NALMEFENE vs NALOXONE — Naloxone has been the drug of choice for emergency treatment of opioid overdose for many years.4 Because the half-life of naloxone (1-2 hours) is shorter than the duration of effect of most opioid agonists, repeat administration of the drug may be needed. In contrast, nalmefene has a longer half-life (~9-11 hours) than most opioid agonists, which could decrease the need for repeat administration, but could cause prolonged withdrawal symptoms in patients who are physically dependent on opioids.5,6

CLINICAL STUDIES — No new clinical efficacy trials were required for FDA approval of Zurnai. In a pharmacodynamic study, 24 opioid-experienced, non-dependent persons were given an IV infusion of fentanyl to induce respiratory depression (~50% reduction in minute ventilation from baseline for 10 minutes), followed by a single 1.5-mg dose of nalmefene via the autoinjector. Reversal of respiratory depression began within 2.5-5 minutes after administration of nalmefene, and full recovery of respiratory drive occurred within 5-15 minutes.7 Clinical data on use of nalmefene for reversal of overdose due to fentanyl or its analogs are lacking.

ADVERSE EFFECTS — The most common adverse effects reported with Zurnai in pharmacologic trials were "feeling hot," chills, nausea, vomiting, dizziness, headache, allodynia, tinnitus, palpitations, and irritability. Severe opioid withdrawal precipitated by nalmefene could result in serious adverse effects, including cardiovascular events and pulmonary edema. In cases of mixed overdose, administration of an opioid antagonist could unmask the effects of other drugs, such as stimulants or nonopioid sedatives.

PREGNANCY — No human data are available on use of nalmefene during pregnancy. Use of high doses of the drug in pregnant rats and rabbits did not result in embryotoxic effects.

DOSAGE AND ADMINISTRATION — Zurnai is available in 1.5 mg/0.5 mL autoinjectors. The recommended dosage is 1.5 mg of nalmefene administered IM or SC (through clothing, if necessary) into the anterolateral aspect of the thigh. According to the manufacturer, additional doses can be given every 2-5 minutes until adequate ventilation is restored or emergency medical personnel arrive.

AVAILABILITY — Unlike naloxone, nalmefene is only available by prescription. Most states have standing orders allowing for distribution of prescription naloxone formulations to first responders and caregivers, but these orders do not always apply to nalmefene.8,9 In most states, access laws that grant civil or criminal immunity to laypersons who administer naloxone appear to also apply to nalmefene.8

CONCLUSION — Zurnai, an autoinjector formulation of the opioid antagonist nalmefene, is now available by prescription for intramuscular or subcutaneous administration to reverse opioid overdose. Nalmefene has a longer duration of action than many opioid analgesics, which could precipitate a prolonged period of withdrawal in patients who are physically dependent on opioids. Naloxone, which is shorter-acting and available for sale over the counter as a nasal spray (Narcan, and others), may be a safer choice.

REFERENCES