In addition to NARCAN (naloxone) , other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary to counteract acute opioid poisoning.
Abrupt postoperative reversal of opioid depression may result in nausea, vomiting,
sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular
tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may
result in death. Excessive doses of NARCAN (naloxone) in postoperative patients may result
in significant reversal of analgesia and may cause agitation (see PRECAUTIONS
and DOSAGE AND ADMINISTRATION; Usage in Adults-Postoperative
Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest have been reported in postoperative patients. Death, coma, and encephalopathy have been reported as sequelae of these events. These have occurred in patients most of whom had pre-existing cardiovascular disorders or received other drugs which may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, NARCAN (naloxone) should be used with caution in patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects, such as hypotension, ventricular tachycardia or fibrillation, and pulmonary edema. It has been suggested that the pathogenesis of pulmonary edema associated with the use of NARCAN (naloxone) is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies in animals to assess the carcinogenic potential of NARCAN (naloxone) have not
been conducted. NARCAN (naloxone) was weakly positive in the Ames mutagenicity and in the
in vitro human lymphocyte chromosome aberration test but was negative
in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and
in the in vivo rat bone marrow chromosome aberration study. Reproduction
studies conducted in mice and rats at doses 4-times and 8-times, respectively,
the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m2),
demonstrated no embryotoxic or teratogenic effects due to NARCAN (naloxone) .
Use in Pregnancy
Teratogenic Effects: Pregnancy Category C: Teratology studies
conducted in mice and rats at doses 4-times and 8-times, respectively, the dose
of a 50 kg human given 10 mg/day (when based on surface area or mg/m2),
demonstrated no embryotoxic or teratogenic effects due to NARCAN (naloxone) . There are,
however, no adequate and well-controlled studies in pregnant women. Because
animal reproduction studies are not always predictive of human response, NARCAN (naloxone)
should be used during pregnancy only if clearly needed.
Non-teratogenic Effects: Risk-benefit must be considered before
NARCAN (naloxone) is administered to a pregnant woman who is known or suspected to be opioid-dependent
since maternal dependence may often be accompanied by fetal dependence. Naloxone
crosses the placenta, and may precipitate withdrawal in the fetus as well as
in the mother. Patients with mild to moderate hypertension who receive naloxone
during labor should be carefully monitored as severe hypertension may occur.
Use in Labor and Delivery
It is not known if NARCAN (naloxone) affects the duration of labor and/or delivery. However, published reports indicated that administration of naloxone during labor did not adversely affect maternal or neonatal status.
It is not known whether NARCAN (naloxone) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NARCAN (naloxone) is administered to a nursing woman.
NARCAN (naloxone hydrochloride injection, USP) may be administered intravenously,
intramuscularly or subcutaneously in children and neonates to reverse the effects
of opiates. The American Academy of Pediatrics, however, does not endorse subcutaneous
or intramuscular administration in opiate intoxication since absorption may
be erratic or delayed. Although the opiate-intoxicated child responds dramatically
to NARCAN (naloxone) , he/she must be carefully monitored for at least 24 hours as a relapse
may occur as naloxone is metabolized.
When NARCAN (naloxone) is given to the mother shortly before delivery, the duration of
its effect lasts only for the first two hours of neonatal life. It is preferable
to administer NARCAN (naloxone) directly to the neonate if needed after delivery. NARCAN (naloxone)
has no apparent benefit as an additional method of resuscitation in the newly
born infant with intrauterine asphyxia which is not related to opioid use.
Usage in Pediatric Patients and Neonates for Septic Shock: The
safety and effectiveness of NARCAN (naloxone) in the treatment of hypotension in pediatric
patients and neonates with septic shock have not been established. One study
of two neonates in septic shock reported a positive pressor response; however,
one patient subsequently died after intractable seizures.
Clinical studies of NARCAN (naloxone) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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.
The safety and effectiveness of NARCAN (naloxone) in patients with renal insufficiency/failure have not been established in well-controlled clinical trials. Caution should be exercised when NARCAN (naloxone) is administered to this patient population
The safety and effectiveness of NARCAN (naloxone) in patients with liver disease have not been established in well-controlled clinical trials. Caution should be exercised when NARCAN (naloxone) is administered to patients with liver disease.