Overview
Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs, particularly within the setting of drug overdoses which are rapidly becoming a leading cause of death worldwide. More specifically, naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors. When taken in large quantities, opioid medications such as morphine, hydromorphone, methadone, heroin, or fentanyl are capable of causing life-threatening symptoms such as respiratory depression, reduced heart rate, slurred speech, drowsiness, and constricted pupils. If untreated, this can progress to vomiting, absent pulse and breathing, loss of consciousness, and even death. Naloxone is indicated for the rapid reversal of these symptoms of central nervous system depression in opioid overdose. It's important to note that naloxone only works on opioid receptors within the body, and is therefore not capable of reversing the effects of non-opioid medications such as stimulants like methamphetamine or cocaine, or benzodiazepines like lorazepam or diazepam. Also known as the brand name product Narcan, naloxone is currently available by intramuscular (IM) or subcutaneous (SubQ) injection, nasal spray, or intravenous (IV) infusion. Naloxone IM injections are commonly available in the form of "kits", which is ideal for making overdose treatment accessible and readily available for administration by minimally trained individuals within the community. Kits commonly include the supplies necessary to treat an overdose in a non-medical setting such as alcohol swabs, syringes, a rescue breathing mask, and instructions for use. Frequently also carried by medical and emergency personnel and at events known to be associated with heavy drug use like music festivals, naloxone kits are considered a key component of harm reduction strategies. There are over-the-counter nasal sprays available. When injected intramuscularly (IM), naloxone acts within three to five minutes. Administration of naloxone is associated with very few side effects. Notably, if injected into a person not currently using opioid medications, there would be no noticeable effects at all. However, for individuals using opioid medications or experiencing an overdose, IM injection of naloxone rapidly reverses opioid effects and can cause the injected individual to immediately experience withdrawal symptoms. Common symptoms of opioid withdrawal include nausea, vomiting, sweating, runny nose, aches, and diarrhea. Although certainly physically uncomfortable, opioid withdrawal symptoms are not life-threatening; administration of naloxone is, therefore, appropriate for any person appearing to have any symptoms of an opioid overdose. Due to its short duration of action, persons injected with naloxone should be monitored for responsiveness and potentially injected a second time or taken to the hospital. Naloxone is also available within the combination product Suboxone with the opioid medication buprenorphine. Suboxone is used for the maintenance treatment of opioid dependence and addiction. When taken orally, naloxone has no pharmacological effect and does not reduce the effectiveness of the opioid effect of buprenorphine. The primary purpose of including naloxone within Suboxone is to act as a deterrent to injection, as injected naloxone would rapidly reverse the effects of buprenorphine. Naloxone was granted FDA approval on 13 April 1971.
Indication
Naloxone nasal sprays are indicated for the reversal of an opioid overdose or suspected opioid overdose: it is intended for immediate administration as emergency therapy in settings where opioids may be present. Intramuscular, intravenous, and subcutaneous injections are indicated for complete or partial reversal of opioid depression, diagnosis of known or suspected opioid overdose, and as an adjunct therapy in the treatment of septic shock. Sublingual tablets and films are formulated with buprenorphine for the treatment of opioid dependence. Naloxone is also formulated with pentazocine as an oral tablet for severe pain. Intramuscular or subcutaneous naloxone autoinjectors are used for the emergency treatment of people 12 years of age and older where the use of high-potency opioids such as fentanyl analogues as a chemical weapon, is suspected. Naloxone has been used off-label for the treatment of neuraxial opioid-induced pruritus.
Associated Conditions
- Opioid Dependence
- Opioid Overdose
- Pruritus
- Respiratory Depression
- Septic Shock
- Severe Pain
- Moderate Pain
- Suspected Opioid Overdose
Research Report
Naloxone (DB01183): A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Public Health Impact
Section 1: Physicochemical Properties and Molecular Identification
This section provides a definitive characterization of naloxone, detailing the fundamental chemical, regulatory, and physical data that form the basis of its pharmacological identity and clinical use. A thorough understanding of its molecular structure and physicochemical properties is essential for appreciating its mechanism of action, pharmacokinetic profile, and the pharmaceutical challenges associated with its formulation.
