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August 21, 2018

Naltrexone vs. Narcan: What Are They, and How are They Used for Opiate Overdoses and Treatment?

doctor doing work on laptopNaloxone vs Naltrexone. They are two must-have tools in the fight against today’s opiate epidemic but what’s the difference? Learn all about them here:

The scourge of opiate addiction and the heartbreaking number of overdose deaths may indeed seem like a plague. It did start slowly in 1999 and gained momentum, sweeping the country and now affecting all demographics. According to the Centers for Disease Control and Prevention (CDC), opiate overdose deaths, including heroin and prescription opiates, quadrupled since 1999, with 115 American deaths each day from an opiate overdose.

Millions using prescribed opiates to relieve chronic pain become addicted to the drug and turn to heroin as a substitute when they no longer have access to prescription opiate painkillers. According to research, nearly 80 percent of those using heroin (including those in treatment), report first misusing prescription opiate drugs. Since 1999, prescription opiate deaths from oxycodone, methadone, hydrocodone, and fentanyl have increased more than five times.

Fortunately, two medications, naltrexone and naloxone (Narcan®), can help address the opiod epidemic and prevent needless deaths from overdoses. Here’s what they are and how they are used in opiate overdoses and treatment.

If you or a love one is suffering from opiate addiction, please review our treatment program and learn how long it takes to withdraw from opiates.  


The U.S. Food and Drug Administration (FDA) approved the prescription drug naltrexone to treat both opiate use disorders and alcohol use disorders. Naltrexone is used during medication-assisted treatment (MAT) programs for individuals who have undergone detoxification (detox) and have been free of opiates for a minimum of 7-10 days. It must not be used by those currently using opiates, as doing so could cause severe withdrawal symptoms. Naltrexone is available in pill form (brand names, ReVia and Depade) or injectable form (brand name Vivitrol).

How Naltrexone Works

Naltrexone belongs to a class of drugs known as opiate antagonists. It works by interfering with or blocking the two major effects users of drugs such as heroin, morphine and codeine seek: sedation and euphoria. Rather than activating the body’s opioid receptors to suppress cravings like the prescription medications methadone and buprenorphine do, naltrexone works to bind and block opioid receptors to reduce cravings. A plus is that naltrexone has no abuse or diversion potential.

Used as Part of a Comprehensive Treatment Plan

During treatment of opiate use disorders, naltrexone is included in the overall treatment plan and is combined with counseling, various treatment modalities, such as cognitive-behavioral therapy (CBT), and participation in social support programs and self-help groups like Narcotics Anonymous (NA).

Careful monitoring by the treatment team ensures that any medication changes necessary, as well as modifications to other aspects of the treatment plan, are implemented quickly. For example, those prescribed oral naltrexone may be transitioned to injectable naltrexone if the treatment team concludes that the injectable form of naltrexone would be more beneficial to continued abstinence. Because treatment with naltrexone reduces tolerance to opiates, clients who relapse may overdose by going back to the same or even lower doses of the drugs they previously took. For this reason, and the fact that relapse risk is greatest for the first 6-12 months following treatment, a solid relapse prevention plan will be an integral part of the overall treatment plan for opiate use disorder.


Naloxone is an ingredient most commonly known for its use in Narcan® and Evzio, which is used for the emergency treatment of a person overdosing (or suspected of overdosing) on opiates such as heroin, prescription painkillers like fentanyl, morphine, codeine, methadone, oxycodone, hydrocodone, hydromorphone, and Vicodin, as well as buprenorphine. When administered to someone experiencing acute opiate overdose, Narcan® can literally save their life. Narcan® is available as an injectable solution, and a prefilled, needle-free nasal spray. Injections can be administered into a vein (intravenously), just under the skin (subcutaneously), or intramuscularly (into a muscle). Evzio markets a prefilled auto-injection device for quicker delivery of naloxone.

