High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.
- Morphabond ER
- Morphine EPD
- Morphine Extra Forte
- Morphine HP
- Morphine LP Epidural
- MS Contin
- MS Contin SRT
Controlled Substance Schedule: II
- Severe pain (the 20 mg/mL oral solution concentration should only be used in opioid-tolerant patients).
- Pain severe enough to require daily, around-the-clock long-term opioid treatment and for which alternative treatment options are inadequate (extended-release).
- Pulmonary edema.
- Pain associated with MI.
Binds to opiate receptors in the CNS. Alters the perception of and response to painful stimuli while producing generalized CNS depression.
Decrease in severity of pain. Addition of naltrexone in Embeda product is designed to prevent abuse or misuse by altering the formulation. Naltrexone has no effect unless the capsule is crushed or chewed.
Absorption: Variably absorbed (about 30%) following oral administration. More reliably absorbed from rectal, subcut, and IM sites. Following epidural administration, systemic absorption and absorption into the intrathecal space via the meninges occurs.
Distribution: Widely distributed. Crosses the placenta; enters breast milk in small amounts.
Protein Binding: Premature infants: <20%; Adults: 35%.
Metabolism and Excretion: Mostly metabolized by the liver. Active metabolites excreted renally.
Half-life: Premature neonates: 10–20 hr; Neonates: 7.6 hr; Infants 1–3 mo: 6.2 hr; Children 6 mo–2.5 yr: 2.9 hr; Children 3–6 yr: 1–2 hr; Children 6–19 yr with sickle cell disease: 1.3 hr; Adults: 2–4 hr.
TIME/ACTION PROFILE (analgesia)
|PO||unknown||60 min||4–5 hr|
|PO-ER||unknown||3–4 hr||8–24 hr|
|IM||10–30 min||30–60 min||4–5 hr|
|Subcut||20 min||50–90 min||4–5 hr|
|Rect||unknown||20–60 min||3–7 hr|
|IV||rapid||20 min||4–5 hr|
|Epidural||6–30 min||1 hr||up to 24 hr|
|IT||rapid (min)||unknown||up to 24 hr|
- Some products contain tartrazine, bisulfites, or alcohol and should be avoided in patients with known hypersensitivity;
- Acute, mild, intermittent, or postoperative pain (extended/sustained-release);
- Significant respiratory depression (extended-release);
- Acute or severe bronchial asthma (extended-release);
- Paralytic ileus (extended-release).
Use Cautiously in:
- Head trauma;
- ↑ intracranial pressure;
- Severe renal, hepatic, or pulmonary disease;
- Seizure disorder;
- Adrenal insufficiency;
- History of substance abuse;
- Undiagnosed abdominal pain;
- Prostatic hyperplasia;
- Patients undergoing procedures that rapidly ↓ pain (cordotomy, radiation); long-acting agents should be discontinued 24 hr before and replaced with short-acting agents;
- Geri: Geriatric or debilitated patients (↑ risk of respiratory depression; dose ↓ suggested);
- OB: Lactation: Avoid chronic use; has been used during labor but may cause respiratory depression in the newborn; prolonged use of extended-release morphine during pregnancy can result in neonatal opioid withdrawal syndrome;
- Pedi: Neonates and infants <3 mo (more susceptible to respiratory depression);
- Pedi: Neonates (oral solution contains sodium benzoate which can cause potentially fatal gasping syndrome).
Adverse Reactions/Side Effects
CNS: confusion, sedation, dizziness, dysphoria, euphoria, floating feeling, hallucinations, headache, unusual dreams
CV: hypotension, bradycardia
Derm: flushing, itching, sweating
EENT: blurred vision, diplopia, miosis
Endo: adrenal insufficiency
GI: constipation, nausea, vomiting
GU: urinary retention
Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA)
Misc: physical dependence, psychological dependence, tolerance
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Use with extreme caution in patients receiving MAO inhibitors within 14 days prior (may result in unpredictable, severe reactions–↓ initial dose of morphine to 25% of usual dose).
- Use with benzodiazepines or other CNS depressants including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
- Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5–HT3 receptor antagonists, linezolid, methylene blue, and triptans ↑ risk of serotonin syndrome.
- Mixed agonist/antagonist analgesics, including nalbuphine or butorphanol and partial agonist analgesics, including buprenorphine , may ↓ morphine's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
- May ↑ the anticoagulant effect of warfarin.
