Naloxone: definition, use, administration, and side effects

Naloxone is an antidote to opioid overdose. It is an opioid antagonist medication that counteracts the effects of opioids by temporarily reversing the impact of opioid drugs, helping the person to restore breathing and regain consciousness.

Use of naloxone is primarily for the emergency treatment of known or suspected opioid overdoses. It is critical in treating opioid-induced consequences such as respiratory depression, drowsiness, and coma. This medicine works quickly to counter the effects of opioids by competitively binding to opioid receptors in the brain, preventing opioid molecules from attaching and so reversing their effects.

Naloxone administration methods are intranasal, intramuscular, subcutaneous, intravenous, and intraosseous. Intravenous injection is preferred for rapid and complete reversal of opioid effects.

Side effects of naloxone include opioid withdrawal effects, allergic reactions, pulmonary complications, and cardiac abnormalities.

What is naloxone?

Naloxone is a Food and Drug Administration (FDA)-approved medication used to rapidly reverse opioid overdoses. By attaching to opioid receptors in the body, it functions as an opioid antagonist, preventing or counteracting the effects of opioids, including heroin, morphine, oxycodone, fentanyl, and prescription painkillers. Naloxone is safe for use across all age groups, including infants, children, and the elderly, in cases of suspected overdose.

According to the article “Naloxone” published by the Alcohol and Drug Foundation in 2023, there is no proof that long-term use of naloxone leads to harmful physical effects or dependence. Individuals using naloxone do not build a tolerance to its effects, and there have been no recorded fatalities due to naloxone overdose.

What is the brand name for naloxone?

The brand names for naloxone include Narcan, Zimhi, Rezenopy, and Kloxxado. Narcan is available both as a brand-name drug and in its generic form, naloxone. Notably, in March 2023, the U.S. The Food and Drug Administration (FDA) approved Narcan (nasal spray) for over-the-counter (OTC) use, enabling its purchase without a prescription at numerous pharmacies. This approval marks a significant step in increasing accessibility to this life-saving medication.

The FDA has approved Zimhi (naloxone hydrochloride injectable) as a prescription treatment for opioid overdoses that are given by family members or caretakers. With the use of a unique hand-held auto-injector made especially for delivering naloxone outside of a medical setting, Zimhii swiftly administers a single dosage of the drug.

What is naloxone used for?

Naloxone is used for intentional or unintentional opioid overdose as well as in cases of acute or chronic toxicity of opioid overdose. It reverses the overdose effects by counteracting life-threatening symptoms like slowed breathing, constricted pupils, and loss of consciousness. While naloxone temporarily restores normal breathing and consciousness, its effects are short-lived.

A 2024 article “Naloxone” by Matthew R. Jordan et al., published by StatPearls, details naloxone’s use for over 50 years. Its effectiveness in preventing opioid overdose deaths led the federal government to recommend its over-the-counter (OTC) availability at most pharmacies. Its OTC access allows family members and caregivers of patients with opioid overdoses to administer naloxone and potentially save lives.

When should naloxone be used?

Naloxone should be used when someone experiences an opioid overdose, as it is fatal without intervention. Immediate medical attention is important for anyone who presents with signs of opioid overdose such as depressed or slowed breathing, pinpoint pupils or loss of consciousness. Naloxone is frequently used to treat drug overdoses, including those involving methadone, oxycodone, hydrocodone, fentanyl, and heroin.

According to the article “Opioid Overdose” published by the World Health Organization (WHO) in 2023, recent global programs have shown significant reductions in drug overdose fatalities by providing naloxone and training on its use and resuscitation techniques to those likely to witness an overdose. This is particularly significant for individuals with opioid use disorder (OUD) and those recently released from prison, as they are at high risk for drug overdose within the first month of release.

The article “Access to Naloxone Can Save a Life During an Opioid Overdose” published by the U.S. Food and Drug Administration, last updated on 03/29/2023, advises carrying naloxone to reduce the risk of death from opioid overdose. This includes individuals who are prescribed opioid pain relievers, those receiving treatment for OUD, people at increased risk of overdose due to the use of substances like alcohol or benzodiazepines, and caregivers of individuals at risk of an opioid overdose.

