Naltrexone

Q: Who makes Naltrexone?

Naltrexone is listed by 1 labeler in the FDA NDC directory, including Amneal Pharmaceuticals NY LLC.

Kit

Prescription (Rx)

Uses

Treatment with naltrexone for extended-release injectable suspension should be part of a comprehensive management program that includes psychosocial support. Naltrexone for extended-release injectable suspension contains naltrexone, an opioid antagonist, and is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with naltrexone for extended-release injectable suspension. Patients should not be actively drinking at the time of initial naltrexone for extended-release injectable suspension administration (1.1) . Naltrexone for extended-release injectable suspension is indicated for the prevention of relapse to opioid dependence, following opioid detoxification (1.2) . Naltrexone for extended-release injectable suspension should be part of a comprehensive management program that includes psychosocial support (1) . 1.1 Alcohol Dependence Naltrexone for extended-release injectable suspension is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with naltrexone for extended-release injectable suspension. Patients should not be actively drinking at the time of initial naltrexone for extended-release injectable suspension administration. 1.2 Opioid Dependence Naltrexone for extended-release injectable suspension is indicated for the prevention of relapse to opioid dependence, following opioid detoxification.

Dosage and administration

Naltrexone for extended-release injectable suspension must be prepared and administered by a healthcare provider (2.1 , 2.6) . Prior to initiating naltrexone for extended-release injectable suspension, an opioid-free duration of a minimum of 7–10 days is recommended for patients, to avoid precipitation of opioid withdrawal that may be severe enough to require hospitalization (2.1) . The recommended dose of naltrexone for extended-release injectable suspension is 380 mg delivered intramuscularly (deep) as a gluteal injection, every 4 weeks or once a month, alternating buttocks for each subsequent injection, using the carton components provided (2.1) . Naltrexone for extended-release injectable suspension must ONLY be administered as a deep intramuscular gluteal injection ( 2.1 ) . See Full Prescribing Information for complete Directions for Use (2.6) . 2.1 Important Dosage and Administration Information Naltrexone for extended-release injectable suspension must be prepared and administered by a healthcare provider. Naltrexone for extended-release injectable suspension must ONLY be administered as a deep intramuscular gluteal injection. Parenteral products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. A properly mixed suspension will be milky white, will not contain clumps, and will move freely down the wall of the vial [see Dosage and Administration ( 2.6 ) ] . Prior to initiating naltrexone for extended-release injectable suspension, an opioid-free duration of a minimum of 7–10 days is recommended for patients, to avoid precipitation of opioid withdrawal that may be severe enough to require hospitalization [see Warnings and Precautions ( 5.3 ) ]. The recommended dose of naltrexone for extended-release injectable suspension is 380 mg delivered intramuscularly (deep) as a gluteal injection every 4 weeks or once a month, alternating buttocks for each subsequent injection, using the carton components provided [see How Supplied/Storage and Handling ( 16 ) ] . The needles provided in the carton are customized needles. Naltrexone for extended-release injectable suspension must not be injected using any other needle. The needle lengths (either 1 1/2 or 2 inches) may not be adequate in every patient because of body habitus. Body habitus should be assessed prior to each injection for each patient to assure that needle length is adequate for intramuscular administration. For patients with a larger amount of subcutaneous tissue overlying the gluteal muscle, the administering healthcare provider may utilize the supplied 2-inch needle with needle protection device to help ensure that the injectate reaches the intramuscular mass. For very lean patients, the 1 1/2-inch needle may be appropriate to prevent the needle contacting the periosteum. Either needle may be used for patients with average body habitus. Healthcare providers should ensure that the naltrexone for extended-release injectable suspension injection is given correctly, and should consider alternate treatment for those patients whose body habitus precludes an intramuscular gluteal injection with one of the provided needles. If a patient misses a dose, he/she should be instructed to receive the next dose as soon as possible. Pretreatment with oral naltrexone is not required before using naltrexone for extended-release injectable suspension. 2.2 Patient Access to an Opioid Reversal Agent for the Emergency Treatment of Opioid Overdose At the initial naltrexone for extended-release injectable suspension injection and with each subsequent injection, inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose after naltrexone for extended-release injectable suspension treatment is discontinued, at the end of the naltrexone for extended-release injectable suspension dosing interval (i.e., near the end of the month that naltrexone for extended-release injectable suspension was administered), or after a dose of naltrexone for extended-release injectable suspension is missed, strongly consider recommending or prescribing an overdose reversal agent for the emergency treatment of opioid overdose [see Warnings and Precautions ( 5.1 ) ] . Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program [see Warning and Precautions (5.1) ] . There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. 2.3 Reinitiation of Treatment in Patients Previously Discontinued There are no data to specifically address reinitiation of treatment. Patients reinitiating treatment with naltrexone for extended-release injectable suspension should be opioid-free at the time of dose administration [see Indications and Usage ( 1 ) , Contraindications ( 4 ) , and Warnings and Precautions ( 5.3 ) ] . 2.4 Switching From Oral Naltrexone There are no systematically collected data that specifically address the switch from oral naltrexone to naltrexone for extended-release injectable suspension.

