Patient Information

Evaluation of efficacy and safety in alcohol dependence

A 24-week, multicenter, double-blind, randomized, placebo-controlled trial1,2

  • Patients were randomized to receive VIVITROL® 380 mg (n=208), VIVITROL 190 mg (n=210), or placebo (n=209) via intramuscular injection every 4 weeks—a total of 6 injections over 24 weeks1,2
  • Patients also received psychosocial support every other week1,2
  • Subjects recorded their drinking events using the timeline follow-back method2
  • Heavy drinking was defined as a self-report of 5 or more standard drinks consumed on a given day for male patients and 4 or more drinks for female patients1,2

VIVITROL and counseling significantly reduced the number of heavy drinking days1,2

Patients treated with VIVITROL 380 mg demonstrated a greater reduction in days of heavy drinking than those treated with placebo (HR=0.75 [0.60-0.94]; P=0.03)1,2

  • In a prespecified subset analysis (n=53, or 8% of the total study population) of patients who were able to abstain from alcohol for 7 days prior to receiving their first injection, those treated with VIVITROL had 92% less heavy drinking vs those treated with placebo (HR=0.20 [0.07-0.62]; P=0.005)1-3
  • In this subset, patients treated with VIVITROL were also more likely than placebo-treated patients to maintain complete abstinence throughout treatment1,2
  • The same treatment effects were not evident in the subset of patients (n=571, or 92% of the total study population) who were actively drinking at the time of treatment initiation1

Injection site reactions

  • 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
  • Injection site reactions not improving may require prompt medical attention, including, in some cases, surgical intervention
  • Inadvertent subcutaneous/adipose layer injection of VIVITROL may increase the likelihood of severe injection site reactions
  • Select proper needle size for patient body habitus, and use only the needles provided in the carton
  • Patients should be informed that any concerning injection site reactions should be brought to the attention of their healthcare provider

Significantly fewer drinking days and increased abstinence in the subset of patients who abstained prior to treatment1,3

  • Patients treated with VIVITROL and psychosocial counseling saw significant reductions in median drinking days and an increase in abstinent days vs those treated with placebo and psychosocial counseling2

Median number of drinking days vs number of days abstinent3

Depression & suicidality: alcohol dependence

  • In controlled clinical trials of VIVITROL administered to adults with alcohol dependence, adverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides) were infrequent overall, but were more common in patients treated with VIVITROL than in patients treated with placebo (1% vs 0). In some cases, the suicidal thoughts or behavior occurred after study discontinuation, but were in the context of an episode of depression that began while the patient was on study drug. Two completed suicides occurred, both involving patients treated with VIVITROL
  • Depression-related events associated with premature discontinuation of study drug were also more common in patients treated with VIVITROL (~1%) than in placebo-treated patients (0)
  • In the 24-week, placebo-controlled pivotal trial in 624 alcohol-dependent patients, adverse events involving depressed mood were reported by 10% of patients treated with VIVITROL 380 mg, as compared to 5% of patients treated with placebo injections

Alcohol withdrawal

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

Adverse reactions

  • Serious adverse reactions that may be associated with VIVITROL therapy in clinical use include severe injection site reactions, eosinophilic pneumonia, serious allergic reactions, unintended precipitation of opioid withdrawal, accidental opioid overdose, and depression and suicidality
  • The adverse events seen most frequently in association with VIVITROL therapy for alcohol dependence include nausea, vomiting, injection site reactions (including induration, pruritus, nodules, and swelling), muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, decreased appetite or other appetite disorders
  • The adverse events seen most frequently in association with VIVITROL in opioid-dependent patients also include hepatic enzyme abnormalities, injection site pain, nasopharyngitis, insomnia, and toothache



References:
1. VIVITROL [prescribing information]. Waltham, MA: Alkermes, Inc; rev Dec 2015.
2. Garbutt JC, Kranzler HR, O’Malley SS, et al; for the Vivitrex Study Group. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005;293(13):1617-1625.
3. Data on file. Alkermes, Inc.

Important Safety Information

INDICATIONS

VIVITROL is indicated for:

  • Treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting. Patients should not be actively drinking at the time of initial VIVITROL administration.
  • Prevention of relapse to opioid dependence, following opioid detoxification.
  • VIVITROL should be part of a comprehensive management program that includes psychosocial support.