How quickly does naloxone need to be given after an opioid overdose?

Naloxone needs to be given as quickly as possible after an opioid overdose is recognized. Signs of an opioid overdose include pinpoint pupils, shallow or difficult breathing, loss of consciousness, and blue or gray-tinged lips, fingernails, or skin.

The research article “Opioid Overdose” by Elizabeth Y. Schiller et al., published in StatPearls in 2023, discusses the importance of managing patients at the scene based on their vital signs. Suspected cases of opioid overdose need to prompt the administration of naloxone to reverse respiratory depression. For comatose patients experiencing respiratory distress, securing the airway through endotracheal intubation is important before any other intervention. However, naloxone has been shown to cause agitation and violence when used to reverse the effects of opioids. As a result, the author recommends taking the lowest effective dose, particularly for drug addicts, to reduce adverse responses.

How long does it take for naloxone to work?

It takes about 2-3 minutes for naloxone to work. If no response is observed after 3 minutes, a second dose is administered. According to the article“Naloxone DrugFacts” published by the National Institute on Drug Abuse (NIDA) in 2022, naloxone reverses opioid overdoses for about 30 to 90 minutes. However, many opioids remain in the bloodstream for longer. As a result, overdose symptoms return as naloxone wears off, and stronger opioids necessitate additional doses of naloxone.

According to the article titled “Opioid Overdose” by Elizabeth Y. Schiller et al. published in StatPearls in 2023, naloxone begins to take effect within three to ten minutes when administered subcutaneously (SC) or intramuscularly (IM).

How often should naloxone be administered?

Naloxone should be administered every 2-3 minutes if there is no response or improvement in the patient’s symptoms after the administration of the initial dose. It’s important to continue administering naloxone and performing rescue breathing, or cardiopulmonary resuscitation (CPR), while waiting for emergency medical services to arrive.

The article “Naloxone” by Matthew R. Jordan et al., published by StatPearls in 2024, outlines naloxone dosing regimens. It states that clinicians administer additional doses of 0.1 mg to 0.4 mg intravenously (IV) or 0.4 mg to 1 mg intranasally (IN), intramuscularly (IM), or subcutaneously (SQ) to any opioid overdose patient until the desired effect is achieved.

How long does the effect of naloxone last?

The effect of naloxone lasts for 30 to 90 minutes, as indicated in the article “Naloxone DrugFacts” published by the National Institute on Drug Abuse (NIDA) in 2022. Even though naloxone remains in the body for a while, it is always important to contact the local emergency number after receiving naloxone. This is because naloxone alone is not sufficient to adequately treat an opioid overdose; additional drugs or therapies are required.

How long does naloxone remain in the body?

Naloxone remains in the body for up to 72 hours after administration. The half-life of naloxone, which denotes the period required for half of the drug to be cleared from the system, varies according to the administration route. For intranasal administration, the half-life ranges between 1.85 to 2.08 hours, whereas for intramuscular injection, it is approximately 1.24 hours. Despite its relatively short half-life, naloxone persists in the body for approximately 10 hours or more before complete clearance.

The clearance rate of naloxone is influenced by individual physiological factors and the specific method of administration. The article “Naloxone” by Matthew R. Jordan et al., published by StatPearls in 2024, indicates that approximately 25% to 40% of naloxone is metabolized and eliminated through urine within the initial 6 hours post-administration. By 72 hours, up to 70% of the administered naloxone dose is excreted.

What are the signs that naloxone has worked?

The signs that naloxone has worked are listed below.

