Narcan naloxone hci

Overdose

There is limited clinical experience with Narcan Naloxone Hci overdosage in humans.

Adult Patients: In one study, volunteers and morphine-dependent subjects who received a single subcutaneous dose of 24mg/70kg did not demonstrate toxicity.

In another study, 36 patients with acute stroke received a loading dose of 4mg/kg (10mg/m2/min) of Narcan Naloxone Hci followed immediately by 2mg/kg/hr for 24 hours. There were a few reports of serious adverse events: seizures (2 patients), severe hypertension (1) and hypotension and/or bradycardia (3).

At doses of 2 mg/kg in normal subjects, memory impairment has been reported.

Paediatric Patients: Up to 11 doses of 0.2mg of Narcan Naloxone Hci (2.2mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulphate. Paediatric reports include a 2½ year old child who inadvertently received a dose of 20mg of Narcan Naloxone Hci and a 4½ year old child who received 11 doses during a 12-hour period, both of whom had no adverse sequelae.

Patient Management: Patients who experience a Narcan Naloxone Hci overdose should be treated symptomatically in a closely-supervised environment. Physicians should contact a poison control centre for the most up-to-date patient management information.

There is limited clinical experience with NARCAN (naloxone) overdosage in humans.

In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity.

In another study, 36 patients with acute stroke received a loading dose of 4 mg/kg (10 mg/m2/min) of NARCAN (naloxone) followed immediately by 2 mg/kg/hr for 24 hours. Twenty-three patients experienced adverse events associated with naloxone use, and naloxone was discontinued in seven patients because of adverse effects. The most serious adverse events were: seizures (2 patients), severe hypertension (1), and hypotension and/or bradycardia (3).

At doses of 2 mg/kg in normal subjects, cognitive impairment and behavioral symptoms, including irritability, anxiety, tension, suspiciousness, sadness, difficulty concentrating, and lack of appetite have been reported. In addition, somatic symptoms, including dizziness, heaviness, sweating, nausea, and stomachaches were also reported. Although complete information is not available, behavioral symptoms were reported to often persist for 2-3 days.

Up to 11 doses of 0.2 mg of naloxone (2.2 mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulfate. Pediatric reports include a 2-1/2 year-old child who inadvertently received a dose of 20 mg of naloxone for treatment of respiratory depression following overdose with diphenoxylate hydrochloride with atropine sulfate. The child responded well and recovered without adverse sequelae. There is also a report of a 4-1/2 year-old child who received 11 doses during a 12-hour period, with no adverse sequelae.

Patients who experience a NARCAN (naloxone) overdose should be treated symptomatically in a closely supervised environment. Physicians should contact a poison control center for the most up-to-date patient management information.

There is limited clinical experience with Narcan Naloxone Hci (naloxone) overdosage in humans.

In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity.

In another study, 36 patients with acute stroke received a loading dose of 4 mg/kg (10 mg/m2/min) of Narcan Naloxone Hci (naloxone) followed immediately by 2 mg/kg/hr for 24 hours. Twenty-three patients experienced adverse events associated with naloxone use, and naloxone was discontinued in seven patients because of adverse effects. The most serious adverse events were: seizures (2 patients), severe hypertension (1), and hypotension and/or bradycardia (3).

At doses of 2 mg/kg in normal subjects, cognitive impairment and behavioral symptoms, including irritability, anxiety, tension, suspiciousness, sadness, difficulty concentrating, and lack of appetite have been reported. In addition, somatic symptoms, including dizziness, heaviness, sweating, nausea, and stomachaches were also reported. Although complete information is not available, behavioral symptoms were reported to often persist for 2-3 days.

Up to 11 doses of 0.2 mg of naloxone (2.2 mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulfate. Pediatric reports include a 2-1/2 year-old child who inadvertently received a dose of 20 mg of naloxone for treatment of respiratory depression following overdose with diphenoxylate hydrochloride with atropine sulfate. The child responded well and recovered without adverse sequelae. There is also a report of a 4-1/2 year-old child who received 11 doses during a 12-hour period, with no adverse sequelae.

Patients who experience a Narcan Naloxone Hci (naloxone) overdose should be treated symptomatically in a closely supervised environment. Physicians should contact a poison control center for the most up-to-date patient management information.

Contraindications

Narcan Naloxone Hci should not be given to patients who are known to be hypersensitive to the drug.

NARCAN (naloxone) is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients in NARCAN (naloxone).

