It’s estimated that five to eight million Americans use opioids to manage chronic pain (i.e., pain lasting longer than three months).1,2 Opioids are also used for acute pain, cancer-related pain, post-surgical pain and vascular pain.1 Though prescription opioids provide effective pain relief, this treatment is associated with significant risks—including fatal opioid overdose.1,3 Approximately 125 million prescriptions were written for opioids in 2023, but research published in 2025 shows that only about 1% of patients who are prescribed opioids also receive a prescription for the opioid overdose reversal medication naloxone.3,4 While healthcare providers recognize the risks associated with opioids, it’s important for patients to understand them as well.3 Remind your patients who take prescription opioids that accidental overdoses can happen—even when prescription opioids are not misused.3 Make sure they know that anyone who takes opioids can be at risk for overdose and even death.3 Talk with them about the risks, and consider co-prescribing KLOXXADO® for your patients taking prescription opioids.5

Accidental overdose may not be an obvious risk to patients prescribed opioids

Opioids can pose a risk to patients.3 Unintended drug interactions, accidentally taking multiple doses (or an incorrect dose) and pre-existing health conditions can all increase the likelihood of a potentially deadly opioid overdose.3 While many patients will probably heed your advice to avoid alcohol while taking prescription opioids, they may not be aware of the dangerous interactions that can occur between opioids and certain other prescription medications.6,7 Side effects of prescription opioids (drowsiness and confusion, for example) can be problematic as well.3 Patients taking prescription opioids could accidentally take too much after misreading a label or forgetting that they already took their medicine.3,8 Pre-existing conditions like sleep apnea or lung disease are another concern.9 Patients may not know that opioids can cause a potentially devastating slowdown in their breathing rate.9 And patients with certain liver or kidney conditions may not make the connection between existing health issues, how they metabolize their medications and how potential drug interactions may impact their risk of accidental opioid overdose.5,9

Co-prescribing naloxone could potentially save a life

Opioids relieve pain by attaching to opioid receptors found on nerve cells throughout the body, including the brain.10 When opioids attach to the opioid receptors in the respiratory center of the brain, they can interfere with the body’s ability to breathe.9 Naloxone is a life-saving medication that can reverse the effects of an opioid overdose.11 KLOXXADO® Nasal Spray blocks the effects of opioids on the brain and can help restore normal breathing within two to three minutes.12 Additional doses may be needed if the patient is not adequately responding, or responds and then relapses back into respiratory depression.12

KLOXXADO® is simple to use and proven safe and effective

Naloxone, the active ingredient in KLOXXADO®, works only if a person has opioids in their system—it’s not harmful to use even if a person hasn’t taken opioids.12,13 The use of KLOXXADO® in patients who are opioid-dependent may precipitate opioid withdrawal.12 Although naloxone has no effect on a person who is not experiencing an opioid overdose, it can save a life in an actual opioid overdose emergency.13 KLOXXADO® is a prefilled, easy-to-use single-dose nasal spray, so anyone can be prepared to reverse an overdose at any time.12

Healthcare providers play a critical role in ensuring that patients receive naloxone

Co-prescribing naloxone could be a matter of life and death for at-risk patients taking opioids for pain.4 In 2022, for example, there were close to 15,000 deaths involving prescription opioids.4 In spite of the risk of opioid overdose, only 1% of prescription opioid patients are co-prescribed naloxone.4

The CDC supports co-prescribing naloxone for patients taking prescription opioids

The CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022 support naloxone co-prescribing for patients at-risk who take prescription opioids.5 The Guidelines recommend naloxone because of the:5

  • High rates of preventable opioid overdose deaths
  • Safety and effectiveness of naloxone as an opioid overdose reversal medication

The FDA maintains that naloxone is a medicine with no abuse potential, and it is not a controlled substance.14

In addition to co-prescribing naloxone to patients who are taking prescription opioids, healthcare providers should also educate caregivers and families on the importance of naloxone and how it can save a life in an emergency overdose situation.15

Co-prescribe KLOXXADO® to your patients taking prescription opioids

Given the lifesaving benefit of naloxone in an opioid overdose emergency, co-prescribing naloxone to patients who are prescribed opioids for pain management makes sense—especially for patients who:3

  • Are 65 years and older
  • Have a history of overdose
  • Have apnea or other sleep-disordered breathing
  • Are taking benzodiazepines
  • Are taking ≥50 morphine milligram equivalents (MME) per day
  • Have a history of substance use disorder

Recognize the signs of opioid overdose

Every second counts in an opioid overdose emergency. Once a person stops breathing as a result of opioid overdose, brain damage can occur within four minutes.16 That’s why it’s so important to take action immediately—even before emergency services arrive.12,16 Teach family members and caregivers to recognize the signs of opioid overdose:12

  • The person will not wake up and does not respond to voice or touch
  • The person’s breathing is very slow, irregular, or has stopped
  • The center part of the person’s eye is very small (also known as “pinpoint pupils”)

Instruct family members and caregivers to take action with naloxone as soon as they suspect an opioid overdose—even if they are not sure—and to seek emergency medical assistance after the first dose of KLOXXADO® is given.11,12 KLOXXADO® is easy for anyone to use—no training is required.12 Because a person suffering an opioid overdose cannot give themselves naloxone, tell the patient to let their family members and caregivers know where it is stored.11

