Morphine Sulfate

Morphine Sulfate

Pronunciation

U.S. Brand Names

Astramorph® PF Injection; Duramorph® Injection; Infumorph® Injection; Kadian® Capsule; MS Contin® Oral; MSIR® Oral; MS/L®; MS/S®; OMS® Oral; Oramorph SR® Oral; RMS® Rectal; Roxanol® Oral; Roxanol Rescudose®; Roxanol SR® Oral

Generic Available

Yes

Canadian Brand Names

Epimorph®; M-Eslon®; Morphine-HP®; MS-IR®; MST Continus; Statex®

Synonyms

Pharmacological Index

Analgesic, Narcotic

Use

Relief of moderate to severe acute and chronic pain; pain of myocardial infarction; relieves dyspnea of acute left ventricular failure and pulmonary edema; preanesthetic medication

Restrictions

C-II

Pregnancy Risk Factor

B/D (if used for prolonged periods or in high doses at term)

Contraindications

Known hypersensitivity to morphine sulfate; increased intracranial pressure; severe respiratory depression

Warnings/Precautions

Some preparations contain sulfites which may cause allergic reactions; infants <3 months of age are more susceptible to respiratory depression, use with caution and generally in reduced doses in this age group; use with caution in patients with impaired respiratory function or severe hepatic dysfunction and in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone). Morphine shares the toxic potential of opiate agonists and usual precautions of opiate agonist therapy should be observed; may cause hypotension in patients with acute myocardial infarction. Tolerance or drug dependence may result from extended use.

Elderly may be particularly susceptible to the CNS depressant and constipating effects of narcotics

Adverse Reactions

Percentage unknown: Flushing, CNS depression, drowsiness, sedation, increased intracranial pressure, antidiuretic hormone release, physical and psychological dependence, diaphoresis

>10%:

Cardiovascular: Palpitations, hypotension, bradycardia

Central nervous system: Dizziness

Gastrointestinal: Nausea, vomiting, constipation, xerostomia

Local: Pain at injection site

Neuromuscular & skeletal: Weakness

Miscellaneous: Histamine release

1% to 10%:

Central nervous system: Restlessness, headache, false feeling of well being, confusion

Gastrointestinal: Anorexia, GI irritation, paralytic ileus

Genitourinary: Decreased urination

Neuromuscular & skeletal: Trembling

Ocular: Vision problems

Respiratory: Respiratory depression, shortness of breath

<1%: Peripheral vasodilation, insomnia, mental depression, hallucinations, paradoxical CNS stimulation, increased intracranial pressure, pruritus, biliary tract spasm, urinary tract spasm, muscle rigidity, miosis, increased liver function tests

Overdosage/Toxicology

Symptoms of overdose include respiratory depression, miosis, hypotension, bradycardia, apnea, pulmonary edema

Treatment of an overdose includes support of the patient's airway, establishment of an I.V. line, and administration of naloxone 2 mg I.V. (0.01 mg/kg for children) with repeat administration as necessary up to a total of 10 mg. Primary attention should be directed to ensuring adequate respiratory exchange.

Drug Interactions

CYP2D6 enzyme substrate

Decreased effect: Phenothiazines may antagonize the analgesic effect of morphine and other opiate agonists

Increased toxicity: CNS depressants, tricyclic antidepressants may potentiate the effects of morphine and other opiate agonists; dextroamphetamine may enhance the analgesic effect of morphine and other opiate agonists

Stability

Refrigerate suppositories; do not freeze; degradation depends on pH and presence of oxygen; relatively stable in pH less than or equal to 4; darkening of solutions indicate degradation; usual concentration for continuous I.V. infusion = 0.1-1 mg/mL in D₅W

Mechanism of Action

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

Pharmacodynamics/Kinetics

Onset of effect:

Oral: 1 hour

I.V.: 5-10 minutes

Peak analgesia:

Tablets: 1 hour

Oral solution: 1 hour

Extended release tablets: 1 hour

Suppository: 20-60 minutes

Subcutaneous injection: 50-90 minutes

I.M. injection: 30-60 minutes

I.V. injection: 20 minutes

Duration:

Tablets: 4-5 hours

Oral solution: 4-5 hours

Extended release tablets: 8-12 hours

Suppository: 3-7 hours

Subcutaneous injection: 4-5 hours

I.M. injection: 4-5 hours

I.V. injection: 4-5 hours

Absorption: Oral: Variable

Metabolism: In the liver via glucuronide conjugation

Half-life: Neonates: 4.5-13.3 hours (mean 7.6 hours); Adults: 2-4 hours

Elimination: Unchanged in urine

Usual Dosage

Doses should be titrated to appropriate effect; when changing routes of administration in chronically treated patients, please note that oral doses are approximately one-half as effective as parenteral dose

Infants and Children:

Oral: Tablet and solution (prompt release): 0.2-0.5 mg/kg/dose every 4-6 hours as needed; tablet (controlled release): 0.3-0.6 mg/kg/dose every 12 hours

