necessary, since the duration of action of some opioids may exceed that of naloxone hydrochloride. respiratory depression due to other drugs naloxone hydrochloride is not effective against respiratory depression due to non-opioid drugs and in the management of acute toxicity caused by levopropoxyphene. reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone. if an incomplete response occurs, respirations should be mechanically assisted as clinically indicated.

of these events. these have occurred in patients most of whom had preexisting 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 hydrochloride should be used with caution in patients with preexisting 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 naloxone hydrochloride 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.

ain 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. 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 are 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 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 ventilationand 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 i.v. 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 l.v. route of administration is not available, naloxone may be administered i.m. or s.c. 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 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. usage in neonates opioid-lnduced depression: the usual initial dose is 0.01 mg/kg body weight administered i.v., i.m., or s.c. this dose may be repeated in accordance with adult administration guidelines for postoperative opioid depression.

drawal 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; hyperactive reflexes (see warnings ). adverse events associated with the postoperative use of naloxone hydrochloride 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 ; usage in adults; postoperative opioid depression .

itored as severe hypertension may occur.

tric patients and neonates for septic shock: the safety and effectiveness of naloxone hydrochloride 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.

de administration and subside in about 2 hours. the severity and duration of the withdrawal syndrome are related to the dose of naloxone hydrochloride and to the degree and type of opioid dependence. while the mechanism of action of naloxone hydrochloride is not fully understood, in vitro evidence suggests that naloxone hydrochloride 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 naloxone hydrochloride 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 naloxone hydrochloride. intramuscular administration produces a more prolonged effect than intravenous administration. since the duration of action of naloxone hydrochloride may be shorter than that of some opiates, the effect of the opiate may return as the effects of naloxone hydrochloride dissipates. the requirement for repeat doses of naloxone hydrochloride will also be dependent upon the amount, type and route of administration of the opioid being antagonized. adjunctive use in septic shock naloxone hydrochloride 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 naloxone hydrochloride 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 naloxone hydrochloride 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.