Naloxone Side Effects and What to Expect After Reversal

If you’re ever worried about giving naloxone because you might hurt someone or make the situation worse, you’re not alone. Many people hesitate during an overdose emergency because they’re afraid they’ll make the wrong decision. Fortunately, the evidence is reassuring: Narcan is a very safe medication, serious naloxone side effects are rare, and giving it during a suspected opioid overdose is almost always safer than waiting.

Naloxone (commonly known by the brand name Narcan) works by temporarily blocking the effects of opioids and restoring normal breathing in someone experiencing an opioid overdose. It has been used by healthcare professionals for more than 50 years and is now available over the counter. This makes it easy for family members, friends, caregivers, and other bystanders to respond quickly during an emergency.

In this guide, we’ll explain naloxone’s side effects, what happens after someone wakes up, why a second overdose is possible, how to store naloxone properly, and when emergency medical care is still needed. Understanding what to expect can help you act with confidence if you ever need to use naloxone to save a life.

Is Naloxone Safe?

Yes. Naloxone is considered a very safe medication. First approved by the U.S. Food and Drug Administration (FDA) in 1971, it has a long history of safely restoring breathing when a person is experiencing an opioid overdose. Today, healthcare professionals, first responders, caregivers, and members of the public carry Narcan with them because of its strong safety profile.

Naloxone is not a controlled substance, cannot produce a high, and has no potential for misuse or addiction. It works by attaching to opioid receptors in the brain and temporarily blocking the effects of opioids. If opioids are not present, naloxone has essentially no effect on the body.

For most people, Narcan side effects are mild or nonexistent. Some people may notice temporary nasal irritation, dryness, or congestion after using a nasal spray.

However, for people who are physically dependent on opioids, naloxone can trigger sudden withdrawal symptoms because it rapidly removes opioids from their receptors. While this reaction can be uncomfortable, it is a sign that the medication is working to reverse a potentially fatal overdose.

Serious side effects from naloxone are uncommon, and the risk of an untreated opioid overdose is far greater than the risk of a reaction to the medication. That’s why public health experts recommend giving naloxone whenever an opioid overdose is suspected. If you’re unsure whether opioids are involved, it’s still safer to administer naloxone than to wait while the person’s breathing slows or stops.

Can Narcan Hurt Someone Who Is Not Overdosing?

No. If someone is not experiencing an opioid overdose, giving naloxone will not harm them. Since naloxone works by blocking opioids from attaching to opioid receptors, it has little to no effect on someone who does not have opioids in their system.

This is one of the main reasons healthcare professionals encourage people to use naloxone whenever an opioid overdose is suspected, even if they aren’t completely sure. It’s smart to carry naloxone and administer it whenever an opioid overdose is suspected.

If the person is experiencing a different medical emergency, such as a stroke, diabetic emergency, or overdose involving only non-opioid drugs, naloxone will not treat the underlying problem. However, it generally will not make the situation worse, either.

This is why calling 911 is always an essential part of responding to a suspected overdose. Emergency responders can identify and treat whatever medical condition is causing the person’s symptoms.

The potential consequences of waiting are far greater than the risks of giving naloxone unnecessarily. If opioids are causing the person’s slowed or stopped breathing, every minute without treatment increases the risk of permanent brain injury or death. If opioids are not involved, naloxone simply won’t have much effect, and it is unlikely to cause harm.

Some parents and caregivers also wonder what would happen if a child accidentally found naloxone at home. Naloxone itself is unlikely to harm a child who is not experiencing an opioid overdose. However, nasal spray devices and injectable naloxone kits should still be stored safely out of children’s reach to prevent choking hazards, accidental needle sticks, or misuse of the packaging.

What Is Precipitated Withdrawal?

One of the most common side effects of naloxone is precipitated withdrawal. This occurs when the medication suddenly removes opioids from the brain’s opioid receptors in someone who is physically dependent on them.

Although the reaction can be intense and happen within minutes, it is not the same as an allergic reaction or medication poisoning, and it is what to expect after giving naloxone. It is a rapid onset of opioid withdrawal caused by naloxone reversing the overdose.

