects of morphine by decreasing metabolism. Avoid or Use Alternate Drug.

            • citalopram

              morphine, citalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • clonidine

              clonidine, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

            • clopidogrel

              morphine will decrease the level or effect of clopidogrel by Other (see comment). Avoid or Use Alternate Drug. coadministration of opioid agonists delay and reduce absorption of clopidogrel, presumably because of slowed gastric emptying, resulting in reduced exposure to its metabolites; consider use of parenteral antiplatelet agents in acute coronary syndrome patients requiring coadministration of morphine or other opioid agonists

            • desvenlafaxine

              morphine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • diazepam intranasal

              diazepam intranasal, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • eluxadoline

              morphine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

            • erdafitinib

              erdafitinib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

            • escitalopram

              morphine, escitalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • fentanyl

              fentanyl, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl intranasal

              fentanyl intranasal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl transdermal

              fentanyl transdermal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl transmucosal

              fentanyl transmucosal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fluoxetine

              fluoxetine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              morphine, fluoxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • hydrocodone

              hydrocodone, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • isocarboxazid

              isocarboxazid and morphine both increase serotonin levels. Avoid or Use Alternate Drug.

              isocarboxazid increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • lasmiditan

              lasmiditan increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • linezolid

              linezolid and morphine both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

              linezolid increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • lumefantrine

              lumefantrine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • methylene blue

              methylene blue and morphine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue morphine (if possible) and monitor for CNS toxicity. Morphine may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • metoclopramide intranasal

              morphine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • nalbuphine

              nalbuphine, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • ozanimod

              ozanimod and morphine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • paroxetine

              paroxetine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              morphine, paroxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • pentazocine

              pentazocine, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • phenelzine

              phenelzine and morphine both increase serotonin levels. Avoid or Use Alternate Drug.

              phenelzine increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • prasugrel

              morphine will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Coadministration of opioid agonists delay and reduce the absorption of prasugrel?s active metabolite presumably because of slowed gastric emptying. Consider using a parenteral antiplatelet agent in acute coronary syndrome patients requiring coadministration of morphine or other opioid agonists. Risks associated with other opioids are unknown.

            • procarbazine

              procarbazine increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

            • quinidine

              quinidine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • rasagiline

              rasagiline increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. May cause additive CNS depression, drowsiness, dizziness or hypotension, so use with MAOIs should be cautious; lower initial dosages of the analgesic are recommended followed by careful titration. Avoid combination within 14 days of MAOI use.

            • selegiline transdermal

              selegiline transdermal increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • selinexor

              selinexor, morphine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • sertraline

              morphine, sertraline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • sodium oxybate

              morphine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • sotorasib

              sotorasib will decrease the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • sufentanil SL

              sufentanil SL, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tepotinib

              tepotinib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • ticagrelor

              morphine will decrease the level or effect of ticagrelor by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of ticagrelor and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

            • tramadol

              tramadol, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

            • tranylcypromine

              tranylcypromine and morphine both increase serotonin levels. Avoid or Use Alternate Drug.

              tranylcypromine increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • valerian

              valerian and morphine both increase sedation. Avoid or Use Alternate Drug.

            • vortioxetine

              morphine, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            Monitor Closely (256)

            • 5-HTP

              5-HTP and morphine both increase serotonin levels. Use Caution/Monitor.

            • albuterol

              morphine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfentanil

              alfentanil and morphine both increase sedation. Use Caution/Monitor.

            • almotriptan

              almotriptan and morphine both increase serotonin levels. Use Caution/Monitor.

            • alprazolam

              alprazolam and morphine both increase sedation. Use Caution/Monitor.

            • amiodarone

              amiodarone will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • amitriptyline

              morphine and amitriptyline both increase sedation. Use Caution/Monitor.

              amitriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • amobarbital

              amobarbital and morphine both increase sedation. Use Caution/Monitor.

            • amoxapine

              morphine and amoxapine both increase sedation. Use Caution/Monitor.

              amoxapine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • apalutamide

              apalutamide will decrease the level or effect of morphine by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

            • apomorphine

              morphine and apomorphine both increase sedation. Use Caution/Monitor.

            • arformoterol

              morphine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aripiprazole

              morphine and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              morphine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • asenapine

              asenapine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • azelastine

              azelastine and morphine both increase sedation. Use Caution/Monitor.

