Naloxone: 7 things you should know

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Aug 2, 2023.

1. How it works

• Naloxone is a pure opioid antagonist and blocks opioid receptors found in the central nervous system and brain. The person who has experienced an opioid overdose may have signs of breathing problems, severe sleepiness, and not being able to respond.
• It reverses the effects of an opioid overdose, including heroin, but has no action in other types of overdoses (for example, benzodiazepines, sedatives or alcohol overdose).
• Naloxone can be used by first responders, consumers and healthcare professionals for the treatment of a known or suspected opioid overdose emergency. It can be used in children and adults for an opioid overdose with signs of respiratory and/or central nervous system depression.
• Examples of opioids are codeine, oxycodone (Oxycontin), heroin, morphine, hydrocodone (Vicodin, Lortab), fentanyl, methadone, oxymorphone, meperidine, tramadol, buprenorphine, and hydromorphone.

2. Upsides

• Naloxone is usually very safe when used as directed. It is not a controlled substance and has no potential for abuse or pharmacologic action in the absence of an actual opioid overdose. Naloxone will not hurt someone who does not have opioids in their system.
• It is regularly used by first responders and can be administered by most lay-people with little training. Nasal sprays and intramuscular injections are available for consumers. Naloxone hydrochloride injection, USP may be administered intravenously, intramuscularly, or subcutaneously by healthcare providers and trained first-responders.
• There are no age restrictions on the use of naloxone; it can be used for suspected overdose in infants, children, adults and elderly people.
• In July 2020 the FDA urged all healthcare providers to discuss the use of naloxone with all patients and caregivers (family, friends) when they are prescribed opioids for pain or for opioid use disorder.
• Nalxone is now approved as an over-the-counter (OTC) product, but products may not be on shelves yet. Previously, all 50 US states have passed laws to improve consumer access to naloxone. Although naloxone is now approved as a nonprescription medicine, you can still obtain naloxone from a pharmacist without a prescription in accordance with state laws until the product is stocked on retail shelves.
• In 2023, the FDA approved an Rx-to-OTC switch for Narcan (naloxone 4 mg) nasal spray and for RiVive (naloxone 3 mg) nasal spray for over-the-counter (OTC), nonprescription use. The FDA’s action now allows these products to be sold directly to consumers in places like drug stores, convenience stores, grocery stores and gas stations, as well as online. Narcan is expected to be available on shelves by the end of the summer, 2023, and ReVive by early 2024. The FDA granted the OTC approval of Narcan to Emergent BioSolutions and RiVive to Harm Reduction Therapeutics (HRT), a nonprofit pharmaceutical company.
• Most major retail and grocery chain pharmacies in the US carry naloxone. Naloxone is available as a generic medicine and, at this time, your insurance will usually help you pay for it. Manufacturers may also offer financial assistance. Insurance coverage may change once products are available over-the-counter.
• Brand names of naloxone include Narcan Nasal, Kloxxado, Zimhi and RiVive.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Stomach-area (abdomen) pain, weakness, dizziness, headache, nose (nasal) discomfort and a feeling like you are going to faint. Zimhi injection may also cause nausea and elevated bilirubin levels.
• A sudden and severe opioid withdrawal in someone who has been using opioids regularly. Opioid withdrawal symptoms can happen right away after receiving naloxone and may include: body aches, diarrhea, stomach cramping, increased heart rate, increased blood pressure, fever, sweating, runny nose, sneezing, goosebumps, shivering or trembling, yawning, nausea or vomiting, nervousness, restlessness or irritability, weakness.
• In infants less than 4 weeks old, sudden opioid withdrawal may be life-threatening if not treated correctly. Signs and symptoms include: seizures, crying more than usual, and increased reflexes.
• Naloxone is not a substitute for emergency medical care. In an overdose situation, first, administer naloxone to the person having the overdose and then immediately call 911 or other emergency medical services, even if the person wakes up.
• More than one dose of naloxone may be needed. People who have overdosed on partial agonists or mixed agonist/antagonists, such as buprenorphine or pentazocine, may require additional doses using a new device (nasal sprayer or prefilled syringe).
• Naloxone should not be used in people known to be allergic to naloxone or to any of the other ingredients contained in the formulation.
• After surgery, excessive doses of naloxone may result in significant reversal of analgesia (pain relief) and serious or deadly side effects have occurred in some patients, especially those with heart disease or at risk of heart side effects due to certain medicines.
• Treatment for an for opioid overdose should not be withheld in a pregnant woman. Animal studies have not shown evidence of an increased occurrence of fetal damage during pregnancy. However, there are no adequate and well-controlled studies in pregnant women. Naloxone crosses the placenta, and may precipitate a withdrawal in the fetus, as well as in the opioid-dependent mother. If you are pregnant or planning a pregnancy, speak to your doctor about the safety of naloxone use.
• There is no information on the presence of naloxone in human milk. Its effect on milk production or on the breastfed infant is not known Because this drug is not orally bioavailable (cannot be absorbed when taken by mouth), it is unlikely to affect the breastfed infant. Some labeling suggests breastfeeding should be avoided for 24 hours after receiving this drug; however, it is not a reason to discontinue breastfeeding.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Naloxone can be used by consumers and the lay-public, first-responders and healthcare providers to help reverse an overdose due to opioids (narcotics), including heroin and prescription opioids. It can be given by family members or caregivers until emergency help arrives. Because the duration of action of most opioids may exceed the duration of naloxone, additional doses of naloxone may be required. Naloxone is not a substitute for emergency medical care. Always call for emergency medical care (911) after you have given a dose of naloxone, as you may not know what the person has overdosed on, and it may be a mixture of substances.

