Zurnai NALMEFENE HYDROCHLORIDE 1.5 mg/.5mL Injection, Solution, 1 syringe
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Opioid Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $100.06 | $50.03 / 0.5 ml |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zurnai 1.5 mg/.5mLthis 59011-0962-01 | Knoa | 1 syringe | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11865112 ↗ | Method of use | U-3630 | Nov 5, 2039 |
| US 11857547 ↗ | Drug product | — | Nov 5, 2039 |
| Code | What it grants | Expires |
|---|---|---|
| NP | New Product | Aug 7, 2027 |
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🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 59011-0962-01 You're viewing this | 1 SYRINGE, GLASS in 1 CARTON (59011-962-01) / .5 mL in 1 SYRINGE, GLASS | 2025-08-07 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 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.
ZURNAI is an opioid antagonist 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. ( 1 ) ZURNAI is intended for immediate administration as emergency therapy in settings where opioids may be present. ( 1 ) ZURNAI is not a substitute for emergency medical care.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION ZURNAI is for intramuscular and subcutaneous use only. ( 2.1 ) Seek emergency medical care immediately after use. ( 2.1 ) Administer ZURNAI to the outer thigh, through clothing if necessary.
( 2.1 ) Administer additional doses of ZURNAI using a new ZURNAI auto-injector for each dose. If the patient does not respond or responds and then relapses into respiratory depression, additional doses of ZURNAI may be given every 2 to 5 minutes until emergency medical assistance arrives. ( 2.2 ) See Full Prescribing Information and Instructions for Use for important information on how to safely administer ZURNAI.
( 2.1 ) Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. ( 2.2 )
2.1Important Administration Instructions All approved nalmefene products achieve plasma concentrations that have been shown to be efficacious in reversing the effects of opioid overdose. Comparing different products on a nominal mg-for-mg basis may be misleading. ZURNAI is for intramuscular and subcutaneous use only.
The device is ready to use. No device assembly is required. Do not prime or test prior to administration.
ZURNAI delivers its entire contents automatically, upon injection. Inject ZURNAI into the anterolateral aspect of the thigh. ZURNAI can be administered through clothing if necessary.
Do not reuse ZURNAI. Each ZURNAI device contains a single dose of nalmefene and cannot be reused. Because treatment of suspected opioid overdose must be performed by someone other than the patient, instruct the prescription recipient to inform those around them about the presence of ZURNAI and the Instructions for Use .
Instruct the patient or caregiver to read the Instructions for Use at the time they receive a prescription for ZURNAI. Emphasize the following instructions to the patient or caregiver: – Administer ZURNAI as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. – Always seek emergency medical assistance after administration of the first dose of ZURNAI in the event of a suspected, potentially life-threatening opioid emergency. Keep the patient under continued surveillance until emergency personnel arrive. – Additional doses of ZURNAI may be required until emergency medical assistance becomes available. – If available, re-administer ZURNAI using a new auto-injector, every 2 to 5 minutes if the patient does not respond or responds and then relapses into respiratory depression. – Once the safety seal is broken and blue cap is removed, ZURNAI must be used immediately or disposed of properly.
Do not attempt to replace the blue cap once it is removed. – Visually inspect ZURNAI through the viewing window for particulate matter and discoloration prior to administration. Do not administer unless the solution is clear, free of particulates, and the glass container is undamaged. – Administer ZURNAI according to the printed instructions on the device label, carton, and the Instructions for Use. ⮚ Place the needle guard of ZURNAI against the outer thigh. Press the needle end firmly into the injection site until you hear a click and then hold for 3 seconds.
After 3 seconds, the viewing window should turn completely orange, signaling that ZURNAI has delivered the intended dose of nalmefene. ⮚ Remove ZURNAI from the outer thigh. ⮚ Call for emergency medical assistance immediately after administration of the first dose of ZURNAI. ⮚ Move the patient on their side (recovery position). Remain with the patient until emergency medical assistance arrives, even if the patient wakes up.
2.2Dosing in Adults and Pediatric Patients 12 Years and Older Initial Dosing : The recommended dose of ZURNAI in adults and pediatric patients aged 12 years and older is 1.5 mg delivered by intramuscular or subcutaneous injection into the anterolateral aspect of the thigh, through clothing if necessary. Repeat Dosing : Seek emergency medic…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 1.5 mg nalmefene base/0.5 mL in a prefilled, single-dose auto-injector ( 3 ) Injection: 1.5 mg/0.5 mL nalmefene (base), clear, colorless to light yellow solution in a pre-filled, single-dose auto-injector. Each ZURNAI auto-injector delivers 1.5 mg nalmefene (base) injection (0.5 mL).