Dosage forms and strengths

Naltrexone for extended-release injectable suspension is an off-white to light tan powder for injectable suspension in a 5 mL single-dose vial. Naltrexone for extended-release injectable suspension contains 380 mg of naltrexone in a microsphere formulation per vial (337 mg of naltrexone per gram of microspheres). Naltrexone for extended-release injectable suspension is an injectable suspension containing 380 mg of naltrexone in a microsphere formulation in a single-dose vial (3) .

Contraindications

Naltrexone for extended-release injectable suspension is contraindicated in: Patients receiving opioid analgesics [see Warnings and Precautions ( 5.3 ) ] . Patients with current physiologic opioid dependence [see Warnings and Precautions ( 5.3 ) ] . Patients in acute opioid withdrawal [see Warnings and Precautions ( 5.3 ) ] . Any individual who has failed the naloxone challenge test or has a positive urine screen for opioids [see Warnings and Precautions ( 5.3 ) ] . Patients who have previously exhibited hypersensitivity to naltrexone, PLG, carboxymethylcellulose, or any other components of the diluent [see Warnings and Precautions ( 5.8 ) ]. Naltrexone for extended-release injectable suspension is contraindicated in: Patients receiving opioid analgesics (4) . Patients with current physiologic opioid dependence (4) . Patients in acute opioid withdrawal (4) . Any individual who has failed the naloxone challenge test or has a positive urine screen for opioids (4) . Patients who have previously exhibited hypersensitivity to naltrexone, polylactide-co-glycolide (PLG), carboxymethylcellulose, or any other components of the diluent (4) .