- Cimetidine ↓ metabolism and may ↑ effects.
- IV morphine may ↓ levels and antiplatelet effects of clopidogrel, prasugrel, and ticagrelor ; consider IV antiplatelet agent as alternative in patients with acute coronary syndrome if morphine concomitantly used.
Larger doses may be required during chronic therapy
PO Rect: (Adults ≥50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 30 mg every 3–4 hr initially or once 24-hr opioid requirement is determined, convert to extended-release morphine by administering total daily oral morphine dose every 24 hr (as Kadian or other ER capsules), 50% of the total daily oral morphine dose every 12 hr (as Kadian, Morphabond, MS Contin ), or 33% of the total daily oral morphine dose every 8 hr (as Morphabond, MS Contin ). See equianalgesic chart, equianalgesic dosing guidelines. Dose of ER capsules (not Kadian ) should not exceed 1600 mg/day because of fumaric acid in formulation.
PO Rect: (Adults and Children <50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 0.3 mg/kg every 3–4 hr initially.
PO (Children >1 mo): Prompt-release tablets and solution– 0.2–0.5 mg/kg every 4–6 hr as needed. Controlled-release tablet– 0.3–0.6 mg/kg every 12 hr.
IM IV SC (Adults ≥50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 4–10 mg every 3–4 hr. MI– 8–15 mg, for very severe pain additional smaller doses may be given every 3–4 hr.
IM IV SC (Adults and Children <50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients– 0.05–0.2 mg/kg every 3–4 hr, maximum: 15 mg/dose.
IM IV SC Neonates: 0.05 mg/kg every 4–8 hr, maximum dose: 0.1 mg/kg. Use preservative-free formulation.
IV SC (Adults): Continuous infusion– 0.8–10 mg/hr; may be preceded by a bolus of 15 mg (infusion rates vary greatly; up to 80 mg/hr have been used).
IV SC (Children >1 mo): Continuous infusion, postoperative pain– 0.01–0.04 mg/kg/hr. Continuous infusion, sickle cell or cancer pain– 0.02–2.6 mg/kg/hr.
IV Neonates: Continuous infusion– 0.01–0.03 mg/kg/hr.
Epidural: (Adults): Intermittent injection– 5 mg/day (initially); if relief is not obtained at 60 min, 1–2 mg increments may be made (total dose not to exceed 10 mg/day). Continuous infusion– 2–4 mg/24 hr; may ↑ by 1–2 mg/day (up to 30 mg/day).
Epidural: (Children >1 mo): 0.03–0.05 mg/kg, maximum dose: 0.1 mg/kg or 5 mg/24 hr. Use preservative-free formulation.
IT (Adults): 0.2–1 mg. Use preservative-free formulation.
Availability (generic available)
Extended-release capsules: 30 mg, 45 mg, 60 mg, 75 mg, 90 mg, 120 mg
Cost: 30 mg $606.31/100, 45 mg $898.99/100, 60 mg $1,177.88/100, 75 mg $1,498.31/100, 90 mg $1,770.29/100, 120 mg $2,088.66/100
Extended-release capsules (Kadian): 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 100 mg, 130 mg, 150 mg, 200 mg
Cost: 10 mg $609.60/100, 20 mg $673.20/100, 30 mg $732.00/100, 40 mg $976.80/100, 50 mg $1,224.00/100, 60 mg $1,465.20/100, 70 mg $1,708.80/100, 80 mg $1,951.20/100, 100 mg $2,407.20/100, 130 mg $3,182.40/100, 150 mg $3,672.00/100, 200 mg $4,946.40/100
Extended-release tablets (Morphabond ER, abuse deterrent): 15 mg, 30 mg, 60 mg, 100 mg
Extended-release tablets (MS Contin): 15 mg, 30 mg, 60 mg, 100 mg, 200 mg
Generic: 15 mg $167.57/100, 30 mg $317.19/100, 60 mg $532.39/100, 100 mg $763.63/100, 200 mg $1,838.19/100
Oral solution: 1 mg/mL , 10 mg/5 mL, 20 mg/5 mL, 5 mg/mL , 100 mg/5 mL
Generic: 4 mg/mL $17.51/100 mL, 20 mg/mL $25.20/30 mL
Rectal suppositories: 5 mg, 10 mg, 20 mg, 30 mg
Generic: 5 mg $60.00/12, 10 mg $75.00/12, 20 mg $90.00/12, 30 mg $112.50/12
Solution for epidural, IV injection (preservative-free): 0.5 mg/mL, 1 mg/mL
Solution for epidural or IT use (continuous microinfusion device; preservative-free): 10 mg/mL, 25 mg/mL
Solution for IM, subcut, IV injection: 1 mg/mL, 2 mg/mL, 4 mg/mL, 5 mg/mL, 8 mg/mL, 10 mg/mL, 25 mg/mL, 50 mg/mL
Solution for IV injection (PCA device): 1 mg/mL, 2 mg/mL, 3 mg/mL, 5 mg/mL
Tablets: 15 mg, 30 mg
Generic: 15 mg $22.17/100, 30 mg $37.77/100
- Assess type, location, and intensity of pain prior to and 1 hr following PO, subcut, IM, and 20 min (peak) following IV administration. When titrating opioid doses, increases of 25–50% should be administered until there is either a 50% reduction in the patient's pain rating on a numerical or visual analogue scale or the patient reports satisfactory pain relief. When titrating doses of short-acting morphine, a repeat dose can be safely administered at the time of the peak if previous dose is ineffective and side effects are minimal.
