These Highlights Do Not Include All The Information Needed To Use Vivitrol®

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 VIVITROL.

MEDICATION GUIDE

VIVITROL ^® (viv-i-trol)

(naltrexone for extended-release injectable suspension)

Read this Medication Guide before you start receiving VIVITROL injections and each time you receive an injection. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about VIVITROL?

VIVITROL can cause serious side effects, including:

• Risk of opioid overdose.
  
  You can accidentally overdose in two ways.
  • VIVITROL blocks the effects of opioids, such as heroin or opioid pain medicines. Do not take large amounts of opioids, including opioid-containing medicines, such as heroin or prescription pain pills, to try to overcome the opioid-blocking effects of VIVITROL. This can lead to serious injury, coma, or death.
  • After you receive a dose of VIVITROL, its blocking effect slowly decreases and completely goes away over time. If you have used opioid street drugs or opioid-containing medicines in the past, using opioids in amounts that you used before treatment with VIVITROL can lead to overdose and death. You may also be more sensitive to the effects of lower amounts of opioids:
    • after you have gone through detoxification
    • when your next VIVITROL dose is due
    • if you miss a dose of VIVITROL
    • after you stop VIVITROL treatment

    It is important that you tell your family and the people closest to you of this increased sensitivity to opioids and the risk of overdose.

    You or someone close to you should call 911 or get emergency medical help right away if you:

  • have trouble breathing
  • become very drowsy with slowed breathing
  • have slow, shallow breathing (little chest movement with breathing)
  • feel faint, very dizzy, confused, or have unusual symptoms

  Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse an opioid overdose. You must call 911 or get emergency medical help right away to treat an opioid overdose or accidental use of an opioid, even if naloxone or nalmefene is administered.

• Severe reactions at the site of the injection (injection site reactions). Some people on VIVITROL have had severe injection site reactions, including tissue death (necrosis). Some of these injection site reactions have required surgery. VIVITROL must be injected by a healthcare provider. Call your healthcare provider right away if you notice any of the following at any of your injection sites:

  intense pain the area feels hard large area of swelling lumps

  blisters an open wound a dark scab

  Tell your healthcare provider about any reaction at an injection site that concerns you, gets worse over time, or does not get better by two weeks after the injection.

• Sudden opioid withdrawal.
  
  Anyone who receives a VIVITROL injection must not use any type of opioid (must be opioid-free) including street drugs, prescription pain medicines, cough, cold, or diarrhea medicines that contain opioids, or opioid dependence treatments, buprenorphine or methadone, for at least 7 to 14 days before starting VIVITROL. Using opioids in the 7 to 14 days before you start receiving VIVITROL may cause you to suddenly have symptoms of opioid withdrawal when you get the VIVITROL injection. Sudden opioid withdrawal can be severe, and you may need to go to the hospital.
  
  You must be opioid-free before receiving VIVITROL unless your healthcare provider decides that you don't need to go through detox first. Instead, your doctor may decide to give your VIVITROL injection in a medical facility that can treat you for sudden opioid withdrawal.
• Liver damage or hepatitis. Naltrexone, the active ingredient in VIVITROL, can cause liver damage or hepatitis.
  
  Tell your healthcare provider if you have any of the following symptoms of liver problems during treatment with VIVITROL:
  • stomach area pain lasting more than a few days
  • dark urine
  • yellowing of the whites of your eyes
  • tiredness

Your healthcare provider may need to stop treating you with VIVITROL if you get signs or symptoms of a serious liver problem.

What is VIVITROL?

VIVITROL is a prescription injectable medicine used to:

• treat alcohol dependence. You should stop drinking before starting VIVITROL.
• prevent relapse to opioid dependence, after opioid detoxification.
  
  This means that if you take opioids or opioid-containing medicines, you must stop taking them before you start receiving VIVITROL. See “What is the most important information I should know about VIVITROL?”

To be effective, treatment with VIVITROL must be used with other alcohol or drug recovery programs such as counseling. VIVITROL may not work for everyone.

It is not known if VIVITROL is safe and effective in children.

Who should not receive VIVITROL?

Do not receive VIVITROL if you:

• are using or have a physical dependence on opioid-containing medicines or opioid street drugs. See “What is the most important information I should know about VIVITROL?”
  
  To see whether you have a physical dependence on opioid-containing medicines or opioid street drugs, your healthcare provider may give you a small injection of a medicine called naloxone. This is called a naloxone challenge test. If you get symptoms of opioid withdrawal after the naloxone challenge test, do not start treatment with VIVITROL at that time. Your healthcare provider may repeat the test after you have stopped using opioids to see whether it is safe to start VIVITROL.
• are having opioid withdrawal symptoms. Opioid withdrawal symptoms may happen when you have been taking opioid-containing medicines or opioid street drugs regularly and then stop.
  
  Symptoms of opioid withdrawal may include: anxiety, sleeplessness, yawning, fever, sweating, teary eyes, runny nose, goose bumps, shakiness, hot or cold flushes, muscle aches, muscle twitches, restlessness, nausea and vomiting, diarrhea, or stomach cramps. See “What is the most important information I should know about VIVITROL?” Tell your healthcare provider if you have any of these symptoms before taking VIVITROL.
• are allergic to naltrexone or any of the ingredients in VIVITROL or the liquid used to mix VIVITROL (diluent). See the end of this Medication Guide for a complete list of ingredients in VIVITROL and the diluent.

What should I tell my healthcare provider before receiving VIVITROL?

Before you receive VIVITROL, tell your healthcare provider if you:

• have liver problems
• use or abuse street (illegal) drugs
• have hemophilia or other bleeding problems
• have kidney problems
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if VIVITROL will harm your unborn baby.
• are breastfeeding. It is not known if VIVITROL passes into your milk, and if it can harm your baby. Naltrexone, the active ingredient in VIVITROL, is the same active ingredient in tablets taken by mouth that contain naltrexone. Naltrexone from tablets passes into breast milk. Talk to your healthcare provider about whether you will breastfeed or take VIVITROL. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Especially tell your healthcare provider if you take any opioid-containing medicines for pain, cough or colds, or diarrhea. See “What is the most important information I should know about VIVITROL?”

If you are being treated for alcohol dependence but also use or are addicted to opioid-containing medicines or opioid street drugs, it is important that you tell your healthcare provider before starting VIVITROL to avoid having sudden opioid withdrawal symptoms when you start VIVITROL treatment.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How will I receive VIVITROL?

• VIVITROL is injected by a healthcare provider, about 1 time each month.
• VIVITROL must be injected by a healthcare provider. Do not attempt to inject yourself with VIVITROL. Serious reactions, some that may require hospitalization, might happen.
• VIVITROL is given as an injection into a muscle in your buttocks using a special needle that comes with VIVITROL.
• After VIVITROL is injected, it lasts for a month and it cannot be removed from the body.
• If you miss your appointment for your VIVITROL injection, schedule another appointment as soon as possible. See “What is the most important information I should know about VIVITROL?”
• Whenever you need medical treatment, be sure to tell the treating healthcare provider that you are receiving VIVITROL injections and mention when you got your last dose. This is important because VIVITROL can also block the effects of opioid-containing medicines that might be prescribed for you for pain, cough or colds, or diarrhea.
• Carry written information with you at all times to alert healthcare providers that you are taking VIVITROL, so that they can treat you properly in an emergency. Ask your healthcare provider how you can get a wallet card to carry with you.

What should I avoid while receiving VIVITROL?

Do not drive a car, operate machinery, or do other dangerous activities until you know how VIVITROL affects you. VIVITROL may make you feel dizzy and sleepy. See “What are the possible side effects of VIVITROL?”

What are the possible side effects of VIVITROL?

VIVITROL can cause serious side effects, including:

• See “What is the most important information I should know about VIVITROL?”
• Depressed mood. Sometimes this leads to suicide, or suicidal thoughts, and suicidal behavior. Tell your family members and people closest to you that you are taking VIVITROL.
  
  You, a family member, or the people closest to you should call your healthcare provider right away if you become depressed or have any of the following symptoms of depression, especially if they are new, worse, or worry you:
  • You feel sad or have crying spells.
  • You are no longer interested in seeing your friends or doing things you used to enjoy.
  • You are sleeping a lot more or a lot less than usual.
  • You feel hopeless or helpless.
  • You are more irritable, angry, or aggressive than usual.
  • You are more or less hungry than usual or notice a big change in your body weight.
  • You have trouble paying attention.
  • You feel tired or sleepy all the time.
  • You have thoughts about hurting yourself or ending your life.
• Pneumonia. Some people receiving VIVITROL treatment have had a certain type of pneumonia that is caused by an allergic reaction. If this happens to you, you may need to be treated in the hospital. Tell your healthcare provider right away if you have any of these symptoms during treatment with VIVITROL:
  • shortness of breath or wheezing
  • coughing that does not go away
• Serious allergic reactions. Serious allergic reactions can happen during or soon after an injection of VIVITROL. Tell your healthcare provider or get medical help right away if you have any of these symptoms of a serious allergic reaction.
  • skin rash
  • swelling of your face, eyes, mouth, or tongue
  • trouble breathing or wheezing
  • chest pain
  • feeling dizzy or faint

Common side effects of VIVITROL may include:

• nausea. Nausea may happen after your first VIVITROL injection and usually improves within a few days. Nausea is less likely with future injections of VIVITROL.
• sleepiness
• headache
• dizziness
• vomiting
• decreased appetite
• painful joints
• muscle cramps
• cold symptoms
• trouble sleeping
• toothache

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the side effects of VIVITROL. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about VIVITROL

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. This Medication Guide summarizes the most important information about VIVITROL. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about VIVITROL that is written for health professionals.

For more information about VIVITROL call 1-800-848-4876, Option #1 or go to www.vivitrol.com.

What are the ingredients in VIVITROL?

Active ingredient: naltrexone

Inactive ingredients: polylactide-co-glycolide (PLG)

Diluent ingredients: carboxymethylcellulose sodium, polysorbate 20, sodium chloride, sodium hydroxide and hydrochloric acid as pH adjusters, in water for injection.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured and marketed by:

Alkermes, Inc.

Waltham, MA 02451

Revised: December 2025

Alkermes^® and VIVITROL^® are registered trademarks of Alkermes, Inc.

PACKAGE LABEL- PRINCIPAL DISPLAY PANEL-VIVITROL® COMMERCIAL KIT CARTON

NDC: 65757-300-01

Rx Only

VIVITROL®

(naltrexone for extended-release injectable suspension)

380 mg/vial

VIVITROL must be injected by a healthcare provider. For gluteal intramuscular injection only.

Severe injection site reactions that required surgery and/or hospitalization have occurred with VIVITROL.

Healthcare provider: Dispense the enclosed Medication Guide to each patient

Please see accompanying full prescribing information.

Dispense the enclosed Medication Guide to each patient.

Must reconstitute VIVITROL Microspheres with enclosed diluent prior to administration. Upon reconstitution with 3.4 mL diluent, each mL will contain 95 mg of naltrexone.

Each Carton Contains:

1) One vial of 380 mg of VIVITROL (naltrexone for extended-release injectable suspension)*

2) One vial containing 4 mL of diluent†

3) One 5-mL prepackaged syringe

4) One 20-gauge 1-inch needle

5) Two 20-gauge 1½-inch safety needles

6) Two 20-gauge 2-Inch safety needles

*VIVITROL Microspheres: 380 mg of naltrexone per vial, contained in a biodegradable matrix of 75:25 polylactide-co-glycolide at a concentration of 337 mg of naltrexone per gram of microspheres.

^†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.

Storage:

Store in outer carton, refrigerated at 2°C to 8°C (36°F to 46°F).

If refrigeration is unavailable, product can be stored at temperatures not exceeding 25 °C (77 °F) for no more than 7 days prior to administration. Do not expose unrefrigerated product to temperatures above 25 °C (77 °F). Do not freeze.

Remove the carton from the refrigerator and allow it to come to room temperature prior to preparation.

Keep out of reach of children.

ALKERMES® and VIVITROL® are registered trademarks of Alkermes, Inc. Manufactured and marketed by Alkermes, Inc. www.vivitrol.com 1-800-848-4876

Alkermes®

There is limited experience with overdose of VIVITROL. 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.

VIVITROL^® (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. VIVITROL 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 C₂₀H₂₃NO₄ 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.

VIVITROL is provided in a carton containing one vial of VIVITROL 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.

VIVITROL 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.

The safety and efficacy of VIVITROL have not been established in the pediatric population. The pharmacokinetics of VIVITROL have not been evaluated in a pediatric population.

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 VIVITROL 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 VIVITROL 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.

Cases of hepatitis and clinically significant liver dysfunction were observed in association with VIVITROL exposure during the clinical development program and in the postmarketing period. Transient, asymptomatic hepatic transaminase elevations were also observed in the clinical trials and postmarketing period. Although patients with clinically significant liver disease were not systematically studied, clinical trials did include patients with asymptomatic viral hepatitis infections. When patients presented with elevated transaminases, there were often other potential causative or contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Although clinically significant liver dysfunction is not typically recognized as a manifestation of opioid withdrawal, opioid withdrawal that is precipitated abruptly may lead to systemic sequelae including acute liver injury.

Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis. Use of VIVITROL should be discontinued in the event of symptoms and/or signs of acute hepatitis.

VIVITROL 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)].

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)]

Patients taking VIVITROL 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.

Pharmacokinetics of VIVITROL 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. VIVITROL 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 VIVITROL to patients with moderate to severe renal impairment [see Clinical Pharmacology (12.3)].

VIVITROL is indicated for the prevention of relapse to opioid dependence, following opioid detoxification.

Naltrexone has few, if any, intrinsic actions besides its opioid blocking properties. However, it does produce some pupillary constriction, by an unknown mechanism.

The administration of VIVITROL is not associated with the development of tolerance or dependence. In subjects physically dependent on opioids, VIVITROL will precipitate withdrawal symptomatology.

Occupation of opioid receptors by naltrexone may block the effects of endogenous opioid peptides. It markedly attenuates or completely blocks, reversibly, the subjective effects of exogenous opioids. The neurobiological mechanisms responsible for the reduction in alcohol consumption observed in alcohol-dependent patients treated with naltrexone are not entirely understood. However, involvement of the endogenous opioid system is suggested by preclinical data.

Naltrexone blocks the effects of opioids by competitive binding at opioid receptors. This makes the blockade produced potentially surmountable, but overcoming full naltrexone blockade by administration of opioids may result in non-opioid receptor-mediated symptoms such as histamine release.

VIVITROL is not aversive therapy and does not cause a disulfiram-like reaction either as a result of opioid use or ethanol ingestion.

VIVITROL 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 VIVITROL. Patients should not be actively drinking at the time of initial VIVITROL administration.

VIVITROL must be prepared and administered by a healthcare provider.

VIVITROL must ONLY be administered as a deep intramuscular gluteal injection.

To ensure proper dosing, it is important that you follow the preparation and administration instructions outlined in this document.

VIVITROL must be suspended only in the diluent supplied in the carton and must be administered only with one of the administration needles supplied in the carton. The microspheres, diluent, preparation needle, and an administration needle with needle protection device are required for preparation and administration. Two thin-walled 1 1/2-inch needles with needle protection device and two 2-inch thin-walled needles with needle protection device have been provided to accommodate varying patient body habitus. 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. A spare administration needle of each size is provided in case of clogging [see How Supplied/Storage and Handling (16)]. Do not substitute any other components for the components of the carton.

Prior to preparation, allow drug to reach room temperature (approximately 45 minutes).

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 Directions for Use, illustration below].

Keep out of reach of children.

Prepare and administer the VIVITROL suspension using aseptic technique.

WARNING: To reduce the risk of a needlestick:

• Do not intentionally disengage the needle protection device.
• Discard bent or damaged needle into a sharps container and use the spare needle provided. Do not attempt to straighten the needle or engage needle protection device if the needle is bent or damaged.
• Do not mishandle the needle protection device in a way that could lead to protrusion of the needle.
• Do not use free hand to press sheath over needle.

THE CARTON SHOULD NOT BE EXPOSED TO TEMPERATURES EXCEEDING 25 °C (77 °F).

The entire carton should be stored in the refrigerator (2 °C to 8 °C, 36 °F to 46 °F). Unrefrigerated, VIVITROL microspheres can be stored at temperatures not exceeding 25 °C (77 °F) for no more than 7 days prior to administration. Do not expose unrefrigerated product to temperatures above 25 °C (77 °F). VIVITROL should not be frozen.

The pharmacokinetics of VIVITROL 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. VIVITROL pharmacokinetics were not evaluated in subjects with severe hepatic impairment [see Clinical Pharmacology (12.3)].

Treatment with VIVITROL should be part of a comprehensive management program that includes psychosocial support.

Use of VIVITROL does not eliminate nor diminish alcohol withdrawal symptoms.

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

The entire dose pack should be stored in the refrigerator (2 °C to 8 °C, 36 °F to 46 °F). Unrefrigerated, VIVITROL 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). VIVITROL should not be frozen.

Keep out of Reach of Children.

• Vulnerability to Opioid Overdose: Following VIVITROL 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 VIVITROL 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: VIVITROL 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 VIVITROL 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 VIVITROL treatment during the clinical development program and in the postmarketing period. Discontinue use of VIVITROL 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 VIVITROL Blockade Is Required for Pain Management: In an emergency situation in patients receiving VIVITROL, 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 VIVITROL (5.8).

In clinical trials with VIVITROL, there was one diagnosed case and one suspected case of eosinophilic pneumonia. Both cases required hospitalization, and resolved after treatment with antibiotics and corticosteroids. Similar cases have been reported in postmarketing use. Should a person receiving VIVITROL develop progressive dyspnea and hypoxemia, the diagnosis of eosinophilic pneumonia should be considered [see Adverse Reactions (6)]. Patients should be warned of the risk of eosinophilic pneumonia, and advised to seek medical attention should they develop symptoms of pneumonia. Clinicians should consider the possibility of eosinophilic pneumonia in patients who do not respond to antibiotics.

• VIVITROL must be prepared and administered by a healthcare provider (2.1, 2.6).
• Prior to initiating VIVITROL, 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 VIVITROL 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).
• VIVITROL must ONLY be administered as a deep intramuscular gluteal injection (2.1).
• See Full Prescribing Information for complete Directions for Use (2.6).

VIVITROL is an off-white to light tan powder for injectable suspension in a 5 mL single-dose vial.

VIVITROL contains 380 mg of naltrexone in a microsphere formulation per vial (337 mg of naltrexone per gram of microspheres).

VIVITROL must be prepared and administered by a healthcare provider.

VIVITROL must ONLY be administered as a deep intramuscular gluteal injection.

VIVITROL injections may be followed by pain, tenderness, induration, swelling, erythema, bruising, or pruritus; however, in some cases injection site reactions may be very severe. In the clinical trials, one patient developed an area of induration that continued to enlarge after 4 weeks, with subsequent development of necrotic tissue that required surgical excision. In the postmarketing period, additional cases of injection site reaction with features including induration, cellulitis, hematoma, abscess, sterile abscess, and necrosis, have been reported. Some cases required surgical intervention, including debridement of necrotic tissue. Some cases resulted in significant scarring. The reported cases occurred primarily in female patients.

VIVITROL is administered as a deep intramuscular gluteal injection, and inadvertent subcutaneous injection of VIVITROL may increase the likelihood of severe injection site reactions. The needles provided in the carton are customized needles. VIVITROL 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 the proper needle is selected and that the 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 VIVITROL 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.

Patients should be informed that any concerning injection site reactions should be brought to the attention of the healthcare provider [see Patient Counseling Information (17)]. Patients exhibiting signs of abscess, cellulitis, necrosis, or extensive swelling should be evaluated by a physician to determine if referral to a surgeon is warranted.

As with any intramuscular injection, VIVITROL should be administered with caution to patients with thrombocytopenia or any coagulation disorder (e.g., hemophilia and severe hepatic failure).

• Caution is recommended in administering VIVITROL to patients with moderate to severe renal impairment (8.6).
• VIVITROL pharmacokinetics have not been evaluated in subjects with severe hepatic impairment (8.7).

Alcohol- and opioid-dependent patients, including those taking VIVITROL, should be monitored for the development of depression or suicidal thinking. Families and caregivers of patients being treated with VIVITROL should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient's healthcare provider.

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 VIVITROL, more than 1100 patients with alcohol and/or opioid dependence have been treated with VIVITROL. Approximately 700 patients have been treated for 6 months or more, and more than 400 for 1 year or longer.

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 VIVITROL.

VIVITROL 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 VIVITROL 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 VIVITROL 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 VIVITROL. Further, emphasize that administration of large doses of heroin or any other opioid to try to bypass the blockade and get high while on VIVITROL 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.

VIVITROL for All Indications:

• Inform patients on VIVITROL that they may not experience the expected effects from opioid-containing analgesic, antidiarrheal, or antitussive medications.
• Instruct patients that VIVITROL must be prepared and administered by a healthcare provider.
• Advise patients that a reaction at the site of VIVITROL 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 VIVITROL 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 VIVITROL 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 VIVITROL to avoid precipitation of opioid withdrawal.
• Advise patients that VIVITROL 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 VIVITROL. It is important that patients inform family members and the people closest to the patient that they are taking VIVITROL and that they should call a doctor right away should they become depressed or experience symptoms of depression.
• Advise patients to carry documentation to alert medical personnel to the fact that they are taking VIVITROL (naltrexone for extended-release injectable suspension). This will help to ensure that patients obtain adequate medical treatment in an emergency.
• Advise patients that VIVITROL may cause an allergic pneumonia. Patients should immediately notify their physician if they develop signs and symptoms of pneumonia, including dyspnea, coughing, or wheezing.
• Advise patients that they should not take VIVITROL if they are allergic to VIVITROL or any of the microsphere or diluent components.
• Advise patients that they may experience nausea following the initial injection of VIVITROL. These episodes of nausea tend to be mild and subside within a few days post-injection. Patients are less likely to experience nausea in subsequent injections. Patients should be advised that they may also experience tiredness, headache, vomiting, decreased appetite, painful joints and muscle cramps.
• Advise patients that because VIVITROL is an intramuscular injection and not an implanted device, once VIVITROL is injected, it is not possible to remove it from the body.
• Advise patients that VIVITROL has been shown to treat alcohol and opioid dependence only when used as part of a treatment program that includes counseling and support.
• Advise patients that dizziness may occur with VIVITROL treatment, and they should avoid driving or operating heavy machinery until they have determined how VIVITROL affects them.
• Advise patients to notify their physician if they:
  • –
    become pregnant or intend to become pregnant during treatment with VIVITROL.
  • –
    are breast-feeding.
  • –
    experience respiratory symptoms such as dyspnea, coughing, or wheezing when taking VIVITROL.
  • –
    experience any allergic reactions when taking VIVITROL.
  • –
    experience other unusual or significant side effects while on VIVITROL therapy.

There are no systematically collected data that specifically address the switch from oral naltrexone to VIVITROL.

