The FDA has issued a complete response letter (CRL) regarding the new drug application (NDA) for naloxone hydrochloride 2.0 mg/0.5 mL nasal spray. Amphastar Pharmaceuticals is seeking approval of the product for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.
The CRL identified several issues, including a human-factors study and a device evaluation, that need to be addressed before the NDA can be approved.
Amphastar will continue to market naloxone in prefilled syringes for intramuscular administration while it pursues the NDA for intranasal naloxone.
Naloxone hydrochloride, the N-allyl derivative of oxymorphone, is the standard of care for opioid overdose. Naloxone acts by competitively binding at opiate receptors. It binds most strongly to the mu receptor but also has antagonistic activity at kappa and sigma receptors. Naloxone has little or no agonist activity and does not cause apnea. It was first approved in 1971 to reverse opioid intoxication or overdose.
Two generic products are currently available for naloxone intramuscular injection: naloxone hydrochloride 0.4 mg (Hospira) and naloxone hydrochloride 2.0 mg (Amphastar Pharmaceuticals/International Medication Systems).