Naloxone vs. Naltrexone: Similarities & Differences

Naloxone and naltrexone are opioid antagonist drugs used to decrease the effect of opioid drugs or other street drugs. These medications belong to the same class but have different indications (approved uses by the Food and Drug Administration [FDA]).

Naloxone is an emergency drug, while naltrexone is used with social support to help people who quit street drugs and alcohol. Naloxone is a short-term drug that can be given to anyone to cope with an opiate overdose and restore breathing.

On the contrary, naltrexone can only be used after quitting the drugs and alcohol in the presence of a healthcare provider. Common brand names of naloxone are available, such as Zimhi, and for naltrexone, there is Vivitrol. 

Opiate overdose is one of the leading causes of drug overdose deaths. In 2021, more than 100,000 people died from an overdose. Most of these deaths involved synthetic opioids, taking the lives of 70,601 people in 2021.

Read below to find how these naloxone vs. naltrexone differ and how they can help prevent a life from drug abuse and overdoses.

What Is Naloxone?

Naloxone is an opioid antagonist. It is a life-saving drug that can quickly reverse the powerful effects of opioids during an overdose.

It is administered in various ways, such as intramuscular injection or nasal spray.

Naloxone is FDA-approved for the following indications:

• To manage the medical emergency treatment of known or suspected opioid overdose in adults and adolescents with respiratory and central nervous system (CNS) depression.
• After surgery, to reverse the effects of opiate medicines given during surgery.
• To newborns to decrease the effects of opiate medicines given to the pregnant person before delivery.

Naloxone can also used alongside bupropion, a partial opioid agonist, as a combinational medication to treat opioid dependence.

Buprenorphine alone and the combination of buprenorphine and naloxone prevent withdrawal symptoms when someone stops taking opioids.

Everyone who overdoses on prescription opioids or a recreational drug can use naloxone. Examples of opioids include heroin, Fentora (fentanyl), OxyContin (oxycodone), Vicodin (hydrocodone), codeine, and morphine.

Naloxone does not affect or cause harm to people without an opioid in their system and has another medical emergency, such as a diabetic coma or cardiac arrest. Administer naloxone to save a life even when unsure about an opioid overdose.

Naloxone is used by police officers, emergency medical technicians, non-emergency first responders, families, and caregivers of people at risk of opioid misuse.

In some states, you can get naloxone from a pharmacist without a prescription. It is also possible to get naloxone from other health clinics.

How Does Naloxone Work?

Naloxone is an opiate antagonist medicine that rapidly reverses an opioid overdose. It works by attaching to opioid receptors to reverse and block the effects of other opioids.

Naloxone can normal breathing within two to three minutes in a person whose breath has slowed, or even stopped, caused by high levels of opiates in the blood.

Naloxone does not affect someone who does not have opioids in their system. It is not a treatment for opioid use disorder. 

The FDA has approved two dosage forms for Naloxone: injectable and prepackaged nasal spray:

• Other prefilled, needle-free, over-the-counter (OTC) devices that require no assembly are sprayed into one nostril while the person lies on their back. Common brand names include Narcan.
• A single-dose, prefilled syringe Zimhi is available on prescription to inject into the muscle or given subcutaneously (under the skin).

Naloxone can be given to people of all ages, including adults, infants, children, and seniors.

What Is Naltrexone?

Naltrexone is an opiate antagonist approved by the FDA to treat opioid use disorder (OUD) and alcohol use disorder (AUD) on prescription. It is administered as an oral, swallowable tablet or via intramuscular injection.

Naltrexone is used in people who have stopped drinking alcohol and are not actively taking it anymore.

It also helps people with opioid dependence after opioid addiction treatment (also called opioid detoxification), along with counseling and social support.

Note that naltrexone should not be used in people still drinking and using opioids or other street drugs.

Other off-label uses of naltrexone may include pain, reduced inflammation, and treatment of conditions and diseases, including immune dysfunction and cancer.

It is also used in dermatology for treating trichotillomania (an urge to pull out one's hair) and different types of pruritus(itching).

Like naloxone, bupropion is also in tandem with naltrexone.

