A Retrospective Analysis & Literature Review Published in Pain Management on the Pharmacokinetic Properties of Naloxone Approved for Community Use Highlights Bioequivalence of Dose & Usability
April 30, 2018
Findings supported the use of FDA-approved community-use intranasal & injectable formulations of naloxone for the emergency treatment of a known or suspected opioid overdose
Dublin – April 30, 2018 – A retrospective literature review published today in Pain Management examined the pharmacokinetic properties of intranasal (2mg or 4mg) and injectable (0.4 mg or 2 mg) formulations of naloxone approved by the U.S. Food and Drug Administration (FDA) to understand the speed of onset, adequacy and duration of the clinical effects. Researchers used MEDLINE and Embase® databases to identify English-language clinical studies and publications from January 2000 to November 2017 that reported prespecified pharmacokinetic (PK) parameters for community-use formulations of naloxone administered to either human volunteers or patients. PK data demonstrated bioequivalence with the previously approved benchmark formulation of naloxone, 0.4 mg intramuscular, indicating naloxone exposure was adequate to reverse an opioid overdose. Funding for the review was provided by Adapt Pharma, Inc. (www.adaptpharma.com).
“Current literature has provided documentation of the factors associated with effective naloxone use in the community, including the route of administration, formulation and dosing considerations,” said lead author Shawn Ryan, MD, MBA. “Our findings reinforce the importance of greater access to naloxone in adequate dosages and easy-to-use formulations, particularly in areas where highly potent synthetic opioids such as fentanyl are present.”
Drug overdoses continue to increase in the United States, and the latest trend data indicates opioid overdose deaths in 2017 have surpassed the previous year.1 Fentanyl is approximately 100 times more potent than morphine and has a rapid onset of action.2 Tragedies from highly potent opioids are affecting both men and women, all races and adults of nearly all ages.3
“We are committed to expanding access to NARCAN® Nasal Spray, the highest concentrated dose of intranasal naloxone currently available, in communities to help people who may be at risk of an opioid overdose, including in areas where synthetic opioids, like fentanyl, may be found,” said Mike Kelly, President of U.S. Operations at Adapt Pharma. “Providers and pharmacists have an important role to play in educating people about naloxone, a potentially life-saving medication, that is available at pharmacies without an individualized prescription in 49 states.”
NARCAN® Nasal Spray 4mg is the first and only FDA-approved, needle-free formulation of naloxone for the emergency treatment of a known or suspected opioid overdose. It does not require assembly or any specialized medical training and is also the highest concentrated dose of intranasal naloxone currently available. NARCAN® Nasal Spray is not a substitute for emergency medical care, and additional doses of NARCAN® Nasal Spray may be required until emergency medical assistance arrives. Seek emergency medical assistance immediately after initial use, keeping the patient under continued surveillance.
Retrospective study of 7 published studies of FDA-approved community-use naloxone formulations (FDA-approved nasal spray NARCAN®, and two FDA-approved intramuscular/subcutaneous auto-injectors), two unapproved intranasal kits and two intranasal products in development. Study concluded that the pharmacokinetics of the FDA-approved nasal spray and auto-injectors demonstrated rapid naloxone plasma uptake exceeding that of the historic benchmark (0.4mg). Limitations included relatively few studies; differences in reference products and study design, and study primarily in healthy volunteers rather than patients at risk.
Please see Indications and Important Safety Information below.
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® (naloxone HCI) 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 at: https://www.narcan.com/pdf/NARCAN-Prescribing-Information.pdf.
For additional information on NARCAN® Nasal Spray, please visit www.NARCAN.com.
For questions regarding NARCAN® Nasal Spray distribution, please call 1-844-4NARCAN® (462-7226).
ABOUT ADAPT PHARMA®
ADAPT Pharma® is a privately-held company committed to expanding affordable access to Narcan® (naloxone HCI) Nasal Spray and to progressing treatment options in the field of addiction. Adapt Pharma’s company headquarters is in Dublin, Ireland with U.S. headquarters in Radnor, Pennsylvania. For more information, please visit www.adaptpharma.com.
ADAPT PHARMA® MEDIA CONTACT INFORMATION
Vice President – Corporate Communications
1 Kounang N. Opioids now kill more people than breast cancer. CNN. December 21, 2017. https://www.cnn.com/2017/12/21/health/drug-overdoses-2016-final-numbers/index.html. Last accessed March 21, 2018.
2 O’Donnell J, Halpin J, Mattson C, Goldberger B, Gladden M. Deaths Involving Fentanyl, Fentanyl Analogs, and U-47700 — 10 States, July–December 2016. Centers for Disease Control and Prevention. https://www.cdc.gov/mmwr/volumes/66/wr/mm6643e1.htm. Published November 2, 2017. Accessed April 19, 2018.
3 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: CDC, National Center for Health Statistics; 2016. Available at http://wonder.cdc.gov