Warnings and precautions

Vulnerability to Opioid Overdose : Following naltrexone for extended-release injectable suspension treatment, opioid tolerance is reduced from pretreatment baseline and patients are vulnerable to potentially fatal overdose at the end of a dosing interval, after missing a dose, or after discontinuing naltrexone for extended-release injectable suspension treatment. Attempts to overcome blockade may also lead to fatal overdose. Strongly consider recommending or prescribing an opioid reversal agent (e.g., naloxone, nalmefene) for the emergency treatment of opioid overdose (5.1) . Injection Site Reactions : Naltrexone for extended-release injectable suspension must be prepared and administered by a healthcare provider. In some cases, injection site reactions may be very severe. Some cases of injection site reactions required surgical intervention (5.2) . Precipitation of Opioid Withdrawal : Opioid-dependent and opioid-using patients, including those being treated for alcohol dependence, should be opioid-free before starting naltrexone for extended-release injectable suspension treatment, and should notify healthcare providers of any recent opioid use. An opioid-free duration of a minimum of 7-10 days is recommended for patients to avoid precipitation of opioid withdrawal that may be severe enough to require hospitalization (5.3) . Hepatotoxicity : Cases of hepatitis and clinically significant liver dysfunction were observed in association with naltrexone for extended-release injectable suspension treatment during the clinical development program and in the postmarketing period. Discontinue use of naltrexone for extended-release injectable suspension in the event of symptoms or signs of acute hepatitis (5.4) . Depression and Suicidality : Monitor patients for the development of depression or suicidal thinking (5.5) . When Reversal of Naltrexone for Extended-Release Injectable Suspension B lockade Is Required for Pain Management : In an emergency situation in patients receiving naltrexone for extended-release injectable suspension, suggestions for pain management include regional analgesia or use of non-opioid analgesics (5.6) . Eosinophilic Pneumonia : Patients who develop dyspnea and hypoxemia should seek medical attention immediately. Consider the possibility of eosinophilic pneumonia in patients who do not respond to antibiotics (5.7) . Hypersensitivity Reactions Including Anaphylaxis : Cases of urticaria, angioedema, and anaphylaxis have been observed with the use of naltrexone for extended-release injectable suspension (5.8) . 5.1 Vulnerability to Opioid Overdose After opioid detoxification, patients are likely to have reduced tolerance to opioids. Naltrexone for extended-release injectable suspension blocks the effects of exogenous opioids for approximately 28 days after administration. However, as the blockade wanes and eventually dissipates completely, patients who have been treated with naltrexone for extended-release injectable suspension may respond to lower doses of opioids than previously used, just as they would have shortly after completing detoxification. This could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids. Cases of opioid overdose with fatal outcomes have been reported in patients who used opioids at the end of a dosing interval, after missing a scheduled dose, or after discontinuing treatment. Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after naltrexone for extended-release injectable suspension treatment is discontinued, especially at the end of a dosing interval (i.e., near the end of the month that naltrexone for extended-release injectable suspension was administered), or after a dose of naltrexone for extended-release injectable suspension is missed. It is important that patients inform family members and the people closest to the patient of this increased sensitivity to opioids and the risk of overdose [see Patient Counseling Information ( 17 ) ]. There is also the possibility that a patient who is treated with naltrexone for extended-release injectable suspension could overcome the opioid blockade effect of naltrexone for extended-release injectable suspension. Although naltrexone for extended-release injectable suspension is a potent antagonist with a prolonged pharmacological effect, the blockade produced by naltrexone for extended-release injectable suspension is surmountable. The plasma concentration of exogenous opioids attained immediately following their acute administration may be sufficient to overcome the competitive receptor blockade. This poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids. Any attempt by a patient to overcome the antagonism by taking opioids is especially dangerous and may lead to life-threatening opioid intoxication or fatal overdose. Patients should be told of the serious consequences of trying to overcome the opioid blockade [see Patient Counseling Information ( 17 ) ] . Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose At the initial naltrexone for extended-release injectable suspension injection and with each subsequent injection, inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because of the risks for opioid overdose described above, both at the initial naltrexone for extended-release injectable suspension injection and with each subsequent injection, strongly consider recommending or prescribing an opioid overdose reversal agent for the emergency treatment of an opioid overdose.