• Return of spontaneous breathing: The study “Effectiveness of bystander naloxone administration and overdose education programs: a meta-analysis” by Rebecca E. Giglio et al., published in the journal Injury Epidemiology in 2015, provides compelling evidence that naloxone is highly effective in rapidly restoring normal breathing in individuals experiencing opioid-induced respiratory depression. The meta-analysis reviewed multiple studies and consistently found that naloxone administration by bystanders resulted in significant improvements in respiratory function and overall survival rates in cases of opioid overdose​.
• Increased respiratory rate: The research article “Naloxone interventions in opioid overdoses: a systematic review protocol” by Lindsay Victoria Shaw et al., published in the journal Systematic Reviews in 2019, explains that naloxone administration typically leads to an increased respiratory rate, accompanying the return of normal breathing. This improvement is a critical indicator that the effects of opioids on the respiratory system are being effectively counteracted.
• Return of consciousness: Administering naloxone reverses the effects of opioid overdose, potentially allowing an individual who was unconscious or deeply sedated to regain consciousness. As naloxone takes effect, the person typically becomes more alert and responsive, demonstrating signs of increased awareness and alertness.
• Return of pain: Naloxone reverses opioid effects by displacing opioids from their receptors, which includes reversing pain relief provided by the opioids. Its brief duration of action and short half-life imply that following administration, particularly through intravenous means, the patient’s pain will quickly return if they had been receiving opioids for pain relief. This return of pain indicates that naloxone has effectively worked to reverse the opioid’s effects.

What are the administration routes for naloxone?

The administration routes for naloxone are listed below.

• Intranasal: According to the article “Naloxone” by Matthew R. Jordan et al., published by StatPearls in 2024, intranasal spray allows for easy and rapid delivery into the nose, making it a convenient option for non-medical personnel. Intranasal administration has advantages over injectable routes, reducing the risk of needle-stick injuries and blood-borne pathogen transmission.
• Intramuscular: Intramuscular injection involves injecting naloxone into the muscle of the upper thigh or upper arm, providing quick absorption into the bloodstream.
• Subcutaneous: Subcutaneous injections are those in which the medicine is administered beneath the skin, and have a slightly slower absorption rate than other procedures. Naloxone for subcutaneous administration is typically administered in the upper arm, shoulder, thigh, outer buttocks, or abdomen, with the exception of the belly button area.
• Intravenous: Intravenous injections are administered into the veins, and they act quickly and completely reverse the effects of opioids in a matter of minutes. It is the method of choice in clinical settings.
• Intraosseous: If intravenous injections are not available, naloxone is administered intraosseously by injecting the drug directly into the bone marrow.

Can anyone administer naloxone?

Yes, anyone can administer naloxone, including non-medical personnel. Naloxone is designed to be user-friendly, particularly in its intranasal and auto-injector forms, to enable immediate intervention in cases of opioid overdose.

The article “Naloxone DrugFacts” published by the National Institute on Drug Abuse (NIDA) in 2022, advises families with members struggling with opioid addiction to keep naloxone accessible, encourage their loved ones to carry it, and inform friends of its location.

Many states in the U.S. have passed laws allowing pharmacists to dispense naloxone without a prescription, as evidenced by the manual “Naloxone Access: Summary of State Laws” published by the Legislative Analysis and Public Policy Association (LAPPA) in January 2023. There are programs in these places to teach caregivers, friends, and family members how to administer the medication. This availability is critical for a prompt response because naloxone quickly reverses the life-threatening consequences of an opioid overdose, making it an important tool in community-based overdose prevention programs.

What are the side effects of naloxone?

The side effects of naloxone are listed below.

• Opioid withdrawal effects: Acute withdrawal symptoms are the primary adverse effects linked to naloxone, typically arising after sudden opioid withdrawal. These symptoms encompass anxiety, aggression, agitation, abdominal cramps, sweating, diarrhea, vomiting, nausea and a runny nose.
• Allergic reactions: Signs of an allergic reaction include hives, difficulty breathing, or swelling of the face, lips, tongue, or throat. If these symptoms are experienced after taking naloxone, immediate medical attention is necessary.
• Pulmonary complications: A study titled “Pulmonary Complications of Opioid Overdose Treated With Naloxone,” conducted by Andrew Farkas et al., published in the journal Annals of Emergency Medicine An International Journal in 2019, indicates that using higher doses of naloxone to treat opioid overdose outside the hospital are associated with a higher incidence of pulmonary complications such as aspiration pneumonia, pulmonary edema, and aspiration pneumonitis.
• Cardiac abnormalities: A study published in the journal Oral Surgery, Oral Medicine, and Oral Pathology in 1981, titled “Naloxone-associated morbidity and mortality,”authored byT J Pallasch and C J Gill, reported that naloxone has been associated with the development of hypertension, pulmonary edema, atrial and ventricular arrhythmias, or cardiac arrest in specific patients, especially those with pre-existing cardiac conditions. These adverse effects arise from increased sympathetic nervous system activity following the reversal of narcotic analgesia, naloxone’s effects on peripheral or central opioid receptors, or interactions with other anesthetic agents.
• Mild side-effects: Other side effects of naloxone include constipation, toothache, muscle spasms, and muscle pain. These side effects are generally less severe compared to the life-threatening effects associated with high doses or rapid infusion of naloxone. However, it is important to monitor for these symptoms and seek medical attention if they persist or worsen.