Narcan Naloxone Hci (naloxone) is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients in Narcan Naloxone Hci (naloxone).

Incompatibilities

It is recommended that infusions of Narcan Naloxone Hci Hydrochloride should not be mixed with preparations containing bisulphite, metabisulphite, long-chain or high molecular weight anions, or solutions with an alkaline pH (Martindale, 1996).

Pharmaceutical form

Undesirable effects

Postoperative: The following adverse effects have been associated with the use of Narcan Naloxone Hci in postoperative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnoea, pulmonary oedema, and cardiac arrest. Death, coma and encephalopathy have been reported as sequelae of these events. Excessive doses of Narcan Naloxone Hci in postoperative patients may result in significant reversal of analgesia and may cause agitation.

Opioid Depression: Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death (see Special Warnings).

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, trembling, nervousness, restlessness, irritability, diarrhoea, nausea, vomiting, abdominal cramps, increased blood pressure and tachycardia. In the neonate, opioid withdrawal may also include convulsions, excessive crying and hyperactive reflexes (see Special Warnings).

Agitation and paraesthesias have been infrequently reported with the use of Narcan Naloxone Hci.

The following adverse events have been associated with the use of NARCAN (naloxone) 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 NARCAN (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; 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).

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; hyperactive reflexes (see WARNINGS).

Adverse events associated with the postoperative use of NARCAN (naloxone) 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, paresthesia, 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.

NARCAN (naloxone) is an opioid antagonist. Physical dependence associated with the use of NARCAN (naloxone) has not been reported. Tolerance to the opioid antagonist effect of NARCAN (naloxone) is not known to occur.

The following adverse events have been associated with the use of Narcan Naloxone Hci (naloxone) 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 Narcan Naloxone Hci (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; 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).

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; hyperactive reflexes (see WARNINGS).

Adverse events associated with the postoperative use of Narcan Naloxone Hci (naloxone) 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, paresthesia, 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.

Narcan Naloxone Hci (naloxone) is an opioid antagonist. Physical dependence associated with the use of Narcan Naloxone Hci (naloxone) has not been reported. Tolerance to the opioid antagonist effect of Narcan Naloxone Hci (naloxone) is not known to occur.

Preclinical safety data

There is no pre-clinical data of relevance to the prescriber which is additional to that already included in other sections of the SPC.

Therapeutic indications

Narcan Naloxone Hci may be used for the complete or partial reversal of opioid depression, including mild to severe respiratory depression induced by natural and synthetic opioids, including dextropropoxyphene, methadone and certain mixed agonist/antagonist analgesics: nalbuphine and pentazocine. It may also be used for the diagnosis of suspected acute opioid overdosage. Narcan Naloxone Hci may also be used to counteract respiratory and other CNS depression in the new-born resulting from the administration of analgesics to the mother during childbirth.

NARCAN (naloxone) 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. NARCAN (naloxone) is also indicated for diagnosis of suspected or known acute opioid overdosage.

NARCAN (naloxone) may be useful as an adjunctive agent to increase blood pressure in the management of septic shock (see CLINICAL PHARMACOLOGY; Adjunctive Use in Septic Shock).

Narcan Naloxone Hci (naloxone) 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. Narcan Naloxone Hci (naloxone) is also indicated for diagnosis of suspected or known acute opioid overdosage.

Narcan Naloxone Hci (naloxone) may be useful as an adjunctive agent to increase blood pressure in the management of septic shock (see CLINICAL PHARMACOLOGY; Adjunctive Use in Septic Shock).

Pharmacodynamic properties

Narcan Naloxone Hci is a competitive antagonist of µ, δ and κ-opioid receptors. Narcan Naloxone Hci is most potent at the µ-receptor. Narcan Naloxone Hci, given on its own, produces very little effect. However, if it is given in higher doses it rapidly reverses the effect of morphine and other opioids, including pentazocine and nalorphine. Narcan Naloxone Hci has little effect on the pain threshold in normal conditions, but causes hyperalgesia in stressful conditions where endogenous opioids are produced. Narcan Naloxone Hci also inhibits acupuncture analgesia, which is associated with the release of opioid peptides. Narcan Naloxone Hci also prevents analgesia produced by PAG (periaqueductal grey matter) stimulation. PAG is one site of action in pain transmission. Narcan Naloxone Hci is given intravenously and its effects are produced immediately. It is rapidly metabolised by the liver, and its effect lasts only 1-2 hours, which is a lot shorter than that of most morphine-like drugs. Thus it may have to be given repeatedly.