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Accidental Opioid Overdose [see Warnings and Precautions ( 5.1 ) ] Injection Site Reactions [see Warnings and Precautions ( 5.2 ) ] Precipitated Opioid Withdrawal [see Warnings and Precautions ( 5.3 ) ] Hepatotoxicity [see Warnings and Precautions ( 5.4 ) ] Depression and Suicidality [see Warnings and Precautions ( 5.5 ) ] Eosinophilic Pneumonia [see Warnings and Precautions ( 5.7 ) ] Hypersensitivity Reactions [see Warnings and Precautions ( 5.8 ) ] The adverse events seen most frequently in association with naltrexone for extended-release injectable suspension therapy for alcohol dependence (i.e., those occurring in ≥5% and at least twice as frequently with naltrexone for extended-release injectable suspension than placebo) include nausea, vomiting, injection site reactions (including induration, pruritus, nodules and swelling), muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, decreased appetite or other appetite disorders (6) . The adverse events seen most frequently in association with naltrexone for extended-release injectable suspension therapy in opioid-dependent patients (i.e., those occurring in ≥2% of patients treated with naltrexone for extended-release injectable suspension and at least twice as frequently with naltrexone for extended-release injectable suspension than placebo) were hepatic enzyme abnormalities, injection site pain, nasopharyngitis, insomnia, and toothache (6) . To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In all controlled and uncontrolled trials during the premarketing development of naltrexone for extended-release injectable suspension, more than 1100 patients with alcohol and/or opioid dependence have been treated with naltrexone for extended-release injectable suspension. Approximately 700 patients have been treated for 6 months or more, and more than 400 for 1 year or longer. Adverse Events Leading to Discontinuation of Treatment Alcohol Dependence In controlled trials of 6 months or less in alcohol-dependent patients, 9% of alcohol-dependent patients treated with naltrexone for extended-release injectable suspension discontinued treatment due to an adverse event, as compared to 7% of the alcohol-dependent patients treated with placebo. Adverse events in the naltrexone for extended-release injectable suspension 380 mg group that led to more dropouts than in the placebo-treated group were injection site reactions (3%), nausea (2%), pregnancy (1%), headache (1%), and suicide-related events (0.3%). In the placebo group, 1% of patients withdrew due to injection site reactions, and 0% of patients withdrew due to the other adverse events. Opioid Dependence In a controlled trial of 6 months, 2% of opioid-dependent patients treated with naltrexone for extended-release injectable suspension discontinued treatment due to an adverse event, as compared to 2% of the opioid-dependent patients treated with placebo. Common Adverse Reactions Alcohol Dependence Table 1 lists all treatment-emergent clinical adverse reactions, regardless of causality, occurring in ≥5% of patients with alcohol dependence, for which the incidence was greater in the combined naltrexone for extended-releaser injectable suspension group than in the placebo group. A majority of patients treated with naltrexone for extended-release injectable suspension in clinical studies had adverse reactions with a maximum intensity of “mild” or “moderate”.

Drug interactions

Patients taking naltrexone for extended-release injectable suspension may not benefit from opioid-containing medicines. Naltrexone antagonizes the effects of opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations and opioid analgesics. Naltrexone antagonizes the effects of opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations, and opioid analgesics (7) .