I.M., I.V., S.C.: 0.1-0.2 mg/kg/dose every 2-4 hours as needed; usual maximum: 15 mg/dose; may initiate at 0.05 mg/kg/dose

I.V., S.C. continuous infusion: Sickle cell or cancer pain: 0.025-2 mg/kg/hour; postoperative pain: 0.01-0.04 mg/kg/hour

Sedation/analgesia for procedures: I.V.: 0.05-0.1 mg/kg 5 minutes before the procedure

Adolescents >12 years: Sedation/analgesia for procedures: I.V.: 3-4 mg and repeat in 5 minutes if necessary

Adults:

Oral: Prompt release: 10-30 mg every 4 hours as needed; controlled release: 15-30 mg every 8-12 hours

I.M., I.V., S.C.: 2.5-20 mg/dose every 2-6 hours as needed; usual: 10 mg/dose every 4 hours as needed

I.V., S.C. continuous infusion: 0.8-10 mg/hour; may increase depending on pain relief/adverse effects; usual range: up to 80 mg/hour

Epidural: Initial: 5 mg in lumbar region; if inadequate pain relief within 1 hour, administer 1-2 mg, maximum dose: 10 mg/24 hours

Intrathecal (1/10 of epidural dose): 0.2-1 mg/dose; repeat doses not recommended

Rectal: 10-20 mg every 4 hours

Dosing adjustment in renal impairment:

Cl_cr 10-50 mL/minute: Administer at 75% of normal dose

Cl_cr <10 mL/minute: Administer at 50% of normal dose

Dosing adjustment/comments in hepatic disease: Unchanged in mild liver disease; substantial extrahepatic metabolism may occur; excessive sedation may occur in cirrhosis

Dietary Considerations

Alcohol: Additive CNS effects, avoid or limit alcohol; watch for sedation

Food:

Glucose may cause hyperglycemia; monitor blood glucose concentrations

Administration of oral morphine solution with food may increase bioavailability (ie, a report of 34% increase in morphine AUC when morphine oral solution followed a high-fat meal). Morphine may cause GI upset. Be consistent when taking morphine with or without meals. Take with food if GI upset.

Monitoring Parameters

Pain relief, respiratory and mental status, blood pressure

Reference Range

Therapeutic: Surgical anesthesia: 65-80 ng/mL (SI: 227-280 nmol/L); Toxic: 200-5000 ng/mL (SI: 700-17,500 nmol/L)

Mental Health: Effects on Mental Status

Sedation is common; may cause dizziness, restlessness, confusion; may rarely cause insomnia, depression, or hallucinations

Mental Health: Effects on Psychiatric Treatment

Concurrent use with psychotropics may produce an increase of decrease in morphine's effect; monitor for clinical changes

Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health: Effects on Dental Treatment

>10% of patients experience dry mouth; anticholinergic side effects can cause a reduction of saliva production or secretion contributes to discomfort and dental disease (ie, caries, oral candidiasis and periodontal disease)

Patient Information

If self-administered, use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. While using this medication, do not use alcohol and other prescription or OTC medications (especially sedatives, tranquilizers, antihistamines, or pain medications) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause hypotension, dizziness, drowsiness, impaired coordination, or blurred vision (use caution when driving, climbing stairs, or changing position - rising from sitting or lying to standing, or when engaging in tasks requiring alertness until response to drug is known); loss of appetite, nausea, or vomiting (frequent mouth care, small frequent meals, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help - if constipation remains an unresolved problem, consult prescriber about use of stool softeners). Report chest pain, slow or rapid heartbeat, acute dizziness, or persistent headache; changes in mental status; swelling of extremities or unusual weight gain; changes in urinary elimination or pain on urination; acute headache; back or flank pain or muscle spasms; blurred vision; skin rash; or shortness of breath. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. If you are breast-feeding, take medication immediately after breast-feeding or 3-4 hours prior to next feeding.

Nursing Implications

Do not crush controlled release drug product, observe patient for excessive sedation, respiratory depression; implement safety measures, assist with ambulation; use preservative-free solutions for intrathecal or epidural use

Dosage Forms

Capsule (MSIR®): 15 mg, 30 mg

Capsule, sustained release (Kadian®): 20 mg, 50 mg, 100 mg

Injection: 0.5 mg/mL (10 mL); 1 mg/mL (10 mL, 30 mL, 60 mL); 2 mg/mL (1 mL, 2 mL, 60 mL); 3 mg/mL (50 mL); 4 mg/mL (1 mL, 2 mL); 5 mg/mL (1 mL, 30 mL); 8 mg/mL (1 mL, 2 mL); 10 mg/mL (1 mL, 2 mL, 10 mL); 15 mg/mL (1 mL, 2 mL, 20 mL); 25 mg/mL (4 mL, 10 mL, 20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL, 40 mL)

Injection:

Preservative free (Astramorph® PF, Duramorph®): 0.5 mg/mL (2 mL, 10 mL); 1 mg/mL (2 mL, 10 mL); 10 mg/mL (20 mL); 25 mg/mL (20 mL)

I.V. via PCA pump: 1 mg/mL (10 mL, 30 mL, 60 mL); 5 mg/mL (30 mL)

I.V. infusion preparation: 25 mg/mL (4 mL, 10 mL, 20 mL)

Solution, oral: 10 mg/5 mL (5 mL, 10 mL, 100 mL, 120 mL, 500 mL); 20 mg/5 mL (5 mL, 100 mL, 120 mL, 500 mL)

MSIR®: 10 mg/5 mL (5 mL, 120 mL, 500 mL); 20 mg/5 mL (5 mL 120 mL, 500 mL); 20 mg/mL (30 mL, 120 mL)

MS/L®: 100 mg/5 mL (120 mL) 20 mg/5 mL

OMS®: 20 mg/mL (30 mL, 120 mL)

Roxanol®: 10 mg/2.5 mL (2.5 mL); 20 mg/mL (1 mL, 1.5 mL, 30 mL, 120 mL, 240 mL)

Suppository, rectal: 5 mg, 10 mg, 20 mg, 30 mg

MS/S®, RMS®, Roxanol®: 5 mg, 10 mg, 20 mg, 30 mg

Tablet: 15 mg, 30 mg

MSIR®: 15 mg, 30 mg

Controlled release:

MS Contin®: 15 mg, 30 mg, 60 mg, 100 mg, 200 mg

Roxanol® SR: 30 mg

Soluble: 10 mg, 15 mg, 30 mg

Sustained release (Oramorph SR®): 30 mg, 60 mg, 100 mg

References

Berde C, Ablin A, Glazer J, et al, "American Academy of Pediatrics Report of the Subcommittee on Disease-Related Pain in Childhood Cancer," Pediatrics, 1990, 86(5 Pt 2):818-25.

Brunk SF and Delle M, "Morphine Metabolism in Man," Clin Pharmacol Ther, 1974, 16(1):51-7.

Capogna G, Celleno D, Zangrillo A, et al, "Addition of Clonidine to Epidural Morphine Enhances Postoperative Analgesia After Cesarean Delivery," Reg Anesth, 1995, 20(1):57-61.

Dampier CD, Setty BN, Logan J, et al, "Intravenous Morphine Pharmacokinetics in Pediatric Patients With Sickle Cell Disease," J Pediatr, 1995, 126(3):461-7.

"Drugs for Pain," Med Lett Drugs Ther, 1998, 40(1033):79-84.

Duthie DJ and Nimmo WS, "Adverse Effects of Opioid Analgesic Drugs," Br J Anaesth, 1987, 59(1):61-77.

Ferrell BA, "Pain Management in Elderly People," J Am Geriatr Soc, 1991, 39(1):64-73.

Gerber N and Apseloff G, "Death From a Morphine Infusion During a Sickle Cell Crisis," J Pediatr, 1993, 123(2):322-5.

Groudine SB, Cresanti-Daknis C, and Lumb PD, "Successful Treatment of a Massive Intrathecal Morphine Overdose," Anesthesiology, 1995, 82(1):292-5.

Henneberg SW, Hole P, Madsen de Haas I, et al, "Epidural Morphine for Postoperative Pain Relief in Children," Acta Anaesthesiol Scand, 1993, 37(7):664-7.

Henry J and Volans G, "ABC of Poisoning. Analgesics: Opioids," Br Med J (Clin Res Ed), 1984, 289(6450):990-3.

Holdsworth MT, Adams VR, Chavez CM, et al, "Continuous Midazolam Infusion for the Management of Morphine-Induced Myoclonus," Ann Pharmacother, 1995, 29(1):25-9.

Inturrisi CE, "Narcotic Drugs," Med Clin North Am, 1982, 66(5):1061-71.

June HL, Stitzer ML, and Cone E, "Acute Physical Dependence: Time Course and Relation to Human Plasma Morphine Concentrations," Clin Pharmacol Ther, 1995, 57(3):270-80.

Kaiko RF, "Age and Morphine Analgesia in Cancer Patients With Postoperative Pain," Clin Pharmacol Ther, 1980, 28(6):823-6.

Kaiko RF, Wallenstein SL, Rogers AG, et al, "Narcotics in the Elderly," Med Clin North Am, 1982, 66(5):1079-89.

McRorie TI, Lynn AM, Nespeca MK, et al, "The Maturation of Morphine Clearance and Metabolism," Am J Dis Child, 1992, 147(8):972-6.

Olkkola KT, Hamunen K, and Maunuksela EL, "Clinical Pharmacokinetics and Pharmacodynamics of Opioid Analgesics in Infants and Children," Clin Pharmacokinet, 1995, 28(5):385-404.

Schug SA, Zech D, and Grond S, "Adverse Effects of Systemic Opioid Analgesics," Drug Saf, 1992, 7(3):200-13.

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