However, in this case, bupropion and naltrexone are used together with a diet/exercise to help adults who are obese or overweight and have weight-related medical problems lose weight and stop excess weight from returning.

Overall, naltrexone is a safe and effective drug when used as prescribed. However, it comes with a liver damage warning when used in large doses. It is a prescription drug and must be administered by a healthcare professional.

How Does Naltrexone Work?

Naltrexone works on opiate receptors to block the euphoric (feeling of excitement and happiness) and sedative effects of opioids and alcohol to reduce and suppress opioid cravings.

It is not addictive and does not cause withdrawal symptoms after discontinuation.

Regarding Naltrexone's affiliated brand names, it is marketed under Vivitrol. Vivitrol is an extended-release (which releases the drug in continued doses over some time) injection for subcutaneous use (under the skin).

In comparison, generic naltrexone is available in tablet form.

Dosing Comparison

The following outlines basic dosing guidelines for the use of naltrexone and naloxone. However, know that your specific dose may vary.

Recommended dosage of naloxone:

Each unit of nasal spray dosage form contains 4 milligrams (mg) of naloxone hydrochloride per device and delivers a single spray containing 4 mg of naloxone hydrochloride:

• Administer one spray intranasally to adults or children into one nostril.
• Administer additional doses every two to three using a new nasal spray device if the person does not respond or relapses into respiratory depression. 
• Call emergency medical assistance and do not leave the collapsed person while awaiting emergency medical assistance. 

Another dosage form of naloxone is 5 mg/0.5 milliliters (mL) naloxone hydrochloride solution in a single-dose, prefilled syringe for intramuscular or subcutaneous use only.

• Anyone above 12, including family, friends, and caregivers, can administer this injection.
• To adult or pediatric people into the thigh, through clothing if necessary. Stay there until emergency help arrives and administer repeated doses if necessary.
• Additional supportive or resuscitative measures may be helpful while awaiting emergency medical assistance.
• In children under 1 year old, pinch the thigh muscle while administering the dose. 

Recommended dosage of injectable naltrexone:

• Naltrexone is available under Vivitrol as an injectable suspension containing 380 mg of naltrexone in a microsphere formulation in a single-dose vial.
• The person receiving naltrexone must have an opioid-free duration of seven to 10 days before drug administration. 
• The recommended dose is 380 mg, delivered intramuscularly (IM) as a gluteal injection every four weeks or once a month.
• Administer in alternating buttocks for each next injection, using the carton components provided. 
• The safety and effectiveness of injectable naltrexone has not been established in children.

Recommended dosage of oral naltrexone:

• Adults: 25 mg (one-half tablet) for the first dose, then another 25 mg one hour later. After that, the dose is 350 mg per week.
• Your healthcare provider will have you divide up the weekly dose and take naltrexone according to one of the following schedules: 50 mg (one tablet) every day or 50 mg a day during the week and 100 mg (two tablets) on Saturday, or 100 mg every other day or 150 mg every three days.
• Children: The healthcare provider will determine the use and dose.

Comparing Efficacy

Naloxone is a short-acting drug used to reverse the effects of an opioid overdose. It is the most effective drug and improves breathing and other symptoms in two to three minutes in the affected person.

The FDA is working with other federal, state, and local officials to help increase the availability of naloxone to combat opioid overdoses.

While naltrexone is a drug for suppressing opioid use disorder and alcohol intake craving, counseling, and social support, it is a prescription and long-acting treatment. 

Clinical studies have shown that naltrexone helps people to remain abstain from alcohol for a longer duration than placebo.

Drug Overdose: Causes & Factors

An overdose is a toxic drug or substance that interferes with the brain and body’s functioning ability. The deaths from drug overdose remain a leading cause of death in the United States.

The majority of overdose deaths involve opioids. Deaths involving opioids such as fentanyl, cocaine, and methamphetamine have increased in recent years.

The number of people who died from a drug overdose in 2021 was over six times the number in 1999.

The number of deaths from drug overdose increased by more than 16% from 2020 to 2021. Over 75% of the nearly 107,000 drug overdose deaths in 2021 involved an opioid.