Use in specific populations

Caution is recommended in administering naltrexone for extended-release injectable suspension to patients with moderate to severe renal impairment (8.6) . Naltrexone for extended-release injectable suspension pharmacokinetics have not been evaluated in subjects with severe hepatic impairment (8.7) . 8.1 Pregnancy Risk Summary The available data from published case series with naltrexone for extended-release injectable suspension use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are clinical considerations (see Clinical Considerations ). Reproduction and developmental animal studies have not been conducted for naltrexone for extended-release injectable suspension. Daily oral administration of naltrexone to female rats and rabbits increased the incidence of early fetal loss at exposures ≥ 11 times and ≥ 2 times the human exposure, respectively. Daily oral administration of naltrexone to pregnant rats and rabbits during the period of organogenesis did not induce malformation at exposures up to 175 times and 14 times the human exposure, respectively (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Published studies have demonstrated that alcohol is associated with fetal harm including growth restriction, facial abnormalities, central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Data Animal Data Reproduction and developmental studies have not been conducted for naltrexone for extended-release injectable suspension. Studies with naltrexone administered via the oral route have been conducted in pregnant rats and rabbits. Daily oral administration of naltrexone has been shown to increase the incidence of early fetal loss when given to rats at doses ≥30 mg/kg/day (11 times the human exposure based on an AUC (0-28d) comparison) and to rabbits at oral doses ≥60 mg/kg/day (2 times the human exposure based on an AUC (0-28d) comparison). Daily oral administration of naltrexone to rats and rabbits during the period of organogenesis did not induce malformations at doses up to 200 mg/kg/day (175- and 14‑times the human exposure based on an AUC (0-28d) comparison, respectively). 8.2 Lactation Risk Summary Naltrexone and its major metabolite, 6β-naltrexol, are present in human milk. There are no data on the effects on the breastfed infant or the effects on milk production. The developmental health benefits of breastfeeding should be considered along with the mother’s clinical need for naltrexone and any potential adverse effects on the breastfed infant from naltrexone or the mother’s underlying maternal condition. 8.4 Pediatric Use The safety and efficacy of naltrexone for extended-release injectable suspension have not been established in the pediatric population. The pharmacokinetics of naltrexone for extended-release injectable suspension have not been evaluated in a pediatric population. 8.5 Geriatric Use In trials of alcohol-dependent subjects, 2.6% (n=26) of subjects were >65 years of age, and one patient was >75 years of age. Clinical studies of naltrexone for extended-release injectable suspension did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects. No subjects over age 65 were included in studies of opioid-dependent subjects. The pharmacokinetics of naltrexone for extended-release injectable suspension have not been evaluated in the geriatric population. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function. 8.6 Renal Impairment Pharmacokinetics of naltrexone for extended-release injectable suspension are not altered in subjects with mild renal insufficiency (creatinine clearance of 50-80 mL/min). Dose adjustment is not required in patients with mild renal impairment. Naltrexone for extended-release injectable suspension pharmacokinetics have not been evaluated in subjects with moderate and severe renal insufficiency. Because naltrexone and its primary metabolite are excreted primarily in the urine, caution is recommended in administering naltrexone for extended-release injectable suspension to patients with moderate to severe renal impairment [see Clinical Pharmacology ( 12.3 ) ] . 8.7 Hepatic Impairment The pharmacokinetics of naltrexone for extended-release injectable suspension are not altered in subjects with mild to moderate hepatic impairment (Groups A and B of the Child-Pugh classification). Dose adjustment is not required in subjects with mild or moderate hepatic impairment. Naltrexone for extended-release injectable suspension pharmacokinetics were not evaluated in subjects with severe hepatic impairment [see Clinical Pharmacology ( 12.3 ) ] .

Pregnancy

8.1 Pregnancy Risk Summary The available data from published case series with naltrexone for extended-release injectable suspension use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are clinical considerations (see Clinical Considerations ). Reproduction and developmental animal studies have not been conducted for naltrexone for extended-release injectable suspension. Daily oral administration of naltrexone to female rats and rabbits increased the incidence of early fetal loss at exposures ≥ 11 times and ≥ 2 times the human exposure, respectively. Daily oral administration of naltrexone to pregnant rats and rabbits during the period of organogenesis did not induce malformation at exposures up to 175 times and 14 times the human exposure, respectively (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Published studies have demonstrated that alcohol is associated with fetal harm including growth restriction, facial abnormalities, central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Data Animal Data Reproduction and developmental studies have not been conducted for naltrexone for extended-release injectable suspension. Studies with naltrexone administered via the oral route have been conducted in pregnant rats and rabbits. Daily oral administration of naltrexone has been shown to increase the incidence of early fetal loss when given to rats at doses ≥30 mg/kg/day (11 times the human exposure based on an AUC (0-28d) comparison) and to rabbits at oral doses ≥60 mg/kg/day (2 times the human exposure based on an AUC (0-28d) comparison). Daily oral administration of naltrexone to rats and rabbits during the period of organogenesis did not induce malformations at doses up to 200 mg/kg/day (175- and 14‑times the human exposure based on an AUC (0-28d) comparison, respectively).

Pediatric use

8.4 Pediatric Use The safety and efficacy of naltrexone for extended-release injectable suspension have not been established in the pediatric population. The pharmacokinetics of naltrexone for extended-release injectable suspension have not been evaluated in a pediatric population.

Geriatric use

8.5 Geriatric Use In trials of alcohol-dependent subjects, 2.6% (n=26) of subjects were >65 years of age, and one patient was >75 years of age. Clinical studies of naltrexone for extended-release injectable suspension did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects. No subjects over age 65 were included in studies of opioid-dependent subjects. The pharmacokinetics of naltrexone for extended-release injectable suspension have not been evaluated in the geriatric population. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.

