NARCAN

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.

2 DOSAGE AND ADMINISTRATION • NARCAN Nasal Spray is for intranasal use only. ( 2.1 ) • Seek emergency medical care immediately after use. ( 2.1 ) • Administration of a single spray of NARCAN Nasal Spray intranasally into one nostril. ( 2.2 ) • Administer additional doses of NARCAN Nasal Spray, using a new nasal spray with each dose, if the patient does not respond or responds and then relapses into respiratory depression, additional doses of NARCAN Nasal Spray may be given every 2 to 3 minutes until emergency medical assistance arrives. ( 2.2 ) • Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. ( 2.2 ) 2.1 Important Administration Instructions NARCAN Nasal Spray is for intranasal use only. No additional device assembly is required. Because treatment of suspected opioid overdose must be performed by someone other than the patient, instruct the prescription recipient to inform those around them about the presence of NARCAN Nasal Spray and the Instructions for Use. Instruct the patient or caregiver to read the Instructions for Use at the time they receive a prescription for NARCAN Nasal Spray. Emphasize the following instructions to the patient or caregiver: • Administer NARCAN Nasal Spray as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. Since the duration of action of most opioids exceeds that of naloxone hydrochloride and the suspected opioid overdose may occur outside of supervised medical settings, seek immediate emergency medical assistance, keep the patient under continued surveillance until emergency personnel arrive, and administer repeated doses of NARCAN Nasal Spray, as necessary. Always seek emergency medical assistance in the event of a suspected, potentially life-threatening opioid emergency after administration of the first dose of NARCAN Nasal Spray. • Additional doses of NARCAN Nasal Spray may be required until emergency medical assistance becomes available. • Do not attempt to reuse NARCAN Nasal Spray. Each NARCAN Nasal Spray contains a single dose of naloxone and cannot be reused. • Re-administer NARCAN Nasal Spray, using a new nasal spray, every 2 to 3 minutes if the patient does not respond or responds and then relapses into respiratory depression. • Administer NARCAN Nasal Spray in alternate nostrils with each dose. • Administer NARCAN Nasal Spray according to the printed instructions on the device label and the Instructions for Use . • Place the patient in the supine position. Prior to administration, be sure the device nozzle is inserted in either nostril of the patient, and provide support to the back of the neck to allow the head to tilt back. Do not prime or test the device prior to administration. • To administer the dose press firmly on the device plunger. • Remove the device nozzle from the nostril after use. • Turn patient on their side as shown in the Instructions for Use and call for emergency medical assistance immediately after administration of the first dose of NARCAN Nasal Spray. 2.2 Dosing in Adults and Pediatric Patients Initial Dosing The recommended initial dose of NARCAN Nasal Spray in adults and pediatric patients is one spray delivered by intranasal administration into one nostril. Repeat Dosing Seek emergency medical assistance as soon as possible after administering the first dose of NARCAN Nasal Spray. The requirement for repeat doses of NARCAN Nasal Spray depends upon the amount, type, and route of administration of the opioid being antagonized. Administer NARCAN Nasal Spray in alternate nostrils with each dose. If the patient responds to NARCAN Nasal Spray and relapses back into respiratory depression before emergency assistance arrives, administer an additional dose of NARCAN Nasal Spray using a new NARCAN Nasal Spray and continue surveillance of the patient. If the desired response is not obtained after 2 or 3 minutes, administer an additional dose of NARCAN Nasal Spray using a new NARCAN Nasal Spray. If there is still no response and additional doses are available, administer additional doses of NARCAN Nasal Spray every 2 to 3 minutes using a new NARCAN Nasal Spray with each dose until emergency medical assistance arrives. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. 2.3 Dosing Modifications due to Partial Agonists or Mixed Agonist/Antagonists Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete and require higher doses of naloxone hydrochloride or repeated administration of NARCAN Nasal Spray using a new nasal spray [see Warnings and Precautions (5.2) ] .

4 CONTRAINDICATIONS NARCAN Nasal Spray is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients. Hypersensitivity to naloxone hydrochloride. ( 4 )

Not available.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • 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 Emergent Devices Inc. at 1-844-4NARCAN (1-844-462-7226) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .