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Pronunciation |
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(MOR
feen SUL
fate) |
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U.S. Brand
Names |
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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 |
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Generic
Available |
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Yes |
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Canadian Brand
Names |
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Epimorph®; M-Eslon®;
Morphine-HP®; MS-IR®; MST Continus;
Statex® |
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Synonyms |
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MS |
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Pharmacological Index |
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Analgesic, Narcotic |
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Use |
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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 |
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Restrictions |
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C-II |
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Pregnancy Risk
Factor |
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B/D (if used for prolonged periods or in high doses at
term) |
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Contraindications |
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Known hypersensitivity to morphine sulfate; increased intracranial pressure;
severe respiratory depression |
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Warnings/Precautions |
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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. |
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Adverse
Reactions |
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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 |
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Overdosage/Toxicology |
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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. |
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Drug
Interactions |
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CYP2D6 enzyme substrate
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 |
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Stability |
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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 |
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Mechanism of
Action |
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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 |
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Pharmacodynamics/Kinetics |
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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 |
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Usual Dosage |
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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
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:
Clcr 10-50 mL/minute: Administer at 75% of normal dose
Clcr <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 |
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Dietary
Considerations |
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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.
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Monitoring
Parameters |
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Pain relief, respiratory and mental status, blood
pressure |
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Reference Range |
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Therapeutic: Surgical anesthesia: 65-80 ng/mL (SI: 227-280 nmol/L); Toxic:
200-5000 ng/mL (SI: 700-17,500 nmol/L) |
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Mental Health: Effects
on Mental Status |
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Sedation is common; may cause dizziness, restlessness, confusion; may rarely
cause insomnia, depression, or hallucinations |
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Mental Health:
Effects on Psychiatric
Treatment |
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Concurrent use with psychotropics may produce an increase of decrease in
morphine's effect; monitor for clinical changes |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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>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) |
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Patient
Information |
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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. |
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Nursing
Implications |
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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 |
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Dosage Forms |
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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
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References |
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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,
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Gerber N and Apseloff G,
"Death From a Morphine Infusion During a Sickle Cell Crisis," J Pediatr,
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Groudine SB, Cresanti-Daknis C, and Lumb PD,
"Successful Treatment of a Massive Intrathecal Morphine Overdose,"
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"Epidural Morphine for Postoperative Pain Relief in Children," Acta
Anaesthesiol Scand, 1993, 37(7):664-7.
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Holdsworth MT, Adams VR, Chavez CM, et al,
"Continuous Midazolam Infusion for the Management of Morphine-Induced Myoclonus,"
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Inturrisi CE, "Narcotic Drugs," Med Clin North Am, 1982,
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June HL, Stitzer ML, and Cone E,
"Acute Physical Dependence: Time Course and Relation to Human Plasma Morphine Concentrations,"
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Kaiko RF,
"Age and Morphine Analgesia in Cancer Patients With Postoperative Pain," Clin
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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,
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Olkkola KT, Hamunen K, and Maunuksela EL,
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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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