DRUG INTERACTIONS Drug Interactions
(See also: WARNINGS)
The concomitant use of other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers and alcohol may produce additive depressant effects. Respiratory depression, hypotension and profound sedation or coma may occur. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Opioid analgesics, including morphine sulfate extended-release tablets, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
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OVERDOSAGE
Acute overdosage with morphine is manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, sometimes, bradycardia and hypotension.
In the treatment of overdosage, primary attention should be given to the re-establishment of a patent airway and institution of assisted or controlled ventilation. The pure opioid antagonist, naloxone, is a specific antidote against respiratory depression which results from opioid overdose. Naloxone (usually 0.4 to 2.0 mg) should be administered intravenously; however, because its duration of action is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. If the response to naloxone is suboptimal or not sustained, additional naloxone may be re-administered, as needed, or given by continuous infusion to maintain alertness and respiratory function; however, there is no information available about the cumulative dose of naloxone that may be safely administered.
Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to morphine overdose. Naloxone should be administered cautiously to persons who are known, or suspected to be physically dependent on morphine sulfate extended-release tablets. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome.
Note: In an individual physically dependent on opioids, administration of the usual dose of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered. Use of an opioid antagonist in such a person should be avoided. If necessary to treat serious respiratory depression in the physically dependent patient, the antagonist should be administered with care and by titration with smaller than usual doses of the antagonist.
Supportive measures (including oxygen, vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.
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CONTRAINDICATIONS
Morphine sulfate extended-release tablets are contraindicated in patients with known hypersensitivity to morphine, or any other component of this product, in patients with respiratory depression in the absence of resuscitative equipment, and in patients with acute or severe bronchial asthma.
Morphine sulfate extended-release tablets are contraindicated in any patient who has or is suspected of having a paralytic ileus.
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