Pharmacokinetic properties

Narcan Naloxone Hci is rapidly absorbed following oral administration but high presystemic metabolism makes this route unreliable. Narcan Naloxone Hci is highly lipid soluble and is thus rapidly distributed throughout the body, with a volume of distribution of 5.1kg -1. High concentrations occur in brain, kidney, lung, heart and skeletal muscle. The brain/serum ratio has been estimated to be 1.5-4.6, approximately 15 times that of morphine. Levels of Narcan Naloxone Hci in the central nervous system are short-lived as rapid redistribution occurs and this could account for the short duration of action. About 50% of Narcan Naloxone Hci is bound to plasma proteins, principally albumin. The plasma half-life is 1-2 hours. When Narcan Naloxone Hci reaches the liver it undergoes extensive biotransformation, almost none of the drug excreted being unchanged. Metabolites are excreted largely in the urine, 70% of the dose being recoverable over 72 hours. In the neonate the elimination half-life is prolonged because of reduced hepatic metabolism.

Name of the medicinal product

Qualitative and quantitative composition

Special warnings and precautions for use

It should be administered cautiously to patients who have received large doses of opioids or to those physically dependent on opioids since too rapid reversal of opioid effects by Narcan Naloxone Hci may precipitate an acute withdrawal syndrome in such patients. The same caution is needed when giving Narcan Naloxone Hci to neonates delivered of such patients.

The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include but are not limited to the following: body aches, diarrhoea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea, vomiting, nervousness, restlessness, irritability, shivering, trembling, abdominal cramps, weakness and increased blood pressure. In the neonate, opioid withdrawal may also include: convulsions, excessive crying and hyperactive reflexes.

Patients who have responded satisfactorily to Narcan Naloxone Hci should be kept under observation. Repeated doses of Narcan Naloxone Hci may be necessary since the duration of action of some opioids may exceed that of Narcan Naloxone Hci.

Narcan Naloxone Hci is not effective against respiratory depression caused by non-opioid drugs. Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs, respiration should be mechanically assisted.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death.

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest have been reported in postoperative patients. Death, coma and encephalopathy have been reported as sequelae of these events. Although a direct cause and effect relationship has not been established, Narcan Naloxone Hci should be used with caution in patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects, such as hypotension, ventricular tachycardia or fibrillation and pulmonary oedema.

In addition to Narcan Naloxone Hci, 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 poisoning.

Renal Insufficiency/Failure: The safety and effectiveness of Narcan Naloxone Hci in patients with renal insufficiency/failure have not been established in clinical trials. Caution should be exercised and patients monitored when Narcan Naloxone Hci is administered to this patient population.

Liver disease: The safety and effectiveness of Narcan Naloxone Hci in patients with liver disease have not been established in well-controlled clinical trials. In one small study in patients with liver cirrhosis, plasma Narcan Naloxone Hci concentrations were approximately six times higher than in patients without liver disease. Narcan Naloxone Hci administration had a diuretic effect in these patients with cirrhosis. Caution should be exercised when Narcan Naloxone Hci is administered to a patient with liver disease.

NARCAN (naloxone) should be administered cautiously to persons including newborns of mothers who are known or suspected to be physically dependent on opioids. In such cases an abrupt and complete reversal of opioid effects may precipitate an acute withdrawal syndrome.

The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include, but are not limited to, the following: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In the neonate, opioid withdrawal may also include: convulsions, excessive crying, and hyperactive reflexes.

The patient who has satisfactorily responded to NARCAN (naloxone) should be kept under continued surveillance and repeated doses of NARCAN (naloxone) should be administered, as necessary, since the duration of action of some opioids may exceed that of NARCAN (naloxone).

NARCAN (naloxone) 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.

In addition to NARCAN (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 opioid poisoning.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may result in death. Excessive doses of NARCAN (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults-Postoperative Opioid Depression)

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest have been reported in postoperative patients. Death, coma, and encephalopathy have been reported as sequelae of these events. These have occurred in 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, NARCAN (naloxone) should be used with caution in patients with pre-existing 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 NARCAN (naloxone) 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.

Studies in animals to assess the carcinogenic potential of NARCAN (naloxone) have not been conducted. NARCAN (naloxone) was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study. Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m2), demonstrated no embryotoxic or teratogenic effects due to NARCAN (naloxone).