How does naloxone work?

Naloxone works as a pure, competitive opioid antagonist by displacing opioids from the opioid receptors. It has the highest affinity for the μ-opioid receptor, allowing it to effectively reverse opioid effects such as slowed breathing, extreme sleepiness, and low blood pressure.

The research article “Naloxone” by Matthew R. Jordan et al., published by StatPearls in 2024, explains that naloxone binds to the μ, κ, and σ-opioid receptors in the central nervous system (CNS), competing with opioids and counteracting their effects. At lower dosages, naloxone minimally blocks δ and κ-opioid receptors while significantly blocking μ-opioid receptors. This mechanism allows naloxone to swiftly reverse the life-threatening symptoms of opioid overdose, such as respiratory depression.

Can naloxone treat opioid addiction?

No, naloxone cannot treat opioid addiction, as outlined in the article “Naloxone DrugFacts” published by the National Institute on Drug Abuse (NIDA) in 2022. Opioid addiction is considered the most severe complication of opioid use disorder (OUD), as highlighted in the article “Opioid Use Disorder” by Alexander M. Dydyk et al., published by StatPearls, updated in January 2024. This addiction entails the continuous use of opioids despite their adverse consequences, stemming from the sensitization of the drug-reward system and the escalation of compulsive drug-seeking behavior. Opioid addiction affects every facet of a person’s life, leading to legal issues, interpersonal relationship challenges, occupational loss, and substantial morbidity and mortality.

Naloxone is a medication specifically designed to counteract the life-threatening effects of opioid addiction and its overdose. Its primary role is to quickly reverse opioid toxicity by binding to opioid receptors in the brain and blocking the effects of opioid drugs. Unlike opioids, naloxone does not produce any euphoric or pleasurable effects. This absence of euphoria means that there is no potential for abuse or addiction to naloxone itself. Its use is strictly medical, aimed at preventing overdose deaths by rapidly restoring normal respiration and consciousness in individuals who have overdosed on opioids.

Can naloxone be used to reverse overdoses from drugs other than opioids?

No, naloxone cannot be used to reverse overdoses from drugs other than opioids. Naloxone is an opioid antagonist, which works by binding to opioid receptors in the brain and blocking the effects of opioids. It does not affect other receptor sites or mechanisms of action associated with other drugs like cocaine or methamphetamine. Each drug class has its own specific mechanisms, and naloxone is not effective in counteracting the effects of non-opioid substances. It is important to use the appropriate treatment based on the type of drug involved in an overdose to ensure effective reversal and management of the overdose situation.

Naloxone is typically not utilized to reverse overdoses from substances other than opioids; however, in instances of mixed-drug overdoses containing opioids, naloxone assists in reversing the opioid aspect of the overdose. One such study was discussed in the article titled “Naloxone Successfully Counters Life-Threatening Toxicity of Benzodiazepine in a Patient in Methadone-Maintenance Treatment” authored by Weiqing Yuan and Barry N Williams, published in The Journal of Neuropsychiatry and Clinical Neurosciences in 2012. The research describes a rare case in which naloxone effectively reversed benzodiazepine toxicity in a patient undergoing methadone maintenance treatment. The authors acknowledge that naloxone is not generally recommended for this purpose and emphasize the need for further research to understand the mechanisms involved in this particular case.