For the person experiencing it, precipitated withdrawal can be unpleasant and sometimes frightening. However, it’s important to remember why it happens: Naloxone is restoring breathing and reversing a potentially fatal overdose.

While withdrawal symptoms are uncomfortable, they are generally not life-threatening. An untreated opioid overdose, on the other hand, can quickly become fatal.

Symptoms of Precipitated Withdrawal

Symptoms can vary depending on the person and the amount of opioids in their system, but they often begin within minutes of giving naloxone.

Common symptoms of precipitated withdrawal include:

• Nausea and vomiting
• Diarrhea or stomach cramps
• Sweating and goosebumps
• Runny nose, sneezing, or yawning
• Body aches and muscle pain
• Shivering or trembling
• Rapid heart rate or increased blood pressure
• Anxiety, irritability, restlessness, or nervousness
• Agitation or confusion after waking

Some people may wake up frightened or disoriented because they do not remember overdosing or understand what has happened. Although stories of people becoming violent after receiving naloxone are common, severe combativeness is relatively uncommon. Most people are simply uncomfortable, confused, and experiencing sudden withdrawal.

Why It Happens

Naloxone has a stronger attraction to opioid receptors than opioid drugs themselves. When it’s administered, it quickly displaces opioids from those receptors, abruptly stopping their effects. For someone whose body has become dependent on opioids, that sudden change triggers withdrawal symptoms almost immediately.

Although precipitated withdrawal can be distressing to witness, it is temporary. Naloxone’s effects typically wear off within 30 to 90 minutes, and there are no known long-term side effects from the medication itself.

Most importantly, the discomfort of withdrawal should never discourage someone from giving naloxone. Restoring breathing and preventing death is always the priority during a suspected opioid overdose.

Can Someone Overdose Again After Narcan Wears Off?

Yes. Although naloxone works quickly to reverse an opioid overdose, its effects are temporary. In most people, naloxone remains active for about 30 to 90 minutes, while many opioids, including fentanyl and methadone, can remain in the body much longer.

This means someone can stop breathing again after the naloxone wears off if the opioids are still affecting their body. It’s important to recognize signs of a second opioid overdose in case the person experiencing the overdose needs a second dose of naloxone.

Whether a second overdose occurs depends on several factors, including the type of opioid involved, how much was taken, the person’s metabolism, liver function, and whether they use more opioids after waking up. Since these factors are impossible to judge during an emergency, you should always assume the person still needs immediate medical attention, even if they seem fully awake and alert.

This is why calling 911 is so important. Naloxone is a bridge to emergency medical care, not a substitute for it. Stay with the person until emergency responders arrive, monitor their breathing, and be prepared to give another dose of naloxone if their symptoms return.

Someone who wakes up in withdrawal may feel a strong urge to use opioids again to relieve their symptoms. While this reaction is understandable, using opioids again before the naloxone has completely worn off can significantly increase the risk of another overdose. Offer reassurance, explain that help is on the way, and encourage them to wait for medical evaluation rather than using again.

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What If the Person Becomes Agitated or Combative?

It’s common for someone to wake up confused, frightened, or upset after receiving naloxone. In many cases, they have no memory of overdosing and may not understand why emergency responders are present or why they suddenly feel sick. These reactions are usually caused by the abrupt onset of opioid withdrawal rather than the naloxone itself.

Most people are not truly combative after naloxone. They may be restless, anxious, irritable, or eager to leave because they’re experiencing uncomfortable withdrawal symptoms. While some people can become aggressive, severe violence is relatively uncommon. Knowing this ahead of time can help you stay calm if someone reacts unexpectedly after waking up.

If the person becomes agitated, try to remain calm and speak in a reassuring voice. If they’re awake enough to understand you, explain what happened simply. For example, you might say something like, “You overdosed, I gave you naloxone, and an ambulance is on the way.”