VIVITROL (naltrexone for extended-release injectable suspension) is supplied in cartons (NDC 65757-300-01). Each carton contains:

• one 380 mg vial of VIVITROL microspheres in a 5 mL single-dose vial,
• one vial containing 4 mL of diluent (to deliver 3.4 mL) for the suspension of VIVITROL,
• 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

VIVITROL must be prepared and administered by a healthcare provider.

After opioid detoxification, patients are likely to have reduced tolerance to opioids. VIVITROL 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 VIVITROL 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 VIVITROL treatment is discontinued, especially at the end of a dosing interval (i.e., near the end of the month that VIVITROL was administered), or after a dose of VIVITROL 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 VIVITROL could overcome the opioid blockade effect of VIVITROL. Although VIVITROL is a potent antagonist with a prolonged pharmacological effect, the blockade produced by VIVITROL 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)].

The symptoms of spontaneous opioid withdrawal (which are associated with the discontinuation of opioid in a dependent individual) are uncomfortable, but they are not generally believed to be severe or necessitate hospitalization. However, when withdrawal is precipitated abruptly by the administration of an opioid antagonist to an opioid-dependent patient, the resulting withdrawal syndrome can be severe enough to require hospitalization. Review of postmarketing cases of precipitated opioid withdrawal in association with naltrexone treatment has identified cases with symptoms of withdrawal severe enough to require hospital admission, and in some cases, management in the intensive care unit.

To prevent occurrence of precipitated withdrawal in patients dependent on opioids, or exacerbation of a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting VIVITROL treatment. An opioid-free interval of a minimum of 7–10 days is recommended for patients previously dependent on short-acting opioids. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks.

If a more rapid transition from agonist to antagonist therapy is deemed necessary and appropriate by the healthcare provider, monitor the patient closely in an appropriate medical setting where precipitated withdrawal can be managed.

In every case, healthcare providers should always be prepared to manage withdrawal symptomatically with non-opioid medications because there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. A naloxone challenge test may be helpful; however, a few case reports have indicated that patients may experience precipitated withdrawal despite having a negative urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of transitioning from buprenorphine treatment). Patients should be made aware of the risks associated with precipitated withdrawal and encouraged to give an accurate account of last opioid use. Patients treated for alcohol dependence with VIVITROL should also be assessed for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment with VIVITROL. Precipitated opioid withdrawal has been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids.

VIVITROL may be cross-reactive with certain immunoassay methods for the detection of drugs of abuse (specifically opioids) in urine. For further information, reference to the specific immunoassay instructions is recommended.

VIVITROL must be prepared and administered by a healthcare provider.

VIVITROL 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 VIVITROL, 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 VIVITROL 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. VIVITROL 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 VIVITROL 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.

Cases of urticaria, angioedema, and anaphylaxis have been observed with use of VIVITROL in the clinical trial setting and in postmarketing use. Patients should be warned of the risk of hypersensitivity reactions, including anaphylaxis. In the event of a hypersensitivity reaction, patients should be advised to seek immediate medical attention in a healthcare setting prepared to treat anaphylaxis. The patient should not receive any further treatment with VIVITROL.

Carcinogenesis: Carcinogenicity studies have not been conducted with VIVITROL.

Carcinogenicity studies of oral naltrexone hydrochloride (administered via the diet) have been conducted in rats and mice.

In a two-year carcinogenicity study in rats, there were small increases in the numbers of testicular mesotheliomas in males and tumors of vascular origin in males and females. The incidence of testicular mesothelioma in males given naltrexone at a dietary dose of 100 mg/kg/day (3-times the human exposure based on an AUC_(0-28d) comparison) was 6%, compared with a maximum historical incidence of 4%. The incidence of vascular tumors in males and females given dietary doses of 100 mg/kg/day was 4% but only the incidence in females was increased compared with a maximum historical control incidence of 2% (3 and 32 times the human exposure based on an AUC_(0-28d) comparison in males and females, respectively). There was no evidence of carcinogenicity in a 2-year dietary study with naltrexone in male and female mice (12 and 3 times the human exposure based on an AUC_(0-28d) comparison, respectively). The clinical significance of these findings is not known.

Mutagenesis: Naltrexone was negative in the following in vitro genotoxicity studies: bacterial reverse mutation assay (Ames test), the heritable translocation assay, CHO cell sister chromatid exchange assay, and the mouse lymphoma gene mutation assay. Naltrexone was also negative in an in vivo mouse micronucleus assay. In contrast, naltrexone tested positive in the following assays: Drosophila recessive lethal frequency assay, non-specific DNA damage in repair tests with E. coli and WI-38 cells, and urinalysis for methylated histidine residues.

Impairment of Fertility: Daily oral administration of naltrexone caused a significant increase in pseudopregnancy and a decrease in pregnancy rates in rats at 100 mg/kg/day (75 times the human exposure based on an AUC_(0-28d) comparison). There was no effect on male fertility at this dose level (6 times the human exposure based on an AUC_(0-28d) comparison). The relevance of these observations to human fertility is not known.

• Can I prepare the suspension prior to my patient's arrival?
  
  No. You may remove the carton from the refrigerator prior to the patient's arrival, but once the diluent is added to the VIVITROL microspheres, the dose should be mixed and the suspension administered immediately. It is very important to use proper aseptic technique when preparing the suspension [see Dosage and Administration (2.6)].
• How much time do I have between preparing and administering the dose?
  
  It is recommended that the suspension be administered immediately once the product has been suspended and transferred into the syringe. If a few minutes' delay occurs after suspension but before transfer into the syringe [see Dosage and Administration (2.6; Figure D)], the vial can be inverted a few times to resuspend and then transferred into the syringe for immediate use [see Dosage and Administration (2.6)].
• Can I use needles other than those provided in the carton?
  
  No. The needles in the carton are specially designed for administration of VIVITROL. Do not make any substitutions for components of the carton [see Dosage and Administration (2.6)].
• The suspension is milky white upon mixing with the diluent. Is this normal?
  
  Yes. VIVITROL microspheres will form a milky suspension when mixed with the provided diluent [see Dosage and Administration (2.6)].
• What if a needle clog occurs during administration of the product?
  
  If a clog occurs during administration, the needle should be withdrawn from the patient, capped with the attached needle protection device, and replaced with the spare administration needle. Gently push on the plunger until a bead of the suspension appears at the tip of the needle. The remainder of the suspension should then be administered into an adjacent site in the same gluteal region [see Dosage and Administration (2.6)].

For additional information, visit www.vivitrol.com or call 1-800-848-4876

Manufactured and marketed by:

Alkermes, Inc.

Waltham, MA 02451

©2025 Alkermes. All rights reserved.

ALKERMES^® and VIVITROL^® are registered trademarks of Alkermes, Inc.

Printed in U.S.A.

REV: December 2025

US Patent No. 7,919,499

There are no data to specifically address reinitiation of treatment. Patients reinitiating treatment with VIVITROL should be opioid-free at the time of dose administration [see Indications and Usage (1), Contraindications (4), and Warnings and Precautions (5.3)].

There are no systematically collected data that specifically address the switch from buprenorphine or methadone to VIVITROL; however, review of postmarketing case reports have indicated that some patients may experience severe manifestations of precipitated withdrawal when being switched from opioid agonist therapy to opioid antagonist therapy [see Warnings and Precautions (5.3)]. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Healthcare providers should be prepared to manage withdrawal symptomatically with non-opioid medications.

In an emergency situation in patients receiving VIVITROL, suggestions for pain management include regional analgesia or use of non-opioid analgesics. If opioid therapy is required as part of anesthesia or analgesia, patients should be continuously monitored in an anesthesia care setting by persons not involved in the conduct of the surgical or diagnostic procedure. The opioid therapy must be provided by individuals specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation.

Irrespective of the drug chosen to reverse VIVITROL blockade, the patient should be monitored closely by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation.