The most common opioid overdoses are caused by substance combinations such as methamphetamine and cocaine, alcohol and benzodiazepines, heroin and benzodiazepines, and others.

Certain factors or causes can increase the risk of an opiate overdose. Some of these factors include:

• Low drug tolerance
• Intravenous routes of drug
• Depression or psychotic disorders
• Recreational substance use

Side Effects & Safety

Naltrexone and naloxone are relatively effective and safe drugs for emergencies. However, like all drugs, they do carry the potential for common, minor side effects and more severe ones.

Be sure to tell your healthcare provider if you have any side effect that bothers you or does not go away. 

Common Side Effects

Common side effects associated with the use of naloxone include:

• Nausea
• Dizziness
• Lightheadedness
• Increased red blood cell breakdown products (bilirubin) in the blood

In comparison, common side effects associated with the use of naltrexone include:

• Nausea
• Headache
• Dizziness
• Vomiting
• Decreased appetite
• Painful joints
• Cold symptoms
• Trouble sleeping
• Toothache

Severe Side Effects

Naloxone may cause serious side effects, including:

• Sudden opioid withdrawal symptoms, such as body aches, fever, sweating, shivering or trembling, nervousness, restlessness or irritability, diarrhea, increased blood flow and heart rate, stomach cramping, and others.
• In infants under 4 weeks old receiving opioids regularly, sudden opioid withdrawal may be life-threatening if not treated immediately. Signs and symptoms include seizures, unusual crying, and increased reflexes.

Call your healthcare provider or ask for immediate medical help if you or anyone develop these symptoms.

Comparatively, naltrexone has some severe side effects that need medical attention, including the onset of depression. 

The depressed mood needs help from family, friends, and a healthcare provider. A depressed person may have the following symptoms such as:

• Suicidal thoughts/behavior
• Antisocial behavior
• Feeling hopelessness
• Sleepiness
• Difficulty to concentrate

Naltrexone is also associated with pneumonia. Pneumonia is associated with shortness of breath, wheezing, or coughing that does not go away.

Allergic reactions to the drug cause symptoms such as:

• Skin rash
• Swelling of your face, eyes, mouth, or tongue
• Trouble breathing or wheezing
• Chest pain

Finally, naltrexone may cause liver damage if taken in higher doses, including symptoms such as stomach area pain, dark urine, yellowing of the whites of the eyes, and tiredness.

Who Should Avoid Naloxone or Naltrexone?

Closely monitor people taking naltrexone drugs for the following problems:

• People who try to overcome this blocking effect by taking large amounts of opioids may experience serious liver injury, coma, or death.
• Drug withdrawal effects
• Depression and suicidal thoughts
• Hypersensitivity reactions

Regarding using naltrexone and naloxone in pregnant and breastfeeding people, those people should use them with care to avoid adverse effects.

Potential for Interaction

Always mention all the drugs you are taking to your healthcare provider before starting treatment with any drug.

Naloxone is an immediate response medicine and is usually safe to administer and does not interact with most drugs.

In comparison, Naltrexone antagonizes (cancels) the effects of opioid-containing medicines, such as cough and cold medication, antidiarrheal preparations, and opioid analgesics, such as Methadose (methadone). These medicines may not be helpful when taking Naltrexone therapy.

Do not take any opioid medications or use opioid street drugs during the past seven to 10 days of treatment with naltrexone.

Summary

From 1999-2021, nearly 645,000 people died from an overdose involving any opioid, including prescription and illegal opioids.

Many lives can be saved by taking swift measures, including emergency help and follow-up support. 

Naloxone and naltrexone are two opiate antagonist drugs that can play a part. These drugs belong to the same class but are used for different purposes. 

Naloxone is an emergency help given to adults and children experiencing an overdose. It works within a few minutes to improve the symptoms.

Call for emergency help after giving naloxone. Carry naloxone or keep it at home if you or someone else is at increased risk for opioid overdose or struggling with OUD.

Naltrexone is a long-term treatment given to people who quit alcohol and opiate drug abuse by a healthcare professional. 

It is not easy to struggle against opioid misuse. Medications, social help, family and friends support, and professional help can play a part. Never be afraid to talk about it and ask for help.