Description: Naloxone hydrochloride, a narcotic antagonist, is a synthetic congener of oxymorphone.  Naloxone hydrochloride occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform. Naloxone Hydrochloride Injection is available as a non-preserved sterile solution for intravenous, intramuscular or subcutaneous administration in 1 mg/mL concentration.

Pharmacological effects: Naloxone hydrochloride prevents or reverses the effects of opioids, including respiratory depression, sedation, and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonist such as pentazocine. Naloxone hydrochloride is an essentially pure narcotic antagonist, i.e., it does not possess the “agonistic” or morphine-like properties characteristic of other narcotic antagonists; naloxone does not produce respiratory depression, psychotomimetic effects or pupillary constriction. In the absence of narcotics or agonistic effects of other narcotic antagonists it exhibits essentially no pharmacologic activity. Naloxone has not been shown to produce tolerance nor to cause physical or psychological dependence. In the presence of physical dependence on narcotics naloxone will produce withdrawal symptoms. The preponderance of evidence suggests that naloxone antagonizes the opioid effects by competing for the same receptor sites. When naloxone hydrochloride is administered intravenously the onset of action is generally apparent within two minutes; the onset of action is only slightly less rapid when it is administered subcutaneously or intramuscularly. The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride. Intramuscular administration produces a more prolonged effect than intravenous administration. The requirement for repeat doses of naloxone, however, will also be dependent upon the amount, type and route of administration of the narcotic being antagonized.

Pharmacokinetics: Following parenteral administration naloxone hydrochloride is rapidly distributed in the body. It is metabolized in the liver, primarily by glucuronide conjugation, and excreted in urine. 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.

Indications: Naloxone hydrochloride injection is indicated for the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids including natural and synthetic narcotics, propoxyphene, methadone and certain narcotic-antagonist analgesics: nalbuphine, pentazocine and butorphanol. Naloxone hydrochloride is also indicated for the diagnosis of suspected acute opioid overdosage.

Precautions: In addition to 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 narcotic poisoning. Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been reported. These have occurred in postoperative 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, naloxone should be used with caution in patients with pre-existing cardiac disease or patients who have received potentially cardiotoxic drugs.

Adverse reaction: Abrupt reversal of narcotic depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures and cardiac arrest. In postoperative patients, Iarger than necessary dosages of naloxone hydrochloride may result in significant reversal of analgesia, and in excitement. Hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been associated with the use of naloxone postoperatively.