Educate patients about the risk of opioid overdose and co-prescribe KLOXXADO®

Talking with your patients about naloxone sounds like a simple task, but the reality is that these conversations might get a little uncomfortable.17,18 Below are some suggestions that may help support your conversations with patients prescribed opioids:17,18

  • Frame the conversation as a safety discussion. Make it clear that every patient who is prescribed opioids is also prescribed naloxone, and that naloxone prescribing is a standard practice meant to help keep patients prepared in case of an opioid emergency. Describe what naloxone is and how it works.
  • Explain that anyone who takes prescription opioids is at risk of accidental overdose and death, even if they take their medicine exactly as directed.
  • Explain that naloxone is a lifesaving medicine that can reverse an opioid overdose in an emergency.
  • Consider comparing naloxone to a fire extinguisher—it’s there in case of emergency. Remind the patient that it’s your job to help them stay safe. Emphasize that prescribing naloxone is a step you are taking to accomplish that.
  • Reiterate that co-prescribing naloxone is a standard care measure that is supported by the CDC. Emphasize that it is a safety precaution, and an action you take with all patients prescribed opioids.

Before your patient leaves the office, remind them to present their prescription for KLOXXADO® with their opioid medication prescription at the pharmacy. For more information about KLOXXADO®, including helpful patient resources and answers to frequently asked questions, visit KLOXXADO.com.

Please see the Full Prescribing Information and Medication Guide for KLOXXADO® for complete product details.

NOTE: This article was not written by a medical professional and is not intended to substitute for the guidance of a physician. These are not Emergent’s recommendations, but rather facts and data collected from various reliable medical sources. See below for a full list of resources and their attributing links. 

References

  1. Kopitnik NL, Huecker MR. Opioid Prescribing. [Updated 2024 Dec 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/sites/books/NBK551720/.
  2. Chronic Pain. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/4798-chronic-pain. Accessed November 18, 2025.
  3. About Prescription Opioids. CDC Overdose Prevention website. Available at: https://www.cdc.gov/overdose-prevention/about/prescription-opioids.html. Accessed November 18, 2025.
  4. Yorkgitis B, Harmon I, Khan A, et al. Naloxone Prescribing Among Long-Term Opioid-Prescribed Patients: Disparities and Opportunities. Cureus. 2025;17(4): e82180. DOI 10.7759/cureus.82180.
  5. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1-95.
  6. Considerations for Clinicians when Co-prescribing Benzodiazepines and Opioids. State of Rhode Island Department of Health website. Available at: https://health.ri.gov/sites/g/files/xkgbur1006/files/publications/guides/ConsiderationsForCliniciansWhenCo-PrescribingBenzodiazepinesAndOpioids.pdf. Accessed November 18, 2025.
  7. Coates S, Lazarus P. Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions. J Pharmacol Exp Ther. 2023 Nov;387(2):150-169.
  8. Opiate Overdose. University of Florida Health website. Available at: https://ufhealth.org/conditions-and-treatments/opiate-overdose. Accessed November 18, 2025.
  9. Opioid Overdose. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/24583-opioid-overdose. Accessed November 18, 2025.
  10. Substance Abuse and Mental Health Services Administration: SAMHSA Overdose Prevention and Response Toolkit. Publication No. PEP23-03-00-001, Substance Abuse and Mental Health Services Administration, 2025.
  11. Lifesaving Naloxone. CDC Stop Overdose website. Available at: https://www.cdc.gov/stop-overdose/caring/naloxone.html. Accessed November 18, 2025.
  12. KLOXXADO® (naloxone HCl) Nasal Spray [prescribing information]. Columbus, OH: Hikma Specialty USA Inc., 2025.
  13. Access to Naloxone Can Save a Life During an Opioid Overdose. US Food and Drug Administration website. Available at: https://www.fda.gov/consumers/consumer-updates/access-naloxone-can-save-life-during-opioid-overdose. Accessed November 18, 2025.
  14. Information about Naloxone and Nalmefene. US Food and Drug Administration website. Available at: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-about-naloxone-and-nalmefene. Accessed December 17, 2025.
  15. Naloxone Toolkit/PDF-When to Offer Naloxone to Patients. CDC Overdose Prevention website. Available at: https://cdc.gov/overdose-prevention/media/pdfs/2024/07/FactSheet-When-to-Offer-Naloxone-to-Patients.pdf. Accessed November 18, 2025.
  16. Cerebral Hypoxia. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/6025-cerebral-hypoxia. Accessed November 18, 2025.
  17. Scripting for talking to patients and their loved ones about naloxone. Kaiser Permanente® Provider website. Available at: https://wa-provider.kaiserpermanente.org/static/pdf/provider/resources/naloxone-prescribing.pdf. Accessed November 18, 2025.
  18. Naloxone Toolkit/PDF-Talking About Naloxone with Patients Prescribed Opioids. CDC Overdose Prevention website. Available at: https://www.cdc.gov/overdose-prevention/media/pdfs/2024/04/Conversation-Starter_Naloxone_FINAL_4_11_2024.pdf. Accessed November 18, 2025.

PP-KLOX-US-00051