The opioid overdose crisis continues to surge in the United States1
ACCORDING TO THE CDC, SYNTHETIC OPIOIDS (OTHER THAN METHADONE) ARE
CURRENTLY THE MAIN DRIVER OF DRUG OVERDOSE DEATHS2
non-fatal opioid-involved overdoses
were treated at emergency departments in 20173
opioid-involved overdose deaths
occurred in the US in 20202
involved synthetic opioids2
*Drug overdose deaths are identified using the International
Classification of Diseases, 10th Revision (ICD–10) underlying
cause-of-death codes X40–X44, X60–X64, X85, and Y10–Y14. Drug overdose
deaths involving selected drug categories are identified by specific
multiple-cause-of-death codes: any opioid, T40.0–T40.4 and T40.6;
heroin, T40.1; natural and semisynthetic opioids, T40.2; methadone,
T40.3; and synthetic opioids other than methadone, T40.4. Deaths
involving more than one opioid category (eg, a death involving both
methadone and a natural or semisynthetic opioid) are counted in both
categories. Natural and semisynthetic opioids include drugs such as
morphine, oxycodone, and hydrocodone; and synthetic opioids other than
methadone include drugs such as fentanyl, fentanyl analogs, and
tramadol. The percentage of drug overdose deaths that identified the
specific drugs involved varied by year, ranging from 75% to 79% from
1999 through 2013 and increasing from 81% in 2014 to 94% in 2020.2
Opioid half-lives can be variable, and different reversal options may be
HALF-LIVES CAN VARY ACROSS OPIOIDS
PLASMA HALF-LIFE (hours)
||3 to 4
||2 to 8
||2 to 3
||3 to 5
The National Institutes of Health (NIH) supports the development of
stronger, longer-acting formulations of opioid antagonists to
counteract high potency synthetic opioids.6
†This is not an exhaustive list of all opioids.
reported are approximations. Patient- and drug-specific variables may
impact the actual half-life of a drug.
Pharmacokinetic data may not
necessarily correlate with clinical effects.
Speak with a representative to learn more about Nalmefene
Nalmefene is a long-acting
opioid overdose reversal option15
IMPORTANT SAFETY INFORMATION AND INDICATION
Nalmefene Hydrochloride injection is contraindicated in patients with a known hypersensitivity to the product.
WARNINGS AND PRECAUTIONS
Use of Nalmefene Hydrochloride injection in Emergencies
Nalmefene Hydrochloride injection, like all drugs in this class, is not the primary treatment for ventilatory failure. In most emergency settings, treatment with Nalmefene Hydrochloride injection should follow, not precede, the establishment of a patent airway, ventilatory assistance, administration of oxygen, and establishment of circulatory access.
Risk of Recurrent Respiratory Depression
Accidental overdose with long acting opioids [such as methadone and levo-alpha-acetylmethadol (LAAM)] may result in prolonged respiratory depression. Respiratory depression in both the postoperative and overdose setting may be complex and involve the effects of anesthetic agents, neuromuscular blockers, and other drugs. While Nalmefene Hydrochloride injection has a longer duration of action than naloxone in fully reversing doses, the physician should be aware that a recurrence of respiratory depression is possible, even after an apparently adequate initial response to Nalmefene Hydrochloride injection treatment.
Patients treated with Nalmefene Hydrochloride injection should be observed until, in the opinion of the physician, there is no reasonable risk of recurrent respiratory depression.
Cardiovascular Risks with Narcotic Antagonists
Pulmonary edema, cardiovascular instability, hypotension, hypertension, ventricular tachycardia, and ventricular fibrillation have been reported in connection with opioid reversal in both postoperative and emergency department settings. In many cases, these effects appear to be the result of abrupt reversal of opioid effects.
Although Nalmefene Hydrochloride injection has been used safely in patients with pre-existing cardiac disease, all drugs of this class should be used with caution in patients at high cardiovascular risk or who have received potentially cardiotoxic drugs
Risk of Precipitated Withdrawal
Nalmefene Hydrochloride injection, like other opioid antagonists, is known to produce acute withdrawal symptoms and, therefore, should be used with extreme caution in patients with known physical dependence on opioids or following surgery involving high doses of opioids. Imprudent use or excessive doses of opioid antagonists in the postoperative setting has been associated with hypertension, tachycardia, and excessive mortality in patients at high risk for cardiovascular complications.