⛔ Contraindications ▾
4 CONTRAINDICATIONS ZURNAI is contraindicated in patients known to be hypersensitive to nalmefene hydrochloride or to any other ingredients in the product. Hypersensitivity to nalmefene hydrochloride or to any other ingredients in ZURNAI. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Risk of Recurrent Respiratory and CNS Depression : A recurrence of respiratory depression is possible, therefore, keep the patient under continued surveillance and administer repeat doses of ZURNAI using a new auto-injector with each dose while awaiting emergency medical assistance. ( 5.1 ) Risk of Limited Efficacy with Partial Agonists or Mixed Agonists/Antagonists : Reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete.
Repeat doses may be required. ( 5.2 ) Precipitation of Severe Opioid Withdrawal : The use of ZURNAI in patients who are opioid dependent may precipitate opioid withdrawal. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated.
Monitor for the development of opioid withdrawal. ( 5.3 ) 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 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 nalmefene hydrochloride. ( 5.3 ) 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. ( 5.4 )
5.1Risk of Recurrent Respiratory and Central Nervous System Depression Respiratory depression in the community overdose setting may be complex and involve the effects of multiple or unknown drugs, some of which may be long-acting opioids. While the duration of action of nalmefene is as long as most opioids, a recurrence of respiratory depression is possible, even after an apparently adequate initial response to ZURNAI treatment [see Clinical Pharmacology (12.3) ]. Therefore, it is necessary to seek emergency medical assistance immediately after administration of the first dose of ZURNAI and to keep the patient under continued surveillance.
A second dose may be necessary if there is recurrence of symptoms of opioid overdose. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance [see Dosage and Administration (2.2) ].
5.2Risk of Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists Reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete. Repeat doses of ZURNAI may be required to antagonize buprenorphine because the latter has a long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor [see Dosage and Administration (2.3) ]. Buprenorphine antagonism is characterized by a gradual onset of the reversal effects and a decreased duration of action of the normally prolonged respiratory depression.
5.3Precipitation of Severe Opioid Withdrawal The use of ZURNAI in patients who are opioid dependent may precipitate opioid withdrawal characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. Abrupt postoperative reversal of opioid depression after using ZURNAI may result in nausea, vomiting, sweating, tremulousness, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest.
Death, coma, and encephalopathy have been reported as sequelae of these events. These events have primarily occurred in patients who had pre-existing cardiovascular disorders or received other drugs that may have similar adverse cardiovascular effects. After use of ZURNAI, monitor patients with pre-…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Recurrent Respiratory and Central Nervous System Depression [see Warnings and Precautions (5.1) ] Precipitation of Severe Opioid Withdrawal [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence > 5%) are feeling hot, nausea, headache, dizziness, chills, vomiting, allodynia, palpitations, tinnitus, ear discomfort, feeling abnormal, burning sensation, hot flush, and irritability. ( 6 ) To report Suspected Adverse Reactions, contact Knoa Pharma LLC at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trial Experience Adult Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of ZURNAI is supported by pharmacokinetic and pharmacodynamic studies of ZURNAI in healthy subjects in a normal state and under steady state opioid agonism. The following adverse reactions were observed.