            • baclofen

              baclofen and morphine both increase sedation. Use Caution/Monitor.

            • belladonna and opium

              morphine and belladonna and opium both increase sedation. Use Caution/Monitor.

            • benperidol

              morphine and benperidol both increase sedation. Use Caution/Monitor.

            • benzphetamine

              morphine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • berotralstat

              berotralstat will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • brexanolone

              brexanolone, morphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and morphine both increase sedation. Use Caution/Monitor.

            • buprenorphine

              buprenorphine and morphine both increase sedation. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal and morphine both increase sedation. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              morphine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

            • bupropion

              bupropion will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • buspirone

              buspirone and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • butabarbital

              butabarbital and morphine both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital and morphine both increase sedation. Use Caution/Monitor.

            • butorphanol

              butorphanol and morphine both increase sedation. Use Caution/Monitor.

            • caffeine

              morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cannabidiol

              cannabidiol will increase the level or effect of morphine by Other (see comment). Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT2B7 activity. Consider reducing the dose when concomitantly using UGT2B7 substrates.

            • captopril

              morphine, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood ressure.

            • carbinoxamine

              carbinoxamine and morphine both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and morphine both increase sedation. Use Caution/Monitor.

            • celecoxib

              celecoxib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate and morphine both increase sedation. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide and morphine both increase sedation. Use Caution/Monitor.

            • chloroquine

              chloroquine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and morphine both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              morphine and chlorpromazine both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

              chlorzoxazone and morphine both increase sedation. Use Caution/Monitor.

            • cimetidine

              cimetidine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and morphine both increase sedation. Use Caution/Monitor.

            • citalopram

              citalopram and morphine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

            • clemastine

              clemastine and morphine both increase sedation. Use Caution/Monitor.

            • clobazam

              morphine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clomipramine

              morphine and clomipramine both increase sedation. Use Caution/Monitor.

              clomipramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • clonazepam

              clonazepam and morphine both increase sedation. Use Caution/Monitor.

            • clorazepate

              clorazepate and morphine both increase sedation. Use Caution/Monitor.

            • clozapine

              morphine and clozapine both increase sedation. Use Caution/Monitor.

            • cocaine

              cocaine and morphine both increase serotonin levels. Use Caution/Monitor.

            • codeine

              codeine and morphine both increase sedation. Use Caution/Monitor.

            • cyclizine

              cyclizine and morphine both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and morphine both increase sedation. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and morphine both increase sedation. Use Caution/Monitor.

            • dantrolene

              dantrolene and morphine both increase sedation. Use Caution/Monitor.

            • darifenacin

              darifenacin will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • desflurane

              desflurane and morphine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

            • desipramine

              morphine and desipramine both increase sedation. Use Caution/Monitor.

              desipramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • deutetrabenazine

              morphine and deutetrabenazine both increase sedation. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine and morphine both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              morphine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              dexfenfluramine and morphine both increase serotonin levels. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine and morphine both increase sedation. Use Caution/Monitor.

            • dexmethylphenidate

              morphine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextroamphetamine

              morphine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              dextroamphetamine and morphine both increase serotonin levels. Use Caution/Monitor.

            • dextromethorphan

              dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dextromoramide

              dextromoramide and morphine both increase sedation. Use Caution/Monitor.

            • diamorphine

              diamorphine and morphine both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and morphine both increase sedation. Use Caution/Monitor.

            • dichlorphenamide

              dichlorphenamide and morphine both decrease serum potassium. Use Caution/Monitor.

            • diethylpropion

              morphine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl and morphine both increase sedation. Use Caution/Monitor.

            • dihydroergotamine

              dihydroergotamine and morphine both increase serotonin levels. Use Caution/Monitor.

            • dihydroergotamine intranasal

              dihydroergotamine intranasal and morphine both increase serotonin levels. Use Caution/Monitor.

            • dimenhydrinate

              dimenhydrinate and morphine both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              diphenhydramine and morphine both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              diphenoxylate hcl and morphine both increase sedation. Use Caution/Monitor.

            • dipipanone

              dipipanone and morphine both increase sedation. Use Caution/Monitor.

            • dobutamine

              morphine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopamine

              morphine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              morphine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dosulepin

              morphine and dosulepin both increase sedation. Use Caution/Monitor.