What is Narcan Used for and How it Works

Naloxone (Narcan®) is an FDA-approved drug in three formulations that reverses the effects of an overdose from heroin and certain types of painkiller medications. This life-saving drug has been used by paramedics and emergency room physicians for years with good success. The medication works by blocking the effects of drugs made from opium. The specific process is that Narcan® binds to mu-receptors in the brain, thereby reversing opioid activity in the body. Opiates use the brain’s mu-receptors to produce their effect on the brain. Since opiates slow breathing, emergency counter-action is required to restore it before serious brain damage or death occurs. Once naloxone has been administered to the person experiencing an overdose, regular breathing resumes, generally within minutes.

Symptoms of Opiate Overdose

Being able to recognize an opiate overdose (or suspected overdose) may make the difference between a life saved and a life lost. Symptoms include:

  • Excessive sleepiness
  • Pale face, in addition to or face that feels clammy to the touch
  • Bluish or purplish lips or fingernails
  • An inability to wake when yelled at in a loud voice or when the chest is pressed or rubbed
  • Breathing that is shallow or stopped
  • Small pupils
  • Vomiting or gurgling
  • Limpness

How to Administer Narcan®

When someone is overdosing, minutes count. Quick action is necessary to save a life, including performing cardiopulmonary resuscitation (CPR). Anyone attempting to resuscitate an overdosing person must ensure they know how to do it effectively. A pharmacist or doctor can train family members, patients and caregivers how to safely administer Narcan®. In addition, the Harm Reduction Coalition lists detailed instructions on the safe administration of Narcan® as a nasal spray or injectable form to someone in an overdose condition. Call 911 immediately after administering Narcan® and remain with the individual until emergency help arrives. If symptoms return before help arrives, another dose of Narcan® can be given every 2-3 minutes.

The Substance Abuse and Mental Health Services Administration (SAMHSA) provides an opioid overdose prevention toolkit available online. This can be a valuable resource to first responders, patients, family members and prescribing physicians.

Don’t let an addicted loved one, family member or friend become an opiate overdose statistic. Education, training and a willingness to spring into action can mean all the difference. When you know what to do and how to help someone struggling with opioid addiction, you’re empowered, confident and perhaps the best-equipped one to encourage professional addiction treatment once the crisis is past.

Used as an Alternative to Suboxone and Methadone

Two other common treatment medications for opioid addiction to substances such as heroin, fentanyl and other opiates are Suboxone and methadone. Both methadone, a once-per-day medication, and Suboxone activate the same neurological receptors as heroin, but prevent withdrawal and relapse. Controversy surrounds methadone, particularly for its use in treating opiate addicts in the criminal justice system, as critics say it’s substituting one addictive drug for another. Methadone can be sold and has been linked with abuse. Some patients enter drug rehab for methadone abuse.

The injectable form of naltrexone, on the other hand, which the FDA approved in 2010, is a once-monthly injection, and is now used in some drug rehab treatment facilities as an alternative to Suboxone and methadone in treating opiate addiction. A University of Pennsylvania School of Medicine study in 2016 found that naltrexone is a viable treatment for heroin addicts, especially those in the criminal justice system considered at high risk of relapse. Results showed no overdoses and lower relapse rate than patients with usual treatment and researchers called for long-term studies of the effectiveness of treatment with extended-release naltrexone.

A separate NIDA clinical trial conducted between 2014 and 2016 compared treatment effectiveness of extended-release injectable naltrexone (XR-NTX) with Suboxone (sublingual buprenorphine and naloxone), and found that both were safe and effective overall, although it was more difficult to initiate patients into the injectable extended-release naltrexone. 24-week relapse events were similar for across groups in the study, while opiate craving was initially less in XR-NTX and converged with Suboxone by week 24, and mild-to-moderate injection site reactions occurred with XR-NTX. There were five overdoses with XR-NTX and three with Suboxone during the clinical trial. The study results called for future work on facilitating induction into XR-NTX and improving treatment retention outcome for both medications.

