1 INDICATIONS AND USAGE NARCAN Nasal Spray is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

NARCAN Nasal Spray is intended for immediate administration as emergency therapy in settings where opioids may be present.

NARCAN Nasal Spray is not a substitute for emergency medical care.

NARCAN Nasal Spray is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

( 1 ) NARCAN Nasal Spray is intended for immediate administration as emergency therapy in settings where opioids may be present.

( 1 ) NARCAN Nasal Spray is not a substitute for emergency medical care.

( 1 ) Limitations of Use: Restrict prescription of NARCAN Nasal Spray 2 mg to opioid-dependent patients expected to be at risk for severe opioid withdrawal in situations where there is a low risk for accidental or intentional opioid exposure by household contacts.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: 1.

Precipitation of Severe Opioid Withdrawal [see Warnings and Precautions (5.3) ] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The following adverse reactions were observed in a NARCAN Nasal Spray clinical study.

In a pharmacokinetic study of 30 healthy adult volunteers exposed to one spray of NARCAN Nasal Spray in one nostril or two sprays of NARCAN Nasal Spray, one in each nostril, the most common adverse reactions were: increased blood pressure, constipation, toothache, muscle spasms, musculoskeletal pain, headache, nasal dryness, nasal edema, nasal congestion, nasal inflammation, rhinalgia, and xeroderma.

The following adverse reactions have been identified primarily during post-approval use of naloxone hydrochloride in the post-operative setting.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest.

Death, coma, and encephalopathy have been reported as sequelae of these events.

Excessive doses of naloxone hydrochloride in post-operative patients have resulted in significant reversal of analgesia, and have caused agitation.

Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome.

Signs and symptoms have included: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia.

In some patients, there may be aggressive behavior upon abrupt reversal of an opioid overdose.

In the neonate, opioid withdrawal signs and symptoms also included convulsions, excessive crying, and hyperactive reflexes.

The following adverse reactions were observed in a NARCAN Nasal Spray clinical study: increased blood pressure, constipation, toothache, muscle spasms, musculoskeletal pain, headache, nasal dryness, nasal edema, nasal congestion, nasal inflammation, rhinalgia, and xeroderma.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Adapt Pharma, Inc.

at 1-844-4NARCAN (1-844-462-7226) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.