In a pharmacokinetic study (NAL1005) of 21 healthy adult volunteers exposed to one dose of ZURNAI the most common adverse reactions were: dizziness and headache. In a pharmacodynamic study (NAL1004) of 23 healthy adult volunteers exposed to one dose of ZURNAI, the most common adverse reactions were: feeling hot, chills, nausea, allodynia, and headache. Table 1: Relative Frequencies of Most Common Adverse Reactions that Occurred in Greater than 5% of Subjects in Study NAL1004 and Study NAL1005 (pooled dataset) Nalmefene Auto-Injector 1.5 mg IM System Organ Class Preferred Term Pooled NAL1004 and NAL1005 N=44 n (%) Study NAL1004 N=23 n (%) Study NAL1005 N=21 n (%) Any AR 28 (63.6) 21 (91.3) 7 (33.3) Cardiac disorders Palpitations 4 (9.1) 4 (17.4) 0 Ear and labyrinth disorders Tinnitus 4 (9.1) 4 (17.4) 0 Ear discomfort 3 (6.8) 3 (13.0) 0 Gastrointestinal disorders Nausea 8 (18.2) 6 (26.1) 2 (9.5) Vomiting 5 (11.4) 3 (13.0) 2 (9.5) General disorders and administration site conditions Feeling hot 11 (25.0) 11 (47.8) 0 Chills 6 (13.6) 6 (26.1) 0 Feeling abnormal 3 (6.8) 3 (13.0) 0 Nervous system disorders Dizziness 7 (15.9) 4 (17.4) 3 (14.3) Headache 8 (18.2) 5 (21.7) 3 (14.3) Allodynia 5 (11.4) 5 (21.7) 0 Burning sensation 3 (6.8) 3 (13.0) 0 Psychiatric disorders Irritability 3 (6.8) 3 (13.0) 0 Vascular disorders Hot flush 3 (6.8) 3 (13.0) 0 Adverse reaction information was obtained following administration of nalmefene hydrochloride injection to 152 healthy volunteers and to 1127 patients in controlled clinical trials for the treatment of opioid overdose or for postoperative opioid reversal.
TABLE 2: Relative Frequencies of Common Adverse Reactions with an Incidence Greater than 1% (all patients, all clinical settings) Adverse Reaction Nalmefene N=1127 Placebo N=77 Nausea 18% 6% Vomiting 9% 4% Tachycardia 5% - Hypertension 5% - Postoperative pain 4% N/A Fever 3% - Dizziness 3% 1% Headache 1% 4% Chills 1% - Hypotension 1% - Vasodilatation 1% - Incidence less than 1% CARDIOVASCULAR: Bradycardia, arrhythmia DIGESTIVE: Diarrhea, dry mouth NERVOUS SYSTEM: Somnolence, depression, agitation, nervousness, tremor, confusion, withdrawal syndrome, myoclonus RESPIRATORY: Pharyngitis SKIN: Pruritus UROGENITAL: Urinary retention The incidence of adverse events was highest in patients who received more than the recommended dose of nalmefene hydrochloride injection.
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of nalmefene. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Abrupt reversal of opioid depression using nalmefene in both postoperative and emergency department set…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Life-sustaining therapy for opioid overdose should not be withheld [see Clinical Considerations ] . There are no available data on nalmefene use in pregnant women to evaluate for a drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, no effects on embryo-fetal development were observed in rats and rabbits treated with nalmefene [see Data ].
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryo/fetal risk 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 on the fetus. Data Animal Data Reproduction studies have been performed in rats and rabbits by oral administration and in rabbits by intravenous administration of nalmefene.
No effects on embryo-fetal development were observed at rat oral doses up to 1200 mg/m 2 /day and rabbit oral doses up to 2400 mg/m 2 /day, and intravenous dose up to 96 mg/m 2 /day, which is 52 times the human dose of 3.0 mg (two ZURNAI administrations) based on body surface area comparison. The treatment in rats did not affect offspring survival.
8.2Lactation Risk Summary There are no data on the presence of nalmefene and its metabolites in human milk, the effects of nalmefene on the breastfed child, or the effects on milk production. Nalmefene and its metabolites are present in rat milk [ see Data ] . When a drug is present in animal milk, it is likely that the drug will be present in human milk.
Data Nalmefene and its metabolites were secreted into rat milk, reaching concentrations approximately three times those in plasma at one hour and decreasing to about half the corresponding plasma concentrations by 24 hours following bolus administration. The concentration of nalmefene in animal milk does not necessarily predict the concentration of drug in human milk.
8.4Pediatric 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 been established in pediatric patients aged 12 years and older. Use for this indication in this age group is supported by adult studies and pharmacokinetic simulation [see Clinical Pharmacology (12.3) ]. There have been no studies conducted to evaluate the use of ZURNAI in pediatric patients.
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.
8.5Geriatric Use Clinical studies of nalmefene hydrochloride injection did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Geriatric patients have a greater frequency of decreased hepatic, renal, or cardiac function, or other drug therapy.
Therefore, the systemic exposure of nalmefene can be higher in these patients.