- Patients on a continuous infusion should have additional bolus doses provided every 15–30 min, as needed, for breakthrough pain. The bolus dose is usually set to the amount of drug infused each hr by continuous infusion.
- Patients taking extended-release morphine may require additional short-acting opioid doses for breakthrough pain. Doses of short-acting opioids should be equivalent to 10–20% of 24 hr total and given every 2 hr as needed.
- An equianalgesic chart (see equianalgesic dosing guidelines) should be used when changing routes or when changing from one opioid to another.
- High Alert: Assess level of consciousness, BP, pulse, and respirations before and periodically during administration. If respiratory rate is <10/min, assess level of sedation. Physical stimulation may be sufficient to prevent significant hypoventilation. Subsequent doses may need to be decreased by 25–50%. Initial drowsiness will diminish with continued use. Geri: Assess geriatric patients frequently; older adults are more sensitive to the effects of opioid analgesics and may experience side effects and respiratory complications more frequently. Pedi: Assess pediatric patient frequently; children are more sensitive to the effects of opioid analgesics and may experience respiratory complications, excitability, and restlessness more frequently.
- Prolonged use may lead to physical and psychological dependence and tolerance. This should not prevent patient from receiving adequate analgesia. Patients who receive morphine for pain rarely develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy.
- Assess bowel function routinely. Institute prevention of constipation with increased intake of fluids and bulk and with laxatives to minimize constipating effects. Administer stimulant laxatives routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid-induced constipation.
- Assess risk for opioid addiction, abuse, or misuse prior to administration. Abuse or misuse of extended-release preparations by crushing, chewing, snorting, or injecting dissolved product will result in uncontrolled delivery of morphine and can result in overdose and death.
Lab Test Considerations:
May ↑ plasma amylase and lipase levels.
If an opioid antagonist is required to reverse respiratory depression or coma, naloxone is the antidote. Dilute the 0.4-mg ampule of naloxone in 10 mL of 0.9% NaCl and administer 0.5 mL (0.02 mg) by IV push every 2 min. For children and adults weighing <40 kg, dilute 0.1 mg of naloxone in 10 mL of 0.9% NaCl for a concentration of 10 mcg/mL and administer 0.5 mcg/kg every 2 min. Titrate dose to avoid withdrawal, seizures, and severe pain.
- High Alert: Do not confuse MS Contin (morphine sulfate) with Oxycontin (oxycodone). Do not confuse morphine (nonconcentrated oral liquid) with morphine (concentrated oral liquid).
- High Alert: Do not confuse morphine with hydromorphone–errors have resulted in death. Use only preservative-free formulations for neonates, and for epidural and intrathecal routes in all patients.
- Abuse deterrent: Embeda is an abuse deterrent formulation that contains naltrexone which remains inactive unless the product is crushed or diluted. Morphabond ER is an abuse deterrent formulation that is difficult to crush and, if crushed results in a gel.
Explain therapeutic value of medication prior to administration to enhance the analgesic effect.
- Regularly administered doses may be more effective than prn administration. Analgesic is more effective if given before pain becomes severe.
- Coadministration with nonopioid analgesics may have additive analgesic effects and may permit lower doses.
