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Naloxone (available in branded products like Narcan) is a safe and effective opioid overdose reversal medication that has been used in emergency medicine for several decades. Naloxone acts as an opioid antagonist that rapidly reverses the effects of opioid drugs, and it is a life-saving medication when used for an opioid overdose. Naloxone can produce some unpleasant side effects, particularly in those who are dependent on opioid drugs. [1][2][3] This article will review common and serious side effects of naloxone.
- Naloxone is an opioid overdose reversal agent that is widely used in emergency medicine to prevent fatal complications related to opioid overdose.
- Naloxone is considered highly safe and effective and rarely causes serious complications or side effects.
- The most common side effect of naloxone is the risk of precipitated withdrawal symptoms in individuals who are opioid dependent.
Naloxone overview
Naloxone is an opioid antagonist medication that can rapidly reverse the effects of an opioid drug, particularly after a suspected overdose. This medication works within minutes of administration to displace opioids from receptors in the brain, potentially reversing respiratory depression associated with opioid overdose. Because opioid overdose is a leading cause of preventable death, naloxone is considered a staple of emergency medicine and essential to public health. [1][3]
Naloxone is considered an extremely safe medication and has been used for over five decades. It has no abuse or addictive potential, and it is linked to only minor side effects in most individuals. When naloxone is given to someone who has no opioids in their system, the medication has virtually no effect at all, so it can be safely given in suspected overdoses when it is not possible to confirm whether a person has taken opioids. [1][2]
Naloxone is available as an intranasal spray (aka Narcan) and also as an injectable formula. The intranasal spray formulation is more widely used by the public. Both versions of the medication work within minutes of being administered and have a similar half-life. Both the injectable and intranasal formulations of naloxone are FDA-approved and are effective at reversing an opioid overdose. [1][2]
When administered, naloxone begins working within approximately 2–3 minutes, and effects typically last between 30–90 minutes. [2] Certain opioids, like methadone and other synthetic opioids, remain active longer than naloxone, so this medication may need to be administered more than once to avoid recurring overdose symptoms. [1] After giving naloxone, emergency medical services should always be contacted, even if the person initially appears to have made a full recovery.
Common side effects of naloxone
The side effects of naloxone are minimal and tend to be mild and transient in nature.
Commonly reported side effects of naloxone include: [2]
- Nasal irritation.
- Increased blood pressure.
- Headaches.
- Musculoskeletal pain.
- Nasal dryness.
- Nasal edema.
- Nasal congestion.
Precipitated withdrawal
Another common side effect of naloxone is precipitated withdrawal. When given to a person with opioid intoxication who also has an existing physical dependence on opioids, naloxone can cause the onset of sudden, intense withdrawal symptoms. This phenomenon, known as precipitated withdrawal, is caused when naloxone rapidly displaces opioids from receptors in the brain. [1][3]
Symptoms of precipitated withdrawal following naloxone administration include the following: [4]
- Extreme nausea and vomiting.
- Severe body aches or pains.
- Stomach cramps and diarrhea.
- Severe agitation, restlessness, and anxiety.
- Chills, shaking, or tremors.
- Sweating and hot flashes.
- Change in pupil size.
- Gooseflesh or chill bumps.
- Excessive yawning.
- Runny nose and watery eyes.
- Muscle twitching or spasms.
- Bone and muscle aches.
- Strong opioid cravings.
- Elevated heart rate and blood pressure.
It’s important to understand that while the above symptoms can be triggered by naloxone, they are actually caused by an underlying opioid dependence. While precipitated withdrawal symptoms are highly uncomfortable and distressing, they are usually not medically dangerous. There is no formal treatment for precipitated withdrawal, but medications may be administered to help provide symptom relief. Most of the time, precipitated withdrawal symptoms subside on their own within 24–48 hours. [4]
Serious side effects of naloxone
In most cases, naloxone side effects are mild and transient in nature. Serious adverse events following naloxone administration are uncommon but have been reported, particularly in those with significant cardiovascular disease or other serious pre-existing conditions.
Potential serious complications include the following: [1][2][3]
- Severe precipitated opioid withdrawal.
- Pulmonary edema (rare).
- Cardiac arrhythmias.
- Significant hypertension.
- Hypotension.
- Cardiac arrest (rare).
- Seizures (rare).
- Severe agitation or aggressive behavior.
- Aspiration due to vomiting.
Most reported serious cardiovascular events either occur in critically ill patients or are related to the physiologic stress associated with overdose reversal rather than direct toxicity from naloxone itself. Overall, the medication remains considerably safer than untreated opioid overdose. [1][3]
Naloxone contraindications and risk factors
There are very few contraindications associated with naloxone, and none that preclude healthcare professionals from using the medicine in emergency situations involving potential opioid overdose. Even if a person is known to have a sensitivity or allergy to naloxone, the benefits of using naloxone in a suspected opioid overdose usually outweigh the risks. [3]
Still, there are certain individuals who are more likely to experience side effects or complications when given naloxone: [3]
- People who are physically dependent on opioids and have opioids in their system.
- People using long-acting opioids, like methadone.
- Older adults and those with pre-existing heart or other medical conditions.
- Pregnant women.
- Newborns who are born opioid-dependent.
How to safely use naloxone
People at increased risk for opioid overdose and those using opioids together with benzodiazepines or other central nervous system depressants should consider carrying naloxone. They should also ensure family members or caregivers know where it is stored and how to use it. Most at-home formulations of naloxone are administered through a nasal spray that is easy to use.
Safe naloxone administration involves several important steps: [1]
- Recognize the signs of opioid overdose, including unresponsiveness, slow or absent breathing, pinpoint pupils, and blue lips or fingernails.
- Call 911 immediately to request on-site medical help.
- Administer naloxone according to the product instructions.
- Begin rescue breathing or CPR if indicated.
- If there is no response after 2–3 minutes, administer another dose.
- Continue monitoring until emergency responders arrive.
- Because naloxone's effects may wear off before the opioid does, monitor for recurrent respiratory depression.
- Provide any information you have to emergency responders, including prescribed medications, substances used, and time and dose.
Final thoughts
Naloxone is a medication that is used as a frontline emergency treatment for opioid overdose. When administered intranasally, naloxone can reverse symptoms of a fatal overdose within minutes. The primary side effect of naloxone is precipitated withdrawal, which is the sudden and intense onset of withdrawal symptoms in individuals with an opioid dependence. Aside from this risk, most people tolerate naloxone well and do not experience any major side effects. [1][2][3]
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