Safety considerations

Important Safety Information

Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses. Naltrexone is contraindicated in acute hepatitis or liver failure, and its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects. The margin of separation between the apparently safe dose of naltrexone and the dose causing hepatic injury appears to be only five-fold or less. VIVITROL does not appear to be a hepatotoxin at the recommended doses. 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.7

Important information about VIVITROL
VIVITROL is contraindicated in patients receiving or dependent on opioids, in acute opioid withdrawal, and in those who have failed the naloxone challenge test or have a positive urine screen for opioids; and in those with previous hypersensitivity to naltrexone, PLG or any other components of the diluent.7

Patients must be opioid free for a minimum of 7-10 days before treatment. Attempts to overcome opioid blockade due to VIVITROL may result in fatal overdose. In prior opioid users, use of opioids after discontinuing VIVITROL may result in fatal overdose because patients may be more sensitive to lower doses of opioids. Patients requiring reversal of the VIVITROL blockade for pain management should be monitored by appropriately trained personnel in a setting equipped for cardiopulmonary resuscitation.7

Consider the diagnosis of eosinophilic pneumonia if patients develop progressive dyspnea and hypoxemia. Injection site reactions not improving may require prompt medical attention. Alcohol-dependent patients, including those taking VIVITROL, should be monitored for the development of depression or suicidal thinking.7 Caution is recommended in administering VIVITROL to patients with moderate to severe renal impairment.7

The most common adverse events associated with VIVITROL in clinical trials were nausea, vomiting, headache, dizziness, asthenic conditions and injection site reactions.7

Side-effect profile

In clinical trials during the premarketing development of VIVITROL, more than 900 patients with alcohol and/or opioid dependence have been treated with VIVITROL. Approximately 400 patients have been treated for 6 months or more, and 230 for 1 year or longer.7

• Discontinuation rates due to adverse events in controlled trials lasting 6 months or less:

- 9% of patients treated with VIVITROL7

- 7% of patients treated with placebo7

• A majority of patients treated with VIVITROL in clinical studies had adverse events with a maximum intensity of "mild" or "moderate"7

Table 1.
Side effects occurring in ≥10% of patients

Injection site reaction includes injection site tenderness, induration, pain, and pruritus.

• Trial dropout rate attributed to injection site reaction was 3%.

Nausea was mild and occurred in the first month of treatment in the majority of reports. It had a median duration of a few days.

• The trial dropout rate attributed to nausea was 2%.

For more information about adverse events with VIVITROL, please read the complete Prescribing Information including boxed warning for VIVITROL.

Other important safety considerations

Hepatic safety profile

• IM administration of VIVITROL reduces first-pass hepatic metabolism as compared to oral naltrexone7
• No significant increase from baseline in mean AST or ALT levels7
• Patients should be warned of the risk of hepatic injury. VIVITROL does not appear to be a hepatotoxin at recommended doses.

Physiologic impact

• The CYP450 system is not involved in naltrexone metabolism7
   - No clinical drug interaction studies have been performed
  
• The safety profile of patients treated with VIVITROL concomitantly with antidepressants was similar to that of patients taking VIVITROL without antidepressants
• VIVITROL is not aversive therapy

VIVITROL is nonaddictive

• No euphoria and does not lead to physical or psychological dependence7

For more information, please read the full Prescribing Information including boxed warning for VIVITROL.