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 VIVITROL.

MEDICATION GUIDE

VIVITROL ^® (viv-i-trol)

(naltrexone for extended-release injectable suspension)

Read this Medication Guide before you start receiving VIVITROL injections and each time you receive an injection. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about VIVITROL?

VIVITROL can cause serious side effects, including:

• Risk of opioid overdose.
  
  You can accidentally overdose in two ways.
  • VIVITROL blocks the effects of opioids, such as heroin or opioid pain medicines. Do not take large amounts of opioids, including opioid-containing medicines, such as heroin or prescription pain pills, to try to overcome the opioid-blocking effects of VIVITROL. This can lead to serious injury, coma, or death.
  • After you receive a dose of VIVITROL, its blocking effect slowly decreases and completely goes away over time. If you have used opioid street drugs or opioid-containing medicines in the past, using opioids in amounts that you used before treatment with VIVITROL can lead to overdose and death. You may also be more sensitive to the effects of lower amounts of opioids:
    • after you have gone through detoxification
    • when your next VIVITROL dose is due
    • if you miss a dose of VIVITROL
    • after you stop VIVITROL treatment

    It is important that you tell your family and the people closest to you of this increased sensitivity to opioids and the risk of overdose.

    You or someone close to you should call 911 or get emergency medical help right away if you:

  • have trouble breathing
  • become very drowsy with slowed breathing
  • have slow, shallow breathing (little chest movement with breathing)
  • feel faint, very dizzy, confused, or have unusual symptoms

  Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse an opioid overdose. You must call 911 or get emergency medical help right away to treat an opioid overdose or accidental use of an opioid, even if naloxone or nalmefene is administered.

• Severe reactions at the site of the injection (injection site reactions). Some people on VIVITROL have had severe injection site reactions, including tissue death (necrosis). Some of these injection site reactions have required surgery. VIVITROL must be injected by a healthcare provider. Call your healthcare provider right away if you notice any of the following at any of your injection sites:

  intense pain the area feels hard large area of swelling lumps

  blisters an open wound a dark scab

  Tell your healthcare provider about any reaction at an injection site that concerns you, gets worse over time, or does not get better by two weeks after the injection.

• Sudden opioid withdrawal.
  
  Anyone who receives a VIVITROL injection must not use any type of opioid (must be opioid-free) including street drugs, prescription pain medicines, cough, cold, or diarrhea medicines that contain opioids, or opioid dependence treatments, buprenorphine or methadone, for at least 7 to 14 days before starting VIVITROL. Using opioids in the 7 to 14 days before you start receiving VIVITROL may cause you to suddenly have symptoms of opioid withdrawal when you get the VIVITROL injection. Sudden opioid withdrawal can be severe, and you may need to go to the hospital.
  
  You must be opioid-free before receiving VIVITROL unless your healthcare provider decides that you don't need to go through detox first. Instead, your doctor may decide to give your VIVITROL injection in a medical facility that can treat you for sudden opioid withdrawal.
• Liver damage or hepatitis. Naltrexone, the active ingredient in VIVITROL, can cause liver damage or hepatitis.
  
  Tell your healthcare provider if you have any of the following symptoms of liver problems during treatment with VIVITROL:
  • stomach area pain lasting more than a few days
  • dark urine
  • yellowing of the whites of your eyes
  • tiredness

Your healthcare provider may need to stop treating you with VIVITROL if you get signs or symptoms of a serious liver problem.

What is VIVITROL?

VIVITROL is a prescription injectable medicine used to:

• treat alcohol dependence. You should stop drinking before starting VIVITROL.
• prevent relapse to opioid dependence, after opioid detoxification.
  
  This means that if you take opioids or opioid-containing medicines, you must stop taking them before you start receiving VIVITROL. See “What is the most important information I should know about VIVITROL?”

To be effective, treatment with VIVITROL must be used with other alcohol or drug recovery programs such as counseling. VIVITROL may not work for everyone.

It is not known if VIVITROL is safe and effective in children.

Who should not receive VIVITROL?

Do not receive VIVITROL if you:

• are using or have a physical dependence on opioid-containing medicines or opioid street drugs. See “What is the most important information I should know about VIVITROL?”
  
  To see whether you have a physical dependence on opioid-containing medicines or opioid street drugs, your healthcare provider may give you a small injection of a medicine called naloxone. This is called a naloxone challenge test. If you get symptoms of opioid withdrawal after the naloxone challenge test, do not start treatment with VIVITROL at that time. Your healthcare provider may repeat the test after you have stopped using opioids to see whether it is safe to start VIVITROL.
• are having opioid withdrawal symptoms. Opioid withdrawal symptoms may happen when you have been taking opioid-containing medicines or opioid street drugs regularly and then stop.
  
  Symptoms of opioid withdrawal may include: anxiety, sleeplessness, yawning, fever, sweating, teary eyes, runny nose, goose bumps, shakiness, hot or cold flushes, muscle aches, muscle twitches, restlessness, nausea and vomiting, diarrhea, or stomach cramps. See “What is the most important information I should know about VIVITROL?” Tell your healthcare provider if you have any of these symptoms before taking VIVITROL.
• are allergic to naltrexone or any of the ingredients in VIVITROL or the liquid used to mix VIVITROL (diluent). See the end of this Medication Guide for a complete list of ingredients in VIVITROL and the diluent.

What should I tell my healthcare provider before receiving VIVITROL?

Before you receive VIVITROL, tell your healthcare provider if you:

• have liver problems
• use or abuse street (illegal) drugs
• have hemophilia or other bleeding problems
• have kidney problems
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if VIVITROL will harm your unborn baby.
• are breastfeeding. It is not known if VIVITROL passes into your milk, and if it can harm your baby. Naltrexone, the active ingredient in VIVITROL, is the same active ingredient in tablets taken by mouth that contain naltrexone. Naltrexone from tablets passes into breast milk. Talk to your healthcare provider about whether you will breastfeed or take VIVITROL. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Especially tell your healthcare provider if you take any opioid-containing medicines for pain, cough or colds, or diarrhea. See “What is the most important information I should know about VIVITROL?”

If you are being treated for alcohol dependence but also use or are addicted to opioid-containing medicines or opioid street drugs, it is important that you tell your healthcare provider before starting VIVITROL to avoid having sudden opioid withdrawal symptoms when you start VIVITROL treatment.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How will I receive VIVITROL?

• VIVITROL is injected by a healthcare provider, about 1 time each month.
• VIVITROL must be injected by a healthcare provider. Do not attempt to inject yourself with VIVITROL. Serious reactions, some that may require hospitalization, might happen.
• VIVITROL is given as an injection into a muscle in your buttocks using a special needle that comes with VIVITROL.
• After VIVITROL is injected, it lasts for a month and it cannot be removed from the body.
• If you miss your appointment for your VIVITROL injection, schedule another appointment as soon as possible. See “What is the most important information I should know about VIVITROL?”
• Whenever you need medical treatment, be sure to tell the treating healthcare provider that you are receiving VIVITROL injections and mention when you got your last dose. This is important because VIVITROL can also block the effects of opioid-containing medicines that might be prescribed for you for pain, cough or colds, or diarrhea.
• Carry written information with you at all times to alert healthcare providers that you are taking VIVITROL, so that they can treat you properly in an emergency. Ask your healthcare provider how you can get a wallet card to carry with you.

What should I avoid while receiving VIVITROL?

Do not drive a car, operate machinery, or do other dangerous activities until you know how VIVITROL affects you. VIVITROL may make you feel dizzy and sleepy. See “What are the possible side effects of VIVITROL?”

What are the possible side effects of VIVITROL?

VIVITROL can cause serious side effects, including:

• See “What is the most important information I should know about VIVITROL?”
• Depressed mood. Sometimes this leads to suicide, or suicidal thoughts, and suicidal behavior. Tell your family members and people closest to you that you are taking VIVITROL.
  
