Numorphan (Oxymorphone Hydrochloride) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug Interactions

The concomitant use of other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, and alcohol may produce additive CNS depressant effects. When such combined therapy is contemplated, the dose of one or both agents should be reduced (see WARNINGS).

Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

It has been reported that the incidence of bradycardia was increased when oxymorphone was combined with propofol for induction of anesthesia.

In addition, CNS toxicity has been reported (confusion, disorientation, respiratory depression, apnea, seizures) following coadministration of cimetidine with opioid analgesics; no clear-cut cause and effect relationship was established.

OVERDOSAGE

Signs and Symptoms

Serious overdosage with NUMORPHAN is characterized by respiratory depression, (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

Treatment

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride (NARCAN^®) is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids including oxymorphone. Therefore, an appropriate dose of naloxone hydrochloride should be administered (usual initial adult dose 0.4 mg-2 mg) preferably by the intravenous route and simultaneously with efforts at respiratory resuscitation. Since the duration of action of oxymorphone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.

Naloxone hydrochloride should not be administered in the absence of clinically significant respiratory or cardiovascular depression. In addition, it should be considered that the use of an opioid antagonist in patients physically dependent on opioids may precipitate an acute withdrawal syndrome that cannot be readily suppressed while the action of the antagonist persists. If respiratory depression is associated with muscular rigidity, administration of a neuromuscular blocking agent may be necessary to facilitate assisted or controlled ventilation. Muscular rigidity may also respond to opioid antagonist therapy.

Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.

CONTRAINDICATIONS

NUMORPHAN should not be administered to patients who are hypersensitive to oxymorphone hydrochloride or to any of the other ingredients in NUMORPHAN, or hypersensitive to morphine analogs.

NUMORPHAN should not be administered to individuals during an acute asthmatic attack or to patients with severe respiratory depression, upper airway obstruction, or any patient who has or is suspected of having a paralytic ileus. NUMORPHAN should not be used in the treatment of pulmonary edema secondary to a chemical respiratory irritant. Opioid analgesics cause pooling of blood in the extremities by decreasing peripheral vascular resistance. This effect results in decreases in venous return, cardiac work, and pulmonary venous pressure, and blood is shifted from the central to peripheral circulation which would not be beneficial in the treatment of pulmonary edema secondary to a chemical respiratory irritant.