1.1 Chemical and Regulatory Identifiers
Naloxone is a well-characterized small molecule drug with a comprehensive set of identifiers used in regulatory, clinical, and research contexts worldwide. It is cataloged in major pharmacological databases under the DrugBank Accession Number DB01183.[1] Its unique chemical identity is universally recognized by its Chemical Abstracts Service (CAS) Number, which is 465-65-6 for the free base form of the molecule.[2] To enhance its solubility for clinical formulations, naloxone is frequently prepared as a salt; the most common of these are naloxone hydrochloride (CAS Number: 357-08-4) and naloxone hydrochloride hydrate (CAS Number: 51481-60-8).[2]
The drug is known by several synonyms and international nonproprietary names, including Naloxona, Nalossone, and Naloxonum, reflecting its global use.[1] Its chemical nomenclature includes systematic names such as (−)-naloxone and 1-N-Allyl-14-hydroxynordihydromorphinone.[1]
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
---|---|---|---|---|---|
2024/12/06 | Phase 1 | Completed | |||
2024/10/30 | Phase 4 | Recruiting | Middle Tennessee Research Institute | ||
2024/05/10 | Phase 3 | Withdrawn | |||
2024/03/12 | Phase 1 | Completed | Parc de Salut Mar | ||
2024/02/09 | Phase 2 | Not yet recruiting | |||
2024/01/19 | Early Phase 1 | Not yet recruiting | |||
2023/10/18 | Phase 3 | Recruiting | |||
2023/05/25 | Phase 4 | Withdrawn | |||
2023/04/12 | Phase 4 | Withdrawn | |||
2022/09/06 | Phase 1 | Recruiting |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
---|---|---|---|---|---|
Physicians Total Care, Inc. | 54868-5707 | SUBLINGUAL | 2 mg in 1 1 | 7/27/2010 | |
INDIVIOR INC. | 12496-1202 | SUBLINGUAL, BUCCAL | 0.5 mg in 1 1 | 6/1/2022 | |
Lannett Company, Inc. | 62175-458 | SUBLINGUAL | 2 mg in 1 1 | 3/26/2024 | |
Lannett Company, Inc. | 62175-452 | SUBLINGUAL | 0.5 mg in 1 1 | 3/26/2024 | |
Baxter Healthcare Corporation | 36000-308 | INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS | 0.4 mg in 1 mL | 2/3/2021 | |
Akorn Operating Company LLC (dba Akorn) | 50383-294 | SUBLINGUAL | 0.5 mg in 1 1 | 10/1/2023 | |
Dr.Reddys Laboratories Inc | 43598-579 | BUCCAL, SUBLINGUAL | 0.5 mg in 1 1 | 11/5/2019 | |
Mylan Institutional LLC | 67457-992 | INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS | 1 mg in 1 mL | 10/22/2021 | |
HF Acquisition Co. LLC, DBA HealthFirst | 51662-1238 | INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS | 0.4 mg in 1 mL | 12/9/2022 | |
Quality Care Products, LLC | 83008-007 | NASAL | 4 mg in 0.1 mL | 3/3/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
---|---|---|---|
Authorised | 9/26/2006 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
MAPIN INJECTION 0.4 mg/ml | SIN10290P | INJECTION | 0.4 mg/ml | 10/23/1998 | |
TARGIN® Prolonged Release Tablets 20mg /10mg | SIN14033P | TABLET, FILM COATED, EXTENDED RELEASE | 10 mg | 10/19/2011 | |
TARGIN® Prolonged Release Tablets 10mg/5mg | SIN14032P | TABLET, FILM COATED, EXTENDED RELEASE | 5 mg | 10/19/2011 | |
NALOXONE HYDROCHLORIDE INJECTION USP 0.4 mg/ml | SIN05964P | INJECTION | 0.4 mg/ml | 5/23/1991 | |