What are the common doses of naloxone?

The common doses of naloxone are listed below.

• 0.4mg to 2mg as intravenous injection (IV): In a medical setting, naloxone is frequently administered intravenously. The initial dose is typically between 0.4 mg and 2 mg. If the desired response is not achieved, the dose is repeated every 2 to 3 minutes. Clinicians administer subsequent doses ranging from 0.1 mg to 0.4 mg IV to any opioid overdose patient until the desired effect is reached.
• 0.4mg to 2mg as intramuscular (IM) or subcutaneous (SQ) injection: The usual dose is 0.4 mg to 2 mg administered by injection into a muscle or under the skin.
• 4mg as intranasal (nasal spray): For the nasal dosage form (Narcan spray), the initial dose for both adults and children is 4 mg, one spray into one nostril. Additional sprays are given into the other nostril every 2 to 3 minutes until the patient responds or until emergency medical assistance is available.
• 5mg as auto-injector (Zimhi): The auto-injector is a battery-operated disposable 5 mg/0.5 mL prefilled syringe device. It is designed for use in the anterolateral (outer) aspect of the thigh through clothing if necessary. If there is no response after 2 or 3 minutes, another dose of Zimhi is administered. If there is still no response and more doses are available, additional doses are administered every 2 to 3 minutes until emergency medical help arrives.

Who should take naloxone?

Naloxone should be taken by individuals experiencing an opioid overdose, including those who have overdosed on prescription opioids, heroin, or synthetic opioids like fentanyl. While not everyone needs to carry naloxone, it’s a crucial tool for specific groups. This includes people who use opioids themselves, as well as those who know someone who does or who is at risk of accidental exposure.

Opioid users, their loved ones, and caregivers have all access to naloxone and are trained on how to use it. Additionally, healthcare providers, first responders, and community members in areas with high opioid use rates carry naloxone. Given the rise in opioid overdoses, understanding naloxone and knowing where to find it benefits everyone in an emergency.

Who should not take naloxone?

Naloxone should not be taken by individuals who have no suspicion of opioid overdose. It is specifically intended for use in cases of opioid overdose and not to be used as a preventive measure or by individuals who are not at immediate risk of opioid overdose. Additionally, naloxone is not to be taken by individuals who are allergic to naloxone or any of its ingredients, or by a woman who is pregnant or nursing.It is important to consult with a healthcare professional before using naloxone to ensure that it is appropriate for the situation.

What happens if naloxone is given to someone who doesn’t need it?

If naloxone is given to someone who doesn’t need it, it is unlikely to cause harm. Naloxone is specifically designed to reverse opioid overdose and will not have an effect if opioids are not present in the person’s system. It is safe to use naloxone on people of all ages, including infants, children, and the elderly, for suspected opioid overdoses. In rare cases, giving naloxone to a person without opioid overdose symptoms causes mild and temporary discomfort or agitation due to the sudden reversal of opioid effects. It is important to always follow the instructions for naloxone administration and seek medical help if unsure whether naloxone is needed.

Where can naloxone be purchased?

Naloxone can be purchased at pharmacies nationwide, including supermarkets, major chain drug stores, and big-box stores. There are three ways to obtain naloxone from a pharmacy or store. First, with a prescription from a healthcare provider, which is filled at the pharmacy. Second, over-the-counter, as Narcan nasal spray is available without a prescription in all states. Third, through a statewide standing order, allowing pharmacists to dispense naloxone without a prescription.

What is naloxone made of?

Naloxone is made of morphinone, a synthetic morphinane alkaloid. It is typically used in its hydrochloride salt form to counteract opioid effects, particularly in cases of opioid overdose. Naloxone acts as a mu-opioid receptor antagonist, a central nervous system depressant, and an antidote for opioid poisoning.

The article “Compound Summary for CID 5284596, Naloxone” published by the National Center for Biotechnology Information in 2004, explains that naloxone is chemically an organic hetero pentacyclic compound, a morphinane alkaloid, and a tertiary alcohol. It originates from a hydride of morphinan and is the conjugate base of naloxone (1+).