Overdosage

There is limited experience with overdose of naltrexone for extended-release injectable suspension. Single doses up to 784 mg were administered to 5 healthy subjects. There were no serious or severe adverse events. The most common effects were injection site reactions, nausea, abdominal pain, somnolence, and dizziness. There were no significant increases in hepatic enzymes. In the event of an overdose, appropriate supportive treatment should be initiated.

Description

Naltrexone for extended-release injectable suspension is supplied as a microsphere formulation of naltrexone for suspension, to be administered by deep intramuscular injection by a healthcare practitioner. Naltrexone for extended-release injectable suspension contains naltrexone base anhydrous as the active pharmaceutical ingredient. Naltrexone is an opioid antagonist with little, if any, opioid agonist activity. Naltrexone is morphinan-6-one, 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-(5α) (CAS Registry # 16590-41-3). The molecular formula is C 20 H 23 NO 4 and its molecular weight is 341.41 in the anhydrous form (ie, < 1% maximum water content). The structural formula is: Naltrexone base anhydrous is an off-white to a light tan powder with a melting point of 168 °C to 170 °C (334 °F to 338 °F). It is insoluble in water and is soluble in ethanol. Naltrexone for extended-release injectable suspension is provided in a carton containing one vial of naltrexone for extended-release injectable suspension microspheres, one vial of diluent, one 5-mL syringe, one 1-inch 20-gauge preparation needle, two 1 1/2-inch 20-gauge, and two 2-inch 20-gauge administration needles with needle protection device. Naltrexone for extended-release injectable suspension microspheres consist of a sterile, off-white to light tan powder that is available in a dosage strength of 380 mg of naltrexone per vial. Naltrexone base anhydrous is incorporated in a biodegradable matrix of 75:25 polylactide-co-glycolide (PLG) at a concentration of 337 mg of naltrexone per gram of microspheres. The diluent is a clear, colorless solution. Each mL of diluent contains 30.0 mg of carboxymethylcellulose sodium, 1.0 mg of polysorbate 20, 9.0 mg of sodium chloride, and sodium hydroxide and hydrochloric acid as pH adjusters, in water for injection. The pH of the diluent is in the range of 5.8 to 7.2. Structural Formula

Mechanism of action

12.1 Mechanism of Action Naltrexone is an opioid antagonist with highest affinity for the mu opioid receptor. Naltrexone has little or no opioid agonist activity.

How supplied

Naltrexone for extended-release injectable suspension is supplied in cartons (NDC 69238-2794-1). Each carton contains: one 380 mg vial of naltrexone for extended-release injectable suspension microspheres in a 5 mL single-dose vial, one vial containing 4 mL of diluent (to deliver 3.4 mL) for the suspension of naltrexone for extended-release injectable suspension, one 5-mL prepackaged syringe, one 20-gauge 1-inch needle, two 20-gauge 1 1/2-inch needles with needle protection devices, and; two 20-gauge 2-inch needles with needle protection devices Naltrexone for extended-release injectable suspension must be prepared and administered by a healthcare provider. 16.1 Storage and Handling The entire dose pack should be stored in the refrigerator (2°C to 8°C, 36°F to 46°F). Unrefrigerated, naltrexone for extended-release injectable suspension can be stored at temperatures not exceeding 25°C (77°F) for no more than 7 days prior to administration. Do not expose the product to temperatures above 25°C (77°F). Naltrexone for extended-release injectable suspension should not be frozen. Keep out of Reach of Children.