  You, a family member, or the people closest to you should call your healthcare provider right away if you become depressed or have any of the following symptoms of depression, especially if they are new, worse, or worry you:
  • You feel sad or have crying spells.
  • You are no longer interested in seeing your friends or doing things you used to enjoy.
  • You are sleeping a lot more or a lot less than usual.
  • You feel hopeless or helpless.
  • You are more irritable, angry, or aggressive than usual.
  • You are more or less hungry than usual or notice a big change in your body weight.
  • You have trouble paying attention.
  • You feel tired or sleepy all the time.
  • You have thoughts about hurting yourself or ending your life.
• Pneumonia. Some people receiving VIVITROL treatment have had a certain type of pneumonia that is caused by an allergic reaction. If this happens to you, you may need to be treated in the hospital. Tell your healthcare provider right away if you have any of these symptoms during treatment with VIVITROL:
  • shortness of breath or wheezing
  • coughing that does not go away
• Serious allergic reactions. Serious allergic reactions can happen during or soon after an injection of VIVITROL. Tell your healthcare provider or get medical help right away if you have any of these symptoms of a serious allergic reaction.
  • skin rash
  • swelling of your face, eyes, mouth, or tongue
  • trouble breathing or wheezing
  • chest pain
  • feeling dizzy or faint

Common side effects of VIVITROL may include:

• nausea. Nausea may happen after your first VIVITROL injection and usually improves within a few days. Nausea is less likely with future injections of VIVITROL.
• sleepiness
• headache
• dizziness
• vomiting
• decreased appetite
• painful joints
• muscle cramps
• cold symptoms
• trouble sleeping
• toothache

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the side effects of VIVITROL. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about VIVITROL

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. This Medication Guide summarizes the most important information about VIVITROL. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about VIVITROL that is written for health professionals.

For more information about VIVITROL call 1-800-848-4876, Option #1 or go to www.vivitrol.com.

What are the ingredients in VIVITROL?

Active ingredient: naltrexone

Inactive ingredients: polylactide-co-glycolide (PLG)

Diluent ingredients: carboxymethylcellulose sodium, polysorbate 20, sodium chloride, sodium hydroxide and hydrochloric acid as pH adjusters, in water for injection.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured and marketed by:

Alkermes, Inc.

Waltham, MA 02451

Revised: December 2025

Alkermes^® and VIVITROL^® are registered trademarks of Alkermes, Inc.

PACKAGE LABEL- PRINCIPAL DISPLAY PANEL-VIVITROL® COMMERCIAL KIT CARTON

NDC: 65757-300-01

Rx Only

VIVITROL®

(naltrexone for extended-release injectable suspension)

380 mg/vial

VIVITROL must be injected by a healthcare provider. For gluteal intramuscular injection only.

Severe injection site reactions that required surgery and/or hospitalization have occurred with VIVITROL.

Healthcare provider: Dispense the enclosed Medication Guide to each patient

Please see accompanying full prescribing information.

Dispense the enclosed Medication Guide to each patient.

Must reconstitute VIVITROL Microspheres with enclosed diluent prior to administration. Upon reconstitution with 3.4 mL diluent, each mL will contain 95 mg of naltrexone.

Each Carton Contains:

1) One vial of 380 mg of VIVITROL (naltrexone for extended-release injectable suspension)*

2) One vial containing 4 mL of diluent†

3) One 5-mL prepackaged syringe

4) One 20-gauge 1-inch needle

5) Two 20-gauge 1½-inch safety needles

6) Two 20-gauge 2-Inch safety needles

*VIVITROL Microspheres: 380 mg of naltrexone per vial, contained in a biodegradable matrix of 75:25 polylactide-co-glycolide at a concentration of 337 mg of naltrexone per gram of microspheres.

^†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.

Storage:

Store in outer carton, refrigerated at 2°C to 8°C (36°F to 46°F).

If refrigeration is unavailable, product can be stored at temperatures not exceeding 25 °C (77 °F) for no more than 7 days prior to administration. Do not expose unrefrigerated product to temperatures above 25 °C (77 °F). Do not freeze.

Remove the carton from the refrigerator and allow it to come to room temperature prior to preparation.

Keep out of reach of children.

ALKERMES® and VIVITROL® are registered trademarks of Alkermes, Inc. Manufactured and marketed by Alkermes, Inc. www.vivitrol.com 1-800-848-4876

Alkermes®

There is limited experience with overdose of VIVITROL. 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.

VIVITROL^® (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. VIVITROL 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 C₂₀H₂₃NO₄ 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.

VIVITROL is provided in a carton containing one vial of VIVITROL 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.

VIVITROL 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.

The safety and efficacy of VIVITROL have not been established in the pediatric population. The pharmacokinetics of VIVITROL have not been evaluated in a pediatric population.

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 VIVITROL 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 VIVITROL 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.

Cases of hepatitis and clinically significant liver dysfunction were observed in association with VIVITROL exposure during the clinical development program and in the postmarketing period. Transient, asymptomatic hepatic transaminase elevations were also observed in the clinical trials and postmarketing period. Although patients with clinically significant liver disease were not systematically studied, clinical trials did include patients with asymptomatic viral hepatitis infections. When patients presented with elevated transaminases, there were often other potential causative or contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Although clinically significant liver dysfunction is not typically recognized as a manifestation of opioid withdrawal, opioid withdrawal that is precipitated abruptly may lead to systemic sequelae including acute liver injury.

Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis. Use of VIVITROL should be discontinued in the event of symptoms and/or signs of acute hepatitis.

VIVITROL 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)].

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)]

Patients taking VIVITROL 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.

Pharmacokinetics of VIVITROL 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. VIVITROL 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 VIVITROL to patients with moderate to severe renal impairment [see Clinical Pharmacology (12.3)].

VIVITROL is indicated for the prevention of relapse to opioid dependence, following opioid detoxification.

Naltrexone has few, if any, intrinsic actions besides its opioid blocking properties. However, it does produce some pupillary constriction, by an unknown mechanism.

The administration of VIVITROL is not associated with the development of tolerance or dependence. In subjects physically dependent on opioids, VIVITROL will precipitate withdrawal symptomatology.

Occupation of opioid receptors by naltrexone may block the effects of endogenous opioid peptides. It markedly attenuates or completely blocks, reversibly, the subjective effects of exogenous opioids. The neurobiological mechanisms responsible for the reduction in alcohol consumption observed in alcohol-dependent patients treated with naltrexone are not entirely understood. However, involvement of the endogenous opioid system is suggested by preclinical data.

Naltrexone blocks the effects of opioids by competitive binding at opioid receptors. This makes the blockade produced potentially surmountable, but overcoming full naltrexone blockade by administration of opioids may result in non-opioid receptor-mediated symptoms such as histamine release.

VIVITROL is not aversive therapy and does not cause a disulfiram-like reaction either as a result of opioid use or ethanol ingestion.

VIVITROL 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 VIVITROL. Patients should not be actively drinking at the time of initial VIVITROL administration.

VIVITROL must be prepared and administered by a healthcare provider.

VIVITROL must ONLY be administered as a deep intramuscular gluteal injection.

To ensure proper dosing, it is important that you follow the preparation and administration instructions outlined in this document.

VIVITROL must be suspended only in the diluent supplied in the carton and must be administered only with one of the administration needles supplied in the carton. The microspheres, diluent, preparation needle, and an administration needle with needle protection device are required for preparation and administration. Two thin-walled 1 1/2-inch needles with needle protection device and two 2-inch thin-walled needles with needle protection device have been provided to accommodate varying patient body habitus. 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. A spare administration needle of each size is provided in case of clogging [see How Supplied/Storage and Handling (16)]. Do not substitute any other components for the components of the carton.

