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DRUG RECORD

 

NALOXONE

OVERVIEW
Naloxone

 

Introduction

Naloxone is an opiate antagonist which is used intravenously in emergency situations to reverse the respiratory depression caused by overdoses of heroin, morphine or other opioids.  Naloxone has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.

 

Background

Naloxone (nal ox’ one) is a derivative of the natural plant alkaloid thebaine and is similar to oxymorphone.  Naloxone, however, is a competitive antagonist of the opiate receptors and has particularly high affinity for the μ opiate receptor and can displace morphine and other full agonists, thereby reversing their effects.  Naloxone causes rapid onset of withdrawal symptoms in opioid dependent persons and is generally used in emergency rooms to treat the respiratory depression caused by opioid overdose.  Naloxone has sometimes been provided to emergency medical personnel and police and fire personnel for use onsite in emergency situations.  Naloxone was first approved for use in the United States in 1971.  It remains available as a solution for injection in generic forms and under the brand name Narcan, typically in concentrations of 0.4 mg/mL to be given intramuscularly or intravenously.  The usual initial dose in adults with suspected opioid overdose is 0.4 to 2.0 mg.  Naloxone is also available in fixed combination with buprenorphine for sublingual use (Suboxone and generic) and with pentazocine for oral use.  Naloxone is poorly absorbed by the sublingual or oral route and is added to discourage the intravenous or parenteral administration of buprenorphine or pentazocine.  Side effects of naloxone in opioid dependent persons include mood changes, sweating, anxiety, restlessness, trembling, dizziness, flushing, headache, nausea, vomiting, cardiac tachyarrhythmias, seizures, chest pain and acute pulmonary edema—symptoms of acute opioid withdrawal.  Naloxone has minimal effects in persons not taking opioids.  Naloxone is not a controlled substance, but its use is sometimes restricted to medical staff trained in emergency medicine or anesthesia.

 

Hepatotoxicity

Therapy with naloxone has not been linked to serum enzyme elevations or to idiosyncratic acute, clinically apparent liver injury.  Patients with opioid overdose often have underlying chronic liver diseases such as alcoholic liver disease, hepatitis B or C, but treatment with naloxone does not appear to exacerbate those conditions.  Naloxone is extensively metabolized in the liver, but largely by conjugation with glucuronide followed by its urinary excretion.

 

Drug Class:  Opioid Antagonists; see also Substance Abuse Treatment Agents

 

Other Drugs in the Class:  Nalmefene; Naloxegol, Naltrexone

 

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REPRESENTATIVE TRADE NAMES
Naloxone – Generic, Narcan®

 

DRUG CLASS
Opioid Antagonists

 

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

 

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DRUG CAS REGISTRY NO. MOLECULAR FORMULA STRUCTURE
Naloxone 357-08-4 C19-H21-N-O4.Cl-H Naloxone Chemical Structure

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References updated: 28 January 2014

  1. Zimmerman HJ. Narcotic analgesics. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 710-11.  (Expert review of hepatotoxicity published in 1999; mentions that trials of naltrexone have reported serum aminotransferase elevations in up to 30% of recipients, an effect that appeared to be partially dose dependent; naloxone not discussed).

  2. Larrey D, Ripault MP. Illegal and recreational compounds. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 456-7.  (Review of hepatotoxicity discusses buprenorphine, an orally available morphine analogue, which has been linked to cases of severe acute liver injury, usually as a result of intravenous administration; naloxone not discussed).

  3. Yaksh TL, Wallace MS. Opioids, analgesia, and pain management. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman.s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 481-525.  (Textbook of pharmacology and therapeutics).

  4. Wiesen RL, Rich CR, Wang RI, Stockdale SL. The safety and value of naloxone as a therapeutic aid. Drug Alcohol Depend 1977; 2: 123-30. PubMed Citation  (Among 343 subjects with suspected opioid dependence given intravenous naloxone to assess the presence and degree of dependence, no patient developed a serious adverse event; no mention of liver injury or ALT levels).

  5. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990; 322: 1405-11. PubMed Citation  (Among 487 patients with acute spinal cord injury treated with intravenous, high dose methylprednisolone, naloxone or placebo, side effects and complications were comparable among the three arms; no mention of ALT elevations or hepatotoxicity).

  6. Olinger CP, Adams HP Jr, Brott TG, Biller J, Barsan WG, Toffol GJ, Eberle RW, et al. High-dose intravenous naloxone for the treatment of acute ischemic stroke. Stroke 1990; 21: 721-5. PubMed Citation  (Among 38 patients with acute ischemic stroke given a 24 hour infusion of naloxone, side effects included nausea, vomiting, hypotension, focal seizures, and mild bilirubin elevations [peak 1.7 mg/dL], which rapidly returned to normal; no mention of ALT elevations or hepatotoxicity).

  7. Kaplan JL, Marx JA, Calabro JJ, Gin-Shaw SL, Spiller JD, Spivey WL, Gaddis GM, Zhao N, Harchelroad FP Jr. Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose. Ann Emerg Med 1999; 34: 42-50. PubMed Citation  (Controlled trial of two doses of nalmefene vs naloxone in 118 patients with suspected opioid overdose found similar rates of response and no serious adverse events).

  8. Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. PubMed Citation  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none to nalmefene, naltrexone or other agents used to treated substance abuse).

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OTHER REFERENCE LINKS
Naloxone
  1. PubMed logoRecent References on Naloxone

  2. Clinical Trials logoTrials on Naloxone

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