Bedside Snapshot
- Use It For
- Known or suspected opioid overdose with respiratory and/or CNS depression (devices: age 12 and older); reversal of postoperative opioid depression (IV, hospital)
- Adult Dose
- Opvee: 2.7 mg IN, one spray; repeat every 2–5 min with a new device
- Zurnai: 1.5 mg IM/SC, thigh; repeat every 2–5 min with a new device
- IV: 0.5 mg/70 kg, then 1 mg/70 kg after 2–5 min (max 1.5 mg/70 kg)
- Pediatric Dose
- Ages 12 and older: adult device dose (device labels). Under 12: not established on the device or IV labels; specialist or medical-control use only; naloxone is the weight-based pediatric option
- Onset / Duration
- IV: onset 2–5 min, duration longer than naloxone; IM and IN: peak about 15 min, half-life about 9–11 hr
- Do Not Give / Hold If
- Known hypersensitivity to nalmefene or any ingredient (the only labeled contraindication). Opioid-dependent patients: expect precipitated withdrawal; use the IV challenge when dependence is suspected
- Watch For
- Precipitated withdrawal (vomiting, tachycardia, hypertension, agitation); recurrent respiratory depression after a response; hypotension, hypertension, VT or VF and pulmonary edema reported with reversal
- Reversal / Rescue
- No separate antidote. If inadequate: ventilate, then repeat every 2–5 min with a new device. Buprenorphine and pentazocine may need repeat doses. Call 911 after the first dose
- Must Remember
- Longer-acting than naloxone, but still needs surveillance: the antagonist lasts about 9–11 hr, yet relapse of respiratory depression is possible; keep the patient under observation and hand off
Indications
Emergency & Prehospital
- Known or suspected opioid overdose with respiratory and/or CNS depression. The label covers the Opvee nasal spray and Zurnai auto-injector for patients 12 years and older
- Patient, family or caregiver use: both devices are prescription products. They are meant for the stretch before emergency medical help arrives
ED / ICU / Transport
- Known or suspected opioid overdose (IV, IM or SC): nalmefene hydrochloride injection is indicated for complete or partial reversal of opioid effects. Respiratory depression is one of those effects
- Postoperative opioid reversal: the label's clinical studies cover reversal of respiratory depression and sedation after surgery
- Intrathecal opioid effects (not a labeled indication): the IV label's clinical trials section describes its use to reverse the systemic effects of intrathecal opioids
Dosing & Administration
Doses vary by protocol; follow local protocols and medical direction.
Available Forms
- Opvee nasal spray: 2.7 mg nalmefene delivered per spray (0.1 mL of 27 mg/mL) into one nostril
- Zurnai auto-injector: 1.5 mg nalmefene (base) in 0.5 mL, single-dose prefilled device for IM or SC use
- Nalmefene hydrochloride injection (IV, IM, SC): 1 mg/mL (1 mg nalmefene base per mL), 2 mL single-dose vial (2 mg)
Adult Dosing
| Indication | Dose & Route | Repeat / Max | Notes |
|---|---|---|---|
| Overdose, nasal spray (Opvee) | 2.7 mg IN: one spray in one nostril | Repeat every 2–5 min with a new device; no fixed max: titrate to effect | Ages 12 and older per label. Opposite nostril only if the patient relapses after a response. |
| Overdose, auto-injector (Zurnai) | 1.5 mg IM or SC, anterolateral thigh, through clothing if needed | Repeat every 2–5 min with a new auto-injector; no fixed max: titrate to effect | Ages 12 and older per label. Single-dose device: do not prime or test. |
| Overdose, IV (not opioid-dependent) | 0.5 mg/70 kg IV (about 7 mcg/kg), then 1 mg/70 kg IV 2–5 min later if needed | Total max 1.5 mg/70 kg; more is unlikely to help | Dosing weight: 70 kg reference per label. Doses at least 2–5 min apart. |
| Opioid dependence suspected (IV challenge) | 0.1 mg/70 kg IV (about 1.4 mcg/kg) | Observe 2 min; if no withdrawal, follow the standard IV dosing | Label recommends this challenge when dependence is suspected. |