Teratogenic Effects: Pregnancy Category C: Teratology studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m2), demonstrated no embryotoxic or teratogenic effects due to NARCAN (naloxone). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, NARCAN (naloxone) should be used during pregnancy only if clearly needed.

Non-teratogenic Effects: Risk-benefit must be considered before NARCAN (naloxone) is administered to a pregnant woman who is known or suspected to be opioid-dependent since maternal dependence may often be accompanied by fetal dependence. Naloxone crosses the placenta, and may precipitate withdrawal in the fetus as well as in the mother. Patients with mild to moderate hypertension who receive naloxone during labor should be carefully monitored as severe hypertension may occur.

It is not known if NARCAN (naloxone) affects the duration of labor and/or delivery. However, published reports indicated that administration of naloxone during labor did not adversely affect maternal or neonatal status.

It is not known whether NARCAN (naloxone) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NARCAN (naloxone) is administered to a nursing woman.

NARCAN (naloxone hydrochloride injection, USP) may be administered intravenously, intramuscularly or subcutaneously in children and neonates to reverse the effects of opiates. The American Academy of Pediatrics, however, does not endorse subcutaneous or intramuscular administration in opiate intoxication since absorption may be erratic or delayed. Although the opiate-intoxicated child responds dramatically to NARCAN (naloxone) , he/she must be carefully monitored for at least 24 hours as a relapse may occur as naloxone is metabolized.

When NARCAN (naloxone) is given to the mother shortly before delivery, the duration of its effect lasts only for the first two hours of neonatal life. It is preferable to administer NARCAN (naloxone) directly to the neonate if needed after delivery. NARCAN (naloxone) has no apparent benefit as an additional method of resuscitation in the newly born infant with intrauterine asphyxia which is not related to opioid use.

Usage in Pediatric Patients and Neonates for Septic Shock: The safety and effectiveness of NARCAN (naloxone) 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.

Clinical studies of NARCAN (naloxone) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

The safety and effectiveness of NARCAN (naloxone) in patients with renal insufficiency/failure have not been established in well-controlled clinical trials. Caution should be exercised when NARCAN (naloxone) is administered to this patient population

The safety and effectiveness of NARCAN (naloxone) in patients with liver disease have not been established in well-controlled clinical trials. Caution should be exercised when NARCAN (naloxone) is administered to patients with liver disease.

Narcan Naloxone Hci (naloxone) should be administered cautiously to persons including newborns of mothers who are known or suspected to be physically dependent on opioids. In such cases an abrupt and complete reversal of opioid effects may precipitate an acute withdrawal syndrome.

The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include, but are not limited to, the following: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In the neonate, opioid withdrawal may also include: convulsions, excessive crying, and hyperactive reflexes.

The patient who has satisfactorily responded to Narcan Naloxone Hci (naloxone) should be kept under continued surveillance and repeated doses of Narcan Naloxone Hci (naloxone) should be administered, as necessary, since the duration of action of some opioids may exceed that of Narcan Naloxone Hci (naloxone).

Narcan Naloxone Hci (naloxone) 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.

In addition to Narcan Naloxone Hci (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 opioid poisoning.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may result in death. Excessive doses of Narcan Naloxone Hci (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults-Postoperative Opioid Depression)

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest have been reported in postoperative patients. Death, coma, and encephalopathy have been reported as sequelae of these events. These have occurred in 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, Narcan Naloxone Hci (naloxone) should be used with caution in patients with pre-existing 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 Narcan Naloxone Hci (naloxone) 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.

Studies in animals to assess the carcinogenic potential of Narcan Naloxone Hci (naloxone) have not been conducted. Narcan Naloxone Hci (naloxone) was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study. Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m2), demonstrated no embryotoxic or teratogenic effects due to Narcan Naloxone Hci (naloxone).

Teratogenic Effects: Pregnancy Category C: Teratology studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m2), demonstrated no embryotoxic or teratogenic effects due to Narcan Naloxone Hci (naloxone). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Narcan Naloxone Hci (naloxone) should be used during pregnancy only if clearly needed.

Non-teratogenic Effects: Risk-benefit must be considered before Narcan Naloxone Hci (naloxone) is administered to a pregnant woman who is known or suspected to be opioid-dependent since maternal dependence may often be accompanied by fetal dependence. Naloxone crosses the placenta, and may precipitate withdrawal in the fetus as well as in the mother. Patients with mild to moderate hypertension who receive naloxone during labor should be carefully monitored as severe hypertension may occur.