Avoid arguing, shouting, or trying to physically restrain them unless it’s necessary to prevent immediate harm. If they’re drowsy or drifting back to sleep, place them in the recovery position and continue monitoring their breathing until emergency responders arrive.

Your own safety also matters. If someone becomes genuinely threatening or violent, move to a safe distance and allow emergency medical personnel or law enforcement to manage the situation.

Even so, the possibility of agitation should never discourage you from giving naloxone during a suspected overdose. Restoring someone’s breathing is always the first priority, and most people wake up confused and uncomfortable, not dangerous.

Does Naloxone Expire? Storage and Shelf Life

Naloxone does not last forever, but it has a relatively long shelf life when stored properly. Most naloxone products have an expiration date approximately 18 to 24 months after they are manufactured. The expiration date indicates how long the manufacturer guarantees the medication will remain at full potency when stored according to instructions.

How to Store Naloxone

To help naloxone remain effective, store it at room temperature in its original packaging until it’s needed. Keep it away from direct sunlight, excessive humidity, and extreme temperatures.

Although it may be convenient to keep naloxone in a car for emergencies, prolonged exposure to very hot or very cold temperatures can reduce its effectiveness. If possible, store it in a location where the temperature remains relatively stable, such as inside your home or in a bag you carry regularly.

You should also avoid refrigerating or freezing naloxone unless the product’s instructions specifically say otherwise. Keeping track of expiration dates and replacing expired kits when possible helps ensure you’ll have the most effective medication available in an emergency.

Can You Use Expired Naloxone?

Yes. If expired naloxone is all you have during a suspected opioid overdose, you should still use it. While the medication may gradually lose some potency after its expiration date, research suggests that naloxone can remain effective beyond the date printed on the package. An expired dose is far better than no dose at all when someone’s breathing has slowed or stopped.

After the emergency, replace expired naloxone with a new kit as soon as you can. Many pharmacies, community organizations, and public health programs offer replacement naloxone at little or no cost. Being mindful of storage conditions and expiration dates can help ensure your naloxone is ready when you need it most.

Allergic Reactions and When to Worry

Serious reactions to naloxone are rare, but as with any medication, they are possible. Most people who receive naloxone experience either no side effects or temporary opioid withdrawal symptoms. True allergic reactions and other severe complications occur infrequently, and they should never prevent someone from giving naloxone during a suspected opioid overdose.

A serious allergic reaction may include symptoms such as swelling of the lips, tongue, or throat, hives, or difficulty breathing. In very rare cases, pulmonary edema (fluid buildup in the lungs) has also been reported after naloxone administration. These reactions require immediate medical attention, but they are uncommon compared with the immediate danger posed by an untreated opioid overdose.

Fortunately, emergency medical care should already be on the way. Anyone who receives naloxone should be evaluated by emergency medical personnel, even if they appear to recover completely. If a rare allergic reaction or another complication develops, emergency responders are equipped to recognize and treat it.

Naloxone is a short-acting medication, and its effects typically wear off within a few hours. There are no known long-term side effects from naloxone itself. For the overwhelming majority of people, the benefits of restoring breathing during an opioid overdose far outweigh the small risk of a serious adverse reaction.

If you ever suspect someone is experiencing an overdose, don’t let fear of naloxone side effects stop you from acting. Administer naloxone, call 911 immediately, and stay with the person until emergency medical help arrives. Acting quickly can save a life.

Frequently Asked Questions

Get Help for Opioid Use Disorder

Naloxone can save a life during an opioid overdose, but it is not a treatment for opioid use disorder. If you or someone you care about has experienced an overdose, needed naloxone, or is struggling with opioid use disorder, professional treatment can provide the support needed for long-term recovery.

Treatment may include medical detox, medication-assisted treatment (MAT), inpatient or outpatient rehabilitation, counseling, behavioral therapies, and ongoing recovery support. The right treatment plan depends on each person’s needs, health history, and recovery goals.

If you or a loved one is ready to take the next step, Rehab.com can help you explore evidence-based treatment options and connect with programs that fit your situation. Recovery is possible, and reaching out today could be the first step toward a healthier, safer future.