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U.S. Department of Health and Human Services

Safety

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Revia (naltrexone HCl) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

 

October 2013

Summary View

 

BOXED WARNING

-removed

CONTRAINDICATIONS

  • Patients currently dependent on opioids including those currently maintained on opiate agonists (e.e. methadone) or partial agonists (e.g. buprenorphine).

 

WARNINGS

Vulnerability to Opioid Overdose
  • After opioid detoxification, patients are likely to have reduced tolerance to opioids. As the blockade of exogenous opioids provided by Revia wanes and eventually dissipates completely, patients who have been treated with Revia may respond to lower doses of opioids than previously used, just as they would 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 after discontinuing treatment.
  • Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after Revia 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.
  • There is also the possibility that a patient who is treated with Revia could overcome the opioid blockade effect of Revia. Although Revia is a potent antagonist, the blockade produced by Revia 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
Precipitated Opioid Withdrawal
  • 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. Symptoms of withdrawal have usually appeared within five minutes of ingestion of REVIA and have lasted for up to 48 hours. Mental status changes including confusion, somnolence and visual hallucinations have occurred. Significant fluid losses from vomiting and diarrhea have... 
Hepatotoxicity
  • Cases of hepatitis and clinically significant liver dysfunction were observed in association with Revia 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. 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... 
Depression and Suicidality
  • Depression, suicide, attempted suicide and suicidal ideation have been reported in the postmarketing experience with REVIA (naltrexone hydrochloride) used in the treatment of opioid dependence. No causal relationship has been demonstrated. In the literature, endogenous opioids have been theorized to contribute to a variety of conditions.
  • Alcohol- and opioid-dependent patients, including those taking REVIA, should be monitored for the development of depression or suicidal thinking. Families and caregivers of patients being treated with REVIA should be alerted to the need to monitor patients...

 

PRECAUTIONS

Information for Patients

You should take REVIA as directed by your physician.

  • 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 after REVIA treatment is discontinued or temporarily interrupted. 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.
  • Advise patients that because REVIA 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 REVIA. Further, emphasize that administration of large doses of heroin or any other opioid to try to bypass the blockade and get high while on REVIA may lead to serious injury, coma, or death.
  • Patients on REVIA may not experience the expected effects from opioid-containing analgesic, antidiarrheal, or antitussive medications.
  • Patients should be off all opioids, including opioid-containing medicines, for a minimum of 7 – 10 days before starting REVIA 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...
  • Advise patients that REVIA 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 REVIA. It is important that patients inform family members and the people closest to the patient...

 

 

ADVERSE REACTIONS

Post-marketing Experience
  • ...and idiopathic thrombocytopenic purpura
Laboratory Tests
  • In a placebo controlled study in which REVIA was administered to obese subjects at a dose approximately five-fold that recommended for the blockade of opiate receptors (300 mg per day), 19% (5/26) of REVIA recipients and 0% (0/24) of placebo-treated patients developed elevations of serum transaminases (i.e., peak ALT values ranging from 121 to 532; or 3 to 19 times their baseline values) after three to eight weeks of treatment. The patients involved were generally clinically asymptomatic, and the transaminase levels of all...