| No IV access (IM or SC) | 1 mg IM or SC | No fixed max stated for IM or SC: follow protocol and the IV total cap | Label: therapeutic plasma concentrations likely within 5–15 min after a 1 mg IM or SC dose in an emergency. Repeat IM/SC dosing needs great care: absorption is variable and the effect cannot be titrated (label). |
| Postoperative opioid reversal (IV, hospital) | Initial doses 0.1, 0.25, 0.5 or 1 mcg/kg IV, titrated to clinical effect | Cumulative total above 1 mcg/kg not recommended (label) | Tachycardia and nausea were reported in the postoperative setting (label, adverse reactions). |
Pediatric Dosing
| Indication | Dose (per kg) & Route | Max Single / Max Total | Notes |
|---|---|---|---|
| Age 12 and older, nasal or auto-injector | Adult device dose: 2.7 mg IN (one spray) or 1.5 mg IM/SC | Same as adult (see Adult Dosing) | Device labels establish safety and effectiveness for ages 12 and older; the adult dose applies. |
| Under 12, nasal or auto-injector | Not established under 12 years | — | Device labels: ages 12 and older. For children use naloxone (weight-based, see Naloxone) or medical-control direction. |
| Overdose, IV | Not established in pediatric patients | — | IV label: safety and effectiveness not established in pediatric patients. Neonates: see Special Populations. |
Not established in children: the Opvee and Zurnai labels start at age 12. The IV label says pediatric safety and effectiveness are not established. For children, naloxone is the weight-based option (see Naloxone).
Preparation & Administration
- Opvee nasal spray: lay the patient on the back and support the neck so the head tilts back; insert the nozzle into one nostril and press. If more is needed, repeat every 2–5 min with a new device; use the other nostril only if the patient relapses after a response.
- Zurnai auto-injector: do not prime or test. Press the needle end firmly against the outer thigh (through clothing if necessary) until it clicks, then hold for 3 seconds. Watch the viewing window. It turns completely orange once the full dose is delivered.
- IV vial: 1 mg/mL in a 2 mL single-dose vial. Guard against the wrong concentration, which the label warns about. The label describes no diluent.
- Renal failure (IV): give incremental doses slowly, over 60 seconds (see Special Populations).
- Infusion: none labeled; no pump is needed.
Contraindications & Precautions
Contraindications
- Known hypersensitivity to nalmefene hydrochloride or any ingredient in the product (labeled for the injection and both devices)
- In life-threatening opioid toxicity, no other absolute contraindication applies. Do not withhold life-sustaining therapy for opioid overdose
Precautions
- Opioid-dependent patients: abrupt withdrawal may follow. Watch for agitation, tachycardia, hypertension, vomiting, diarrhea, sweating, fever and body aches. Withdrawal is unlikely when the patient is not dependent.
- Partial or mixed agonists (buprenorphine, pentazocine): a full reversal may not happen, and repeat doses may be needed.
- Long-acting opioids (for example, methadone): respiratory depression can run long. Relapse can follow a response that looked adequate.
- Non-opioid causes: when opioids are not behind the sedation and hypoventilation, the IV label reports no effect.
Hold / Reassess If
- After each dose (every 2–5 min): check breathing, SpO₂, EtCO₂ and consciousness again. If breathing is still inadequate, the next dose goes in with a new device.
- Reversal endpoint: reversal, as the label trials measured it, means at least a 5 breaths/min rise and a respiratory rate of at least 12/min. Fall short of that and you ventilate, then repeat the dose.
- Ventricular arrhythmia, hypotension or hypertension, or pulmonary edema: keep the ECG and blood pressure in view. Treat per current ACLS guidance and local protocol.
Do not chase the reversal with opioids: trying to beat the blockade with high or repeated opioid doses can bring on opioid intoxication. It can kill.
