Morphine (Pf) (morphine sulfate)

To relieve pain in adults with ST-segment-elevation myocardial infarction (STEMI), an initial morphine sulfate dose of 2-4 mg IV is recommended; additional doses of 2-8 mg may be administered every 5-15 minutes as needed. In patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS) who continue to experience pain despite maximally tolerated anti-ischemic therapy, experts state that a morphine sulfate dose of 1-5 mg IV may be administered during IV nitroglycerin therapy; additional doses may be given every 5-30 minutes to relieve symptoms and maintain patient comfort.

For the management of neonatal opiate abstinence syndrome+, use of protocols that base initiation, adjustment, and tapering of morphine sulfate dosage on standardized patient assessments performed at regular intervals is recommended. The most commonly used tool for assessing severity of withdrawal in term neonates is the Finnegan scoring system (original or modified versions) performed every 3-4 hours. Treatment protocols vary in recommended dosages, thresholds for initiation of therapy, incremental changes and thresholds for dosage adjustment, and tapering strategies.

Under various protocols, treatment with morphine sulfate oral solution is initiated at a dosage of 0.04-0.05 mg/kg every 3-4 hours based on Finnegan score (e.g., score exceeds 8 on at least 2 or 3 occasions, the sum of 3 consecutive scores is 24 or greater, a single score or 2 consecutive scores are 12 or greater); under other protocols, initial dosage may vary depending on the severity of withdrawal manifestations, with higher initial dosages recommended for neonates with higher Finnegan scores. Some clinicians state that initial dosage usually ranges from 0.03-0.1 mg/kg every 3-4 hours. If Finnegan score remains elevated (e.g., a single score or 2 consecutive scores are 12 or greater, 2 consecutive scores are 8 or greater, the sum of 3 scores is 24 or greater), dosage may be increased, generally by 0.02-0.05 mg/kg per dose or by 10-20% depending on the protocol and/or Finnegan score, to achieve stabilization. Some clinicians have recommended a usual maximum dosage of 1.2-1.3 mg/kg daily or 0.2 mg/kg per dose. Once patients are stable (generally, no score exceeds 8 ) for at least 48 hours, morphine sulfate dosage typically is tapered in decrements of approximately 0.02 mg/kg per dose or approximately 10% of the highest (stabilization) dose at intervals of approximately 24-48 hours. Protocols vary in terms of the dosage at which morphine sulfate can be discontinued. However, neonates should be monitored for at least 48 hours after the drug has been discontinued. Specialized protocols should be consulted for further information on morphine sulfate dosage and monitoring of Finnegan scores in neonates with opiate abstinence syndrome. Further study is needed to define optimal dosing strategies.

Morphine sulfate should be given at the lowest effective dosage and for the shortest duration of therapy consistent with the treatment goals of the patient.

Titrate the dose based on the individual patient's response to their initial dose of morphine sulfate to a dose that provides adequate analgesia and minimizes adverse reactions. Continually re-evaluate patients to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions as well as to reassess for the development of addiction, abuse, or misuse.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Morphine sulfate is administered by the oral, rectal, IV, IM, intrathecal, or epidural routes.

No dosing information is available for this tab.

No dosing information is available for this tab.

Morphine is not significantly metabolized by cytochrome P-450 (CYP) isoenzyme 3A4; the drug does not induce or inhibit CYP enzymes. Morphine is a substrate of the efflux transporter P-glycoprotein (P-gp). Morphine is mainly metabolized by UDP-glucuronosyltransferases (UGTs) with a specific affinity for the UGT2B7 isoenzyme.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Significant respiratory depression.

*Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.

*Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days.

*Known or suspected GI obstruction, including paralytic ileus.

*Hypersensitivity to morphine (e.g., anaphylaxis).

*Neuraxial administration of morphine sulfate injection (Duramorph(R)) in patients with infection at the injection microinfusion site, concomitant anticoagulant therapy, uncontrolled bleeding diathesis, or the presence of any other concomitant therapy or medical condition which would render epidural or intrathecal administration especially hazardous.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Common adverse effects reported in adults receiving morphine include constipation, nausea, somnolence, lightheadedness, dizziness, sedation, vomiting, headache, and sweating. Serious adverse effects include apnea, circulatory depression, respiratory depression or arrest, shock, and cardiac arrest.