Patient information

Advise the patient to read the FDA-Approved patient labeling ( Medication Guide ). Physicians should include the following issues in discussions with patients for whom they prescribe naltrexone for extended-release injectable suspension. Naltrexone for Extended-Release Injectable Suspension for Opioid Use Disorder: Advise patients that if they previously used opioids, they may be more sensitive to lower doses of opioids and at risk of accidental overdose should they use opioids when their next dose is due, if they miss a dose, or after naltrexone for extended-release injectable suspension treatment is discontinued. It is important that patients inform family members and the people closest to the patient of this increased sensitivity to opioids and the risk of overdose. Educate patients and caregivers on how to recognize the signs and symptoms of an opioid overdose. Advise patients that because naltrexone for extended-release injectable suspension can block the effects of opioids, patients will not perceive any effect if they attempt to self-administer heroin or any other opioid drug in small doses while on naltrexone for extended-release injectable suspension. Further, emphasize that administration of large doses of heroin or any other opioid to try to bypass the blockade and get high while on naltrexone for extended-release injectable suspension may lead to serious injury, coma, or death. Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because of the vulnerability to opioid overdose described above, discuss with the patient and caregiver the importance of having access to an opioid overdose reversal agent [see Warnings and Precautions ( 5.1 ) ] . Discuss with the patient options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter (some products), or as part of a community-based program) [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) ] . There are important differences among the opioid overdose reversal agents. Be familiar with these differences, as outlined in the approved labeling for such products, prior to recommending or prescribing such an agent. Educate patients and caregivers on how to recognize the signs and symptoms of an opioid overdose. Explain to patients and caregivers that effects of opioid overdose reversal agents like naloxone and nalmefene are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if an opioid overdose reversal agent is administered. Advise patients and caregivers: how to treat with an opioid overdose reversal agent in the event of an opioid overdose. to tell family and the people closest to the patient about their opioid overdose reversal agent and to keep it in a place where family and the people closest to the patient can access it in an emergency. to read the Patient Information (or other educational material) that will come with their opioid overdose reversal agent. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do. Naltrexone for Extended-Release Injectable Suspension for All Indications: Inform patients on naltrexone for extended-release injectable suspension that they may not experience the expected effects from opioid-containing analgesic, antidiarrheal, or antitussive medications. Instruct patients that naltrexone for extended-release injectable suspension must be prepared and administered by a healthcare provider. Advise patients that a reaction at the site of naltrexone for extended-release injectable suspension injection may occur. Reactions include pain, tenderness, induration, swelling, erythema, bruising, or pruritus. Serious injection site reactions including necrosis may occur. Some of these injection site reactions have required surgery. Patients should be advised to seek medical attention for worsening skin reactions. Advise patients that they should be off all opioids, including opioid-containing medicines, for a minimum of 7 – 10 days before starting naltrexone for extended-release injectable suspension in order to avoid precipitation of opioid withdrawal. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks. Ensure that patients understand that withdrawal precipitated by administration of an opioid antagonist may be severe enough to require hospitalization if they have not been opioid-free for an adequate period of time, and is different from the experience of spontaneous withdrawal that occurs with discontinuation of opioid in a dependent individual. Advise patients that they should not take naltrexone for extended-release injectable suspension if they have any symptoms of opioid withdrawal. Advise all patients, including those with alcohol dependence, that it is imperative to notify healthcare providers of any recent use of opioids or any history of opioid dependence before starting naltrexone for extended-release injectable suspension to avoid precipitation of opioid withdrawal. Advise patients that naltrexone for extended-release injectable suspension may cause liver injury. Patients should immediately notify their physician if they develop symptoms and/or signs of liver disease. Advise patients that they may experience depression while taking naltrexone for extended-release injectable suspension. It is important that patients inform family members and the people closest to the patient that they are taking naltrexone for extended-release injectable suspension and that they should call a doctor right away should they become depressed or experience symptoms of depression.

Label text from the FDA structured product label by Amneal Pharmaceuticals NY LLC (revised Jan 30, 2026). Long sections are shortened; the complete label is on DailyMed.

Naltrexone NDC products (1)

NDC	Strength & form	Labeler	Type
69238-2794	Kit	Amneal Pharmaceuticals NY LLC	NDA

Frequently asked questions

What is Naltrexone used for?

What are the side effects of Naltrexone?

Who makes Naltrexone?

Naltrexone is listed by 1 labeler in the FDA NDC directory, including Amneal Pharmaceuticals NY LLC.