Adverse Effects & Toxicity
| Effect | Recognition | Management |
|---|---|---|
| Precipitated opioid withdrawal | Body aches, fever, sweating, diarrhea, vomiting, tachycardia, hypertension, agitation or aggression; neonates: convulsions, excessive crying | Supportive care and symptom control per protocol; avoid high or repeated opioid doses; consult toxicology or poison control (1-800-222-1222) |
| Recurrent respiratory depression | Falling respiratory rate or SpO₂ after a response, or as the dose wears off | Ventilate; repeat every 2–5 min with a new device; continued surveillance |
| Cardiovascular events | Pulmonary edema, hypotension, hypertension, ventricular tachycardia or fibrillation (reported with opioid reversal) | Monitor ECG and blood pressure; treat per current ACLS guidance and local protocol |
| Opioid intoxication | Sudden return of opioid effect after opioid use to overcome the blockade | Treat as recurrent overdose: ventilate and follow the dosing table, with the IV total cap of 1.5 mg/70 kg |
Overdose & Toxicity Management
- Nalmefene excess: in healthy volunteers, IV doses up to 24 mg given without opioid agonists produced no serious adverse reactions. The IV label says a total above 1.5 mg/70 kg is not recommended in overdose. Adverse events rise with higher doses.
- Who to treat: the IV label advises treating only when an opioid overdose is likely. Judge that from the history or from respiratory depression with pupillary constriction.
- Withdrawal: this is precipitated withdrawal, and it is not overdose. Manage symptoms per protocol and keep the patient under observation.
- Antidote note: nalmefene has no separate antidote. Naloxone is the usual first-line agent, and its duration is shorter (see Naloxone).
Monitoring
| Parameter | When / How Often | Target / Act If |
|---|---|---|
| Clinical: breathing | Respiratory rate, SpO₂ and EtCO₂; after each dose and every 2–5 min | Respiratory rate under 12/min or SpO₂ falling: ventilate and repeat the dose with a new device |
| Clinical: consciousness | Level of consciousness and protective airway reflexes; after each dose | Still unresponsive or not protecting the airway: ventilate; the next dose is at least 2–5 min after the last |
| Clinical: withdrawal | Ongoing after dosing | New vomiting, agitation, tachycardia or hypertension: treat per protocol; do not give opioids to overcome the blockade |
| Clinical: circulation | Heart rhythm, blood pressure and lung exam; continuous monitoring when available | Ventricular arrhythmia, hypotension, hypertension or pulmonary edema: ACLS and local protocol |
| Observation | After reversal, until EMS or hospital care, then per local policy | Relapse is possible; the labels give no fixed observation time, and nalmefene lasts longer than naloxone |
Interactions & Compatibility
Clinically Significant Interactions
| Drug / Class | Effect | What To Do |
|---|---|---|
| Fentanyl, morphine, hydromorphone (full agonists) | Antagonized; respiratory depression returns if the agonist exceeds the blockade | |
| Buprenorphine, pentazocine (partial or mixed agonists) | Reversal may be incomplete; slow dissociation prolongs the effect | Repeat doses with new devices; watch for recurrence |
| Methadone and other long-acting opioids | Prolonged respiratory depression; relapse after an apparent response | Continued surveillance; hand off the full dosing history |
| Benzodiazepines, inhalational anesthetics, muscle relaxants | Nalmefene has been given after these with no deleterious interaction (IV label) | No dose change; keep monitoring for their own effects |
| Flumazenil | Both can cause seizures in animals; rodent co-administration produced fewer seizures than expected (IV label) | No adverse interaction expected; watch for seizures with either agent |
IV Compatibility
- The labels offer no diluent or Y-site compatibility data.
- Verify with an institutional compatibility resource.
Special Populations
- Pediatrics: device labels start at age 12. The IV label says safety and effectiveness are not established in pediatric patients. Go to the Pediatric Dosing table, because no pediatric dose is established.
- Neonates: neonatal opioid withdrawal can be life-threatening: convulsions, excessive crying, hyperactive reflexes. The labels say an alternative, titratable antagonist may be preferable for neonates exposed to maternal opioids.
- Pregnancy: there are no adequate human data. Rat and rabbit studies showed no embryo-fetal effects. Do not withhold life-sustaining treatment for overdose. The device label advises that an exposed newborn be evaluated.
- Lactation: there are no human milk data. Nalmefene and its metabolites are present in rat milk. Treat the overdose. The labels do not change that.