            • doxepin

              morphine and doxepin both increase sedation. Use Caution/Monitor.

              doxepin and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • doxylamine

              doxylamine and morphine both increase sedation. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • droperidol

              morphine and droperidol both increase sedation. Use Caution/Monitor.

            • duloxetine

              duloxetine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              duloxetine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • elagolix

              elagolix will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • eletriptan

              eletriptan and morphine both increase serotonin levels. Use Caution/Monitor.

            • eliglustat

              eliglustat increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

            • eltrombopag

              eltrombopag increases levels of morphine by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

            • ephedrine

              morphine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              morphine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              morphine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ergotamine

              ergotamine and morphine both increase serotonin levels. Use Caution/Monitor.

            • escitalopram

              escitalopram and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • esketamine intranasal

              esketamine intranasal, morphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • estazolam

              estazolam and morphine both increase sedation. Use Caution/Monitor.

            • ethanol

              morphine and ethanol both increase sedation. Use Caution/Monitor.

            • etomidate

              etomidate and morphine both increase sedation. Use Caution/Monitor.

            • fenfluramine

              morphine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              fenfluramine and morphine both increase serotonin levels. Use Caution/Monitor.

            • flibanserin

              morphine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

            • fluoxetine

              fluoxetine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • fluphenazine

              morphine and fluphenazine both increase sedation. Use Caution/Monitor.

            • flurazepam

              flurazepam and morphine both increase sedation. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • formoterol

              morphine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fostamatinib

              fostamatinib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • frovatriptan

              frovatriptan and morphine both increase serotonin levels. Use Caution/Monitor.

            • gabapentin

              gabapentin, morphine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

              gabapentin, morphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, morphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • haloperidol

              haloperidol will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              morphine and haloperidol both increase sedation. Use Caution/Monitor.

            • hydromorphone

              hydromorphone and morphine both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and morphine both increase sedation. Use Caution/Monitor.

            • iloperidone

              morphine and iloperidone both increase sedation. Use Caution/Monitor.

            • imatinib

              imatinib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • imipramine

              morphine and imipramine both increase sedation. Use Caution/Monitor.

              imipramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • isoniazid

              isoniazid and morphine both increase serotonin levels. Use Caution/Monitor.

            • isoproterenol

              morphine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • ivacaftor

              ivacaftor increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ketamine

              ketamine and morphine both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

              morphine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • L-tryptophan

              L-tryptophan and morphine both increase serotonin levels. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, morphine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, morphine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • levalbuterol

              morphine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levomilnacipran

              levomilnacipran and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of morphine by unknown mechanism. Use Caution/Monitor.

            • levorphanol

              levorphanol and morphine both increase sedation. Use Caution/Monitor.

            • lisdexamfetamine

              morphine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lithium

              lithium and morphine both increase serotonin levels. Use Caution/Monitor.

            • lofepramine

              morphine and lofepramine both increase sedation. Use Caution/Monitor.

              lofepramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lofexidine

              morphine and lofexidine both increase sedation. Use Caution/Monitor.

            • lonafarnib

              lonafarnib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

            • loprazolam

              loprazolam and morphine both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam and morphine both increase sedation. Use Caution/Monitor.

            • lormetazepam

              lormetazepam and morphine both increase sedation. Use Caution/Monitor.

            • loxapine

              morphine and loxapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              morphine and loxapine inhaled both increase sedation. Use Caution/Monitor.

            • lsd

              lsd and morphine both increase serotonin levels. Use Caution/Monitor.

            • lurasidone

              lurasidone, morphine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              morphine and maprotiline both increase sedation. Use Caution/Monitor.

              maprotiline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • maraviroc

              maraviroc will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • marijuana

              marijuana will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              morphine and marijuana both increase sedation. Use Caution/Monitor.

            • melatonin

              morphine and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              meperidine and morphine both increase sedation. Use Caution/Monitor.

              meperidine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • meprobamate

              morphine and meprobamate both increase sedation. Use Caution/Monitor.

            • metaproterenol

              morphine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaxalone

              metaxalone and morphine both increase sedation. Use Caution/Monitor.

            • methadone

              methadone and morphine both increase sedation. Use Caution/Monitor.

            • methamphetamine

              morphine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and morphine both increase sedation. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              morphine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • midazolam

              midazolam and morphine both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

              midazolam intranasal, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • midodrine

              morphine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • milnacipran

              milnacipran and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • mirtazapine

              morphine and mirtazapine both increase sedation. Use Caution/Monitor.

              mirtazapine and morphine both increase serotonin levels. Use Caution/Monitor.

