NDC 0093-2165 Naloxone Hydrochloride

Naloxone Hydrochloride

NDC Product Code 0093-2165

NDC 0093-2165-68

Package Description: 2 BLISTER PACK in 1 CARTON > 1 VIAL, SINGLE-DOSE in 1 BLISTER PACK (0093-2165-19) > .1 mL in 1 VIAL, SINGLE-DOSE

NDC Product Information

Naloxone Hydrochloride with NDC 0093-2165 is a a human prescription drug product labeled by Teva Pharmaceuticals Usa, Inc.. The generic name of Naloxone Hydrochloride is naloxone hydrochloride. The product's dosage form is spray, metered and is administered via nasal form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 1725059.

Dosage Form: Spray, Metered - A non-pressurized dosage form consisting of valves which allow the dispensing of a specified quantity of spray upon each activation.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Naloxone Hydrochloride Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7)
  • EDETATE DISODIUM (UNII: 7FLD91C86K)
  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Nasal - Administration to the nose; administered by way of the nose.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Opioid Antagonist - [EPC] (Established Pharmacologic Class)
  • Opioid Antagonists - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Teva Pharmaceuticals Usa, Inc.
Labeler Code: 0093
FDA Application Number: ANDA209522 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 12-22-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Naloxone Hydrochloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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.Limitations of Use:Restrict prescription of naloxone hydrochloride nasal spray 2 mg to opioid-dependent patients expected to be at risk for severe opioid withdrawal in situations where there is a low risk for accidental or intentional opioid exposure by household contacts.

2.1 Important 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.

2.2 Dosing In Adults And Pediatric Patients

Initial DosingThe recommended initial dose of naloxone hydrochloride nasal spray in adults and pediatric patients is one spray delivered by intranasal administration into one nostril.Repeat DosingSeek 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 naloxone hydrochloride nasal spray and relapses back into respiratory depression before emergency assistance arrives, administer an additional dose of naloxone hydrochloride nasal spray using a new naloxone hydrochloride nasal spray and continue surveillance of the patient.If the desired response is not obtained after 2 or 3 minutes, administer an additional dose of naloxone hydrochloride nasal spray using a new naloxone hydrochloride nasal spray. If there is still no response and additional doses are available, administer additional doses of naloxone hydrochloride nasal spray every 2 to 3 minutes using a new naloxone hydrochloride nasal spray with each dose until emergency medical assistance arrives.Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance.

2.3 Dosing Modifications Due To 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 and require higher doses of naloxone hydrochloride or repeated administration of naloxone hydrochloride nasal spray using a new nasal spray [see Warnings and Precautions (5.2)].

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.

4 Contraindications

Naloxone hydrochloride nasal spray is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients.

5.1 Risk 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.

5.2 Risk 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.

5.3 Precipitation 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.There are limited data to inform if the 2 mg dose of naloxone hydrochloride nasal spray will avoid precipitation of severe opioid withdrawal in the setting of opioid dependence. However, the 2 mg dose may not provide an adequate and timely reversal in persons who may be exposed to an overdose of a potent or very high dose of opioids.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 similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, after use of naloxone hydrochloride, monitor patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects for hypotension, ventricular tachycardia or fibrillation, and pulmonary edema in an appropriate healthcare setting. It has been suggested that the pathogenesis of pulmonary edema associated with the use of naloxone hydrochloride is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures.There may be clinical settings, particularly the postpartum period in neonates with known or suspected exposure to maternal opioid use, where it is preferable to avoid the abrupt precipitation of opioid withdrawal symptoms. In these settings, consider use of an alternative, naloxone­containing product that can be titrated to effect and, where applicable, dosed according to weight [see Use in Specific Populations (8.4)].

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.

8.1 Pregnancy

Risk SummaryThe 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 ConsiderationsFetal/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.DataAnimal DataNaloxone 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).

8.2 Lactation

Risk SummaryThere 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.

8.4 Pediatric 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.

8.5 Geriatric 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.

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: C19H22NO4Cl•2H2O M.W. 399.87Naloxone 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.

12.1 Mechanism 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.

12.2 Pharmacodynamics

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.

12.3 Pharmacokinetics

In a pharmacokinetic study in 30 healthy adult subjects, the relative bioavailability (BA) of one nasal spray in one nostril, consisting of a 2 mg total dose (0.1 mL of 20 mg/mL naloxone hydrochloride solution) and a 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, consisting of a 4 mg total dose (0.1 mL of 20 mg/mL naloxone hydrochloride solution in each nostril) and an 8 mg total dose (0.1 mL of 40 mg/mL naloxone hydrochloride solution in each nostril), were 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 Hydrochloride Nasal Spray and Intramuscular Injection of Naloxone HCl to Healthy SubjectsParameter2 mg– One Nasal Spray in one nostril 20 mg/ml (N=29)4 mg – Two Nasal Sprays, one in each nostril 20 mg/ml (N=29) 4 mg – One Nasal Spray in one nostril40 mg/ml(N=29)8 mg –Two Nasal Sprays, one in each nostril40 mg/ml(N=29)0.4 mgIntramuscular Injection(N=29)tmax (h)10.33 (0.25, 1.00)0.33 (0.17, 0.57)0.50 (0.17, 1.00)0.33 (0.17, 1.00)0.38 (0.08, 2.05)Cmax (ng/mL)2.91 (35)6.30 (34)4.83 (43)9.70 (36)0.88 (31)AUCt (hr ng/mL)4.60 (27)9.64 (24)7.87 (37)15.3 (23)1.75 (23)AUC0-inf (h*ng/mL)4.66 (27)9.74 (24)7.95 (37)15.5 (23)1.79 (23)t1/2 (h)1.85 (33)2.19 (33)2.08 (30)2.10 (32)1.24 (26)Dose normalized Relative BA (%) vs. IM51.7 (22)54.0 (23)44.2 (31)243.1 (24)1001. tmax reported as median (minimum, maximum)2. 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 InjectionThe median naloxone tmax after intranasal administration of naloxone hydrochloride nasal spray (one nasal spray in one nostril (2 mg or 4 mg) or two nasal sprays as one spray in each nostril (4 mg or 8 mg) 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 (2 mg or 4 mg) or two doses (4 mg or 8 mg) of naloxone hydrochloride nasal spray as compared to the 0.4 mg dose of naloxone hydrochloride administered by intramuscular injection was 52%, 44%, 54%, and 43%, respectively.DistributionFollowing 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.EliminationFollowing a single intranasal administration of naloxone hydrochloride nasal spray (2 mg or 4 mg dose of naloxone hydrochloride), the mean plasma half-life of naloxone in healthy adults was approximately 1.85 (33% CV) hours and 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.MetabolismNaloxone hydrochloride is metabolized in the liver, primarily by glucuronide conjugation, with naloxone-3-glucoronide as the major metabolite.ExcretionAfter an oral or intravenous dose, about 25 to 40% of naloxone is excreted as metabolites in urine within 6 hours, about 50% in 24 hours, and 60 to 70% in 72 hours.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisLong-term animal studies to evaluate the carcinogenic potential of naloxone have not been completed.MutagenesisNaloxone was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study.Impairment of FertilityMale rats were treated with 2 or 10 mg/kg naloxone for 60 days prior to mating. Female rats treated for 14-days prior to mating and throughout gestation with the same doses of naloxone (up to 12-times a human dose of 8 mg/day (two naloxone hydrochloride nasal sprays) based on body surface area comparison). There was no adverse effect on fertility.

16.1 How 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.

16.2 Storage 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.

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 OverdoseInform 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:MiosisBradycardia and/or hypotension.Risk of Recurrent Respiratory and Central Nervous System DepressionInstruct 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/AntagonistsInstruct 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 WithdrawalInstruct 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 InstructionsInstruct 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 19454Rev. D 11/2020

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