It is not known if Narcan Naloxone Hci (naloxone) affects the duration of labor and/or delivery. However, published reports indicated that administration of naloxone during labor did not adversely affect maternal or neonatal status.

It is not known whether Narcan Naloxone Hci (naloxone) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Narcan Naloxone Hci (naloxone) is administered to a nursing woman.

Narcan Naloxone Hci (naloxone hydrochloride injection, USP) may be administered intravenously, intramuscularly or subcutaneously in children and neonates to reverse the effects of opiates. The American Academy of Pediatrics, however, does not endorse subcutaneous or intramuscular administration in opiate intoxication since absorption may be erratic or delayed. Although the opiate-intoxicated child responds dramatically to Narcan Naloxone Hci (naloxone) , he/she must be carefully monitored for at least 24 hours as a relapse may occur as naloxone is metabolized.

When Narcan Naloxone Hci (naloxone) is given to the mother shortly before delivery, the duration of its effect lasts only for the first two hours of neonatal life. It is preferable to administer Narcan Naloxone Hci (naloxone) directly to the neonate if needed after delivery. Narcan Naloxone Hci (naloxone) has no apparent benefit as an additional method of resuscitation in the newly born infant with intrauterine asphyxia which is not related to opioid use.

Usage in Pediatric Patients and Neonates for Septic Shock: The safety and effectiveness of Narcan Naloxone Hci (naloxone) 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.

Clinical studies of Narcan Naloxone Hci (naloxone) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

The safety and effectiveness of Narcan Naloxone Hci (naloxone) in patients with renal insufficiency/failure have not been established in well-controlled clinical trials. Caution should be exercised when Narcan Naloxone Hci (naloxone) is administered to this patient population

The safety and effectiveness of Narcan Naloxone Hci (naloxone) in patients with liver disease have not been established in well-controlled clinical trials. Caution should be exercised when Narcan Naloxone Hci (naloxone) is administered to patients with liver disease.

Dosage (Posology) and method of administration

Narcan Naloxone Hci is for intravenous, intramuscular or subcutaneous injection or intravenous infusion.

Intravenous infusion: Narcan Naloxone Hci may be diluted for intravenous infusion in normal saline (0.9%) or 5% dextrose in water or saline: the addition of 2mg (2ml of 1mg/1ml concentration) of Narcan Naloxone Hci in 500ml of either solution provides a concentration of 4 micrograms/ml. Mixtures should be used within 12 hours. After 12 hours, the remaining unused solution must be discarded. The rate of administration should be titrated in accordance with the patient's response to both Narcan Naloxone Hci infusion and to any previous bolus doses administered.

Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration whenever solution and container permit.

Adults:

Opioid overdosage (known or suspected)

An initial dose of 400 to 2000 micrograms of Narcan Naloxone Hci may be administered intravenously. If the desired degree of counteraction and improvement in respiratory function is not obtained it may be repeated at 2 to 3 minute intervals. If no response is observed after 10mg of Narcan Naloxone Hci have been administered the diagnosis of opioid-induced or partial opioid induced toxicity should be questioned. Intramuscular or subcutaneous administration may be necessary if dosing by the intravenous route is not feasible.

N.B. The duration of action of certain opioids can outlast that of an IV bolus of Narcan Naloxone Hci, e.g. dextropropoxyphene (present in commonly prescribed analgesics which in over-dosage have been associated with suicide), dihydrocodeine and methadone. In situations where one of these opioids is known or suspected it is recommended that an infusion of Narcan Naloxone Hci be used to produce sustained antagonism to the opioid without repeated injection.

Post Operative Use

When Narcan Naloxone Hci is used postoperatively, the dose should be titrated for each patient in order to obtain optimum respiratory response while maintaining adequate analgesia. Intravenous doses of 100-200 micrograms (approximately 1.5-3 micrograms/kg body weight) are usually sufficient, but a full two minutes should be allowed between each 100 micrograms increment of Narcan Naloxone Hci administered. Further intramuscular doses may be needed within one to two hours, depending on the interval since the last opioid administration and the amount and type (i.e. long or short-acting) of drug used. Alternatively Narcan Naloxone Hci may be administered as an intravenous infusion (see above).

Children

The usual initial dose in children is 10 micrograms/kg body weight given i.v. If this dose does not result in the desired degree of clinical improvement, a subsequent dose of 100 micrograms/kg of bodyweight may be administered. Narcan Naloxone Hci may be required by infusion as described above. If an i.v. route of administration is not feasible, Narcan Naloxone Hci may be administered i.m. or s.c. in divided doses.

