Action And Clinical Pharmacology: Naloxone prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension.
Naloxone is an essentially pure narcotic antagonist which does not possess the ‘agonistic’ or morphine-like properties characteristic of other narcotic antagonists. It does not produce respiratory depression, psychotomimetic effects or pupillary constriction. In the absence of narcotic or agonistic effects of other narcotic antagonists, it exhibits essentially no pharmacologic activity.
In the presence of narcotic addiction, naloxone will produce withdrawal symptoms; it has not been shown to cause addiction.
Mechanism of Action: While the mechanism of action is not fully understood, the preponderance of evidence suggests that naloxone antagonizes the opioid effects by competing for the same receptor sites.
When naloxone is administered i.v. the onset of action is generally apparent within 2 minutes; the onset of action is only slightly less rapid when it is administered s.c. or i.m. The duration of action is dependent on the dose and route of administration of naloxone. I.M. administration produces a more prolonged effect than i.v. 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 (see Warnings).
Following parenteral administration, naloxone 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 (mean 64±12) minutes. In a neonatal study the mean plasma half-life was observed to be 3.1±0.5 hours.
Single s.c. doses of naloxone as high as 24 mg/70 kg (0.343 mg/kg) and multiple doses of 90 mg daily for 2 weeks administered to normal volunteers produced no behavioral or physiologic changes, yet its antagonistic activity to subsequent morphine challenge persisted.
Indications And Clinical Uses: The complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids including natural and synthetic narcotics, propoxyphene, methadone and the agonist-antagonist analgesics such as pentazocine, butorphanol and nalbuphine.
Also indicated for the diagnosis of suspected acute opioid overdosage.
Contra-Indications: Known hypersensitivity to naloxone.
Manufacturers’ Warnings In Clinical States: 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 narcotic effects may precipitate an acute abstinence syndrome. The severity of such a syndrome will depend on the degree of physical dependence and the dose of antagonist administered. In the presence of serious respiratory depression in a physically dependent individual, the antagonist, when indicated, should be administered with extreme care, under close monitoring, by using appropriate titration with smaller doses than usual. The patient who has satisfactorily responded to naloxone should be kept under surveillance and repeated doses should be administered, as necessary, since the duration of action of some narcotics may exceed that of naloxone.
Naloxone is not effective in counteracting depression due to barbiturates, tranquilizers, or other non-narcotic anesthetics or sedatives. It has been safely administered to patients who received both narcotic and non-narcotic drugs.
Reversal of buprenorphine induced respiratory depression may be incomplete. If an incomplete response occurs, respirations should be mechanically assisted.
Pregnancy: Safe use during pregnancy (other than labor) has not been established. Although animal reproduction studies have not demonstrated teratogenic or other embryotoxic effects, naloxone should be administered to pregnant patients only when, in the judgement of the physician, potential benefits outweigh possible hazards.
Lactation: It is not known whether naloxone is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when naloxone is administered to a nursing woman.
Precautions: 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 in whom pre-existing cardiovascular disorders or other drugs may have contributed to the adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, naloxone should be administered very cautiously for postoperative narcotic reversal, particularly in patients with pre-existing cardiac disease or patients who have received potentially cardiotoxic drugs. The clinical course should be monitored by ECG (see Dosage).
Adverse Reactions: Abrupt reversal of narcotic depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness and cardiac arrest. In postoperative patients, excessive dosage of naloxone may result in excitement and significant reversal of analgesia. Hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been associated with naloxone use postoperatively (see Precautions and Dosage, Postoperative Narcotic Depression). Seizures have been reported to occur infrequently after the administration of naloxone; however, a causal relationship has not been established.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: There have been no experiences of overdosage. tag_DosageDosage
Dosage And Administration:
Naloxone may be administered i.v., i.m. or s.c. The most rapid onset of action is achieved by i.v. administration and it is recommended in emergency situations.
Since the duration of action of some narcotics may exceed that of naloxone, the patient should be kept under continued surveillance and repeated doses of naloxone should be administered as necessary.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. 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 naloxone unless its effect on the chemical and physical stability of the solution has first been established.
Adults: Narcotic overdose, known or suspected: The usual initial dose is 0.4 to 2 mg administered i.v. 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 10 mg, the diagnosis of narcotic- induced or partial narcotic-induced toxicity should be questioned. I.M. or s.c. administration may be necessary if i.v. route is not available.
I.V. infusion: Naloxone may be diluted for i.v. infusion in normal saline or 5% dextrose solutions. The addition of 2 mg in 500 mL of either solution provides a concentration of 4 Âµg (0.004 mg)/mL. Mixtures should be used within 24 hours. After 24 hours, the remaining unused solution must be discarded.
Infusion may be useful in cases of overdose with long-acting drugs such as methadone and propoxyphene. The infusion rate for adults is approximately 100 mL/hr (0.4 mg/hr). Infusion rate and concentration should be individually adjusted to obtain the desired antagonist effect without fluid overload or production of withdrawal.
Postoperative Narcotic Depression: For the partial reversal of narcotic depression following the use of narcotics during surgery, smaller doses of naloxone are usually sufficient. The dose should be titrated according to the patient’s response. For the initial reversal of respiratory depression, inject naloxone slowly in increments of 100 to 200 µg (0.1 to 0.2 mg) i.v. at 2 to 3 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 (see Precautions).
Repeat doses of naloxone may be required within 1 to 2 hour intervals depending upon the amount, type (i.e., short or long-acting) and time interval since last administration of narcotic. Supplemental i.m. doses have been shown to produce a longer lasting effect.
Children: Narcotic Overdose-known or suspected: The usual initial dose is 10 µg (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 100 µg (0.1 mg)/kg body weight may be administered. If an i.v. route of administration is not available, naloxone may be administered i.m. or s.c. in divided doses. If necessary, naloxone can be diluted with sterile water for injection.
I.V. Infusion: I.V. Infusion may be useful in cases of overdose with long-acting drugs such as methadone and propoxyphene (see Adults). The infusion rate for children should be suitably adjusted according to the patient’s weight and response.
Postoperative Narcotic Depression: Follow the recommendations and cautions under Adult Postoperative Depression. For the initial reversal of respiratory depression naloxone should be injected in increments of 5 to 10 µg (0.005 mg to 0.01 mg) i.v. at 2 to 3 minute intervals to the desired degree of reversal. Neonates: Narcotic-induced Depression: The usual initial dose is 10 Âµg (0.01 mg)/kg body weight administered by i.v., i.m., or s.c. routes. This dose may be repeated in accordance with adult administration guidelines for postoperative narcotic depression.
SuppliedSupplied: 0.02 mg/mL: Each mL of aqueous injectable solution contains: naloxone HCl 20 µg. Also contains sodium chloride. pH is adjusted to 3.5±0.5 with hydrochloric acid. Ampuls of 2 mL, boxes of 10. Labels are blue coded.
0.4 mg/mL: Each mL of aqueous injectable solution contains: naloxone HCl 400 µg. Also contains methyl- and propylparaben (vial format only) and sodium chloride. Ampuls of 1 mL, boxes of 10. Vials of 10 mL. Labels are orange coded.
1 mg/mL: Each mL of aqueous injectable contains: naloxone HCl 1 000 µg. Also contains sodium chloride. pH is adjusted to 3.5±0.5 with hydrochloric acid. Ampuls of 2 mL, boxes of 10. Labels are red and white color coded.
NARCAN® DuPont Pharma Naloxone HCl Narcotic Antagonist