Vulnerability to Opioid Overdose

• After opioid detoxification, patients are likely to have a reduced tolerance to opioids. VIVITROL blocks the effects of exogenous opioids for approximately 28 days after administration. As the blockade wanes and eventually dissipates completely, 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.
• 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 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.
• Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose: At the initial VIVITROL injection and with each subsequent injection, inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone and nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Strongly consider recommending or prescribing an opioid overdose reversal agent for the emergency treatment of an opioid overdose.

Injection Site Reactions

• VIVITROL must be prepared and administered by a healthcare provider and must ONLY be administered as a deep intramuscular gluteal injection.
• 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.
• 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.
• 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.
• Patients should be informed that any concerning injection site reactions should be brought to the attention of their healthcare provider.

Precipitation of Opioid Withdrawal

• When withdrawal is precipitated abruptly by administration of an opioid antagonist to a patient with opioid dependence, the resulting withdrawal syndrome can be severe. Some cases have been severe enough to require hospitalization and/or management in the ICU.
• To prevent occurrence of precipitated withdrawal, patients with opioid dependence, 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 precipitated withdrawal for as long as 2 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.
• Patients should be made aware of the risk associated with precipitated withdrawal and be encouraged to give an accurate account of last opioid use, as precipitated opioid withdrawal has been observed in patients with alcohol dependence in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids.

Hepatotoxicity

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

Depression and Suicidality

• Patients with alcohol dependence or opioid dependence 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

• 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.

Hypersensitivity Reactions including Anaphylaxis

• Patients should be warned of the risk of hypersensitivity reactions, including anaphylaxis, and should be advised to seek immediate medical attention in a healthcare setting prepared to treat anaphylaxis should a hypersensitivity reaction occur. The patient should not receive any further treatment with VIVITROL.

Intramuscular Injections

• As with any intramuscular injection, VIVITROL should be administered with caution to patients with thrombocytopenia or any coagulation disorder.

Alcohol Withdrawal

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

Interference With Laboratory Tests

• 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.

Adverse Reactions

• The adverse events seen most frequently in association with VIVITROL therapy for alcohol dependence (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), arthralgia, arthritis, or joint stiffness, 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 patients with opioid dependence (occurring in ≥2% and at least twice as frequently with VIVITROL than placebo) include hepatic enzyme abnormalities, injection site pain, nasopharyngitis, insomnia, and toothache.