RECENT MAJOR CHANGES

Indications and Usage, Opioid Dependence (1.2) 10/2010

Dosage and Administration, Directions for Use (2.3) 08/2010

INDICATIONS AND USAGE

VIVITROL is an opioid antagonist. Opioid-dependent patients, including those being treated for alcohol dependence, must be opioid-free at the time of initial VIVITROL administration.

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

• 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 (1.1).
• VIVITROL is indicated for the prevention of relapse to opioid dependence, following opioid detoxification (1.2).

DOSAGE AND ADMINISTRATION

The recommended dose of VIVITROL is 380 mg delivered intramuscularly every 4 weeks or once a month. The injection should be administered by a healthcare professional as an intramuscular (IM) gluteal injection, alternating buttocks for each subsequent injection, using the carton components provided (2 and 16.1).

VIVITROL must not be administered intravenously or subcutaneously.

The entire dose pack should be stored in the refrigerator (2-8°C, 36-46°F) (2.3 and 16.1).

Do not expose the product to temperatures above 25°C (77°F). VIVITROL should not be frozen (2.3).

DOSAGE FORMS AND STRENGTHS

VIVITROL is an injectable suspension containing 380 mg of naltrexone

in a microsphere formulation and 4 mL diluent (3).

CONTRAINDICATIONS

VIVITROL is contraindicated in:

• Patients with acute hepatitis or liver failure (5.1).
• Patients receiving opioid analgesics (5.5).
• Patients with current physiologic opioid dependence (5.5).
• Patients in acute opioid withdrawal (5.5).
• Any individual who has failed the naloxone challenge test or has a positive urine screen for opioids (4).
• Patients who have previously exhibited hypersensitivity to naltrexone, polylactide-co-glycolide (PLG), carboxymethylcellulose, or any other components of the diluent (4).

WARNINGS AND PRECAUTIONS

• Hepatotoxicity: Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses and is contraindicated in acute hepatitis or liver failure. Use of VIVITROL should be discontinued in the event of symptoms or signs of acute hepatitis (5.1).
• Injection Site Reactions: In some cases injection site reactions may be very severe. Some cases of injection site reactions required surgical intervention (5.2).
• Eosinophilic pneumonia: VIVITROL patients should be warned of the risk of eosinophilic pneumonia, and advised to seek medical attention should they develop symptoms of pneumonia (5.3).
• Hypersensitivity: Patients should be warned of the risk of hypersensitivity reactions, including anaphylaxis (5.4).
• Unintended Precipitation of Opioid Withdrawal: Opioid-dependent and opioid-using patients, including those being treated for alcohol dependence, must be opioid-free for a minimum of 7-10 days before starting VIVITROL treatment (5.5).
• Opioid Overdose at the End of a Dosing Interval, After Missing a Dose and Following an Attempt to Overcome Opioid Blockade: Use of lower doses of opioids after VIVITROL treatment is discontinued, at the end of a dosing interval, or after missing a dose could result in life-threatening opioid intoxication. Any attempt by a patient to overcome the blockade produced by VIVITROL by taking opioids is very dangerous and may lead to fatal overdose (5.6).
• Depression and Suicidality: VIVITROL patients should be monitored for the development of depression or suicidal thinking (5.7).
• Intramuscular Injections: VIVITROL should be administered with caution to patients with thrombocytopenia or any coagulation disorder (5.8).
• 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 (5.9).

ADVERSE REACTIONS

The adverse events seen most frequently in association with VIVITROL therapy for alcohol dependence (i.e., those occurring in ≥5% and at least twice as frequently with VIVITROL than placebo) include nausea, vomiting, injection site reactions (including induration, pruritus, nodules and swelling), muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, decreased appetite or other appetite disorders (6).

The adverse events seen most frequently in association with VIVITROL therapy in opioid-dependent patients (i.e., those occurring in ≥2% and at least twice as frequently with VIVITROL than placebo) were hepatic enzyme abnormalities, injection site pain, nasopharyngitis, insomnia, and toothache (6).

To report SUSPECTED ADVERSE REACTIONS, contact Alkermes, Inc. at 1-800-VIVITROL (1-800-848-4876) and/or email: usmedinfo@alkermes.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Naltrexone antagonizes the effects of opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations and opioid analgesics (7).

USE IN SPECIFIC POPULATIONS

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