TARGIN® Prolonged Release Tablets 5mg/2.5mg | SIN14031P | TABLET, FILM COATED, EXTENDED RELEASE | 2.5 mg | 10/19/2011 | |
Suboxone 8 mg/2 mg sublingual tablets | SIN13405P | TABLET, ORALLY DISINTEGRATING | 2.44MG | 1/28/2008 | |
Suboxone 2 mg/0.5 mg sublingual tablets | SIN13404P | TABLET, ORALLY DISINTEGRATING | 0.61MG | 1/28/2008 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
---|---|---|---|---|---|
No NMPA approvals found for this drug. |
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
---|---|---|---|---|---|
MAPIN INJ 0.4MG/ML | N/A | wings pharmaceutical ltd | N/A | N/A | 8/18/2000 |
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
---|---|---|---|---|---|
No TGA approvals found for this drug. |
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
---|---|---|---|---|---|
S.O.S. NALOXONE HYDROCHLORIDE INJECTION | 02453266 | Solution - Intramuscular
,
Intravenous
,
Subcutaneous | 1 MG / ML | N/A | |
TEVA-NALOXONE NASAL SPRAY | teva canada limited | 02511568 | Spray, Metered Dose - Nasal | 4 MG / 0.1 ML | 1/8/2024 |
TARGIN | purdue pharma | 02339617 | Tablet (Extended-Release) - Oral | 10 MG | 10/5/2010 |
NALOXONE HYDROCHLORIDE INJECTION USP | sterinova inc. | 02548194 | Solution - Subcutaneous
,
Intramuscular | 0.4 MG / ML | 9/26/2024 |
NARCAN NASAL SPRAY | emergent operations ireland limited | 02458187 | Spray, Metered Dose - Nasal | 4 MG / 0.1 ML | 7/7/2017 |
TARGIN | purdue pharma | 02339625 | Tablet (Extended-Release) - Oral | 20 MG | 10/5/2010 |
NALOXONE HYDROCHLORIDE INJECTION, USP | auro pharma inc | 02515261 | Solution - Intravenous
,
Subcutaneous
,
Intramuscular | 0.4 MG / ML | N/A |
NALOXONE HYDROCHLORIDE INJECTION, USP | eugia pharma inc. | 02534967 | Solution - Intravenous
,
Subcutaneous
,
Intramuscular | 0.4 MG / ML | N/A |
KLOXXADO | hikma canada limited | 02555441 | Spray, Metered Dose - Nasal | 8 MG / 0.1 ML | N/A |
NALOXONE HYDROCHLORIDE INJECTION, USP | auro pharma inc | 02515288 | Solution - Intramuscular
,
Subcutaneous
,
Intravenous | 4 MG / 10 ML | N/A |
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
---|---|---|---|---|---|
SUBOXONE 2 MG/0,5 MG COMPRIMIDOS SUBLINGUALES | 06359001 | COMPRIMIDO SUBLINGUAL | Diagnóstico Hospitalario. Psicótropos | Not Commercialized | |
SUBOXONE 8 MG/2 MG COMPRIMIDOS SUBLINGUALES | 06359003 | COMPRIMIDO SUBLINGUAL | Diagnóstico Hospitalario. Psicótropos | Not Commercialized | |
SUBOXONE 2 MG/0,5 MG COMPRIMIDOS SUBLINGUALES | 106359002 | COMPRIMIDO SUBLINGUAL | Diagnóstico Hospitalario. Psicótropos | Not Commercialized | |
SUBOXONE 8 MG/2 MG COMPRIMIDOS SUBLINGUALES | 106359004 | COMPRIMIDO SUBLINGUAL | Diagnóstico Hospitalario. Psicótropos | Not Commercialized |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
No Philippines FDA approvals found for this drug. |
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
No Saudi SFDA approvals found for this drug. |
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
No Malaysia NPRA approvals found for this drug. |
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
---|---|---|---|---|---|
No UK EMC drug information found for this drug. |
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