- Older Adults: higher early concentrations showed up in elderly men (lower central volume). Clearance and half-life did not differ significantly, and no specific adjustment is established. The Zurnai label says there were not enough subjects aged 65 and over to tell whether they respond differently.
- Renal Impairment: in end-stage renal disease, clearance fell about 25–27% and half-life rose to about 26 hr (IV label). For a single episode, no adjustment is required. Give IV doses over 60 seconds. The device labels note that renal PK was not studied.
- Hepatic Impairment: in hepatic disease, clearance fell 28% and half-life rose to 11.9 hr. No dose adjustment is recommended for an acute course (IV label).
- Obesity / Dosing Weight: IV doses use a 70 kg reference per label. Device doses are fixed. Population PK predicted about 18% higher peak concentration in the lightest quartile and about 15% lower in the heaviest (Zurnai label).
- Opioid-Dependent Patients: precipitated withdrawal is the main concern. When dependence is suspected, use the 0.1 mg/70 kg IV challenge. Avoid higher doses or shorter intervals. They increase withdrawal (IV label).
Field & Transport Considerations
- Scope: varies by state and agency protocol. The nasal spray and auto-injector are prescriptions for patients, families and caregivers. Whether an agency stocks the IV, IM or SC vial, or may give it, is a local decision.
- Storage & Stability: Zurnai at 20–25 °C (68–77 °F), excursions 5–40 °C (41–104 °F); do not freeze or refrigerate; protect from light; check the viewing window every 30 days (label). Opvee at 15–25 °C (59–77 °F), excursions 4–40 °C; do not freeze; protect from light. IV vial at 20–25 °C; protect from light; store in the carton.
- Carried Concentration: the IV vial is 1 mg/mL (2 mg per 2 mL). Confirm the concentration and volume before drawing. The device doses (2.7 mg, 1.5 mg) and the IV totals (1.5 mg/70 kg) are different numbers. Do not mix units.
- Infusions in Transport: none labeled; no pump or infusion line is needed.
- Altitude / Environment: the labels give no altitude instructions. Follow the storage limits above.
- Handoff Essentials: product and route (device or IV), the time and number of each dose, the response (respiratory rate, SpO₂, EtCO₂, consciousness) and any withdrawal signs. Say it out loud: nalmefene lasts about 9–11 hours, so the receiving team keeps the patient under observation.
Clinical Pearls
Longer than naloxone, not proven faster in overdose: Nalmefene's half-life runs about 9–11 hr. Naloxone's is about 1 hr. Healthy volunteers on fentanyl were the model. IM nalmefene 1.5 mg by auto-injector lifted minute ventilation more than IN naloxone 4 mg at 5 minutes (4.59 vs 1.99 L/min). Those subjects were not in overdose. Sponsor ties are present: the authors come from Imbrium Therapeutics, a Purdue Pharma subsidiary. The record has no funding statement. With 24 healthy volunteers, this is physiologic evidence. It is not clinical-outcome evidence.
Surveillance, not discharge: after the first dose, the labels call for emergency care. A patient who wakes up has responded, and that is not the same as being safe. Keep watching. Relapse can follow an adequate response.
Precipitated withdrawal: expect it in opioid-dependent patients: the labels carry that warning. A 2025 post-marketing review (authors include Indivior staff) found 2 precipitated withdrawal reports among 15 adverse-event reports for intranasal nalmefene. You cannot read an incidence from spontaneous reports. Bigger doses or closer intervals push withdrawal up (IV label).
Naloxone vs nalmefene (FP-C, CCP-C):
- Duration: nalmefene about 9–11 hr; naloxone about 1 hr
- Labeled age: nalmefene devices 12 and older; naloxone pediatric dosing is on its own page
- Dose comparisons: the Zurnai label warns that mg-for-mg comparisons across nalmefene products may mislead
- Position: ACMT and AACT (2024) take the position that nalmefene should not replace naloxone as the primary opioid antidote at this time
Buprenorphine: reversal may be incomplete. Onset is gradual, and the effect lasts a long time. Repeat doses with new devices and keep the patient under observation.