- When transferring from other opioids or other forms of morphine to extended-release tablets, administer a total daily dose of oral morphine equivalent to previous daily dose (see equianalgesic dosing guidelines) and divided every 8 hr (MS Contin), every 12 hr (Embeda, Kadian, MS Contin), every 24 hr (Kadian).
- Morphine should be discontinued gradually to prevent withdrawal symptoms after long-term use. For patients on long-acting agents who are physically opioid-dependent, initiate the taper by a small enough increment (no greater than 10% to 25% of total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 wk. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
Doses may be administered with food or milk to minimize GI irritation.
- Administer oral solution with properly calibrated measuring device; may be diluted in a glass of fruit juice just prior to administration to improve taste. Verify correct dose (mg) and correct volume (mL) prior to administration. Use an oral syringe when using 20 mg/mL concentration of oral solution.
- Swallow extended-release tablets whole; do not break, crush, dissolve, or chew (could result in rapid release and absorption of a potentially toxic dose).
- Embeda and Kadian capsules may be opened and the pellets sprinkled onto applesauce immediately prior to administration. Patients should rinse mouth and swallow to assure ingestion of entire dose. Pellets should not be chewed, crushed, or dissolved. Kadian capsules may also be opened and sprinkled on approximately 10 mL of water and flushed while swirling through a pre-wetted 16 French gastrostomy tube fitted with a funnel at the port end. Additional water should be used to transfer and flush any remaining pellets. Kadian should not be administered via a nasogastric tube.
- Rect: MS Contin has been administered rectally.
- IM SC Use IM route for repeated doses, because morphine is irritating to subcut tissues.
- FDA strongly encourages health care professionals to complete a REMS-compliant education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain, available at www.fda.gov/OpioidAnalgesicREMSBlueprint. Information on programs can be found at 1-800-503-0784 or www.opioidanalgesicrems.com.
- Epidural: Administer undiluted. Do not use an in-line filter. Do not admix or administer other medications in epidural space for 48 hr after administration. Administer within 4 hr after removing from vial. Store in refrigerator; do not freeze.
- IV Solution is colorless; do not administer discolored solution.
- IV Push: Diluent: Do not dilute prior to injection..
- Rate: High Alert: Administer slowly at 2.5–15 mg over 5 min. Rapid administration may lead to increased respiratory depression, hypotension, and circulatory collapse.
- Continuous Infusion: Diluent: May be added to D5W, D10W, 0.9% NaCl, 0.45% NaCl, Ringer's or LR, dextrose/saline solution, or dextrose/Ringer's or LR. Concentration: 0.1–1 mg/mL or greater for continuous infusion.
- Rate: Administer via infusion pump to control the rate. Dose should be titrated to ensure adequate pain relief without excessive sedation, respiratory depression, or hypotension. May be administered via patient-controlled analgesia (PCA) pump.
- Y-Site Compatibility
- aminocaproic acid
- ascorbic acid
- calcium chloride
- calcium gluconate
- doxorubicin hydrochloride
- epoetin alfa
- etoposide phosphate
- leucovorin calcium
- magnesium sulfate
- penicillin G
- potassium acetate
- potassium chloride
- sodium acetate
- sodium bicarbonate
- vitamin B complex with C
- zoledronic acid
- Y-Site Incompatibility
- amphotericin B lipid complex
- amphotericin B liposome
- doxorubicin liposomal
- folic acid
- Instruct patient how and when to ask for pain medication. Do not stop taking without discussing with health care professional; may cause withdrawal symptoms if discontinued abruptly after prolonged use.Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide (PCG) is available at www.fda.gov/OpioidAnalgesicREMSPCG.
- May cause drowsiness or dizziness. Caution patient to call for assistance when ambulating or smoking and to avoid driving or other activities requiring alertness until response to medication is known.
- Advise patient that morphine is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
- Advise patient to change positions slowly to minimize orthostatic hypotension.
- Caution patient to avoid concurrent use of alcohol or other CNS depressants with this medication.
- Encourage patients who are immobilized or on prolonged bedrest to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
- Rep: Advise patient to notify health care professional if pregnancy is planned or suspected, or if breast feeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal (irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight); usually occur the first days after birth.
- Home Care Issues:
High Alert: Explain to patient and family how and when to administer morphine and how to care for infusion equipment properly. Pedi: Teach parents or caregivers how to accurately measure liquid medication and to use only the measuring device dispensed with the medication.
- Emphasize the importance of aggressive prevention of constipation with the use of morphine.
- Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.
- Decrease in symptoms of pulmonary edema.
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