            • modafinil

              morphine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • motherwort

              morphine and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              morphine and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              morphine and nabilone both increase sedation. Use Caution/Monitor.

            • nalbuphine

              morphine and nalbuphine both increase sedation. Use Caution/Monitor.

            • naratriptan

              naratriptan and morphine both increase serotonin levels. Use Caution/Monitor.

            • nefazodone

              nefazodone and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nilotinib

              nilotinib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • norepinephrine

              morphine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nortriptyline

              morphine and nortriptyline both increase sedation. Use Caution/Monitor.

              nortriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • olanzapine

              morphine and olanzapine both increase sedation. Use Caution/Monitor.

            • oliceridine

              oliceridine, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • opium tincture

              morphine and opium tincture both increase sedation. Use Caution/Monitor.

            • orphenadrine

              orphenadrine and morphine both increase sedation. Use Caution/Monitor.

            • oxazepam

              oxazepam and morphine both increase sedation. Use Caution/Monitor.

            • oxycodone

              morphine and oxycodone both increase sedation. Use Caution/Monitor.

            • oxymorphone

              morphine and oxymorphone both increase sedation. Use Caution/Monitor.

            • paliperidone

              morphine and paliperidone both increase sedation. Use Caution/Monitor.

            • papaveretum

              morphine and papaveretum both increase sedation. Use Caution/Monitor.

            • papaverine

              morphine and papaverine both increase sedation. Use Caution/Monitor.

            • parecoxib

              parecoxib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • paroxetine

              paroxetine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • pegvisomant

              morphine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

            • pentazocine

              morphine and pentazocine both increase sedation. Use Caution/Monitor.

              morphine and pentazocine both increase serotonin levels. Use Caution/Monitor.

            • pentobarbital

              pentobarbital and morphine both increase sedation. Use Caution/Monitor.

            • perampanel

              perampanel and morphine both decrease sedation. Use Caution/Monitor.

            • perphenazine

              perphenazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              morphine and perphenazine both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              morphine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenobarbital

              phenobarbital and morphine both increase sedation. Use Caution/Monitor.

            • phentermine

              morphine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine

              morphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine PO

              morphine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • pholcodine

              morphine and pholcodine both increase sedation. Use Caution/Monitor.

            • pimozide

              morphine and pimozide both increase sedation. Use Caution/Monitor.

            • pirbuterol

              morphine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ponatinib

              ponatinib increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • pregabalin

              pregabalin, morphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone and morphine both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              morphine and prochlorperazine both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and morphine both increase sedation. Use Caution/Monitor.

            • propafenone

              propafenone will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • propofol

              propofol and morphine both increase sedation. Use Caution/Monitor.

            • propylhexedrine

              morphine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              morphine and protriptyline both increase sedation. Use Caution/Monitor.

              protriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • quazepam

              quazepam and morphine both increase sedation. Use Caution/Monitor.

            • quetiapine

              morphine and quetiapine both increase sedation. Use Caution/Monitor.

            • quinacrine

              quinacrine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ramelteon

              morphine and ramelteon both increase sedation. Use Caution/Monitor.

            • ranolazine

              ranolazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • remimazolam

              remimazolam, morphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • risperidone

              morphine and risperidone both increase sedation. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • rizatriptan

              rizatriptan and morphine both increase serotonin levels. Use Caution/Monitor.

            • salmeterol

              morphine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • SAMe

              morphine and SAMe both increase serotonin levels. Use Caution/Monitor.

            • sarecycline

              sarecycline will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • scullcap

              morphine and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital and morphine both increase sedation. Use Caution/Monitor.

            • selegiline

              selegiline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.

            • selegiline transdermal

              selegiline transdermal and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sertraline

              sertraline will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              sertraline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sevoflurane

              sevoflurane and morphine both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              morphine and shepherd's purse both increase sedation. Use Caution/Monitor.

            • St John's Wort

              morphine and St John's Wort both increase serotonin levels. Modify Therapy/Monitor Closely.

            • stiripentol

              stiripentol will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

              stiripentol, morphine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil

              morphine and sufentanil both increase sedation. Use Caution/Monitor.

