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Complete or Partial Reversal of Opioid Depression
NARCAN (naloxone) prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, NARCAN (naloxone) can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
NARCAN (naloxone) is an essentially pure opioid antagonist, i.e., it does not possess the "agonistic" or morphine-like properties characteristic of other opioid antagonists. When administered in usual doses and in the absence of opioids or agonistic effects of other opioid antagonists, it exhibits essentially no pharmacologic activity.
NARCAN (naloxone) has not been shown to produce tolerance or cause physical or psychological dependence. In the presence of physical dependence on opioids, NARCAN (naloxone) will produce withdrawal symptoms. However, in the presence of opioid dependence, opiate withdrawal symptoms may appear within minutes of NARCAN (naloxone) administration and subside in about 2 hours. The severity and duration of the withdrawal syndrome are related to the dose of NARCAN (naloxone) and to the degree and type of opioid dependence.
While the mechanism of action of NARCAN (naloxone) is not fully understood, in vitro evidence suggests that NARCAN (naloxone) antagonizes opioid effects by competing for the µ, κ and σ opiate receptor sites in the CNS, with the greatest affinity for the µ receptor.
When NARCAN (naloxone) is administered intravenously (I.V.), the onset of action is generally apparent within two minutes. The onset of action is slightly less rapid when it is administered subcutaneously (S.C.) or intramuscularly (I.M.). The duration of action is dependent upon the dose and route of administration of NARCAN (naloxone) . Intramuscular administration produces a more prolonged effect than intravenous administration. Since the duration of action of NARCAN (naloxone) may be shorter than that of some opiates, the effects of the opiate may return as the effects of NARCAN (naloxone) dissipates. The requirement for repeat doses of NARCAN (naloxone) will also be dependent upon the amount, type and route of administration of the opioid being antagonized.
Adjunctive Use in Septic Shock
NARCAN (naloxone) has been shown in some cases of septic shock to produce a rise in blood pressure that may last up to several hours; however, this pressor response has not been demonstrated to improve patient survival. In some studies, treatment with NARCAN (naloxone) in the setting of septic shock has been associated with adverse effects, including agitation, nausea and vomiting, pulmonary edema, hypotension, cardiac arrhythmias, and seizures. The decision to use NARCAN (naloxone) in septic shock should be exercised with caution, particularly in patients who may have underlying pain or have previously received opioid therapy and may have developed opioid tolerance.
Because of the limited number of patients who have been treated, optimal dosage and treatment regimens have not been established.
Following parenteral administration, NARCAN (naloxone) is rapidly distributed in the body and readily crosses the placenta. Plasma protein binding occurs but is relatively weak. Plasma albumin is the major binding constituent but significant binding of naloxone also occurs to plasma constituents other than albumin. It is not known whether naloxone is excreted into human milk.
Metabolism and Elimination
NARCAN (naloxone) is metabolized in the liver, primarily by glucuronide conjugation with naloxone-3-glucoronide as the major metabolite. In one study the serum half-life in adults ranged from 30 to 81 minutes (mean 64 ± 12 minutes). In a neonatal study the mean plasma half-life was observed to be 3.1 ± 0.5 hours. After an oral or intravenous dose, about 25-40% of the drug is excreted as metabolites in urine within 6 hours, about 50% in 24 hours, and 60-70% in 72 hours.
Last reviewed on RxList: 3/20/2009
This monograph has been modified to include the generic and brand name in many instances.
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