Prior to preparation, allow drug to reach room temperature (approximately 45 minutes).

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 Directions for Use, illustration below].

Keep out of reach of children.

Prepare and administer the VIVITROL suspension using aseptic technique.

WARNING: To reduce the risk of a needlestick:

• Do not intentionally disengage the needle protection device.
• Discard bent or damaged needle into a sharps container and use the spare needle provided. Do not attempt to straighten the needle or engage needle protection device if the needle is bent or damaged.
• Do not mishandle the needle protection device in a way that could lead to protrusion of the needle.
• Do not use free hand to press sheath over needle.

THE CARTON SHOULD NOT BE EXPOSED TO TEMPERATURES EXCEEDING 25 °C (77 °F).

The entire carton should be stored in the refrigerator (2 °C to 8 °C, 36 °F to 46 °F). Unrefrigerated, VIVITROL microspheres can be stored at temperatures not exceeding 25 °C (77 °F) for no more than 7 days prior to administration. Do not expose unrefrigerated product to temperatures above 25 °C (77 °F). VIVITROL should not be frozen.

The pharmacokinetics of VIVITROL 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. VIVITROL pharmacokinetics were not evaluated in subjects with severe hepatic impairment [see Clinical Pharmacology (12.3)].

Treatment with VIVITROL should be part of a comprehensive management program that includes psychosocial support.

Use of VIVITROL does not eliminate nor diminish alcohol withdrawal symptoms.

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

The entire dose pack should be stored in the refrigerator (2 °C to 8 °C, 36 °F to 46 °F). Unrefrigerated, VIVITROL 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). VIVITROL should not be frozen.

Keep out of Reach of Children.

• Vulnerability to Opioid Overdose: Following VIVITROL 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 VIVITROL 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: VIVITROL 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 VIVITROL 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 VIVITROL treatment during the clinical development program and in the postmarketing period. Discontinue use of VIVITROL 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 VIVITROL Blockade Is Required for Pain Management: In an emergency situation in patients receiving VIVITROL, 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 VIVITROL (5.8).

In clinical trials with VIVITROL, there was one diagnosed case and one suspected case of eosinophilic pneumonia. Both cases required hospitalization, and resolved after treatment with antibiotics and corticosteroids. Similar cases have been reported in postmarketing use. Should a person receiving VIVITROL develop progressive dyspnea and hypoxemia, the diagnosis of eosinophilic pneumonia should be considered [see Adverse Reactions (6)]. Patients should be warned of the risk of eosinophilic pneumonia, and advised to seek medical attention should they develop symptoms of pneumonia. Clinicians should consider the possibility of eosinophilic pneumonia in patients who do not respond to antibiotics.

• VIVITROL must be prepared and administered by a healthcare provider (2.1, 2.6).
• Prior to initiating VIVITROL, 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 VIVITROL 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).
• VIVITROL must ONLY be administered as a deep intramuscular gluteal injection (2.1).
• See Full Prescribing Information for complete Directions for Use (2.6).

VIVITROL is an off-white to light tan powder for injectable suspension in a 5 mL single-dose vial.

VIVITROL contains 380 mg of naltrexone in a microsphere formulation per vial (337 mg of naltrexone per gram of microspheres).

VIVITROL must be prepared and administered by a healthcare provider.

VIVITROL must ONLY be administered as a deep intramuscular gluteal injection.

VIVITROL injections may be followed by pain, tenderness, induration, swelling, erythema, bruising, or pruritus; however, in some cases injection site reactions may be very severe. In the clinical trials, one patient developed an area of induration that continued to enlarge after 4 weeks, with subsequent development of necrotic tissue that required surgical excision. In the postmarketing period, additional cases of injection site reaction with features including induration, cellulitis, hematoma, abscess, sterile abscess, and necrosis, have been reported. Some cases required surgical intervention, including debridement of necrotic tissue. Some cases resulted in significant scarring. The reported cases occurred primarily in female patients.

VIVITROL is administered as a deep intramuscular gluteal injection, and inadvertent subcutaneous injection of VIVITROL may increase the likelihood of severe injection site reactions. The needles provided in the carton are customized needles. VIVITROL 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 the proper needle is selected and that the 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 VIVITROL 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.

Patients should be informed that any concerning injection site reactions should be brought to the attention of the healthcare provider [see Patient Counseling Information (17)]. Patients exhibiting signs of abscess, cellulitis, necrosis, or extensive swelling should be evaluated by a physician to determine if referral to a surgeon is warranted.

As with any intramuscular injection, VIVITROL should be administered with caution to patients with thrombocytopenia or any coagulation disorder (e.g., hemophilia and severe hepatic failure).

• Caution is recommended in administering VIVITROL to patients with moderate to severe renal impairment (8.6).
• VIVITROL pharmacokinetics have not been evaluated in subjects with severe hepatic impairment (8.7).

Alcohol- and opioid-dependent patients, including those taking VIVITROL, should be monitored for the development of depression or suicidal thinking. Families and caregivers of patients being treated with VIVITROL should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient's healthcare provider.

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 VIVITROL, more than 1100 patients with alcohol and/or opioid dependence have been treated with VIVITROL. Approximately 700 patients have been treated for 6 months or more, and more than 400 for 1 year or longer.

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 VIVITROL.

VIVITROL 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 VIVITROL 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 VIVITROL 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 VIVITROL. Further, emphasize that administration of large doses of heroin or any other opioid to try to bypass the blockade and get high while on VIVITROL 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.

VIVITROL for All Indications:

• Inform patients on VIVITROL that they may not experience the expected effects from opioid-containing analgesic, antidiarrheal, or antitussive medications.
• Instruct patients that VIVITROL must be prepared and administered by a healthcare provider.
• Advise patients that a reaction at the site of VIVITROL 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 VIVITROL 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 VIVITROL 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 VIVITROL to avoid precipitation of opioid withdrawal.
• Advise patients that VIVITROL 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 VIVITROL. It is important that patients inform family members and the people closest to the patient that they are taking VIVITROL and that they should call a doctor right away should they become depressed or experience symptoms of depression.
• Advise patients to carry documentation to alert medical personnel to the fact that they are taking VIVITROL (naltrexone for extended-release injectable suspension). This will help to ensure that patients obtain adequate medical treatment in an emergency.
• Advise patients that VIVITROL may cause an allergic pneumonia. Patients should immediately notify their physician if they develop signs and symptoms of pneumonia, including dyspnea, coughing, or wheezing.
• Advise patients that they should not take VIVITROL if they are allergic to VIVITROL or any of the microsphere or diluent components.
• Advise patients that they may experience nausea following the initial injection of VIVITROL. These episodes of nausea tend to be mild and subside within a few days post-injection. Patients are less likely to experience nausea in subsequent injections. Patients should be advised that they may also experience tiredness, headache, vomiting, decreased appetite, painful joints and muscle cramps.
• Advise patients that because VIVITROL is an intramuscular injection and not an implanted device, once VIVITROL is injected, it is not possible to remove it from the body.
• Advise patients that VIVITROL has been shown to treat alcohol and opioid dependence only when used as part of a treatment program that includes counseling and support.
• Advise patients that dizziness may occur with VIVITROL treatment, and they should avoid driving or operating heavy machinery until they have determined how VIVITROL affects them.
• Advise patients to notify their physician if they:
  • –
    become pregnant or intend to become pregnant during treatment with VIVITROL.
  • –
    are breast-feeding.
  • –
    experience respiratory symptoms such as dyspnea, coughing, or wheezing when taking VIVITROL.
  • –
    experience any allergic reactions when taking VIVITROL.
  • –
    experience other unusual or significant side effects while on VIVITROL therapy.

There are no systematically collected data that specifically address the switch from oral naltrexone to VIVITROL.

