INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATIONS

NARCAN® (naloxone hydrochloride) 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. 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.

IMPORTANT SAFETY INFORMATION

NARCAN® Nasal Spray is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients.

Seek emergency medical assistance immediately after initial use, keeping the patient under continued surveillance.

Risk of Recurrent Respiratory and CNS Depression: Due to the duration of action of naloxone relative to the opioid, keep the patient under continued surveillance and administer repeat doses of naloxone using a new nasal spray with each dose, as necessary, while awaiting emergency medical assistance.

Risk of Limited Efficacy with Partial Agonists or Mixed Agonists/Antagonists: Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine and pentazocine, may be incomplete. Larger or repeat doses may be required.

Precipitation of Severe Opioid Withdrawal: Use in patients who are opioid dependent may precipitate opioid withdrawal characterized by 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, and tachycardia. In some patients, there may be aggressive behavior upon abrupt reversal of an opioid overdose. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may also include convulsions, excessive crying, and hyperactive reflexes. Monitor for the development of opioid withdrawal.

Risk of Cardiovascular (CV) Effects: Abrupt postoperative reversal of opioid depression may result in adverse CV effects. These events have primarily occurred in patients who had pre-existing CV disorders or received other drugs that may have similar adverse CV effects. Monitor these patients closely in an appropriate healthcare setting after use of naloxone hydrochloride.

Adverse Reactions: 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.

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.

Please see full Prescribing Information.

References: 1. Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017/ CDC. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA. 2. Surgeon General’s Advisory on Naloxone and Opioid Overdose. U.S. Department of Health and Human Services. Prevention. Guideline for prescribing opioids for chronic pain. Available at: www.cdc.gov/drugoverdose/prescribing/guideline.html. Accessed May 2018. 3. NARCAN® Nasal Spray. Prescribing Information. Adapt Pharma, Inc. Radnor, PA; 2017. 4. Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Ann Intern Med. 2016;165(4):245-52. 5. Centers for Disease Control and Prevention. Opioid Overdose. Available at: https://www.cdc.gov/drugoverdose/index.html. Accessed August 12, 2018. 6. World Health Organization. Information Sheet on Opioid Overdose. Available at: http://www.who.int/substance_abuse/information-sheet/en/. Accessed August 12, 2018. 7. Centers for Disease Control and Prevention. Guideline for prescribing opioids for chronic pain. Available at: www.cdc.gov/drugoverdose/prescribing/guideline.html. Accessed August 12, 2018. 8. CDC. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics: 2015. 9. Krieter P, Chiang N, Gyaw S, et al. Pharmacokinetic properties and human use characteristics of an FDA-approved intranasal naloxone product for the treatment of opioid overdose. J Clin Pharmacol. 2016;56(10):1243-53. 10. Mell HK et al. Emergency medical services response times in rural, suburban, and urban areas. JAMA Surg. 2017 Jul 19; [e-pub]. (http://dx.doi.org/10.1001/jamasurg.2017.2230). 11. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Chronic Pain – United States, 2016. Morb Mortal Wkly Rep. 2016;65(1):1-49. 12. National Safety Council. Prescription Opioid Painkiller Public Opinion Poll. October 2017. Available at: NSC.org. 13. CDC Wonder Database Multiple Cause of Death MCD - ICD-10 Codes: T40.1 (Heroin), T40.2 (Other Opioids), T40.3 (Methadone), T40.4 (Other synthetic narcotics) 2013.

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATIONS

NARCAN® (naloxone hydrochloride) 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. 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.

IMPORTANT SAFETY INFORMATION

NARCAN® Nasal Spray is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients.

Seek emergency medical assistance immediately after initial use, keeping the patient under continued surveillance.

Risk of Recurrent Respiratory and CNS Depression: Due to the duration of action of naloxone relative to the opioid, keep the patient under continued surveillance and administer repeat doses of naloxone using a new nasal spray with each dose, as necessary, while awaiting emergency medical assistance.

Risk of Limited Efficacy with Partial Agonists or Mixed Agonists/Antagonists: Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine and pentazocine, may be incomplete. Larger or repeat doses may be required.

Precipitation of Severe Opioid Withdrawal: Use in patients who are opioid dependent may precipitate opioid withdrawal characterized by 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, and tachycardia. In some patients, there may be aggressive behavior upon abrupt reversal of an opioid overdose. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may also include convulsions, excessive crying, and hyperactive reflexes. Monitor for the development of opioid withdrawal.

Risk of Cardiovascular (CV) Effects: Abrupt postoperative reversal of opioid depression may result in adverse CV effects. These events have primarily occurred in patients who had pre-existing CV disorders or received other drugs that may have similar adverse CV effects. Monitor these patients closely in an appropriate healthcare setting after use of naloxone hydrochloride.

Adverse Reactions: 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.

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.

Please see full Prescribing Information.

References: 1. Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017/ CDC. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA. 2. Surgeon General’s Advisory on Naloxone and Opioid Overdose. U.S. Department of Health and Human Services. Prevention. Guideline for prescribing opioids for chronic pain. Available at: www.cdc.gov/drugoverdose/prescribing/guideline.html. Accessed May 2018. 3. NARCAN® Nasal Spray. Prescribing Information. Adapt Pharma, Inc. Radnor, PA; 2017. 4. Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Ann Intern Med. 2016;165(4):245-52. 5. Centers for Disease Control and Prevention. Opioid Overdose. Available at: https://www.cdc.gov/drugoverdose/index.html. Accessed August 12, 2018. 6. World Health Organization. Information Sheet on Opioid Overdose. Available at: http://www.who.int/substance_abuse/information-sheet/en/. Accessed August 12, 2018. 7. Centers for Disease Control and Prevention. Guideline for prescribing opioids for chronic pain. Available at: www.cdc.gov/drugoverdose/prescribing/guideline.html. Accessed August 12, 2018. 8. CDC. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics: 2015. 9. Krieter P, Chiang N, Gyaw S, et al. Pharmacokinetic properties and human use characteristics of an FDA-approved intranasal naloxone product for the treatment of opioid overdose. J Clin Pharmacol. 2016;56(10):1243-53. 10. Mell HK et al. Emergency medical services response times in rural, suburban, and urban areas. JAMA Surg. 2017 Jul 19; [e-pub]. (http://dx.doi.org/10.1001/jamasurg.2017.2230). 11. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Chronic Pain – United States, 2016. Morb Mortal Wkly Rep. 2016;65(1):1-49. 12. National Safety Council. Prescription Opioid Painkiller Public Opinion Poll. October 2017. Available at: NSC.org. 13. CDC Wonder Database Multiple Cause of Death MCD - ICD-10 Codes: T40.1 (Heroin), T40.2 (Other Opioids), T40.3 (Methadone), T40.4 (Other synthetic narcotics) 2013.