Naloxone: uses, dosing, side effects & brands

Naloxone (Naloxone Hydrochloride) is an opioid antagonist used to treat Opioid-Related Disorders, Respiration Disorders, Septic Shock.

The FDA classifies naloxone as an opioid antagonist. Opioid antagonists attach to the same brain and body receptors that opioids use, but without switching them on. By occupying those receptors, they block opioids from binding and can rapidly reverse an overdose or curb opioid cravings. If you are checking whether it is safe to combine with something else, the class is what matters — two drugs from the same class usually should not be stacked.

The elimination half-life of naloxone is 30 to 81 minutes (mean 64 ± 12 minutes) — that is how long the body takes to clear half of a dose. This is the serum elimination half-life in adults with normal organ function; naloxone is metabolized in the liver by glucuronide conjugation (major metabolite naloxone-3-glucuronide, which is inactive) and excreted in urine. The half-life is much longer in neonates (mean 3.1 ± 0.5 hours). Because naloxone's half-life is short — often shorter than that of the opioids it reverses — its effects can wear off before the opioid does, so repeat dosing may be needed. Half-life is a pharmacokinetic elimination measure, not a drug-test detection window. Half-life is not the same as how long a drug test can detect the drug, and it varies with age, kidney and liver function.

It depends on the medicine. We check it against the FDA labels rather than guessing: our interaction checker searches each drug's own label for the other and quotes what it says, naming the section it came from. Run naloxone against whatever else you take — and remember that a label not naming a drug is not the same as that combination being safe.

We track 7 naloxone-containing products in the U.S.: Naloxone, Evzio, Evzio (Autoinjector), Naloxone Hydrochloride, Narcan, Rezenopy and Zimhi. They are the same active ingredient; they differ in form, manufacturer, price and FDA recall record.

Across the brands we track, naloxone is currently marketed as injectable, solution and spray/inhaler, per the FDA's National Drug Code Directory. Each form is dosed differently — follow the label for the exact product you were prescribed.

Yes. Our catalog lists 2 generic naloxone products alongside the brand versions. A generic has the same active ingredient and must meet the FDA's bioequivalence standard; it usually costs less. Ask your pharmacist which one your plan covers.

Mostly the effects of sudden opioid withdrawal in someone who is opioid-dependent. The over-the-counter Drug Facts panel puts it plainly: "some people may experience symptoms when they wake up, such as shaking, sweating, nausea, or feeling angry. This is to be expected." In the clinical study behind the prescribing information, reported reactions were increased blood pressure, constipation, toothache, muscle spasms, musculoskeletal pain, headache, nasal dryness, nasal swelling, nasal congestion, nasal inflammation, nose pain and dry skin. This answers for the 4 mg nasal spray, the form sold over the counter and the one people mean by "Narcan."

No. The only contraindication in the FDA label is known hypersensitivity to naloxone hydrochloride or the other ingredients in the spray. Naloxone works by displacing opioids from their receptors; if there are no opioids on board, there is nothing for it to reverse and essentially nothing happens. That asymmetry is the whole point of the OTC approval — the label's use statement is "to revive someone during an overdose from many prescription pain medications or street drugs such as heroin. This medicine can save a life." If you are unsure whether it is an opioid overdose, give it.

Yes, and this is the single most important thing on the label. Most opioids last longer than naloxone does, so breathing can slow or stop again after the naloxone wears off — the label calls this risk of recurrent respiratory and CNS depression. That is why the instructions are: give one spray, call 911 immediately, and stay with the person under continued watch until emergency help arrives, giving another dose every 2 to 3 minutes if they do not respond or if they slip back. Never give a dose and leave. The label also stresses giving it as fast as possible, because prolonged respiratory depression can cause brain damage or death.

Yes, and abruptly. The FDA label warns that use in opioid-dependent people may precipitate severe opioid withdrawal — shaking, sweating, nausea and vomiting, body aches, agitation and anger, fast heartbeat and raised blood pressure. This is expected, and it is not a reason to withhold naloxone from someone who is not breathing. The one group where withdrawal itself is dangerous is newborns of opioid-dependent mothers, where the label warns precipitated withdrawal can be life-threatening and requires immediate medical care.

Yes. The label warns of limited efficacy with partial agonists and mixed agonist-antagonists such as buprenorphine and pentazocine: reversal of their effects may be incomplete, and larger or repeat doses may be required. Naloxone also does nothing for overdoses that do not involve opioids — alcohol, benzodiazepines alone, or stimulants — although it is still worth giving when opioids might be part of the mix, since many street drugs are contaminated with fentanyl. In every case the response is the same: call 911 first, give naloxone, repeat every 2 to 3 minutes, and stay until help arrives.