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Opioid Overdose Reversal Medications (OORM)


Opioid overdose reversal medications (OORMs) are lifesaving medications approved by the Food and Drug Administration (FDA) to reverse an opioid overdose. Two FDA-approved OORMs are naloxone and nalmefene. Examples of opioids include heroin, fentanyl, oxycodone (OxyContin®), hydrocodone (Vicodin®), codeine, and morphine.

OORMs are effective in reversing opioid overdose, even in instances when opioids are used in combination with other sedatives or stimulants. OORMs are not effective in treating overdoses of benzodiazepines or stimulant overdoses involving cocaine and amphetamines.

It is critical to obtain medical intervention as soon as possible after administering/receiving an OORM.

You can learn how to administer an OORM from a doctor, pharmacist, or staff at a local harm reduction center. Additionally, there are online resources for naloxone administration and rescue breathing.

What Is Naloxone?

Naloxone is a medication approved by the Food and Drug Administration (FDA) designed to rapidly reverse opioid overdose. It is an opioid antagonist—meaning that it binds to opioid receptors and can reverse and block the effects of other opioids, such as heroin, morphine, and oxycodone. Administered when a patient is showing signs of opioid overdose, naloxone is a temporary treatment and its effects do not last long.

The medication can be given by intranasal spray (into the nose), intramuscular (into the muscle), subcutaneous (under the skin), or intravenous (into a vein) injection.

A practitioner should assess the need to prescribe naloxone for patients who are taking methadone or buprenorphine receiving or otherwise considered a risk for opioid overdose.

In March 2023, the FDA approved naloxone nasal spray as the first over the counter OORM and is available in many pharmacies, through community-based distribution programs, local public health organizations or local health departments, free of charge. Check with your state for your local naloxone availability and restrictions.

Learn more about non-prescription (“Over-the-Counter”) Naloxone using our frequently asked questions.

What Is Nalmefene?

Nalmefene is another FDA-approved OORM nasal spray that is available by prescription only and is intended for use in health care and community settings for individuals who are 12 years old and over.

Nalmefene is an opioid receptor antagonist used to treat acute opioid overdose. However, it has a higher half-life than naloxone which means it can stay in the body for longer. This can make withdrawal symptoms more severe and last longer.

Candidates for OORMs are those who:

  • Take high doses of opioids for long-term management of chronic pain
  • Receive rotating opioid medication regimens
  • Have been discharged from emergency medical care following opioid poisoning or intoxication
  • Take certain extended-release or long-acting opioid medication
  • Those who have had a period of abstinence to include those recently released from incarceration.

Pregnant women can be safely given both naloxone and nalmefene in limited doses under the supervision of a doctor. Nalmefene can cause opioid withdrawal in an unborn baby so it is important that practitioners know the medication has been used so the patient and baby can be monitored.

Patients prescribed an automatic injection device for naloxone or who use the nasal spray should keep the item available at all times. It is important to remember to replace medication when the expiration date passes and if exposed to temperatures below 39°F or above 104°F.

Nalmefene should be kept at room-temperature and away from direct sunlight. It is important to remember to replace medication when the expiration date passes.

Side Effects of OORMS

Serious side effects should be taken seriously, as some of them may indicate an emergency. Patients should stop taking methadone and contact a doctor or emergency services right away. Patients and practitioners are encouraged to report all side effects online to MEDWatch, FDA’s medical product safety reporting program for health care professionals, patients, and consumers or by calling 1-800-FDA-1088.

Patients who experience an allergic reaction, such as hives or swelling in the face, lips, or throat, should seek medical help immediately. They should not drive or perform other potentially unsafe tasks.

Use of OORMs causes symptoms of opioid withdrawal. Medical assistance must be obtained as soon as possible after administering/receiving an OORM.

Opioid withdrawal symptoms include:

  • Feeling nervous, restless, or irritable
  • Body aches
  • Dizziness or weakness
  • Diarrhea, stomach pain, or nausea
  • Fever, chills, or goose bumps
  • Sneezing or runny nose in the absence of a cold

Opioid Overdose

Opioid overdose is life-threatening and requires immediate emergency attention. Recognizing the signs of opioid overdose is essential to saving lives.

Opioid overdose can happen when:

Opioid overdose can happen when:

  • A patient misunderstands the directions for use, accidentally takes an extra dose, or deliberately misuses a prescription opioid
  • A person uses illicit drugs
  • A person takes opioid medications prescribed for someone else
  • A person mixes opioids with other medications, alcohol, or over-the-counter drugs
Signs of opioid overdose:

Signs of opioid overdose:

  • Person does not wake or respond to touch or voice
  • Breathing is not normal, very slow, or has stopped
  • Pin-point sized pupils
  • Bluish lips and nose
SAMHSA’s Efforts to Expand the Use of Naloxone

SAMHSA’s Efforts to Expand the Use of Naloxone

SAMHSA continues to work with its federal partners, states, first responders, and other stakeholders to educate on the use of and increase access to naloxone.

In 2024, SAMHSA updated the Overdose Prevention and Response Toolkit released in 2018. The revised toolkit provides guidance to a wide range of individuals on preventing and responding to an overdose. The toolkit also emphasizes that harm reduction and access to treatment are essential aspects of overdose prevention.

The toolkit serves as a foundation for educating and training:

  • Communities
  • Prescribers of opioid pain medications
  • First responders
  • Patients who are prescribed opioid medications
  • Individuals and family members who have experienced an opioid overdose

Resources and Publications

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Overdose Prevention and Response Toolkit

Communities and local governments with material to develop policies and practices to help prevent opioid-related overdoses and deaths.

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Opioid Treatment Program Directory

Search by state to find treatment programs that are accredited to treat opioid use disorders such as prescription pain medications and heroin.

Need Help?

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Contact Information

Opioid Treatment Program Contacts
For information about Medications for Opioid Use Disorder (MOUD) or the certification of opioid treatment programs (OTPs), contact the SAMHSA Division of Pharmacologic Therapies at 240-276-2700 or DPT@SAMHSA.HHS.Gov. For assistance with the Opioid Treatment Program Extranet, contact the OTP helpdesk at 1-866-348-5741 or

Provider Support Contacts
For general information, providers can contact SAMHSA's Center for Substance Abuse Treatment (CSAT) at 1-866-287-2728 or email

Last Updated
Last Updated: 03/26/2024
Last Updated