Naltrexone Pros and Cons

Hailed as an opioid dependence treatment medication that may replace other older or currently-used medications, naltrexone has its pros and cons, just as most other medications do.

Naltrexone Pros

Among the notable benefits for using naltrexone:

  • It may help prevent drug use and relapse.
  • The medication is a non-addictive opiate antagonist.
  • Administered as a once-a-month injection, naltrexone is convenient and easier to remember to take.
  • Naltrexone may have less severe effects than other forms of medications used in the treatment of opioid dependence.
  • Blood levels may stay more stable than with other oral forms of naltrexone.

Naltrexone Cons

Some of the cons for naltrexone use include:

  • The patient must be clean from opiates and alcohol for a period of 7-10 days prior to starting naltrexone.
  • Cravings may be intense during the first week prior to starting naltrexone, and treatment providers should provide the patient with appropriate coping approaches.
  • Patients transitioning from buprenorphine or methadone to naltrexone may be vulnerable to precipitation of withdrawal symptoms for up to two weeks.
  • Naltrexone may not be appropriate or safe for pregnant or breastfeeding women.
  • After detoxing and treatment with naltrexone, patients have less tolerance to opiates as naltrexone blocks the opiate’s effects for 28 days. Opiate intoxication may occur if the patient resorts to previously-used doses of opiates.
  • Fatal overdose is possible due to taking more of the drug to feel its effects, and can cause severe respiratory depression resulting in death.
  • Severe liver damage can result if naltrexone is taken in larger than recommended doses.
  • Injection site reactions may range from mild to intense pain, swelling, redness, nodules and infection.


With the potential to save a human life from opiate overdose, reversing the effects of opioids, Naloxone is legitimately considered a “miracle” drug. Still, naloxone hydrochloride (Narcan) has a list of pros and cons to keep in mind.

Naloxone (Narcan) Pros

  • In the case of opiate overdose, minutes count. Prompt administration of Narcan can save a life.
  • Now the life-saving medication is available in more states to first responders and law enforcement officials.
  • Injectable naloxone is convenient and ready to use in an emergency.
  • Family members and non-emergency personnel now have access to prescription Narcan to give emergency treatment to loved ones having or suspected of having an opioid overdose. State laws governing naloxone dispensing vary, yet 51 percent of states have naloxone access laws on the books and 50 percent of states allow pharmacies to dispense naloxone without an individual prescription.
  • Easier access to naloxone means opiate users, family members and friends can obtain the life-saving medication through pharmacies such as Walmart, CVS, Rite Aid, Target, Walgreens and others.

Naloxone (Narcan) Cons

  • Acute opiate withdrawal can be precipitated in opiate-dependent patients and those with substance abuse issues.
  • Narcan should be used with caution in patients with hepatic disease, as naloxone is metabolized in the liver.
  • Elderly patients are more likely to have age-related heart, kidney or liver problems which may require caution in administering Narcan.
  • Interaction with other drugs, both prescription and over-the-counter (OTC) drugs, vitamins and herbal products may occur.
  • Individuals with paraben sensitivity should not be given Narcan, as the solution contains methylparaben and propylparaben.
  • Death can occur if EMS has not been summoned and arrives in time after the first dose, since the duration of opiates likely exceeds that of naloxone. Fentanyl and fentanyl analogs (synthetic fentanyl), for example, is so powerful that repeated administration of Narcan may be required to restore respiration in the event the patient has stopped breathing or breathing has slowed.
  • Lack of proper training on how to continue to administer naloxone may result in deaths of those overdosing from opiates.


Why is Vivitrol the preferred treatment approach for some individuals in recovery? Vivitrol has been used to treat dependence on both opiate drugs and alcohol. The drug only affects the way the body responds to the narcotic drugs or alcohol, helping prevent relapse by turning off receptivity in the brain to the pleasurable effects of the substances.