8.6Hepatic Impairment Hepatic impairment substantially reduces the clearance of nalmefene [see Clinical Pharmacology (12.3) ] . For single episodes of opioid antagonism, adjustment of ZURNAI dosage is not required.
8.7Renal Impairment Renal impairment substantially reduces the clearance of nalmefene [see Clinical Pharmacology (12.3) ] . For single…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Life-sustaining therapy for opioid overdose should not be withheld [see Clinical Considerations ] . There are no available data on nalmefene use in pregnant women to evaluate for a drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, no effects on embryo-fetal development were observed in rats and rabbits treated with nalmefene [see Data ].
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryo/fetal risk 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 on the fetus. Data Animal Data Reproduction studies have been performed in rats and rabbits by oral administration and in rabbits by intravenous administration of nalmefene.
No effects on embryo-fetal development were observed at rat oral doses up to 1200 mg/m 2 /day and rabbit oral doses up to 2400 mg/m 2 /day, and intravenous dose up to 96 mg/m 2 /day, which is 52 times the human dose of 3.0 mg (two ZURNAI administrations) based on body surface area comparison. The treatment in rats did not affect offspring survival.
🧒 Pediatric Use ▾
8.4Pediatric 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 been established in pediatric patients aged 12 years and older. Use for this indication in this age group is supported by adult studies and pharmacokinetic simulation [see Clinical Pharmacology (12.3) ]. There have been no studies conducted to evaluate the use of ZURNAI in pediatric patients.
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 ▾
8.5Geriatric Use Clinical studies of nalmefene hydrochloride injection did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Geriatric patients have a greater frequency of decreased hepatic, renal, or cardiac function, or other drug therapy.
Therefore, the systemic exposure of nalmefene can be higher in these patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action ZURNAI is an antagonist at opioid receptors.
12.2Pharmacodynamics Nalmefene reverses the effects of natural and synthetic opioids, including respiratory depression, sedation, and hypotension. Pharmacodynamic studies have shown that nalmefene injection has a longer duration of action than naloxone injection at fully reversing doses. Nalmefene has no opioid agonist activity.
The effect of ZURNAI was studied in an experimental clinical opioid-induced respiratory depression (OIRD) model in twenty-four opioid-experienced, non-opioid dependent subjects (NAL1004). This model assessed changes in minute ventilation (MV) during administration of a 3-step intravenous fentanyl infusion. In step 1, fentanyl was infused until MV nadir (functional OIRD) was achieved.
MV nadir was defined as a 50% reduction in MV from baseline or the MV reduction achieved following the maximum permitted fentanyl titration. Following attainment of MV nadir, the fentanyl infusion rate was decreased (step 2) to maintain the fentanyl concentrations. ZURNAI was administered at 10 minutes following MV nadir.
Ten minutes following ZURNAI administration, the fentanyl infusion rate was further decreased (step 3) to maintain constant fentanyl concentrations for the remaining duration of the reversal session. Following ZURNAI administration the time to onset of effect, that is onset of reversal of respiratory depression, was observed between 2.5 to 5 minutes (Figure 1 and Figure 2). At 5 minutes mean change in MV from nadir was
4.42L/min (Figure 1). Full recovery of respiratory drive was noted between 5 and 15 minutes after ZURNAI administration (Figure 1 and Figure 2). Figure 1: Reversal of Fentanyl-Induced Respiratory Depression in adult healthy volunteers treated with ZURNAI (nalmefene) Figure 2: Percent Recovery of Respiratory Drive after Fentanyl Infusion in Minute Ventilation (Mean SD) in Adult Healthy Volunteers with ZURNAI 1.5 mg Nalmefene is not known to produce respiratory depression, psychotomimetic effects, or pupillary constriction.
No pharmacological activity was observed when nalmefene was administered in the absence of opioid agonists. Nalmefene has not been shown to produce tolerance, physical dependence, or abuse potential. Nalmefene can produce acute withdrawal symptoms in individuals who are opioid dependent.
