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Does Naloxone Have Any Drug Interactions?

Claire Wilcox, MD profile image
Medically Reviewed By Claire Wilcox, MD • Updated Aug 11, 2023 • 6 cited sources

Naloxone quickly kicks opioids off receptors in the brain to temporarily stop overdoses, so someone overdosing on opioids has time to get emergency medical treatment. Although naloxone is not addictive and has very few physical side effects, the medicine can interfere with some prescription drugs.

Some prescription medications can interact with naloxone, which means  it might reduce or increase the effectiveness of these medicines or, conversely, the intensity of its effect might be altered by these medications.  Additionally, there are some known interactions with over-the-counter drugs and herbal supplements.

Talk to your doctor about any prescription medicines, physical or mental health issues, and any routine over-the-counter drugs you take.

Naloxone: A Lifesaving Drug

Naloxone is a fast-acting opioid antagonist (an antagonist is a molecule that blocks the chemical effect of another molecule in the body) approved by the United States Food and Drug Administration (FDA) to quickly, and temporarily, stop opioid overdoses.

This medication is now widely available across the US in pharmacies, doctors’ offices, and other locations, even without a prescription. Making naloxone available to almost anyone means that more people can get emergency medical treatment when they experience an opioid overdose.

This medication quickly binds to opioid receptors in the brain, kicking the opioid drug off. This stops the opioid overdose, and can trigger withdrawal symptoms, for as long as naloxone remains in the body. However, naloxone metabolizes out of the body faster than most opioids, so it is important to call 911 and get emergency treatment when naloxone is administered. This is because when naloxone wears off, the opioid that’s already in their system from previous use will rapidly take effect, yet again, increasing the risk of oversedation and death by blocking respirations.

Naloxone is typically said to not have any side effects, and it is not addictive. It mainly interacts with the brain’s opioid receptors. However, this drug can interfere with other medications that are related to opioids.

We’ve outlined some of naloxone’s drug interactions below.

Prescription Drugs & Interactions With Naloxone

Naloxone is designed to temporarily stop opioid drugs from binding to brain receptors, so if you take prescription opioids for pain, naloxone will block this medicine’s effectiveness and potentially induce a withdrawal syndrome. Using naloxone will stop the effectiveness of these drugs for 30 to 90 minutes. This might precipitate withdrawal symptoms like nausea, vomiting, or muscle pain, if you take any of the following:

  • Morphine
  • Methadone
  • Buprenorphine (Suboxone, Subutex)
  • Oxycodone
  • Hydrocodone
  • Codeine
  • Imodium

For someone taking opioids as part of their medical treatment, this can be risky. However, it is becoming more common for people prescribed opioids for chronic pain to also receive a prescription for naloxone in the unlikely event of an overdose, since opioid withdrawal is only uncomfortable but not life-threatening, and preferable to coma or death.

Naloxone may also reduce or stop the effectiveness of these prescription medications:

  • Some HIV/AIDS drugs like abacavir
  • Some cancer treatment medications, like acalabrutinib (Calquence) and abemaciclib (Verzenio)
  • Herpes virus treatments like acyclovir
  • Hemophilia treatments 
  • Gout treatments
  • Cannabidiol (CBD) for anxiety, insomnia, or pain
  • Antibacterial medicines
  • Anti-seizure medications

This is not an exhaustive list. Talk to your doctor if you have any physical or mental health conditions that require prescription medication that could either interfere with the metabolism of naloxone or become less or more effective after a dose of naloxone.

Over-the-Counter Drugs That Interact With Naloxone

Opioids are not available over the counter in the United States, but some drugs might still be impacted by naloxone. These include the following:

  • Acetaminophen
  • Benadryl, dextromethorphan, and other cough suppressants
  • Vitamin C

Herbal supplements like St. John’s wort, which interferes with numerous other medications, may also make naloxone less effective.

Naloxone & Your Health

If your doctor prescribes naloxone to you, discuss the following with them:

  • Any allergic reactions to other medications, both prescription and over the counter
  • Any physical health issues, especially heart disease
  • Any psychiatric issues 
  • All other medications being taken, including vitamin or herbal supplements
  • Any nonmedical treatments like counseling or therapy
  • Any misuse of drugs or alcohol
  • Pregnancy and breastfeeding

The most reported drug interaction with naloxone is an allergic reaction, which is still a rare side effect. Signs of an allergic reaction include trouble breathing, rash, itchy skin or face, and tongue swelling.

This is also considered a medical emergency, so report any signs of an allergic reaction to 911 operators as well. If you receive a prescription for naloxone, discuss any allergies you have with your physician.

Evzio, an injectable form of naloxone, has been associated with dizziness and redness at the injection site.

Currently, little information on naloxone’s interactions with pregnant or breastfeeding individuals exists. Naloxone given to pregnant people can also precipitate withdrawal symptoms in the fetus, so it is important for medical providers to evaluate the baby for signs of distress.

There is no information so far on naloxone’s transmission through breast milk, but the medication does not affect prolactin and oxytocin hormone levels, which are important for milk production.

Naloxone Improves Overdose Survival

Some recent research found that co-prescribing naloxone with prescription opioids reduces the risk of overdose or prescription drug abuse, even when the prescription for naloxone was not filled. Researchers concluded that naloxone seemed to be an important part of educating the individual on the risks associated with opioid misuse and abuse, so the Centers for Disease Control and Prevention (CDC) began recommending this approach to co-prescription in 2016.

Wider access to naloxone has improved opioid overdose survival rates all over the US. If you know someone struggling with opioid addiction, it is important to support them in getting treatment, including Medication for Addiction Treatment (MAT). You can also ask about a prescription for naloxone to help keep your loved one safe.

Medically Reviewed By Claire Wilcox, MD

Claire Wilcox, MD, is a general and addiction psychiatrist in private practice and an associate professor of translational neuroscience at the Mind Research Network in New Mexico; and has completed an addictions fellowship, psychiatry residency, and internal ... Read More

  1. Naloxone. Substance Abuse and Mental Health Services Administration (SAMHSA). July 2021. Accessed February 2022. 
  2. Naloxone DrugFacts. National Institute on Drug Abuse (NIDA). January 2022. Accessed February 2022. 
  3. Naloxone. Accessed February 2022. 
  4. Naloxone Interactions. Accessed February 2022. 
  5. Naloxone (Narcan, Evzio). National Institute on Mental Illness (NAMI). January 2021. Accessed February 2022.
  6. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. Centers for Disease Control and Prevention (CDC). March 2016. Accessed February 2022.

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