Can naloxone cause addiction?

No, naloxone cannot cause addiction as it is an opioid antagonist, meaning it blocks the effects of opioids by binding to opioid receptors in the brain without activating them. This mechanism enables naloxone to reverse the effects of opioid overdose without producing the euphoric effects or physical dependence characteristic of opioids.

In the article “Naloxone: Frequently Asked Questions” published by the Anne Arundel County Department of Health, Maryland, naloxone is described as a substance that is not classified as a controlled substance, does not have a street value, and is not considered addictive.

What precautions should be taken when using naloxone?

Precautions that should be taken when using naloxone are listed below.

• Close monitoring: According to the article “Naloxone DrugFacts” published by the National Institute on Drug Abuse (NIDA) in 2022, individuals receiving naloxone need to be closely monitored until emergency medical assistance arrives and for an additional 2 hours after the last dose to ensure their breathing remains stable. Furthermore, it is recommended to continuously monitor all patients who have responded to naloxone for 6 to 12 hours as the half-life of certain opioids like methadone, fentanyl, and buprenorphine is longer than naloxone.
• Precautions for high opioid dosages: In their 2024 research article “Naloxone” authored by Matthew R. Jordan et al., published by StatPearls, they emphasized the importance of implementing additional precautions when a patient’s total opioid dosage exceeds 50 morphine milligrams equivalent (MME)/day. This includes seeing the doctor more often and ensuring both the patient and their family receive naloxone and training on how to use it in case of an overdose.
• Proper storage and replacement of naloxone: It’s important to not only store naloxone correctly, but to replace it if it’s expired or been exposed to extreme temperatures such as below 3.8 °C or above 40 °C.

Can naloxone be prescribed alongside other medications?

Yes, naloxone can be prescribed alongside other medications. Its primary use is to reverse opioid overdoses, and it is often included in treatment plans for patients at risk of opioid overdose, including those prescribed opioids for pain management.

The article “Naloxone Prescribing with Opioid Prescriptions” published by the Washington State Department of Health in 2019, addresses whether naloxone is prescribed alongside other medications by highlighting the encouragement for healthcare providers to prescribe naloxone to patients at high risk of opioid overdose. This includes patients prescribed opioids at high dosages, those taking benzodiazepines with opioids, and those receiving treatment for opioid use disorder with medications such as methadone, buprenorphine, or naltrexone. It demonstrates that naloxone is prescribed in conjunction with these other medications to reduce the risk of overdose deaths.

What is the difference between fentanyl and naloxone?

The difference between fentanyl and naloxone lies in their uses, mechanisms, and effects. Fentanyl, a potent synthetic opioid analgesic, is utilized to manage severe pain, particularly in those undergoing surgery. It operates by binding to opioid receptors in the brain, altering pain perception, and inducing feelings of euphoria and relaxation. However, due to its high potency, fentanyl poses a high risk of overdose and is fatal if misused.

In contrast, naloxone serves as an opioid antagonist, blocking the effects of opioids at receptor sites. It is primarily employed in emergencies to reverse opioid overdose, especially when respiratory depression, a life-threatening complication, occurs. By binding to opioid receptors and displacing any opioids present, naloxone swiftly restores normal respiration and consciousness to individuals experiencing an overdose.

A fundamental difference between fentanyl and naloxone lies in their mechanisms of action. Fentanyl acts as an opioid agonist, activating opioid receptors to provide pain relief and euphoria. In contrast, naloxone acts as an antagonist, blocking these receptors and reversing the effects of opioids. This distinction underlies their contrasting roles in opioid use.

Moreover, fentanyl’s safety profile includes a significant risk of overdose, especially when used improperly or in excessive doses, which leads to respiratory depression, coma, and death. On the other hand, naloxone is relatively safe with minimal side effects when used as directed. It is not addictive, and it does not produce euphoria or other psychoactive effects.

In summary, fentanyl is a potent pain medication with a high risk of overdose, contributing to fentanyl addiction, while naloxone is non addictive and effective medication for reversing opioid overdose.