            • sumatriptan

              sumatriptan and morphine both increase serotonin levels. Use Caution/Monitor.

            • sumatriptan intranasal

              sumatriptan intranasal and morphine both increase serotonin levels. Use Caution/Monitor.

            • suvorexant

              suvorexant and morphine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

            • tapentadol

              morphine and tapentadol both increase sedation. Use Caution/Monitor.

            • temazepam

              temazepam and morphine both increase sedation. Use Caution/Monitor.

            • tenofovir DF

              tenofovir DF increases levels of morphine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • terbutaline

              morphine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thioridazine

              thioridazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              morphine and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              morphine and thiothixene both increase sedation. Use Caution/Monitor.

            • tipranavir

              tipranavir will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • topiramate

              morphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tramadol

              morphine and tramadol both increase sedation. Use Caution/Monitor.

              morphine and tramadol both increase serotonin levels. Use Caution/Monitor.

            • trazodone

              morphine and trazodone both increase sedation. Use Caution/Monitor.

              trazodone and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • triazolam

              triazolam and morphine both increase sedation. Use Caution/Monitor.

            • triclofos

              triclofos and morphine both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              morphine and trifluoperazine both increase sedation. Use Caution/Monitor.

            • trimipramine

              morphine and trimipramine both increase sedation. Use Caution/Monitor.

              trimipramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • triprolidine

              triprolidine and morphine both increase sedation. Use Caution/Monitor.

            • trospium chloride

              morphine, trospium chloride. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • tucatinib

              tucatinib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • venlafaxine

              venlafaxine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              venlafaxine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • xylometazoline

              morphine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              morphine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              morphine and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              morphine and ziprasidone both increase sedation. Use Caution/Monitor.

            • zolmitriptan

              zolmitriptan and morphine both increase serotonin levels. Use Caution/Monitor.

            • zotepine

              morphine and zotepine both increase sedation. Use Caution/Monitor.

            Minor (10)

            • benazepril

              morphine, benazepril. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. May increase risk of hypotension.

            • brimonidine

              brimonidine increases effects of morphine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • celandine

              celandine increases effects of morphine by unspecified interaction mechanism. Minor/Significance Unknown. Based on animal studies.

            • dextroamphetamine

              dextroamphetamine increases effects of morphine by unspecified interaction mechanism. Minor/Significance Unknown.

            • eucalyptus

              morphine and eucalyptus both increase sedation. Minor/Significance Unknown.

            • lidocaine

              lidocaine increases toxicity of morphine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

            • rifabutin

              rifabutin decreases levels of morphine by increasing metabolism. Minor/Significance Unknown.

            • rifampin

              rifampin decreases levels of morphine by increasing metabolism. Minor/Significance Unknown.

            • sage

              morphine and sage both increase sedation. Minor/Significance Unknown.

            • ziconotide

              ziconotide, morphine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

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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

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers Healthcare providers are strongly encouraged to
            • Healthcare providers are strongly encouraged to
              • Complete a REMS-compliant education program
              • Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
              • Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
              • Consider other tools to improve patient, household, and community safety

            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

            Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper

            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

            Due to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose

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

            After chronic maternal exposure to opioids, 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

            Risk of seizures

            • Morphine may increase frequency of seizures in patients with seizure disorders, and may increase risk of seizures occurring in other clinical settings associated with seizures
            • Monitor patients with a history of seizure disorders for worsened seizure control during morphine sulfate injection therapy
            • Excitation of central nervous system, resulting in convulsions, may accompany high doses of morphine given intravenously

            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; if concomitant use with benzodiazepine warranted, consider prescribing naloxone for emergency treatment of opioid overdose
            • Not indicated for PRN use

            Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
            • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; Use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
            • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
            • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
            • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint

