Following parenteral administration, 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
Naloxone is metabolized in the liver primarily by glucuronide conjugation with naloxone-3-glucuronide 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.
USAGE IN ADULTS
Opioid Overdose – Known or Suspected: An initial dose of 0.4 mg to 2 mg of naloxone hydrochloride may be administered intravenously. If the desired degree of counteraction and improvement in respiratory functions is not obtained, it may be repeated at two to three minute intervals. If no response is observed after 10 mg of naloxone hydrochloride have been administered, the diagnosis of opioid-induced or partial opioid-induced toxicity should be questioned. Intramuscular or subcutaneous administration may be necessary if the intravenous route is not available.
Postoperative Opioid-Induced Depression: For the partial reversal of opioid depression following the use of opioids during surgery, smaller doses of naloxone hydrochloride are usually sufficient. The dose of naloxone hydrochloride should be titrated according to the patient's response. For the initial reversal of respiratory depression, naloxone hydrochloride should be injected in increments of 0.1 to 0.2 mg intravenously at two to three minute intervals to the desired degree of reversal, i.e., adequate ventilation and alertness without significant pain or discomfort. Larger than necessary dosage of naloxone may result in significant reversal of analgesia and increase in blood pressure. Similarly, too rapid reversal may induce nausea, vomiting, sweating or circulatory stress.
Repeat doses of naloxone may be required within one to two hour intervals depending upon the amount, type (i.e., short or long acting) and time interval since last administration of opioid. Supplemental intramuscular doses have been shown to produce a longer lasting effect.
Septic Shock: The optimal dosage of naloxone hydrochloride or duration of therapy for the treatment of hypotension in septic shock patients has not been established (see CLINICAL PHARMACOLOGY).
USAGE IN CHILDREN
Opioid Overdose – Known or Suspected: The usual initial dose in children is 0.01 mg/kg body weight given intravenously. If this dose does not result in the desired degree of clinical improvement, a subsequent dose of 0.1 mg/kg body weight may be administered. If an intravenous route of administration is not available, naloxone may be administered intramuscularly or subcutaneously in divided doses. If necessary, naloxone hydrochloride injection can be diluted with sterile water for injection.
Postoperative Opioid Depression: Follow the recommendations and cautions under Adult Postoperative Opioid Depression. For the initial reversal of respiratory depression naloxone hydrochloride should be injected in increments of 0.005 mg to 0.01 mg intravenously at two to three minute intervals to the desired degree of reversal.