CONTRAINDICATIONS

VIVITROL is contraindicated in patients:

  • Receiving opioid analgesics
  • With current physiologic opioid dependence
  • In acute opioid withdrawal
  • Who have failed the naloxone challenge test or have a positive urine screen for opioids
  • Who have exhibited hypersensitivity to naltrexone, polylactide-co-glycolide (PLG), carboxymethylcellulose, or any other components of the diluent

WARNINGS/PRECAUTIONS

Vulnerability to Opioid Overdose: Because VIVITROL blocks the effects of exogenous opioids for approximately 28 days after administration, patients are likely to have a reduced tolerance to opioids after opioid detoxification. As the blockade dissipates, use of previously tolerated doses of opioids could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc). 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 and caregivers should be told of this increased sensitivity to opioids and the risk of overdose.

Any attempt by a patient to overcome the VIVITROL blockade by taking opioids may lead to fatal overdose. Patients should be told of the serious consequences of trying to overcome the opioid blockade.

Injection Site Reactions: 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. Injection site reactions not improving may require prompt medical attention, including, in some cases, surgical intervention. Inadvertent subcutaneous/adipose layer injection of VIVITROL may increase the likelihood of severe injection site reactions. Select proper needle size for patient body habitus, and use only the needles provided in the carton. Patients should be informed that any concerning injection site reactions should be brought to the attention of their healthcare provider.

Precipitation of Opioid Withdrawal: Withdrawal precipitated by administration of VIVITROL may be severe. Some cases of withdrawal symptoms have been severe enough to require hospitalization and management in the ICU. To prevent precipitated withdrawal, patients, including those being treated for alcohol dependence:

  • Should be opioid-free (including tramadol) for a minimum of 7–10 days before starting VIVITROL.
  • Patients transitioning from buprenorphine or methadone may be vulnerable to precipitated withdrawal for as long as two weeks.

Patients should be made aware of the risk associated with precipitated withdrawal and be encouraged to give an accurate account of last opioid use.

Hepatotoxicity: Cases of hepatitis and clinically significant liver dysfunction have been observed in association with VIVITROL. Warn patients of the risk of hepatic injury; advise them to seek help if experiencing symptoms of acute hepatitis. Discontinue use of VIVITROL in patients who exhibit acute hepatitis symptoms.

Depression and Suicidality: Alcohol- and opioid-dependent patients taking VIVITROL should be monitored for depression or suicidal thoughts. Alert families and caregivers to monitor and report the emergence of symptoms of depression or suicidality.

When Reversal of VIVITROL Blockade Is Required for Pain Management: For VIVITROL patients in emergency situations, suggestions for pain management include regional analgesia or use of non-opioid analgesics. If opioid therapy is required to reverse the VIVITROL blockade, patients should be closely monitored by trained personnel in a setting staffed and equipped for CPR.

Eosinophilic Pneumonia: Cases of eosinophilic pneumonia requiring hospitalization have been reported. Warn patients of the risk of eosinophilic pneumonia and to seek medical attention if they develop symptoms of pneumonia.

Hypersensitivity Reactions: Patients should be warned of the risk of hypersensitivity reactions, including anaphylaxis.

Intramuscular Injections: As with any IM injection, VIVITROL should be administered with caution to patients with thrombocytopenia or any coagulation disorder.

ADVERSE REACTIONS

Serious adverse reactions that may be associated with VIVITROL therapy in clinical use include severe injection site reactions, eosinophilic pneumonia, serious allergic reactions, unintended precipitation of opioid withdrawal, accidental opioid overdose, and depression and suicidality. The adverse events seen most frequently in association with VIVITROL therapy for alcohol dependence include nausea, vomiting, injection site reactions (including induration, pruritus, nodules, and swelling), muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, decreased appetite or other appetite disorders. The adverse events seen most frequently in association with VIVITROL in opioid-dependent patients also include hepatic enzyme abnormalities, injection site pain, nasopharyngitis, insomnia, and toothache.

You are encouraged to report negative side effects to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

As of December 8, 2015, VIVITROL® (naltrexone for extended-release injectable suspension) has new Prescribing Information (12/2015). The Dosage and Administration, Section 2.4 Directions for Use has been updated. When administering VIVITROL, please refer to Section 2.4 Directions for Use in the VIVITROL Prescribing Information that is provided in the carton you are administering.