The medication should only be administered by a healthcare provider as an intramuscular gluteal injection. According to the drug manufacturer, Alkermes, Inc., Vivitrol must not be injected subcutaneously or intravenously.

Side Effects

Side effects and adverse reactions to medications, including those used during MAT therapy for opiate dependence should always be explained to the patient.

Side effects of Naltrexone (Vivitrol) include:


  • Allergic reaction
  • Anxiety
  • Decreased sex drive
  • Depressed mood
  • Dizziness
  • Headache
  • Increased thirst
  • Insomnia
  • Irritability


  • Liver damage
  • Loss of appetite
  • Muscle or joint aches
  • Nausea
  • Nervousness
  • Pneumonia
  • Restlessness
  • Tiredness
  • Vomiting


Serious side effects include blurred vision, rapid heartbeat, difficulty breathing, hallucinations, confusion, thoughts of suicide, dark urine, clay-colored stools and jaundice.

Adverse reactions of Naltrexone (Vivitrol), occurring in less than two percent of opiate-dependent patients include:

  • Hepatic enzyme abnormalities
  • Injection site pain
  • Insomnia
  • Nasopharyngitis
  • Toothache

Side effects of naloxone (Narcan) include:


  • Body aches
  • Convulsions
  • Cramps in the abdomen or stomach
  • Diarrhea
  • Difficulty breathing, shallow breathing
  • Fever
  • Goose bumps
  • Irritability
  • Nausea


  • Nervousness
  • Pale (or blue) lips, skin and fingernails
  • Rapid or irregular heartbeat or pulse
  • Runny nose, sneezing
  • Shivering
  • Sweating
  • Vomiting
  • Weakness
  • Yawning


Narcan adverse reactions include:


  • Agitation
  • Confusion
  • Constipation
  • Dental pain
  • Dizziness
  • Drug interactions
  • Hallucinations
  • Hot flashes
  • Hypoxia


  • Potential adverse cardiac effects, such as hypotension, ventricular tachycardia or fibrillation, and pulmonary edema in patients with cardiac disease or receiving cardiac drugs
  • Respiratory depression
  • Risks to the fetus of an opioid-dependent mother, neo-natal abstinence syndrome
  • Tremor
  • Withdrawal


For related information, see these articles:



Centers for Disease Control and Prevention. “Understanding the Epidemic,” “Drug overdose deaths in the United States continue to increase in 2015.” Retrieved from “Naloxone Side Effects.” Retrieved from “Naltrexone.” Retrieved from

Harm Reduction Coalition, “Administer Naloxone: Overdose Response.” Retrieved from

Lancet. “Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label randomised controlled trial.” Retrieved from

National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA). “America’s Addiction to Opioids: Heroin and Prescription Drug Abuse.” Retrieved from

National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA). “Federal Efforts to Combat the Opioid Crisis: A Status Update on CARA and Other Initiatives.” Retrieved from

National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA). “Opioid Overdose Reversal with Naloxone (Narcan, Evzio). Retrieved from

New England Journal of Medicine. “Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders.” Retrieved from

Partnership for Drug-Free Kids. “How to Use Naloxone to Reverse Opioid Overdose and Save Lives.” “Where can I get naloxone?” Retrieved from

Prescribers’ Digital Reference. “naloxone hydrochloride – Drug Summary.” Retrieved from

Substance Abuse and Mental Health Services Administration (SAMHSA). “Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid-Use Disorder: A Brief Guide,” “Monitoring Patient Progress and Adjusting the Treatment Plan.” Retrieved from

Substance Abuse and Mental Health Services Administration (SAMHSA). “Naltrexone,” “How Naltrexone Works.” Retrieved from

Substance Abuse and Mental Health Services Administration (SAMHSA). “SAMHSA Opioid Overdose Prevention Toolkit.” Retrieved from  

Vivitrol. “Vivitrol. [naltrexone for extended-release injectable suspension].” Retrieved from

WebMD. “Treating a Drug Overdose With Naloxone.” Retrieved from