Naloxone Hydrochloride 4 mg/.1mL Spray, Metered
🆔 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
Prescription and nonprescription (over the counter) naloxone nasal spray is used along with emergency medical treatment to reverse the life-threatening effects of a known or suspected opiate (narcotic) overdose in adults and children. Naloxone nasal spray is in a class of medications called opiate antagonists. It works by blocking the effects of opiates to relieve dangerous symptoms caused by high levels of opiates in the blood.
Read the full MedlinePlus article ↗- Naloxone is an emergency medicine that rapidly reverses the effects of an opioid overdose — things like very slow or stopped breathing, extreme drowsiness, or unconsciousness. You...
- What exactly does naloxone do, and when should I use it?
- Give one spray into one nostril. The device is ready to use — no assembly needed for most products like Narcan or Kloxxado. If the person doesn't improve within 2 to 3 minutes, giv...
- How do I actually use the nasal spray, and what if it doesn't seem to work?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Naloxone Hydrochloride — tap one for details:
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 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 ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $34.270 | $68.54 / 2 vials |
| Medicaid paysCMS SDUD · 12 mo | $387.94 | $775.87 / 2 vials |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Narcan 4 mg/.1mL 69547-0627-02 | Emergent | 2 vials | $16.680 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mL 00480-3478-68 | Teva | 1 vial | $16.922 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mL 45802-0578-84 | Padagis | 2 vials | $16.922 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mL 46122-0812-71 | AMERISOURCE | 2 vials | $16.922 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mL 60219-2104-07 | Amneal | 2 vials | $16.922 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mL 68001-0645-45 | BluePoint | 2 vials | $16.922 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mL 69238-2104-07 | Amneal | 2 vials | $16.922 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mL 70677-1283-01 | Strategic | 2 vials | $16.922 | — | Availability likely | save 51% |
| Naloxone Hydrochloride 4 mg/.1mLthis 00093-2165-68 | Teva | 1 vial | $34.270 | — | Discontinued | — |
| Narcan 4 mg/.1mL 69547-0353-02 | Emergent | 2 vials | $59.869 | — | Discontinued | +75% |
| Naloxone Hydrochloride 4 mg/.1mL 00363-2140-02 | Walgreen | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 00591-3871-99 | Actavis | 1 vial | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 42291-0493-02 | AvKARE | 2 vials | — | — | FDA listed | — |
| Narcan 4 mg/.1mL 50090-2422-00 | A-S | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 50090-5908-00 | A-S | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 50090-6710-00 | A-S | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 50090-6963-00 | A-S | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 51316-0210-02 | CVS | 2 vials | — | — | FDA listed | — |
| Narcan Naloxone Hci 4 mg/.1mL 51662-1240-01 | HF | 1 ml | — | — | FDA listed | — |
| NALOXONE HCl 4 mg/.1mL 51662-1620-01 | HF | 1 ml | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 51662-1659-02 | HF | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 67296-1928-02 | Redpharm | 1 vial | — | — | Discontinued | — |
| Narcan 4 mg/.1mL 71205-0528-02 | Proficient | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 71205-0707-02 | Proficient | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 72162-2376-02 | Bryant | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 76420-0867-02 | Asclemed | 1 vial | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 80425-0409-01 | Advanced | 2 vials | — | — | FDA listed | — |
| Narcan 4 mg/.1mL 85766-0076-02 | Sportpharm | 2 vials | — | — | FDA listed | — |
| Naloxone Hydrochloride 4 mg/.1mL 85766-0228-02 | Sportpharm | 1 vial | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00093-2165-68 You're viewing this | 2 BLISTER PACK in 1 CARTON (0093-2165-68) / 1 VIAL, SINGLE-DOSE in 1 BLISTER PACK (0093-2165-19) / .1 mL in 1 VIAL, SINGLE-DOSE | 2021-12-22 | Discontinued by firm |
🧭 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) | ✓ Available |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| 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) | ✓ Available |
Questions about this listing
What does the discontinued status mean for this NDC?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Naloxone hydrochloride nasal spray is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. Naloxone hydrochloride nasal spray is intended for immediate administration as emergency therapy in settings where opioids may be present. Naloxone hydrochloride nasal spray is not a substitute for emergency medical care.
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. ( 1 ) Naloxone hydrochloride nasal spray is intended for immediate administration as emergency therapy in settings where opioids may be present. ( 1 ) Naloxone hydrochloride nasal spray is not a substitute for emergency medical care.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Naloxone hydrochloride nasal spray is for intranasal use only. ( 2.1 ) Seek emergency medical care immediately after use. ( 2.1 ) Administration of a single spray of naloxone hydrochloride nasal spray intranasally into one nostril.
( 2.2 ) Administer additional doses of naloxone hydrochloride nasal spray, using a new nasal spray with each dose, if the patient does not respond or responds and then relapses into respiratory depression, additional doses of naloxone hydrochloride nasal spray may be given every 2 to 3 minutes until emergency medical assistance arrives. ( 2.2 ) Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance. ( 2.2 )
2.1Important Administration Instructions Naloxone hydrochloride nasal spray is for intranasal use only. No additional device assembly is required. 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 naloxone hydrochloride nasal spray and the Instructions for Use .
Instruct the patient or caregiver to read the Instructions for Use at the time they receive a prescription for naloxone hydrochloride nasal spray. Emphasize the following instructions to the patient or caregiver: Administer naloxone hydrochloride nasal spray as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. Since the duration of action of most opioids exceeds that of naloxone hydrochloride and the suspected opioid overdose may occur outside of supervised medical settings, seek immediate emergency medical assistance, keep the patient under continued surveillance until emergency personnel arrive, and administer repeated doses of naloxone hydrochloride nasal spray, as necessary.
Always seek emergency medical assistance in the event of a suspected, potentially life-threatening opioid emergency after administration of the first dose of naloxone hydrochloride nasal spray. Additional doses of naloxone hydrochloride nasal spray may be required until emergency medical assistance becomes available. Do not attempt to reuse naloxone hydrochloride nasal spray.
Each naloxone hydrochloride nasal spray contains a single dose of naloxone and cannot be reused. Re-administer naloxone hydrochloride nasal spray, using a new nasal spray, every 2 to 3 minutes if the patient does not respond or responds and then relapses into respiratory depression. Administer naloxone hydrochloride nasal spray in alternate nostrils with each dose.
Administer naloxone hydrochloride nasal spray according to the printed instructions on the device label and the Instructions for Use . Place the patient in the supine position. Prior to administration, be sure the device nozzle is inserted in either nostril of the patient, and provide support to the back of the neck to allow the head to tilt back.
Do not prime or test the device prior to administration. To administer the dose press firmly on the device plunger. Remove the device nozzle from the nostril after use.
Turn patient on their side as shown in the Instructions for Use and call for emergency medical assistance immediately after administration of the first dose of naloxone hydrochloride nasal spray.
2.2Dosing in Adults and Pediatric Patients Initial Dosing The recommended initial dose of naloxone hydrochloride nasal spray in adults and pediatric patients is one spray delivered by intranasal administration into one nostril. Repeat Dosing Seek emergency medical assistance as soon as possible after administering the first dose of naloxone hydrochloride nasal spray. The requirement for repeat doses of naloxone hydrochloride nasal spray depends upon the amount, type, and route of administration of the opioid being antagonized.
Administer naloxone hydrochloride nasal spray in alternate nostrils with each dose. If the patient responds to naloxo…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Naloxone hydrochloride nasal spray is supplied as a single-dose intranasal spray containing 4 mg of naloxone hydrochloride in 0.1 mL. Nasal spray: 4 mg of naloxone hydrochloride in 0.1 mL. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Naloxone hydrochloride nasal spray is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients. Hypersensitivity to naloxone hydrochloride. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Risk of Recurrent Respiratory and CNS Depression: Due to the duration of action of naloxone relative to the opioid, keep 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. ( 5.1 ) 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. ( 5.2 ) Precipitation of Severe Opioid Withdrawal: Use 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 naloxone hydrochloride. ( 5.3 )
5.1Risk of Recurrent Respiratory and Central Nervous System Depression The duration of action of most opioids may exceed that of naloxone hydrochloride nasal spray resulting in a return of respiratory and/or central nervous system depression after an initial improvement in symptoms. Therefore, it is necessary to seek emergency medical assistance immediately after administration of the first dose of naloxone hydrochloride nasal spray and to keep the patient under continued surveillance. Administer additional doses of naloxone hydrochloride nasal spray if the patient is not adequately responding or responds and then relapses back into respiratory depression, as necessary [see Dosage and Administration ( 2.2 )] .
Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance.
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. Larger or repeat doses of naloxone hydrochloride 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 naloxone hydrochloride nasal spray 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. 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. Abrupt postoperative reversal of opioid depression after using naloxone hydrochloride 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 simila…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Precipitation of Severe Opioid Withdrawal [see Warnings and Precautions ( 5.3 )] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice. The following adverse reactions were observed in a naloxone hydrochloride nasal spray clinical study.
In a pharmacokinetic study of 30 healthy adult volunteers exposed to one spray of naloxone hydrochloride nasal spray in one nostril or two sprays of naloxone hydrochloride nasal spray, one in each nostril, the most common adverse reactions were: increased blood pressure, constipation, toothache, muscle spasms, musculoskeletal pain, headache, nasal dryness, nasal edema, nasal congestion, nasal inflammation, rhinalgia, and xeroderma. The following adverse reactions have been identified primarily during post-approval use of naloxone hydrochloride in the post-operative setting.
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: Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in post-operative patients have resulted in significant reversal of analgesia, and have caused agitation.
Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome. Signs and symptoms have included: 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, tachycardia. In some patients, there may be aggressive behavior upon abrupt reversal of an opioid overdose.
In the neonate, opioid withdrawal signs and symptoms also included convulsions, excessive crying, and hyperactive reflexes. The following adverse reactions were observed in a naloxone hydrochloride 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. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary The limited available data on naloxone use in pregnant women are not sufficient to inform a drug-associated risk. However, there are clinical considerations [see Clinical Considerations] . In animal reproduction studies, no embryotoxic or teratogenic effects were observed in mice and rats treated with naloxone hydrochloride during the period of organogenesis at doses equivalent to 6-times and 12-times, respectively, a human dose of 8 mg/day (two naloxone hydrochloride nasal sprays) based on body surface area comparison [see Data] .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 Fetal/Neonatal adverse reactions Naloxone hydrochloride crosses the placenta, and may precipitate withdrawal in the fetus, as well as in the opioid-dependent mother [see Warnings and Precautions ( 5.3 )] .
The fetus should be evaluated for signs of distress after naloxone hydrochloride nasal spray is used. Careful monitoring is needed until the fetus and mother are stabilized. Data Animal Data Naloxone hydrochloride was administered during organogenesis to mice and rats at subcutaneous doses up to 10 mg/kg/day (equivalent to 6-times and 12-times, respectively, a human dose of 8 mg (two naloxone hydrochloride nasal sprays) (based on body surface area comparison).
These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride. Pregnant female rats were administered 2 or 10 mg/kg naloxone subcutaneously from Gestation Day 15 to Postnatal day 21. There were no adverse effects on the offspring (up to 12-times a human dose of 8 mg/day (two naloxone hydrochloride nasal sprays) based on body surface area comparison).
8.2Lactation Risk Summary There is no information regarding the presence of naloxone in human milk, or the effects of naloxone on the breastfed infant or on milk production. Studies in nursing mothers have shown that naloxone does not affect prolactin or oxytocin hormone levels. Naloxone is minimally orally bioavailable.
8.4Pediatric Use The safety and effectiveness of naloxone hydrochloride nasal spray have been established in pediatric patients of all ages for known or suspected opioid overdose as manifested by respiratory and/or central nervous system depression. Use of naloxone hydrochloride in all pediatric patients is supported by adult bioequivalence studies coupled with evidence from the safe and effective use of other naloxone hydrochloride drug products. No pediatric studies were conducted for naloxone hydrochloride nasal spray.
Absorption of naloxone hydrochloride following intranasal administration in pediatric patients may be erratic or delayed. Even when the opiate-intoxicated pediatric patient responds appropriately to naloxone hydrochloride, he/she must be carefully monitored for at least 24 hours, as a relapse may occur as naloxone hydrochloride is metabolized. In opioid-dependent pediatric patients, (including neonates), administration of naloxone hydrochloride may result in an abrupt and complete reversal of opioid effects, precipitating an acute opioid withdrawal syndrome.
Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening, if not recognized, and should be treated according to protocols developed by neonatology experts [see Warnings and Precautions ( 5.3 )] . In settings such as in neonates with known or suspected exposure to maternal opioid use, where it may be preferable to avoid the abrupt precipitation of opioid withdrawal symptoms, consider use of an alternate naloxone-containing product that can be dosed according to weight and titrated to effect.
Also, in situations where the primary concern is for infants at risk fo…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The limited available data on naloxone use in pregnant women are not sufficient to inform a drug-associated risk. However, there are clinical considerations [see Clinical Considerations] . In animal reproduction studies, no embryotoxic or teratogenic effects were observed in mice and rats treated with naloxone hydrochloride during the period of organogenesis at doses equivalent to 6-times and 12-times, respectively, a human dose of 8 mg/day (two naloxone hydrochloride nasal sprays) based on body surface area comparison [see Data] .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 Fetal/Neonatal adverse reactions Naloxone hydrochloride crosses the placenta, and may precipitate withdrawal in the fetus, as well as in the opioid-dependent mother [see Warnings and Precautions ( 5.3 )] .
The fetus should be evaluated for signs of distress after naloxone hydrochloride nasal spray is used. Careful monitoring is needed until the fetus and mother are stabilized. Data Animal Data Naloxone hydrochloride was administered during organogenesis to mice and rats at subcutaneous doses up to 10 mg/kg/day (equivalent to 6-times and 12-times, respectively, a human dose of 8 mg (two naloxone hydrochloride nasal sprays) (based on body surface area comparison).
These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride. Pregnant female rats were administered 2 or 10 mg/kg naloxone subcutaneously from Gestation Day 15 to Postnatal day 21. There were no adverse effects on the offspring (up to 12-times a human dose of 8 mg/day (two naloxone hydrochloride nasal sprays) based on body surface area comparison).
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of naloxone hydrochloride nasal spray have been established in pediatric patients of all ages for known or suspected opioid overdose as manifested by respiratory and/or central nervous system depression. Use of naloxone hydrochloride in all pediatric patients is supported by adult bioequivalence studies coupled with evidence from the safe and effective use of other naloxone hydrochloride drug products. No pediatric studies were conducted for naloxone hydrochloride nasal spray.
Absorption of naloxone hydrochloride following intranasal administration in pediatric patients may be erratic or delayed. Even when the opiate-intoxicated pediatric patient responds appropriately to naloxone hydrochloride, he/she must be carefully monitored for at least 24 hours, as a relapse may occur as naloxone hydrochloride is metabolized. In opioid-dependent pediatric patients, (including neonates), administration of naloxone hydrochloride may result in an abrupt and complete reversal of opioid effects, precipitating an acute opioid withdrawal syndrome.
Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening, if not recognized, and should be treated according to protocols developed by neonatology experts [see Warnings and Precautions ( 5.3 )] . In settings such as in neonates with known or suspected exposure to maternal opioid use, where it may be preferable to avoid the abrupt precipitation of opioid withdrawal symptoms, consider use of an alternate naloxone-containing product that can be dosed according to weight and titrated to effect.
Also, in situations where the primary concern is for infants at risk for opioid overdose, consider whether the availability of alternate naloxone-containing products may be better suited than naloxone hydrochloride nasal spray.