VIVITROL (naltrexone for extended-release injectable suspension) is supplied in cartons (NDC 65757-300-01). Each carton contains:

• one 380 mg vial of VIVITROL microspheres in a 5 mL single-dose vial,
• one vial containing 4 mL of diluent (to deliver 3.4 mL) for the suspension of VIVITROL,
• 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

VIVITROL must be prepared and administered by a healthcare provider.

After opioid detoxification, patients are likely to have reduced tolerance to opioids. VIVITROL 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 VIVITROL 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 VIVITROL treatment is discontinued, especially at the end of a dosing interval (i.e., near the end of the month that VIVITROL was administered), or after a dose of VIVITROL 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 VIVITROL could overcome the opioid blockade effect of VIVITROL. Although VIVITROL is a potent antagonist with a prolonged pharmacological effect, the blockade produced by VIVITROL 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)].

The symptoms of spontaneous opioid withdrawal (which are associated with the discontinuation of opioid in a dependent individual) are uncomfortable, but they are not generally believed to be severe or necessitate hospitalization. However, when withdrawal is precipitated abruptly by the administration of an opioid antagonist to an opioid-dependent patient, the resulting withdrawal syndrome can be severe enough to require hospitalization. Review of postmarketing cases of precipitated opioid withdrawal in association with naltrexone treatment has identified cases with symptoms of withdrawal severe enough to require hospital admission, and in some cases, management in the intensive care unit.

To prevent occurrence of precipitated withdrawal in patients dependent on opioids, or exacerbation of a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting VIVITROL treatment. An opioid-free interval of a minimum of 7–10 days is recommended for patients previously dependent on short-acting opioids. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks.

If a more rapid transition from agonist to antagonist therapy is deemed necessary and appropriate by the healthcare provider, monitor the patient closely in an appropriate medical setting where precipitated withdrawal can be managed.

In every case, healthcare providers should always be prepared to manage withdrawal symptomatically with non-opioid medications because there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. A naloxone challenge test may be helpful; however, a few case reports have indicated that patients may experience precipitated withdrawal despite having a negative urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of transitioning from buprenorphine treatment). Patients should be made aware of the risks associated with precipitated withdrawal and encouraged to give an accurate account of last opioid use. Patients treated for alcohol dependence with VIVITROL should also be assessed for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment with VIVITROL. Precipitated opioid withdrawal has been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids.

VIVITROL may be cross-reactive with certain immunoassay methods for the detection of drugs of abuse (specifically opioids) in urine. For further information, reference to the specific immunoassay instructions is recommended.

VIVITROL must be prepared and administered by a healthcare provider.

VIVITROL 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 VIVITROL, 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 VIVITROL 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. VIVITROL 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 VIVITROL 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.

Cases of urticaria, angioedema, and anaphylaxis have been observed with use of VIVITROL in the clinical trial setting and in postmarketing use. Patients should be warned of the risk of hypersensitivity reactions, including anaphylaxis. In the event of a hypersensitivity reaction, patients should be advised to seek immediate medical attention in a healthcare setting prepared to treat anaphylaxis. The patient should not receive any further treatment with VIVITROL.

Carcinogenesis: Carcinogenicity studies have not been conducted with VIVITROL.

Carcinogenicity studies of oral naltrexone hydrochloride (administered via the diet) have been conducted in rats and mice.

In a two-year carcinogenicity study in rats, there were small increases in the numbers of testicular mesotheliomas in males and tumors of vascular origin in males and females. The incidence of testicular mesothelioma in males given naltrexone at a dietary dose of 100 mg/kg/day (3-times the human exposure based on an AUC_(0-28d) comparison) was 6%, compared with a maximum historical incidence of 4%. The incidence of vascular tumors in males and females given dietary doses of 100 mg/kg/day was 4% but only the incidence in females was increased compared with a maximum historical control incidence of 2% (3 and 32 times the human exposure based on an AUC_(0-28d) comparison in males and females, respectively). There was no evidence of carcinogenicity in a 2-year dietary study with naltrexone in male and female mice (12 and 3 times the human exposure based on an AUC_(0-28d) comparison, respectively). The clinical significance of these findings is not known.

Mutagenesis: Naltrexone was negative in the following in vitro genotoxicity studies: bacterial reverse mutation assay (Ames test), the heritable translocation assay, CHO cell sister chromatid exchange assay, and the mouse lymphoma gene mutation assay. Naltrexone was also negative in an in vivo mouse micronucleus assay. In contrast, naltrexone tested positive in the following assays: Drosophila recessive lethal frequency assay, non-specific DNA damage in repair tests with E. coli and WI-38 cells, and urinalysis for methylated histidine residues.

Impairment of Fertility: Daily oral administration of naltrexone caused a significant increase in pseudopregnancy and a decrease in pregnancy rates in rats at 100 mg/kg/day (75 times the human exposure based on an AUC_(0-28d) comparison). There was no effect on male fertility at this dose level (6 times the human exposure based on an AUC_(0-28d) comparison). The relevance of these observations to human fertility is not known.

• Can I prepare the suspension prior to my patient's arrival?
  
  No. You may remove the carton from the refrigerator prior to the patient's arrival, but once the diluent is added to the VIVITROL microspheres, the dose should be mixed and the suspension administered immediately. It is very important to use proper aseptic technique when preparing the suspension [see Dosage and Administration (2.6)].
• How much time do I have between preparing and administering the dose?
  
  It is recommended that the suspension be administered immediately once the product has been suspended and transferred into the syringe. If a few minutes' delay occurs after suspension but before transfer into the syringe [see Dosage and Administration (2.6; Figure D)], the vial can be inverted a few times to resuspend and then transferred into the syringe for immediate use [see Dosage and Administration (2.6)].
• Can I use needles other than those provided in the carton?
  
  No. The needles in the carton are specially designed for administration of VIVITROL. Do not make any substitutions for components of the carton [see Dosage and Administration (2.6)].
• The suspension is milky white upon mixing with the diluent. Is this normal?
  
  Yes. VIVITROL microspheres will form a milky suspension when mixed with the provided diluent [see Dosage and Administration (2.6)].
• What if a needle clog occurs during administration of the product?
  
  If a clog occurs during administration, the needle should be withdrawn from the patient, capped with the attached needle protection device, and replaced with the spare administration needle. Gently push on the plunger until a bead of the suspension appears at the tip of the needle. The remainder of the suspension should then be administered into an adjacent site in the same gluteal region [see Dosage and Administration (2.6)].

For additional information, visit www.vivitrol.com or call 1-800-848-4876

Manufactured and marketed by:

Alkermes, Inc.

Waltham, MA 02451

©2025 Alkermes. All rights reserved.

ALKERMES^® and VIVITROL^® are registered trademarks of Alkermes, Inc.

Printed in U.S.A.

REV: December 2025

US Patent No. 7,919,499

There are no data to specifically address reinitiation of treatment. Patients reinitiating treatment with VIVITROL should be opioid-free at the time of dose administration [see Indications and Usage (1), Contraindications (4), and Warnings and Precautions (5.3)].

There are no systematically collected data that specifically address the switch from buprenorphine or methadone to VIVITROL; however, review of postmarketing case reports have indicated that some patients may experience severe manifestations of precipitated withdrawal when being switched from opioid agonist therapy to opioid antagonist therapy [see Warnings and Precautions (5.3)]. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Healthcare providers should be prepared to manage withdrawal symptomatically with non-opioid medications.

In an emergency situation in patients receiving VIVITROL, suggestions for pain management include regional analgesia or use of non-opioid analgesics. If opioid therapy is required as part of anesthesia or analgesia, patients should be continuously monitored in an anesthesia care setting by persons not involved in the conduct of the surgical or diagnostic procedure. The opioid therapy must be provided by individuals specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation.

Irrespective of the drug chosen to reverse VIVITROL blockade, the patient should be monitored closely by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation.