KLOXXADO Naloxone HCL 8 mg/.1mL Spray, 1 mL
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Opioid Antagonist class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 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 nasal spray reverses an opioid overdose. If you come across someone who may have taken too much of an opioid — whether a prescription painkiller, heroin, or fentanyl — and...
- What exactly does naloxone nasal spray do, and when should I use it?
- This is actually very common, and it's important to be prepared for it. Naloxone wears off faster than most opioids, so the overdose can come back. If there's no response after 2 t...
- What if I give it and the person doesn't wake up, or they seem to get better and then get worse again?
Patient education
Supplement & herbal interactions
Where does this data come from?
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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 3K9958V90M
A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
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UNII 7FLD91C86K
Edetate disodium is a chemical compound that binds and removes certain metal ions. In medicines, it acts as a preservative and stabilizer by preventing metals like calcium from interfering with the product's shelf life and consistency.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.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 | $59.774 | $59.77 / 1 vial |
| Medicaid paysCMS SDUD · 12 mo | $62.34 | $62.34 / 1 vial |
| Medicare drug plans payPart D · Q2 2026 | $60.83 | $60.83 / 1 vial |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Kloxxado 8 mg/.1mLthis 59467-0679-01 | Hikma | 1 ml | $59.774 | — | Availability likely | — |
Where does this data come from?
⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
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 11617713 ↗ | Method of use | U-3110 | Aug 26, 2034 |
| US 11628139 ↗ | Method of use | U-3110 | Aug 26, 2034 |
| US 10973814 ↗ | Method of use | U-3110 | Aug 26, 2034 |
| US 10722510 ↗ | Method of use | U-3110 | Aug 26, 2034 |
| US 11975096 ↗ | Drug product | — | Aug 26, 2034 |
| US 12414915 ↗ | Drug product | — | Aug 26, 2034 |
| US 11135155 ↗ | Drug product | — | Aug 26, 2034 |
Is there a generic version of KLOXXADO 8 MG NASAL SPRAY?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 59467-0679-01 You're viewing this | .1 mL in 1 VIAL, SINGLE-DOSE (59467-679-01) | 2021-08-03 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE KLOXXADO is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, for adult and pediatric patients. KLOXXADO is intended for immediate administration as emergency therapy in settings where opioids may be present. KLOXXADO is not a substitute for emergency medical care.
KLOXXADO 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, for adult and pediatric patients. (1) KLOXXADO is intended for immediate administration as emergency therapy in settings where opioids may be present. KLOXXADO is not a substitute for emergency medical care.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • KLOXXADO is for intranasal use only. ( 2.1 ) • Seek emergency medical care immediately after use. ( 2.1 ) • All approved naloxone hydrochloride products achieve plasma concen- trations effective at reversing the effects of opioid overdose.
Comparing products on a nominal mg-for-mg basis may be misleading. ( 2.1 ) • Administer a single spray of KLOXXADO to adult or pediatric patients intranasally into one nostril. ( 2.2 ) • Administer additional doses of KLOXXADO, 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 KLOXXADO 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 Dosage and Administration Instructions • KLOXXADO is for intranasal use only. • One spray delivers the entire contents of the drug product. • All approved naloxone hydrochloride 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 [see Clinical Pharmacology ( 12.3 )] . • The device is ready to use. Do not prime or test prior to administration. • Do not attempt to reuse KLOXXADO.
Each KLOXXADO contains a single dose of naloxone and cannot be reused. • Because suspected opioid overdose is usually managed by someone other than the patient, instruct the prescription recipient to inform those around them about the presence of KLOXXADO and the Instructions for Use . Instruct the patient or caregiver to read the Instructions for Use at the time they receive a prescription for KLOXXADO. Emphasize the following instructions to the patient or caregiver. • Administer KLOXXADO as quickly as possible because prolonged respiratory depression may result in damage to the central nervous system or death. • Always seek immediate emergency medical assistance after the first dose of KLOXXADO has been administered in the event of a suspected, potentially life-threatening opioid emergency because the duration of action of most opioids exceeds that of naloxone hydrochloride.
Keep the patient under continued surveillance and administer repeated doses of KLOXXADO, as necessary, until emergency personnel arrive [see Warnings and Precautions ( 5.1 )]. • Administer KLOXXADO according to the printed instructions on the carton 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 and remove the device nozzle from the nostril after use.
Place the patient in recovery position by turning him/her onto their side as shown in the Instructions for Use and call for emergency medical assistance immediately after the first dose of KLOXXADO. • Administer additional doses of KLOXXADO, using a new nasal spray, every 2 to 3 minutes as needed if the patient does not respond or responds and then relapses into respiratory depression. Administer KLOXXADO in alternate nostrils with each dose [see Dosing and Administration (2.2)].
2.2Dosing in Adult and Pediatric Patients Initial Dosing KLOXXADO nasal spray, 8 mg The recommended initial dose of KLOXXADO in adult and pediatric patients is one spray delivered by intranasal administration into one nostril, which delivers 8 mg of naloxone hydrochloride to adult or pediatric patients. Repeat Dosing Seek emergency medical assistance as soon as possible, after administering the first dose of KLOXXADO. If the desired response is not obtained after 2 or 3 minutes, administer an additional dose using a new KLOXXADO in alter…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Nasal spray: a clear, colorless to yellow solution filled into a clear glass vial, stoppered, and fitted with a unit-dose nasal spray device containing 8 mg of naloxone hydrochloride (equivalent to 7.2 mg naloxone) in 0.1 mL of spray. Nasal spray : • 8 mg naloxone hydrochloride in 0.1 mL. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS KLOXXADO is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients in KLOXXADO. Hypersensitivity to naloxone hydrochloride or to any of the other ingredients. ( 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 Agonist/Antagonists : Reversal of respiratory depression caused by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete.
Larger or repeat doses may be necessary. ( 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 KLOXXADO 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 assistance immediately after administration of the first dose of KLOXXADO and to keep the patient under continued surveillance. Administer additional doses of KLOXXADO 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 measure 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/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 ( 2.2 )] . 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 KLOXXADO in patients who are opioid-dependent may precipitate opioid withdrawal; the risk and severity of withdrawal increases as naloxone exposure increases. Opioid withdrawal is 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: convulsion, 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 similar adverse car…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed 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 )] The following adverse reactions were reported with KLOXXADO in two adult subjects each: abdominal pain, asthenia, dizziness, headache, nasal discomfort, and presyncope. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Specialty USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience 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. KLOXXADO nasal spray, 4 mg No adverse events were reported in a pharmacokinetic study of 72 healthy adult volunteers exposed to one spray of 4 mg KLOXXADO nasal spray in one nostril. KLOXXADO nasal spray, 8 mg In two pharmacokinetic studies a total of 47 healthy adult volunteers were exposed to a single dose of KLOXXADO nasal spray 8 mg, one spray in one nostril.
The following adverse reactions were reported in two subjects each: abdominal pain, asthenia, dizziness, headache, nasal discomfort, and presyncope. On local tissue assessments for nasal irritation, signs of nasal inflammation and nasal congestion were observed.
6.2Postmarketing Experience The following adverse events have been identified during the post-approval use of naloxone hydrochloride injection in the postoperative 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 postoperative 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 was aggressive behavior upon abrupt reversal of an opioid overdose. In the neonate, opioid withdrawal has included: convulsions, excessive crying, hyperactive reflexes [see Warnings and Precautions ( 5.3 )] . The following most frequently reported events (in decreasing frequency) have been identified primarily during post-approval use of naloxone hydrochloride (all routes of administration): withdrawal syndrome, vomiting, nonresponsiveness to stimuli, drug ineffective, agitation, somnolence, and loss of consciousness.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Available data from retrospective cohort studies on naloxone use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Naloxone may precipitate opioid withdrawal in the pregnant woman and fetus [see Warnings and Precautions ( 5.3 ) and 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 3-times and 6-times, respectively, a human dose of 16 mg (see Data ) .
The estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 Maternal and 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 KLOXXADO 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 doses 3-times and 6-times, respectively, a human dose of 16 mg based on body surface area comparison. These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride.
8.2Lactation Risk Summary There is no information regarding the presence of naloxone in human milk, 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 available and is unlikely to affect the breastfed infant.
8.4Pediatric Use The safety and effectiveness of KLOXXADO 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 pediatric patients is supported by evidence from adult bioavailability studies with additional evidence from the reported safe and effective use of other naloxone hydrochloride products. No pediatric studies were conducted for KLOXXADO.
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.
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. Unlike acute opioid withdrawal in adults, acute opioid withdrawal in neonates manifesting as seizures may be life-threatening if not recognized and properly treated. Other signs and symptoms in neonates may include excessive crying and hyperactive reflexes.
In these settings where it may be preferable to avoid the abrupt precipitation of acute opioid withdrawal symptoms, consider use of an alternative, naloxone hydrochloride product that can be dosed according to weight and titrated to effect [see Warnings and Precautions ( 5.3 )]. Also, in situations where the primary concern is for infants at risk for opi…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available data from retrospective cohort studies on naloxone use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Naloxone may precipitate opioid withdrawal in the pregnant woman and fetus [see Warnings and Precautions ( 5.3 ) and 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 3-times and 6-times, respectively, a human dose of 16 mg (see Data ) .
The estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 Maternal and 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 KLOXXADO 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 doses 3-times and 6-times, respectively, a human dose of 16 mg based on body surface area comparison. These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of KLOXXADO 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 pediatric patients is supported by evidence from adult bioavailability studies with additional evidence from the reported safe and effective use of other naloxone hydrochloride products. No pediatric studies were conducted for KLOXXADO.
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.
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. Unlike acute opioid withdrawal in adults, acute opioid withdrawal in neonates manifesting as seizures may be life-threatening if not recognized and properly treated. Other signs and symptoms in neonates may include excessive crying and hyperactive reflexes.
In these settings where it may be preferable to avoid the abrupt precipitation of acute opioid withdrawal symptoms, consider use of an alternative, naloxone hydrochloride product that can be dosed according to weight and titrated to effect [see Warnings and Precautions ( 5.3 )]. 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 KLOXXADO. Juvenile Animal Study In a juvenile animal study, male and female juvenile rats were administered a single intranasal dose of saline, vehicle consisting of 20% alcohol and 5% propylene glycol, or naloxone (123 mg/kg, 185 mg/kg, and 246 mg/kg) on postnatal day 7 (PND 7).
There were no test article-related findings on sexual maturation, neuroapoptosis, or on a limited number of neurocognitive endpoints which included social interactions as well as learning and memory. The no-effect dose level for neurodevelopmental toxicity was the high dose tested, which is 2.7-times a neonate dose based on body surface area comparison and a neonate weight of 2.5 kg.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of KLOXXADO 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🧬 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. Administration of 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 up to 72 healthy adult volunteers under fasting conditions, the bioavailability (BA) of a single 4 mg dose (one spray) of KLOXXADO was compared to a single 8 mg nasal dose of KLOXXADO and a single 4 mg nasal dose of a previously approved naloxone nasal spray. Naloxone plasma concentration versus time profiles are shown in Figure 1. The pharmacokinetic parameters of naloxone are summarized in Table 1.
Figure 1. Mean ± SD Plasma Concentration Time Profiles of Naloxone Following a Single Dose of Kloxxado nasal spray 4 mg versus Kloxxado 8 mg nasal spray, and a Previously Approved naloxone nasal spray 4 mg in Healthy Subjects (A: 0-4h and B: 0-30 min) Kloxxado nasal spray 4 mg, Kloxxado nasal spray 8 mg, and a Previously Approved Naloxone Nasal Spray 4 mg Administration in Healthy Subjects Kloxxado nasal spray 4 mg, Kloxxado nasal spray 8 mg, and a Previously Approved Naloxone Nasal Spray 4 mg Administration in Healthy Subjects Parameter Kloxxado Nasal Spray 4 mg Previously Approved Naloxone Nasal Spray 4 mg Kloxxado Nasal Spray 8 mg N 71 N=71 due to withdrawal.
70 N=70 due to withdrawal. 70 T max (h) T max reported as median (minimum – maximum). 0.17 (0.07-0.50) 0.25 (0.13-1.00) 0.25 (0.07-1.00) C max (ng/mL) 11.11 (41.74) 6.56 (35.87) 14.41 (47.17) AUC last (ngh/mL) 12.31 (31.61) 10.14 (35.44) 19.57 (35.39) AUC 0inf (ngh/mL) 12.57 (30.63) 10.41 (33.82) 19.81 (34.73) T 1/2 (h) 1.27 (26.32) 1.30 (26.22) 1.56 (126.82) In two pharmacokinetic studies in up to 24 healthy adult volunteers for each study, the bioavailability (BA) of a single 8 mg dose (one spray) of KLOXXADO was compared to a single 0.4 mg intramuscular dose and a single 2 mg intravenous dose of naloxone.
Naloxone plasma concentration versus time profiles are shown in Figure 2. The pharmacokinetic parameters of naloxone are summarized in Table 2. Figure 2.
Mean ± SD Plasma Concentration-Time Profiles of Naloxone Following A Single Dose of Intranasal versus Intramuscular/Intravenous Administration in Healthy Subjects. (A: 0-4 h and B: 0-30 min.) Table 2. Mean (CV%) Plasma Pharmacokinetic Parameters of Naloxone Following a Single Dose of Intranasal and Intramuscular/Intravenous Administration in Healthy Subjects Parameter KLOXXADO 8 mg Intramuscular Injection 0.4 mg Intravenous Injection 2 mg Study Study I Study II Study I Study II Study II N 24 23 N=23 due to one subject withdrawal.
24 23 24 T max (h) T max reported as median (minimum – maximum). 0.25 (0.10 – 1.00) 0.25 (0.10 – 1.00) 0.25 (0.13 – 1.00) 0.25 (0.10 – 1.00) NA C max (ng/mL) 12.3 (55.4) 12.8 (37.0) 0.876 (36.7) 0.910 (36.8) 26.2 (82.4) C max of Intravenous Injection 2 mg was observed value from the first sampling time of 2 minutes post-dose. AUC last (ng•h/mL) 18.0 (29.6) 18.4 (33.4) 1.82 (24.0) 1.87 (24.7) 12.7 (27.6) AUC 0-inf (ng•h/mL) 16.7 (31.9) N=15 19.0 (32.7) N=19 1.94 (20.9) N=22 for AUC 0-inf and t 1/2 1.95 (21.9) 12.8 (27.5) t 1/2 (h) 2.69 (69.9) 1.76 (39.7) 1.41 (20.0) 1.40 (38.9) 1.22 (16.4) Dose normalized Relative BA (%) vs IM Injection 41.6 47.4 100 100 NA Dose normalized Absolute BA (%) vs IV Injection NA
36.6NA 77.2 100 NA= Not applicable Absorption The median T max for n…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Naloxone hydrochloride is an opioid antagonist that antagonizes opioid effects by competing for the same receptor sites. Administration of 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 KLOXXADO (naloxone hydrochloride) nasal spray is a clear, colorless to yellow solution supplied in a single-dose spray device that consists of a stoppered glass vial encased in a container holder fitted with a spray actuator, cannula, and spray pin. It delivers a single dose of 8 mg of naloxone hydrochloride (equivalent to 7.2 mg naloxone) in 0.1 mL. Each KLOXXADO carton contains two individual blisters sealed with a paper backing with a “peel off” feature.
The carton contains abbreviated instructions-for-use printed on the back. In addition, a quick instructions leaflet is attached to the bottom of each individual blister. KLOXXADO nasal spray, 8 mg 1 Carton containing two nasal spray devices: NDC# 59467-679-01 Not made with natural rubber latex.
Storage and Handling Store KLOXXADO in the blister and cartons provided. Store at 20ºC to 25ºC (68ºF to 77ºF), with excursions permitted to 40°C (104°F) and to 5°C (41°F). Do not store at or above 40°C (104°F).
Do not freeze. Protect from light. KLOXXADO freezes at temperatures below -15°C (5°F).
If this happens, the device will not spray. If KLOXXADO is frozen and is needed in an emergency, do NOT wait for KLOXXADO to thaw. Get emergency medical help right away.
However, KLOXXADO 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 KLOXXADO (naloxone hydrochloride) nasal spray contains the active moiety naloxone, an opioid antagonist, in the form of hydrochloride salt. The chemical name of Naloxone hydrochloride dihydrate is 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride dihydrate. It has the molecular weight of 399.87 g/mol.
Naloxone hydrochloride dihydrate molecular formula is C 19 H 21 NO 4· HCl · 2H 2 O, and it has the following chemical structure, as shown below. Naloxone hydrochloride occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform. KLOXXADO (naloxone hydrochloride) nasal spray is supplied in a pre-filled, single-dose intranasal spray.
Each spray or 0.1 mL of KLOXXADO (naloxone hydrochloride) nasal spray contains 8 mg of naloxone hydrochloride (equivalent to 8.79 mg of naloxone hydrochloride dihydrate, USP or 7.2 mg naloxone). Inactive ingredients are dehydrated alcohol (8 mg strength: 20% (w/w)), edetate disodium dihydrate, USP, propylene glycol, USP, and sodium hydroxide, NF and hydrochloric acid, NF as pH adjusters, in purified water, USP. The pH range for KLOXXADO (naloxone hydrochloride) nasal spray is from 4.0 to 5.5. image-chemical-structure-usp.jpg
💬 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, because the duration of action of most opioids may exceed that of KLOXXADO, they must seek immediate emergency medical assistance after the first dose of KLOXXADO 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 KLOXXADO, using a new nasal spray 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 KLOXXADO 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 KLOXXADO is present and readily available in locations where a person may be intentionally or accidentally exposed to an opioid overdose (i.e., opioid emergencies). • Administer KLOXXADO 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. KLOXXADO is not a substitute for emergency medical care [see Dosage and Administration ( 2.1 )]. • Lay the patient on their back and administer KLOXXADO 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, DO NOT test or prime prior to use [see Dosage and Administration ( 2.1 )]. • Place patient in a recovery position by turning him/her to their side as shown in the Instructions for Use and call for emergency medical assistance immediately after administration of the first dose of KLOXXADO.
Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance [see Dosage and Administration ( 2.1 )]. • Monitor patients and administer additional dose of KLOXXADO using a new KLOXXADO every 2 to 3 minutes, if the patient is not responding or responds and then relapses back into respiratory depression. Administer KLOXXADO in alternate nostrils with each dose [see Dosage and Administration ( 2.1 )]. • Replace KLOXXADO before its expiration date. Distributed by: Hikma Specialty USA Inc.
Columbus, OH 43228 C50001066/03 Revised September 2025 KLOXXADO ® is a registered trademark of Hikma Pharmaceuticals USA Inc.