5. Tips

• Before you use naloxone, tell your healthcare provider if you have heart problems, are pregnant or plan to become pregnant, or are breastfeeding. Also tell them about the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal or dietary supplements.
• Family members, caregivers, or other people who may have to use naloxone in an opioid overdose emergency should know where the medicine is stored and how to give it BEFORE an opioid emergency happens. Always carry your naloxone with you in case of an opioid emergency.
• Review the Patient Instructions for Use or Drug Facts Label found in your medicine package to learn how to give naloxone before an emergency occurs. If you are not sure how to administer your naloxone, ask your pharmacist or health care provider how to use the devices. Naloxone is either given as a nasal spray from a spray device (brand name: Narcan Nasal, Kloxxado, RiVive), or as an injection from a prefilled syringe (brand name: Zimhi).
• Kloxxado nasal spray contains 8 mg per spray, which is double the amount in Narcan Nasal. RiVive nasal spray contains 3 mg per spray.
• Zimhi is intended to be administered by people 12 years of age or older. The prefilled syringe may be difficult for younger people to use. Other forms of injectable naloxone exist, but are not typically used by the lay-public.
• Store naloxone at room temperature: 68ºF to 77ºF (20°C to 25°C). Protect from light and heat. Do not store naloxone in your vehicle and do not store it in the refrigerator or freezer.
• Naloxone nasal spray (Narcan Nasal, Kloxxado, RiVive) may freezes at temperatures below 5°F (-15°C) and will not spray if frozen. Call for emergency medical help right away if this happens, do not wait for the medicine to thaw. Naloxone nasal spray may still be used if it has thawed after being previously frozen.
• Replace your naloxone before it reaches the expiration date.

6. Response and effectiveness

• Naloxone can counter overdose effects (depressed breathing, drowsiness, and loss of consciousness) usually within 2 to 3 minutes after administration. Naloxone works to reverse opioid overdose in the body for only 30 to 90 minutes. Repeat doses may be needed.

• In clinical studies, one dose of Narcan Nasal 4 mg resulted in similar levels to intramuscular (IM) injected naloxone 0.4 mg/mL and at roughly the same time.

• Signs and symptoms of an opioid emergency may include:

  • Unusual sleepiness and you are not able to wake up the person with a loud voice or by rubbing firmly on the middle of their chest
  • Breathing problems like slow or shallow breathing in someone difficult to awaken or who looks like they are not breathing
  • The pupils in the eye appear very small (“pinpoint pupils”) in someone difficult to awaken. The pupil is the black circle in the center of the colored part of the eye.

• One dose of naloxone may not be enough to reverse the effects of an opioid overdose. If you are using the nasal spray and this happens, give another dose after 2 to 3 minutes using a new spray bottle. Watch the person closely until emergency medical help starts to administer care. If additional doses are needed, give naloxone nasal spray in the other nostril.

• If the signs and symptoms of an opioid overdose return after Zimhi is given, inject additional doses using a new Zimhi pre-filled syringe every 2 to 3 minutes and watch the person closely until emergency help is received.
• Rescue breathing or CPR (cardiopulmonary resuscitation) may be given while waiting for emergency medical help.
• In someone who is dependent on (addicted to) opioids, opiate withdrawal symptoms may appear within minutes of naloxone administration but may not subside until two hours later. How severe and how long the withdrawal is are related to the dose of naloxone and to the degree and type of opioid dependence.
• For families or friends that elect to carry the devices or store these medications in their home, learning how to use them ahead of time may save time.

7. Interactions

• Larger doses of naloxone may be required to reverse the effects of some opioids like buprenorphine. Buprenorphine has a long duration of action and stays on the opiate receptor for a prolonged period.
• The barbiturate methohexital appears to block the acute onset of withdrawal symptoms induced by naloxone in opiate addicts.

Note that this list is not all-inclusive and includes only common medications that may interact with naloxone. You should refer to the prescribing information or the OTC Drug Facts Label for naloxone for a complete and updated list of interactions.

References

• FDA Approves RiVive (naloxone hydrochloride) Over-the-Counter Nasal Spray for the Emergency Treatment of Opioid Overdose. Drugs.com. July 28, 2023. Accessed Aug 2, 2023 at https://www.drugs.com/newdrugs/fda-approves-rivive-naloxone-hydrochloride-over-counter-nasal-emergency-opioid-overdose-6068.html
• U.S. FDA Approves Over-the-Counter Designation for Emergent BioSolutions’ Narcan Nasal Spray, a Historic Milestone for the Opioid Overdose Emergency Treatment. Drugs.com. Accessed Mar 29, 2023 at https://www.drugs.com/newdrugs/u-s-fda-approves-over-counter-designation-emergent-biosolutions-narcan-nasal-historic-milestone-5992.html
• NIDA. 2022, January 11. Naloxone DrugFacts. Retrieved from https://nida.nih.gov/publications/drugfacts/naloxone on 2022, August 4
• Naloxone injection. Drug Label Information. Daily Med. Updated June 15, 2020. Accessed Aug. 4, 2022 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm
• Kloxxado (naloxone HCl) Nasal Spray [prescribing information]. Columbus, OH: Hikma Specialty USA Inc., 2021 Update April 2021. Accessed Aug. 4, 2022 at https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ebf0f833-c1c0-487c-8f29-01fa8c61b6cb&version=1
• Zimhi (naloxone HCL) injection for intramuscular or subcutaneous use [prescribing information]. San Diego, CA: Adamis Pharmaceuticals, Updated 10/2021. Accessed Aug. 4, 2022 at https://zimhi.com/wp-content/uploads/2022/03/ZIMHI_Prescribing_Information.pdf

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Naloxone only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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