NALOXONE HYDROCHLORIDE

Naloxone hydrochloride, an opioid antagonist, is a synthetic congener of oxymorphone. In structure it differs from oxymorphone in that the methyl group on the nitrogen atom is replaced by an allyl group. It is known chemically as 17-allyl-4,5α-epoxy,3-14-dihydroxymorphinan-6-one hydrochloride. It has a molecular weight of 363.84, and the following structural formula: 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 sterile solution for intravenous, intramuscular, and subcutaneous administration. Each mL contains 0.4 mg of naloxone hydrochloride. Each mL contains 8.9 mg of sodium chloride. The pH is adjusted between 3.0 to 6.5 with hydrochloric acid or sodium hydroxide. The air in the cartridges has been displaced by nitrogen gas. STRUCTURE

INDICATIONS & USAGE Naloxone hydrochloride injection is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids including propoxyphene, methadone, and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine, butorphanol, and cyclazocine. Naloxone hydrochloride is also indicated for the diagnosis of suspected or known acute opioid overdosage. Naloxone hydrochloride injection may be useful as an adjunctive agent to increase blood pressure in the management of septic shock (see INDICATIONS & USAGE : Adjunctive Use in Septic Shock).

Naloxone hydrochloride injection may be administered intravenously, intramuscularly, or subcutaneously. The most rapid onset of action is achieved by intravenous administration and it is recommended in emergency situations. Since the duration of action of some opioids may exceed that of naloxone the patient should be kept under continued surveillance. Repeated doses of naloxone should be administered, as necessary. Intravenous Infusion Naloxone hydrochloride injection may be diluted for intravenous infusion in 0.9% sodium chloride or 5% dextrose injection. The addition of 2 mg of naloxone hydrochloride in 500 mL of either solution provides a concentration of 0.004 mg/mL. Mixtures should be used within 24 hours. After 24 hours, the remaining unused solution must be discarded. The rate of administration should be titrated in accordance with the patient's response. Naloxone hydrochloride injection should not be mixed with preparations containing bisulfite, metabisulfite, long-chain or high molecular weight anions, or any solution having an alkaline pH. No drug or chemical agent should be added to naloxone hydrochloride injection unless its effect on the chemical and physical stability of the solution has first been established. General Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Naloxone hydrochloride injection is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or any of the other ingredients contained in the formulation.

Postoperative The following adverse events have been associated with the use of naloxone hydrochloride injection in postoperative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION AND, USAGE IN ADULTS , Postoperative Opioid Depression). Opioid Depression Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may result in death (see PRECAUTIONS ). Opioid Dependence Abrupt reversal of opioid effects in persons who are physically dependent on opioids may precipitate an acute withdrawal syndrome which may include, but is not limited to the following signs and symptoms: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal may also include: convulsions, excessive crying, and hyperactive reflexes (see WARNINGS ). Adverse events associated with the postoperative use of naloxone hydrochloride injection are listed by organ system and in decreasing order of frequency as follows: Cardiac Disorders: pulmonary edema, cardiac arrest or failure, tachycardia, ventricular fibrillation, and ventricular tachycardia. Death, coma, and encephalopathy have been reported as sequelae of these events. Gastrointestinal Disorders: vomiting, nausea Nervous System Disorders: convulsions, paraesthesia, grand mal convulsion Psychiatric Disorders: agitation, hallucination, tremulousness Respiratory, Thoracic, and Mediastinal Disorders: dyspnea, respiratory depression, hypoxia Skin and Subcutaneous Tissue Disorders: nonspecific injection site reactions, sweating Vascular Disorders: hypertension, hypotension, hot flushes, or flushing See also PRECAUTIONS and DOSAGE AND ADMINISTRATION and USAGE IN ADULTS , Postoperative Opioid Depression.