Figure 1 Figure 2
12.3Pharmacokinetics In a pharmacokinetic study (NAL1005) in 24 healthy adult subjects, the relative bioavailability of one dose of ZURNAI administered intramuscularly was compared to a single dose of nalmefene 1.0 mg administered as an intramuscular injection. The pharmacokinetic parameters obtained in this study are shown in Table 3 and the plasma concentration time profiles of nalmefene are presented in Figure 3. Table 3: Geometric Mean (CV%) Nalmefene PK Parameters after Administration of 1.5 mg ZURNAI Intramuscular (IM), 1.0 mg Nalmefene IM, and 1.0 mg Nalmefene Intravenous (IV) Parameter ZURNAI 1.5 mg Nalmefene IM 1.0 mg Nalmefene IV 1.0 mg NA = Not applicable.
T max (h) T max presented as median (range) 0.25 (0.083-1.00) 0.50 (0.083-2.00) 0.083 (0.083 -0.25) C max (ng/mL) 7.37 (47.5) 2.39 (32.6) 6.94 (55.7) AUC 0-2.5min (ng-hr/mL) Arithmetic mean 0.011 (288) 0.001 (241) 0.062 (56.1) AUC 0-5min (ng-hr/mL) 0.077 (144) 0.010 (209) 0.299 (40.4) AUC 0-10min (ng-hr/mL) 0.320 (85.8) 0.047 (107) 0.768 (46.2) AUC 0-15min (ng-hr/mL) 0.831 (62.7) 0.152 (64.8) 1.16 (46.1) AUC 0-20min (ng-hr/mL) 1.31 (51.3) 0.315 (48.3) 1.50 (41.7) AUC 0-30min (ng-hr/mL) 2.24 (39.3) 0.647 (40.7) 2.07 (34.0) AUC 0-inf (ng-hr/mL) 30.53 (16.0) 17.98 (21.0) 18.22 (15.3) F rel (%) 113 (13.0) NA NA T ½ (h) 9.07 (26.6) 7.74 (24.3) 9.12 (16.5) Figure 3: Mean Plasma Concentration-Time Profiles of Nalmefene (a) 0-12 hours and (b) 0- 60 minutes Following Administration of 1.5 mg ZURNAI Intramuscular (IM), 1.0 mg Nalmefene IM, and 1.0 mg Nalmefene Intravenous (IV) (a) (b) Absorption After administration of one…
🧬 Mechanism of Action ▾
12.1Mechanism of Action ZURNAI is an antagonist at opioid receptors.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Each single-dose auto-injector delivers 1.5 mg of nalmefene in 0.5 mL. Each carton contains one single-dose ZURNAI (nalmefene injection). NDC 59011-962-01: One carton containing one single-dose auto-injector. ZURNAI is not made with natural rubber latex.
16.2Storage and Handling Store at controlled room temperature 20°C to 25°C (68°F to 77°F), with excursions permitted between 5°C to 40°C (41°F to 104°F). During storage, check ZURNAI through the viewing window of the auto-injector every 30 days. The liquid should be clear, colorless to light yellow.
If the ZURNAI liquid is discolored, cloudy, or contains solid particles, replace it with a new ZURNAI. DO NOT FREEZE OR REFRIGERATE. Store in a clean dry place.
Protect from light. Keep ZURNAI in the carton until use. Store ZURNAI securely and dispose of properly in a sharps container.
For detailed disposal instructions, see the Instructions for Use . KEEP ZURNAI AND ALL MEDICINES OUT OF THE REACH OF CHILDREN. Before using, check to make sure the solution in the auto-injector is not discolored.
Replace ZURNAI if the solution is discolored or contains a precipitate. Each ZURNAI can only be used one time and cannot be re-used.
📦 Storage and Handling ▾
16.2Storage and Handling Store at controlled room temperature 20°C to 25°C (68°F to 77°F), with excursions permitted between 5°C to 40°C (41°F to 104°F). During storage, check ZURNAI through the viewing window of the auto-injector every 30 days. The liquid should be clear, colorless to light yellow.
If the ZURNAI liquid is discolored, cloudy, or contains solid particles, replace it with a new ZURNAI. DO NOT FREEZE OR REFRIGERATE. Store in a clean dry place.
Protect from light. Keep ZURNAI in the carton until use. Store ZURNAI securely and dispose of properly in a sharps container.
For detailed disposal instructions, see the Instructions for Use . KEEP ZURNAI AND ALL MEDICINES OUT OF THE REACH OF CHILDREN. Before using, check to make sure the solution in the auto-injector is not discolored.
Replace ZURNAI if the solution is discolored or contains a precipitate. Each ZURNAI can only be used one time and cannot be re-used.