🧓 Geriatric Use ▾
8.5Geriatric Use Geriatric patients have a greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Therefore, the systemic exposure of naloxone hydrochloride can be higher in these patients. Clinical studies of naloxone hydrochloride did not include sufficient numbers 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Naloxone hydrochloride is an opioid antagonist that antagonizes opioid effects by competing for the same receptor sites. Naloxone hydrochloride reverses the effects of opioids, including respiratory depression, sedation, and hypotension. It can also reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
12.2Pharmacodynamics When naloxone hydrochloride is administered intravenously, the onset of action is generally apparent within two minutes. The time to onset of action is shorter for intravenous compared to subcutaneous or intramuscular routes of administration. The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride.
12.3Pharmacokinetics In a pharmacokinetic study in 30 healthy adult subjects, the relative bioavailability (BA) of one nasal spray in one nostril, (4 mg total dose, 0.1 mL of 40 mg/mL naloxone hydrochloride solution), and two nasal sprays administered as one nasal spray in each nostril (8 mg total dose, 0.1 mL of 40 mg/mL naloxone hydrochloride solution in each nostril) was compared to a single dose of 0.4 mg naloxone hydrochloride intramuscular injection. For intranasal administration, the subjects were instructed not to breathe through the nose during administration of the nasal spray, and remained fully supine for approximately one hour post-dose.
For intramuscular administration, naloxone was administered as a single injection in the gluteus maximus muscle. The pharmacokinetic parameters obtained in the study are shown in Table 1. Table 1 Mean Pharmacokinetic Parameters (CV%) for Naloxone Following Naloxone HCl Nasal Spray and Intramuscular Injection of Naloxone HCl to Healthy Subjects Parameter 4 mg – One Nasal Spray in one nostril 40 mg/ml (N=29) 8 mg – Two Nasal Sprays, one in each nostril 40 mg/ml (N=29) 0.4 mg Intramuscular Injection (N=29) t max (h) † 0.50 (0.17, 1.00) 0.33 (0.17, 1.00) 0.38 (0.08, 2.05) C max (ng/mL) 4.83 (43) 9.70 (36) 0.88 (31) AUC t (hr . ng/mL) 7.87 (37) 15.3 (23) 1.75 (23) AUC 0-inf (h*ng/mL) 7.95 (37) 15.5 (23) 1.79 (23) t 1/2 (h) 2.08 (30) 2.10 (32) 1.24 (26) Dose normalized Relative BA (%) vs.
IM 44.2 (31) †† 43.1 (24) 100 † t max reported as median (minimum, maximum) †† N=28 for Relative BA. Figure 1 Mean ± SD Plasma Concentration of Naloxone, (a) 0 to 6 h and (b) 0 to 1h Following Intranasal Administration and Intramuscular Injection The median naloxone t max after intranasal administration of naloxone hydrochloride nasal spray (one nasal spray in one nostril or two nasal sprays as one spray in each nostril was not significantly different compared to the 0.4 mg dose of naloxone hydrochloride intramuscular injection (Table 1).
The dose normalized relative bioavailability of one dose (4 mg) or two doses (8 mg) of naloxone hydrochloride nasal spray as compared to the 0.4 mg dose of naloxone hydrochloride administered by intramuscular injection was 44% and 43%, respectively. Distribution Following parenteral administration, naloxone is distributed in the body and readily crosses the placenta. Plasma protein binding occurs but is relatively weak.
Plasma albumin is the major binding constituent, but significant binding of naloxone also occurs to plasma constituents other than albumin. It is not known whether naloxone is excreted into human milk. Elimination Following a single intranasal administration of naloxone hydrochloride nasal spray (4 mg dose of naloxone hydrochloride), the mean plasma half-life of naloxone in healthy adults was approximately 2.08 (30% CV) hours; respectively, which was longer than that observed after administrations of a 0.4 mg naloxone hydrochloride intramuscular injection, where the half-life was 1.24 hours (26% CV).
