The overdose crisis is increasingly driven by potent synthetic opioids, such as fentanyl,1 which may outlast the effects of shorter acting overdose reversal agents. This evolving risk underscores the need for a range of opioid overdose response options.
Knoa Pharma’s FDA-approved nalmefene portfolio includes Nalmefene Hydrochloride Injection and Zurnai (nalmefene injection) Auto-Injector, the first and only nalmefene autoinjector, designed to be used by anyone in the community.
These medicines are made available at or below cost and at no profit to the company, consistent with Knoa Pharma’s public health mission.
INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR NALMEFENE HYDROCHLORIDE INJECTION AND ZURNAI (NALMEFENE INJECTION) AUTO-INJECTOR
Nalmefene Hydrochloride Injection
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.
IMPORTANT SAFETY INFORMATION
Contraindications
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.
ADVERSE REACTIONS
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%).
Please read Full Prescribing Information here.
To report SUSPECTED ADVERSE REACTIONS, contact Knoa Pharma LLC at 1-888-726-7535, option 2, or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.
Zurnai (nalmefene injection) Auto-Injector
INDICATIONS AND USAGE
ZURNAI is indicated for the emergency treatment of known or suspected opioid overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression.
ZURNAI is intended for immediate administration as emergency therapy in settings where opioids may be present.
ZURNAI is not a substitute for emergency medical care.
IMPORTANT SAFETY INFORMATION
Contraindications
ZURNAI is contraindicated in patients known to be hypersensitive to nalmefene hydrochloride or to any other ingredients in the product.
WARNINGS AND PRECAUTIONS
Risk of Recurrent Respiratory and Central Nervous System Depression
A recurrence of respiratory depression is possible, therefore, keep the patient under continued surveillance and administer repeat doses of ZURNAI if necessary, using a new auto-injector with each dose while awaiting emergency medical assistance.
Risk of Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists
Reversal of respiratory depression by partial agonists or mixed agonists/antagonists such as buprenorphine and pentazocine, may be incomplete. Repeat doses of ZURNAI may be required.
Precipitation of Severe Opioid Withdrawal
The use of ZURNAI in patients who are opioid dependent may precipitate opioid withdrawal.
Abrupt postoperative reversal of opioid depression may result in adverse cardiovascular (CV) effects. These events have primarily occurred in patients who had preexisting 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 ZURNAI.
In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes. Monitor the patient for the development of the signs and symptoms of opioid withdrawal.
Risk of Opioid Overdose from Attempts to Overcome the Blockade
Attempts to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids may lead to opioid intoxication and death.
ADVERSE REACTIONS
Most common adverse reactions (> 5%) are feeling hot, nausea, headache, dizziness, chills, vomiting, allodynia, palpitations, tinnitus, ear discomfort, feeling abnormal, burning sensation, hot flush, and irritability.
USE IN SPECIFIC POPULATIONS
Pregnancy
An opioid overdose is a medical emergency and can be fatal for the pregnant woman and fetus if left untreated. Treatment with ZURNAI for opioid overdose should not be withheld because of potential concerns regarding the effects of ZURNAI in the fetus.
Pediatric Use
The safety and effectiveness of ZURNAI for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, have not been established in pediatric patients younger than 12 years of age.
Geriatric Use
Clinical studies of nalmefene hydrochloride injection did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Please read Full Prescribing Information.
To report SUSPECTED ADVERSE REACTIONS, contact Knoa Pharma LLC at 1-888-726-7535, option 2, or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.
Intended for healthcare professionals of the United States of America only.
References:
- Ahmad FB, Cisewski JA, Rossen LM, Sutton P. Provisional drug overdose death counts. National Center
for Health Statistics. 2026. DOI: https://dx.doi.org/10.15620/cdc/20250305008
Over-the-counter Nasal Naloxone
The predecessor organization to Knoa Pharma played a critical role in enabling the development of the first nonprofit, over‑the‑counter naloxone nasal spray for the emergency treatment of opioid overdose. This work included providing financial support, technical expertise, and access to essential data necessary to advance development and FDA approval.
The product is available over the counter, no prescription is needed.
It was developed and is distributed at or below cost by an independent nonprofit organization committed to preventing overdose deaths. The organization’s mission is to expand access to low‑cost, over‑the‑counter naloxone across the United States, with a focus on community‑based harm reduction distribution models designed to reach individuals and communities at highest risk of opioid overdose.