📋 Description ▾
11 DESCRIPTION ZURNAI™ (nalmefene injection) is a sterile, pre-filled, single-dose auto-injector designed to deliver a dose of 1.5 mg nalmefene (provided as nalmefene hydrochloride) in 0.5 mL. Nalmefene hydrochloride, an opioid antagonist, is a 6-methylene analogue of naltrexone. The molecular structure of nalmefene is presented below: Molecular Formula: C 21 H 25 NO 3 ∙HCl Molecular Weight: 375.9, CAS# 58895-64-0 Chemical Name: 17-(Cyclopropylmethyl)-4,5α-epoxy-6-methylenemorphinan-3,14-diol, hydrochloride salt Nalmefene is a white to off-white crystalline powder which is freely soluble in water up to 130 mg/mL and slightly soluble in chloroform up to 0.13 mg/mL, with a pKa of 7.63.
Each ZURNAI auto-injector delivers 1.5 mg nalmefene (equivalent to 1.7 mg nalmefene hydrochloride) in 0.5 mL solution. The pH range is 3.5 to 4.5. The inactive ingredients in ZURNAI nalmefene injection include: hydrochloric acid to adjust pH; magnesium chloride, 4.7 mg; and water for injection.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient and family members or caregivers to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Instruct patients and their family members or caregivers to become familiar with all information contained in the carton as soon as they receive ZURNAI. Recognition of Opioid Overdose Instruct patients and their family members or caregivers about how to recognize the signs and symptoms of an opioid overdose, such as the following: Extreme somnolence – inability to awaken a patient verbally or upon a firm sternal rub Respiratory depression – this can range from slow or shallow respiration to no respiration in a patient who is unarousable Other signs and symptoms that may accompany somnolence and respiratory depression include the following: Miosis Bradycardia and/or hypotension Risk of Recurrent Respiratory and Central Nervous System Depression While the duration of action of nalmefene is as long as most opioids, instruct patients and their family members or caregivers that they must seek immediate emergency medical assistance after administration of the first dose of ZURNAI, and keep the patient under continued surveillance even after an apparently adequate initial response to ZURNAI.
A second dose may be necessary if there is recurrence of symptoms of opioid overdose [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) ]. Limited Efficacy for/with Partial Agonists or Mixed Agonist/Antagonists Instruct patients and their family members or caregivers that the reversal of respiratory depression caused by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete and may require repeated administration of ZURNAI, using a new ZURNAI auto-injector each time [see Dosage and Administration (2.2) , Warnings and Precautions (5.2) ].
Precipitation of Severe Opioid Withdrawal Instruct patients and their family members or caregivers that the use of ZURNAI in patients who are opioid dependent may precipitate opioid withdrawal [see Warnings and Precautions (5.3) , Adverse Reactions (6) ]. Administration Instructions Instruct patients and their family member or caregivers to: Ensure ZURNAI is readily available in locations where persons may be intentionally or accidentally exposed to an opioid overdose (i.e., opioid emergencies). Use ZURNAI one time only.
DO NOT test or prime prior to use [see Dosage and Administration (2.1) ]. Carefully read the Instructions for Use that comes with ZURNAI. Administer ZURNAI as quickly as possible if a person is unresponsive and an opioid overdose is suspected, even when in doubt, because prolonged respiratory depression may result in damage to the central nervous system or death.
ZURNAI is not a substitute for emergency medical care [see Dosage and Administration (2.1) ] . Administer ZURNAI directly into the outer thigh. Press the needle end firmly into the injection site (through clothing, if necessary) and hold for 3 seconds [see Dosage and Administration (2.1) ].
After 3 seconds, the viewing window should turn completely orange, signaling that ZURNAI has delivered the intended dose of nalmefene. Remove ZURNAI from the outer thigh. Call 911 immediately after injecting the first dose of ZURNAI.
Move the person to the recovery position by turning them to their side. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance [see Dosage and Administration (2.1) ]. Watch the person carefully.
Wait 2 to 5 minutes to see if the person wakes up. If the person is not responding or responds and then relapses back into respiratory depression, administer additional doses of ZURNAI every 2 to 5 minutes using a new ZURNAI auto-injector [see Dosage and Administration (2.1) ]. Remain with the person until emergency medical help arrives, even if they wake up.
Visually inspect the nalmefene solution through the viewing window every 30 da…