The recent increase in deaths from heroin overdose in the US has led to renewed interest in the opioid antagonist naloxone, particularly in making it available as an intranasal spray to paramedics and possibly to relatives and close friends of heroin users. Intravenous (IV) administration is preferred, but peripheral venous access may be difficult to obtain in IV drug abusers, and exposure to their blood may be hazardous.

A recent Medical Letter article reported renewed interest in the intranasal administration (off-label) of the opioid antagonist naloxone because of an increase in deaths from opioid overdose in the US.1 Now the FDA has approved a more practical alternative for emergency treatment of life-threatening opioid overdose in adults and children: a single-dose naloxone auto-injector (Evzio – Kaleo) for intramuscular or subcutaneous use.Evzio will be available in kits containing two prefilled 0.4-mg auto-injectors with voice guidance and a "trainer" device that also has voice guidance, but does not...

The recent increase in deaths due to overdose of heroin and prescription opioids in the US has renewed interest in the opioid antagonist naloxone, particularly in making it available to first responders and to relatives and close friends of persons using heroin or taking prescription opioids. IV or IM administration by healthcare professionals is preferred, but peripheral venous access may be difficult to obtain in IV drug abusers, and exposure to their blood may be hazardous.

A new sublingual tablet formulation of the partial opioid agonist buprenorphine combined with the opioid antagonist naloxone (Zubsolv – Orexo) has been approved by the FDA for maintenance treatment of opioid dependence. Zubsolv tablets have relatively greater bioavailability than previously approved sublingual film (Suboxone) and sublingual tablet formulations of buprenorphine/naloxone and, according to an open-label survey, they taste better. The new tablets are smaller and dissolve faster than other tablet formulations, and they are individually sealed in child-resistant...

The FDA has approved a higher-dose injectable formulation of the opioid antagonist naloxone (Zimhi – Adamis) for emergency treatment of opioid overdose. A single IM or SC injection of the new formulation delivers 5 mg of naloxone; injectable formulations that deliver 0.4 mg or 2 mg of the drug have been available for years. Naloxone is also available in intranasal formulations for the same indication (see Table 1).

The FDA has approved a buccal film formulation of the partial opioid agonist buprenorphine combined with the opioid antagonist naloxone (Bunavail – BioDelivery Sciences) for maintenance treatment of opioid dependence. Sublingual tablet and film formulations of the same combination were approved earlier. The manufacturer of Bunavail claims that the new product is superior to sublingual formulations because of the convenience of buccal administration and better absorption into the blood, permitting use of lower doses.

The FDA has approved RiVive (Harm Reduction Therapeutics), a 3-mg naloxone nasal spray, as an over-the-counter (OTC) product for emergency treatment of opioid overdose. Two 4-mg naloxone nasal spray formulations, Narcan and one of its generics, were approved for OTC sale in 2023.

The FDA has approved a higher-dose intranasal naloxone formulation (Kloxxado – Hikma) for emergency treatment of opioid overdose. A single spray of the new formulation delivers 8 mg of naloxone; a formulation that delivers 4 mg per spray (Narcan) was approved in 2015.

The FDA has approved the over-the-counter (OTC) sale of Narcan (Emergent), a nasal spray that delivers 4 mg of the opioid antagonist naloxone. Narcan nasal spray has been available by prescription since 2015 for emergency treatment of opioid overdose. Generic formulations of Narcan have also been approved; the manufacturers of these products will be required to switch them to OTC status and amend their labeling accordingly. Kloxxado, an 8-mg naloxone nasal spray, remains available only by prescription.

The FDA has approved an intranasal formulation of the opioid antagonist nalmefene (Opvee – Indivior) for emergency treatment of known or suspected opioid overdose in persons ≥12 years old. Nalmefene, which is available by prescription, is the second opioid antagonist to become available as a nasal spray for this indication; the first was naloxone, which is now available for sale over the counter (Narcan, and generic). Other nasal spray formulations of naloxone and injectable formulations of nalmefene and naloxone are available by prescription (see Table 2).