OVERDOSAGE
Symptoms
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, pulmonary
edema, bradycardia, hypotension and death. Marked mydriasis rather than miosis
may be seen due to severe hypoxia in overdose situations.
Treatment
Primary attention should be given to the re-establishment of a
patent airway and institution of assisted or controlled ventilation. Gastric
contents may need to be emptied to remove unabsorbed drug when an
extended-release formulation such as KADIAN® has been
taken. Care should be taken to secure the airway before attempting treatment by
gastric emptying or activated charcoal.
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.
The pure opioid antagonists, naloxone or nalmefene, are specific antidotes to
respiratory depression which results from opioid overdose. Since the duration
of reversal would be expected to be less than the duration of action of
KADIAN®, the patient must be carefully monitored until
spontaneous respiration is reliably re-established. KADIAN® will continue to release and add to the morphine load for up
to 24 hours after administration and the management of an overdose should be
monitored accordingly. If the response to opioid antagonists is suboptimal or
not sustained, additional antagonist should be given as directed by the
manufacturer of the product.
Opioid antagonists should not be administered in the absence of clinically
significant respiratory or circulatory depression secondary to morphine
overdose. Such agents should be administered cautiously to persons who are
known, or suspected to be physically dependent on KADIAN®. In such cases, an abrupt or complete reversal of opioid
effects may precipitate an acute abstinence syndrome.
Opioid Tolerant Individuals: In an individual
physically dependent on opioids, administration of the usual dose of the
antagonist will precipitate an acute withdrawal. The severity of the withdrawal
produced will depend on the degree of physical dependence and the dose of the
antagonist administered. Use of an opioid antagonist should be reserved for
cases where such treatment is clearly needed. If it is necessary to treat
serious respiratory depression in the physically dependent patient,
administration of the antagonist should be begun with care and by titration with
smaller than usual doses of the antagonist.
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