Neonatal Use

An adequate airway should be established in the apnoeic infant before Narcan Naloxone Hci is administered. The usual dose is for opioid-induced depression is 10 micrograms/kg body weight administered i.v., i.m., or s.c.. If the desired degree of counteraction and improvement in respiratory function is not obtained it may be repeated at 2-3 minute intervals. Alternatively, a single dose of 200 micrograms, approximately 60 micrograms/kg body weight may be given intramuscularly at birth.

It should, however, be noted that onset of action is slower following i.m. injection. In neonates needing infusion of Narcan Naloxone Hci in saline, care should be taken to avoid excessive sodium intake.

Elderly

There have been no specific studies for use in the elderly.

NARCAN (naloxone) may be administered intravenously, intramuscularly, or subcutaneously. The most rapid onset of action is achieved by intravenous administration, which is recommended in emergency situations.

Since the duration of action of some opioids may exceed that of NARCAN (naloxone) , the patient should be kept under continued surveillance. Repeated doses of NARCAN (naloxone) should be administered, as necessary.

NARCAN (naloxone) may be diluted for intravenous infusion in normal saline or 5% dextrose solutions. The addition of 2 mg of NARCAN (naloxone) 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 mixture must be discarded. The rate of administration should be titrated in accordance with the patient's response.

NARCAN (naloxone) 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 NARCAN (naloxone) unless its effect on the chemical and physical stability of the solution has first been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Opioid Overdose-Known or Suspected: An initial dose of 0.4 mg to 2 mg of NARCAN (naloxone) 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 NARCAN (naloxone) 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 NARCAN (naloxone) are usually sufficient. The dose of NARCAN (naloxone) should be titrated according to the patient's response. For the initial reversal of respiratory depression, NARCAN (naloxone) 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 NARCAN (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 NARCAN (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 an opioid. Supplemental intramuscular doses have been shown to produce a longer lasting effect.

Septic Shock: The optimal dosage of NARCAN (naloxone) or duration of therapy for the treatment of hypotension in septic shock patients has not been established (see CLINICAL PHARMACOLOGY).

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 I.V. route of administration is not available, NARCAN (naloxone) may be administered I.M. or S.C. in divided doses. If necessary, NARCAN (naloxone) 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, NARCAN (naloxone) 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.

Opioid-induced 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.

Narcan Naloxone Hci (naloxone) may be administered intravenously, intramuscularly, or subcutaneously. The most rapid onset of action is achieved by intravenous administration, which is recommended in emergency situations.

Since the duration of action of some opioids may exceed that of Narcan Naloxone Hci (naloxone) , the patient should be kept under continued surveillance. Repeated doses of Narcan Naloxone Hci (naloxone) should be administered, as necessary.

Narcan Naloxone Hci (naloxone) may be diluted for intravenous infusion in normal saline or 5% dextrose solutions. The addition of 2 mg of Narcan Naloxone Hci (naloxone) 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 mixture must be discarded. The rate of administration should be titrated in accordance with the patient's response.

Narcan Naloxone Hci (naloxone) 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 Narcan Naloxone Hci (naloxone) unless its effect on the chemical and physical stability of the solution has first been established.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Opioid Overdose-Known or Suspected: An initial dose of 0.4 mg to 2 mg of Narcan Naloxone Hci (naloxone) 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 Narcan Naloxone Hci (naloxone) 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 Narcan Naloxone Hci (naloxone) are usually sufficient. The dose of Narcan Naloxone Hci (naloxone) should be titrated according to the patient's response. For the initial reversal of respiratory depression, Narcan Naloxone Hci (naloxone) 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 Narcan Naloxone Hci (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 Narcan Naloxone Hci (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 an opioid. Supplemental intramuscular doses have been shown to produce a longer lasting effect.

Septic Shock: The optimal dosage of Narcan Naloxone Hci (naloxone) or duration of therapy for the treatment of hypotension in septic shock patients has not been established (see CLINICAL PHARMACOLOGY).

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 I.V. route of administration is not available, Narcan Naloxone Hci (naloxone) may be administered I.M. or S.C. in divided doses. If necessary, Narcan Naloxone Hci (naloxone) 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, Narcan Naloxone Hci (naloxone) 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.

Opioid-induced 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.

Special precautions for disposal and other handling

Use once and discard any remaining solution.