Common adverse effects reported in pediatric patients (>5%) receiving morphine include nausea, vomiting, constipation, decreased oxygen saturation, and flatulence.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and effectiveness of morphine in pediatric patients vary based on the route of administration and characteristics of the preparation.

The safety and effectiveness of immediate-release morphine sulfate tablets administered orally have been established for the management of pediatric patients weighing at least 50 kg with acute pain severe enough to require an opioid analgesic when alternative treatments are inadequate. Use of the immediate-release tablets in this age group is supported by clinical evidence in adults and supportive data from an open-label, safety and pharmacokinetic study in pediatric patients 2 through 17 years of age with postoperative acute pain. The safety and effectiveness of immediate-release morphine sulfate tablets have not been established in pediatric patients weighing less than 50 kg because the recommended dosage cannot be achieved with available tablet strengths. Consider use of another morphine sulfate product in patients who cannot swallow oral tablets or who weigh less than 50 kg.

The safety and effectiveness of morphine sulfate oral solution (2 mg/mL and 4 mg/mL) have been established for the management of pediatric patients 2 to 17 years of age with acute pain severe enough to require an opioid analgesic when alternative treatments are inadequate. The safety and effectiveness of the oral solution have not been established in pediatric patients younger than 2 years of age. The safety and effectiveness of morphine sulfate oral solution 20 mg/mL have not been established in pediatric patients. The safety and effectiveness of morphine sulfate oral solution have not been established for the management of pediatric patients 2 years of age and older with chronic pain severe enough to require an opioid analgesic when alternative treatments are inadequate.

The safety and effectiveness of continuous IV infusion of morphine have been established for the management of pain in pediatric patients of all age groups. Such use is supported by evidence from randomized controlled studies in pediatricpatients. Monitor cardiorespiratory function in children younger than 3 months of age. Adjust the infusion rate based on clinical signs of inadequate pain relief and/or increased somnolence. For premature infants and former premature infants with chronic lung disease and up to 5 to 6 months of age, careful monitoring for depressed hypoxic drive is required following continuous IV infusion of the opioid.

Safety and efficacy of morphine sulfate suppositories in pediatric patients have not been established.

Safety and efficacy of epidural or intrathecal injection of morphine in pediatric patients have not been established and such injections are not recommended. Safety and efficacy of patient-controlled analgesia (PCA) have not been established in pediatric patients.

Safety and efficacy of morphine sulfate extended-release capsules in children younger than 18 years of age have not been established. In addition, the manufacturers state that commercially available strengths of morphine sulfate extended-release capsules are not appropriate for children and that the contents of the capsules should not be sprinkled onto applesauce for administration to children.

Safety and efficacy of morphine sulfate extended-release tablets in children have not been established.

There are no available data with morphine use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Clinical studies of morphine use during pregnancy have not reported a clear association between morphine and major birth defects. Based on findings from animal studies, advise pregnant women of the potential risk to a fetus.

Opioids cross the 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 the neonate. Morphine 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, including morphine, can prolong labor through actions that temporarily reduce the 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 may shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excessive sedation and respiratory depression.

Use of opioid analgesics for an extended period during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly.

Morphine should be used with caution in nursing women, since the drug has been reported to distribute into human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for morphine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. Because of the potential for serious adverse reactions, including excessive sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with morphine sulfate extended-release capsules or tablets.

Monitor infants exposed to morphine 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.

Elderly patients (65 years of age or older) may have increased sensitivity to morphine. In general, use caution when selecting a dose for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Titrate the dosage of morphine sulfate slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression.

The pharmacodynamic effects of neuraxial morphine in the elderly are more variable than in the younger population. Patients will vary widely in the effective initial dose, rate of development of tolerance and the frequency and magnitude of associated adverse effects as the dosage is increased. Initial doses should be based on careful clinical observation following "test doses", after making allowances for the effects of the patient's age and infirmity on his/her ability to clear the drug, particularly in patients receiving epidural morphine.

Patients 65 years of age or older may have increased sensitivity to morphine. In general, use caution when selecting dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the main risk for geriatric patients treated with opioids and has occurred after administration of large initial doses in patients who were not opioid-tolerant or when opioids were co-administered with other drugs that depress respiration. Titrate the dosage of morphine sulfate slowly in geriatric patients and frequently reevaluate the patient for signs of CNS and respiratory depression.

Morphine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; regular evaluation of renal function should occur.