            Patient access to naloxone for emergency treatment of opioid overdose

            • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
            • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
            • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
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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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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
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            20 mg capsule
            morphine oral
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            200 mg tablet
            morphine oral
            -
            100 mg tablet
            morphine oral
            -
            30 mg capsule
            morphine oral
            -
            20 mg capsule
            morphine oral
            -
            10 mg capsule
            morphine oral
            -
            30 mg tablet
            morphine oral
            -
            100 mg tablet
            morphine oral
            -
            60 mg tablet
            morphine oral
            -
            60 mg tablet
            morphine oral
            -
            30 mg tablet
            morphine oral
            -
            15 mg tablet
            morphine oral
            -
            200 mg tablet
            morphine oral
            -
            200 mg tablet
            morphine oral
            -
            80 mg capsule
            morphine oral
            -
            60 mg capsule
            morphine oral
            -
            50 mg capsule
            morphine oral
            -
            10 mg/5 mL solution
            morphine oral
            -
            100 mg tablet
            morphine oral
            -
            50 mg capsule
            morphine oral
            -
            20 mg/5 mL (4 mg/mL) solution
            morphine oral
            -
            20 mg/5 mL (4 mg/mL) solution
            morphine oral
            -
            10 mg/5 mL solution
            morphine oral
            -
            10 mg/5 mL solution
            morphine oral
            -
            30 mg tablet
            morphine oral
            -
            100 mg capsule
            morphine oral
            -
            30 mg capsule
            morphine oral
            -
            100 mg capsule
            morphine oral
            -
            60 mg tablet
            morphine oral
            -
            30 mg tablet
            morphine oral
            -
            30 mg tablet
            morphine oral
            -
            15 mg tablet
            morphine oral
            -
            90 mg capsule
            morphine intravenous
            -
            4 mg/mL vial
            morphine intravenous
            -
            50 mg/mL vial
            morphine intravenous
            -
            4 mg/mL vial
            morphine intravenous
            -
            8 mg/mL vial
            morphine intravenous
            -
            25 mg/mL vial
            morphine intravenous
            -
            50 mg/mL vial
            MS Contin oral
            -
            200 mg tablet
            MS Contin oral
            -
            100 mg tablet
            MS Contin oral
            -
            15 mg tablet
            MS Contin oral
            -
            30 mg tablet
            MS Contin oral
            -
            60 mg tablet
            morphine intramuscular
            -
            10 mg/0.7 mL injection
            morphine injection
            -
            10 mg/mL solution
            morphine injection
            -
            8 mg/mL solution
            morphine injection
            -
            5 mg/mL solution
            morphine injection
            -
            4 mg/mL solution
            morphine injection
            -
            2 mg/mL solution

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            Patient Handout

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            Patient Education
            morphine oral

            MORPHINE SUSTAINED-ACTION CAPSULE - ORAL

            (MORE-feen)

            COMMON BRAND NAME(S): Kadian

            WARNING: Morphine has a risk for abuse and addiction, which can lead to overdose and death. Morphine may also cause severe, possibly fatal, breathing problems. To lower your risk, your doctor should have you take the smallest dose of morphine that works, and take it for the shortest possible time. See also How to Use section for more information about addiction.The risk for severe breathing problems is higher when you start this medication and after a dose increase, or if you take the wrong dose/strength. Taking this medication with alcohol or other drugs that can cause drowsiness or breathing problems may cause very serious side effects, including death. Be sure you know how to take morphine and what other drugs you should avoid taking with it. See also Drug Interactions section. Get medical help right away if any of these very serious side effects occur: slow/shallow breathing, unusual lightheadedness, severe drowsiness/dizziness, difficulty waking up.Do not crush, chew, or dissolve this medication or the contents of the capsules. Taking crushed, chewed, or dissolved forms of sustained-action morphine could cause a fatal overdose.Keep this medicine in a safe place to prevent theft, misuse, or abuse. If someone accidentally swallows this drug, get medical help right away.Before using this medication, women of childbearing age should talk with their doctor(s) about the risks and benefits. Tell your doctor if you are pregnant or if you plan to become pregnant. During pregnancy, this medication should be used only when clearly needed. It may slightly increase the risk of birth defects if used during the first two months of pregnancy. Also, using it for a long time or in high doses near the expected delivery date may harm the unborn baby. To lessen the risk, take the smallest effective dose for the shortest possible time. Babies born to mothers who use this drug for a long time may develop severe (possibly fatal) withdrawal symptoms. Tell the doctor right away if you notice any symptoms in your newborn baby such as crying that doesn't stop, slow/shallow breathing, irritability, shaking, vomiting, diarrhea, poor feeding, or difficulty gaining weight.

            USES: This medication is used to help relieve severe ongoing pain (such as due to cancer). Morphine belongs to a class of drugs known as opioid analgesics. It works in the brain to change how your body feels and responds to pain.The higher strengths of this drug (100 milligrams per capsule and higher) should be used only if you have been regularly taking moderate to large amounts of an opioid pain medication. These strengths may cause overdose (even death) if taken by a person who has not been regularly taking opioids.Do not use the sustained-action form of morphine to relieve pain that is mild or that will go away in a few days. This medication is not for occasional ("as needed") use.