In a neonatal study of naloxone hydrochloride injection, the mean (± SD) plasma half-life was observed to be 3.1 (± 0.5) hours. Metabolism Naloxone hydrochloride is metabolized in the liver, primarily by…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Naloxone hydrochloride is an opioid antagonist that antagonizes opioid effects by competing for the same receptor sites. Naloxone hydrochloride reverses the effects of opioids, including respiratory depression, sedation, and hypotension. It can also reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Naloxone hydrochloride nasal spray 4 mg is supplied as a carton containing two blister packages (NDC 0093-2165-68) each with a single spray device. Naloxone hydrochloride nasal spray is not made with natural rubber latex.
16.2Storage and Handling Store naloxone hydrochloride nasal spray in the blister and cartons provided. Store below 77°F (25°C). Excursions permitted up to 104°F (40°C).
Do not freeze or expose to excessive heat above 104°F (40°C). Protect from light. Naloxone hydrochloride nasal spray freezes at temperatures below 5°F (-15°C).
If this happens, the device will not spray. If naloxone hydrochloride nasal spray is frozen and is needed in an emergency, do NOT wait for naloxone hydrochloride nasal spray to thaw. Get emergency medical help right away.
However, naloxone hydrochloride nasal spray may be thawed by allowing it to sit at room temperature for 15 minutes, and it may still be used if it has been thawed after being previously frozen.
📋 Description ▾
11 DESCRIPTION Naloxone hydrochloride nasal spray is a pre-filled, single dose intranasal spray. Chemically, naloxone hydrochloride dihydrate is the hydrochloride salt of (5R,9R,13S,14S)-17-Allyl-3,14-dihydroxy-4,5-epoxymorphinan-6-on hydrochloride dihydrate with the following structure: C 19 H 22 NO 4 Cl•2H 2 O M.W. 399.87 Naloxone hydrochloride, USP an opioid antagonist, occurs as a white to slightly off-white powder, and is freely soluble in water, soluble in ethanol (96%) and practically insoluble in toluene.
Each naloxone hydrochloride nasal spray contains a 4 mg single dose of naloxone hydrochloride, USP (equivalent to 3.6 mg of naloxone) in a 0.1 mL (100 microliter) aqueous solution. Inactive ingredients include benzalkonium chloride (preservative), edetate disodium (stabilizer), sodium chloride, sodium hydroxide/hydrochloric acid to adjust pH, and purified water. The pH range is 3.5 to 5.5.
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 ). Recognition of Opioid Overdose Inform 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 Instruct patients and their family members or caregivers that, since the duration of action of most opioids may exceed that of naloxone hydrochloride nasal spray, they must seek immediate emergency medical assistance after the first dose of naloxone hydrochloride nasal spray and keep the patient under continued surveillance [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.3 )] .
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 higher doses of naloxone hydrochloride or repeated administration of naloxone hydrochloride nasal spray, using a new nasal spray each time [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.2 )] . Precipitation of Severe Opioid Withdrawal Instruct patients and their family members or caregivers that the use of naloxone hydrochloride nasal spray 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 members or caregivers to: Ensure naloxone hydrochloride nasal spray is present whenever persons may be intentionally or accidentally exposed to an opioid overdose (i.e., opioid emergencies). Administer naloxone hydrochloride nasal spray as quickly as possible if a patient 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. Naloxone hydrochloride nasal spray is not a substitute for emergency medical care [see Dosage and Administration ( 2.1 )] .
Lay the patient on their back and administer naloxone hydrochloride nasal spray into one nostril while providing support to the back of the neck to allow the head to tilt back [see Dosage and Administration ( 2.1 )] . Use each nasal spray only one time [see Dosage and Administration ( 2.1 )] . Turn patient on their side as shown in the Instructions for Use and call for emergency medical assistance immediately after administration of the first dose of naloxone hydrochloride nasal spray.
Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance [see Dosage and Administration ( 2.1 )] . Monitor patients and re-administer naloxone hydrochloride nasal spray using a new naloxone hydrochloride nasal spray every 2 to 3 minutes, if the patient is not responding or responds and then relapses back into respiratory depression. Administer naloxone hydrochloride nasal spray in alternate nostrils with each dose [see Dosage and Administration ( 2.1 )] .
Replace naloxone hydrochloride nasal spray before its expiration date. Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 Rev.
F 3/2023