Exam discriminator (NREMT, CCRN): which antagonist lasts longer, nalmefene or naloxone? Nalmefene, with a half-life of about 9–11 hr. Ventilation is still the first step.
Pharmacology
Mechanism of Action
- Target: opioid receptor antagonist with no opioid agonist activity (label)
- Physiologic effect: blocks brain opioid receptors. A 1 mg dose blocked over 80% of them within 5 minutes (IV label)
- Clinical consequence: it reverses respiratory depression, sedation and hypotension. A strong blockade can precipitate withdrawal
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IV (1 mg) | Reversal within 2–5 min in overdose trials | No Tmax in label (5-minute concentration measured) | Terminal half-life 10.8 hr |
| IM (Zurnai 1.5 mg) | Minute ventilation rose by 5 min in healthy volunteers | Median 0.25 hr (about 15 min) | Half-life 9.07 hr |
| IN (Opvee 2.7 mg) | Time to EC50 about 4 min (Opvee label) | Median 0.25 hr (about 15 min) | Half-life 11.4 hr |
- Half-life: 9.07 hr (IM device), 11.4 hr (IN device), 10.8 hr (IV terminal). In end-stage renal disease, 26.1 hr
- Metabolism: hepatic glucuronide conjugation, with a trace N-dealkylated metabolite. Enterohepatic recycling is suspected (Zurnai label)
- Active metabolites: the glucuronide is inactive. The N-dealkylated metabolite has minimal activity
- Elimination: under 5% excreted unchanged in urine; about 17% in feces
Names & Classification
- Generic name
- Nalmefene hydrochloride
- Brand names
- Opvee (nasal spray; Indivior Inc.); Zurnai (auto-injector; KNOA Pharma LLC); nalmefene hydrochloride injection, 1 mg/mL vial (unbranded; KNOA Pharma LLC per DailyMed)
- Pharmacologic class
- Opioid antagonist
- Therapeutic class
- Opioid overdose reversal agent
- Controlled substance
- Not controlled (label: no abuse potential, not a controlled substance)
- Look-alike / sound-alike
- None commonly reported (naloxone is a different antagonist with a shorter duration; see Pearls)
References
- Indivior Inc. (2026). OPVEE (nalmefene hydrochloride) nasal spray: Prescribing information. DailyMed, U.S. National Library of Medicine (label published January 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=999a4269-9e54-4801-b2ac-2a7276f0b94f
- KNOA Pharma LLC (2026). ZURNAI (nalmefene hydrochloride) injection, auto-injector: Prescribing information. DailyMed (label published August 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a59a5847-9fe4-4341-a203-be0a5e6d3e36
- KNOA Pharma LLC (2026). Nalmefene hydrochloride injection, solution (1 mg/mL): Prescribing information. DailyMed (label published May 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3abfbffc-9e52-4fc6-ae92-6e0a97f4afe7
- Stolbach, A. I., Mazer-Amirshahi, M., Nelson, L. S., & Cole, J. B. (2024). American College of Medical Toxicology and the American Academy of Clinical Toxicology position statement: Nalmefene should not replace naloxone as the primary opioid antidote at this time. Journal of Medical Toxicology, 20(1), 64–67. https://doi.org/10.1007/s13181-023-00981-z
- Cipriano, A., et al. (2025). Reversal of fentanyl-induced respiratory depression in healthy subjects by intramuscular nalmefene administered by auto-injector versus intranasal naloxone. Journal of Clinical Pharmacology, 65(12), 1661–1675. Authors are affiliated with Imbrium Therapeutics (a Purdue Pharma subsidiary); no funding statement is in the record. https://doi.org/10.1002/jcph.70088
- Paavola, J., & Skolnick, P. (2025). Post-marketing surveillance of intranasal nalmefene: Prevalence and clinical relevance of precipitated withdrawal. Cureus. https://doi.org/10.7759/cureus.95174
Medical Disclaimer
- For Educational Purposes Only: This content is intended for educational reference and should not be used for clinical decision-making.
- Not a Substitute for Professional Judgment: Always consult your local protocols, institutional guidelines, and supervising physicians.
- Verify Before Acting: Users are responsible for verifying information through authoritative sources before any clinical application.
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