            HOW TO USE: See also Warning section.Read the Medication Guide provided by your pharmacist before you start using morphine and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Take this medication on a regular schedule as directed by your doctor, not as needed for sudden (breakthrough) pain. Take this drug with or without food, usually once or twice daily (every 12 or 24 hours). If you have nausea, it may help to take this drug with food. Ask your doctor or pharmacist about other ways to decrease nausea (such as lying down for 1 to 2 hours with as little head movement as possible).Swallow the capsules whole. Adults who have trouble swallowing the capsule may open the capsule and carefully sprinkle its contents on a spoonful of soft, cool applesauce. Swallow all of the drug/food mixture right away without chewing. Then rinse your mouth and swallow the rinse liquid to make sure that you have swallowed all of the dose. Do not chew the mixture or prepare a supply in advance. Do not give this medication to a child this way, since they might chew the mixture and overdose. For children who have trouble swallowing the capsule, ask the doctor about using a different form of morphine instead.The dosage is based on your medical condition and response to treatment. Do not increase your dose, take the medication more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.If you are giving this medication through a certain tube into the stomach (gastric tube), ask your health care professional for detailed instructions on how to give it.Before you start taking this medication, ask your doctor or pharmacist if you should stop or change how you use your other opioid medication(s). Other pain relievers (such as acetaminophen, ibuprofen) may also be prescribed. Ask your doctor or pharmacist about using morphine safely with other drugs.Suddenly stopping this medication may cause withdrawal, especially if you have used it for a long time or in high doses. To prevent withdrawal, your doctor may lower your dose slowly. Tell your doctor or pharmacist right away if you have any withdrawal symptoms such as restlessness, mental/mood changes (including anxiety, trouble sleeping, thoughts of suicide), watering eyes, runny nose, nausea, diarrhea, sweating, muscle aches, or sudden changes in behavior.When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.Tell your doctor if your pain does not get better or if it gets worse.

            SIDE EFFECTS: See also Warning section.Nausea, vomiting, constipation, lightheadedness, dizziness, or drowsiness may occur. Some of these side effects may decrease after you have been using this medication for a while. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.To prevent constipation, eat dietary fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your pharmacist which type of laxative is right for you.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: interrupted breathing during sleep (sleep apnea), mental/mood changes (such as agitation, confusion, hallucinations), severe stomach/abdominal pain, difficulty urinating, signs of your adrenal glands not working well (such as loss of appetite, unusual tiredness, weight loss).Get medical help right away if you have any very serious side effects, including: fainting, seizure, slow/shallow breathing, severe drowsiness/difficulty waking up.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking morphine, tell your doctor or pharmacist if you are allergic to it; or to other opioid pain medications (such as codeine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), kidney disease, liver disease, mental/mood disorders (such as confusion, depression), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol), stomach/intestinal problems (such as blockage, constipation, diarrhea due to infection, paralytic ileus), difficulty urinating (such as due to enlarged prostate), disease of the pancreas (pancreatitis), gallbladder disease.This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially confusion, dizziness, drowsiness, and slow/shallow breathing.During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor. (See also Warning section.)This drug passes into breast milk and may have undesirable effects on a nursing infant. Tell the doctor right away if your baby develops unusual sleepiness, difficulty feeding, or trouble breathing. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also Warning section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: certain pain medications (mixed opioid agonist-antagonists such as pentazocine, nalbuphine, butorphanol), naltrexone.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are taking other products such as other opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.This medication may interfere with certain laboratory tests (including amylase/lipase levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, give them naloxone if available, then call 911. If the person is awake and has no symptoms, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: slow/shallow breathing, slow heartbeat, coma.

            NOTES: Do not share this medication with others. Sharing it is against the law.This medication has been prescribed for your current condition only. Do not use it later for another condition unless told to do so by your doctor. A different medication may be necessary in that case.Ask your doctor or pharmacist if you should have naloxone available to treat opioid overdose. Teach your family or household members about the signs of an opioid overdose and how to treat it.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets. See also Warning section.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. For more details, read the Medication Guide, or consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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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.
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            • 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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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.