Incomplete Reversal of Buprenorphine
Preclinical studies have shown that nalmefene at doses up to 10 mg/kg (437 times the maximum recommended human dose) produced incomplete reversal of buprenorphine-induced analgesia in animal models. This appears to be a consequence of a high affinity and slow displacement of buprenorphine from the opioid receptors. Hence, Nalmefene Hydrochloride injection may not completely reverse buprenorphine-induced respiratory depression.
Use in Pediatric Patients
Safety and effectiveness of nalmefene hydrochloride injection in pediatric patients have not been established.
The most common adverse reactions (>1%) reported in clinical trials with nalmefene injection were nausea (18%), vomiting (9%), tachycardia (5%), hypertension (5%), postoperative pain (4%), fever (3%), and dizziness (3%).
INDICATIONS AND USAGE
Nalmefene Hydrochloride Injection is indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. Nalmefene Hydrochloride Injection is indicated in the management of known or suspected opioid overdose.
To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please read Full Prescribing Information available here.
United States of America Commission on Combating Synthetic Opioid Trafficking. Final Report.
Published February 2022. Accessed June 30, 2022. https://www.rand.org/content/dam/rand/pubs/external_publications/EP60000/EP68838/RAND_EP68838.pdf 2.
Hedegaard H, Miniño AM, Spencer MR, Warner M. Drug overdose deaths in the United States, 1999-2020. December 2021. Accessed June 30, 2022. https://www.cdc.gov/nchs/data/databriefs/db428.pdf 3.
Vivolo-Kantor AM, Hoots BE, Scholl L, et al. Nonfatal drug overdoses treated in emergency departments—United States, 2016–2017. MMWR Morb Mortal Wkly Rep.
2020;69(13):371-376. doi:10.15585/mmwr.mm6913a3 4.
Mattson CL, Tanz LJ, Quinn K, Kariisa M, Patel P, Davis NL. Trends and geographic patterns in drug and synthetic opioid overdose deaths—United States, 2013-2019. MMWR Morb Mortal Wkly Rep.
2021;70(6):202-207. doi:10.15585/mmwr.mm7006a4 5.
National Institute on Drug Abuse. Fentanyl drug facts. June 2021. Accessed June 30, 2022. https://nida.nih.gov/publications/drugfacts/fentanyl 6.
National Institute on Drug Abuse. Naloxone Drug Facts. June 2021. Accessed June 30, 2022. https://nida.nih.gov/publications/drugfacts/naloxone 7.
Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med.
2013;41(1):263-306. doi:10.1097/CCM.0b013e3182783b72 8.
Fentanyl Citrate Injection. Package insert. Akorn, Inc.; 2012. 9.
Holley FO, Van Steennis C. Postoperative analgesia with fentanyl: pharmacokinetics and pharmacodynamics of constant-rate iv and transdermal delivery. Br J Anaesth.
1988;60(6):608-613. doi:10.1093/bja/60.6.608 10.
Ahonen J, Olkkola KT, Hynynen M, et al. Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery. Br J Anaesth.
2000;85(4):533-540. doi:10.1093/bja/85.4.533 11.
Leen JLS, Juurlink DN. Carfentanil: a narrative review of its pharmacology and public health concerns. Can J Anaesth.
2019;66(4):414-421. doi:10.1007/s12630-019-01294-y 12.
. Prescribing information. Janssen Ortho, LLC; 2008. 13.
Lautieri A. How long does heroin stay in your system? Updated June 28, 2022. Accessed June 30, 2022. https://americanaddictioncenters.org/heroin-treatment/ how-long-in-system 14.
American Addiction Centers. How long do opiates stay in your system? Updated June 29, 2022. Accessed June 30, 2022. https://americanaddictioncenters.org/ prescription-drugs/how-long-in-system 15.
Nalmefene HCl Injection Full Prescribing Information. Purdue Pharma L.P.; 2022.