Naloxone is administered through three main routes: as a nasal spray, an intramuscular injection, or an intravenous injection. The nasal spray is the most common method used outside of hospitals because it requires no medical training. Intravenous delivery works fastest, reversing an overdose in one to two minutes, while intramuscular and nasal routes take two to five minutes.
Nasal Spray
Nasal spray naloxone is the form most widely distributed in community overdose prevention programs. It comes as a single-dose, prefilled device that delivers the medication into one nostril. The standard nasal spray (Narcan) contains 4 mg per dose, while a higher-strength version (Kloxxado) delivers 8 mg. A 10 mg version has also been reviewed by the FDA. None of these devices need priming or testing before use, and each one can only be used once.
To use nasal spray naloxone, lay the person on their back and support the neck so the head tilts slightly backward. Hold the device with your thumb on the bottom of the plunger and your index and middle fingers on either side of the nozzle. Insert the nozzle tip into one nostril until your fingers rest against the base of the nose, then press the plunger firmly. After delivering the dose, place the person on their side in the recovery position and call emergency services immediately. If there’s no response after two to three minutes, a second dose can be given in the other nostril.
Intramuscular and Subcutaneous Injection
Injectable naloxone comes in two forms: vials paired with a separate syringe and needle, or prefilled auto-injector devices. The standard injectable dose ranges from 0.4 mg to 2 mg. For auto-injectors like Zimhi, the dose is higher at 5 mg, designed for the current landscape of potent synthetic opioids.
The preferred injection site is the outer middle thigh (the vastus lateralis muscle). If the thigh isn’t accessible, the upper outer arm (deltoid muscle) is an alternative, though absorption may be slightly slower. The needle goes in at a 90-degree angle. With Zimhi specifically, you push the plunger all the way down until it clicks, hold for two seconds, then slide the safety guard over the needle using one hand. Injection through clothing is acceptable when time is critical.
After injection, place the person on their side in the recovery position. If breathing doesn’t improve within two to three minutes, give another dose if one is available. Continue repeating every two to three minutes until the person responds or emergency help arrives.
Intravenous Administration
Intravenous naloxone is the fastest route, with effects beginning within one to two minutes. This method is used primarily by paramedics and emergency department staff because it requires vein access. The starting dose is typically 0.4 mg to 2 mg. Because healthcare providers can titrate the dose in real time, IV administration allows more precise control over how much naloxone a person receives.
Why Multiple Doses May Be Needed
Naloxone has a half-life of roughly 60 minutes, though it can range from 30 to 90 minutes depending on the person. Many opioids stay active far longer than that, which creates a real risk: someone can wake up after naloxone, seem fine, and then stop breathing again once the naloxone wears off. This is called re-narcotization, and one study found it happened in about 31% of people who initially responded, occurring anywhere from 3 to 120 minutes after the first dose. It was more common with long-acting opioids like methadone.
Fentanyl presents its own challenge. Because fentanyl is extremely potent and binds tightly to opioid receptors, a single standard dose of naloxone often isn’t enough. Before the rise of synthetic opioids, community naloxone programs reported nearly 100% survival with approved doses. Now, overdoses involving fentanyl frequently require two or more sequential doses. Even more potent analogues like carfentanil may require still higher amounts. This is one reason newer products like the 8 mg nasal spray and 5 mg auto-injector were developed.
What Happens After Naloxone Works
When naloxone reverses an overdose in someone whose body is dependent on opioids, it can trigger precipitated withdrawal within minutes. Symptoms include watery eyes, runny nose, yawning, sweating, hot flashes, and noticeably dilated pupils. These effects are uncomfortable but not life-threatening, and they typically fade as the naloxone leaves the body.
The more important concern is what happens in the hours that follow. People who respond to a low dose (0.4 to 2 mg) are generally observed in an emergency room for two to four hours. Those who took long-acting opioids like methadone or fentanyl need monitoring for 6 to 12 hours, since the opioid will still be active long after the naloxone has worn off. Anyone discharged after an overdose reversal should have someone who can drive them home and stay with them for 12 to 24 hours.
Storing Naloxone So It’s Ready When Needed
Naloxone should be stored at room temperature, between 68°F and 77°F, and kept out of direct sunlight. Brief exposure to temperatures between 41°F and 104°F won’t affect its effectiveness. Below 5°F it will freeze, but it returns to normal after thawing at room temperature for about 15 minutes.
Sustained heat above 104°F is the main concern. If your naloxone has been sitting in a hot car on a summer day, consider replacing it. That said, in an actual emergency, use whatever naloxone you have, even if it’s been exposed to extreme temperatures. A potentially weakened dose is always better than no dose at all.