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Cases of hepatitis and clinically significant liver dysfunction were observed in association with REVIA exposure during the clinical development program and in the postmarketing periodTransientasymptomatic hepatic transaminase elevations were also observed in the clinical trials and postmarketing periodWhen patients presented with elevated transaminasesthere were often other potential causative or contributory etiologies identifiedincluding pre-existing alcoholic liver diseasehepatitis B and/or C infectionand concomitant usage of other potentially hepatotoxic drugsAlthough clinically significant liver dysfunction is not typically recognized as a manifestation of opioid withdrawalopioid withdrawal that is precipitated abruptly may lead to systemic sequelaeincluding acute liver injury.

After opioid detoxificationpatients are likely to have reduced tolerance to opioidsAs the blockade of exogenous opioids provided by REVIA wanes and eventually dissipates completelypatients who have been treated with REVIA may respond to lower doses of opioids than previously usedjust as they would shortly after completing detoxification.

REVIA should be considered as only one of many factors determining the success of treatmentTo achieve the best possible treatment outcomeappropriate compliance-enhancing techniques should be implemented for all components of the treatment programincluding medication compliance.

The mechanism of action of REVIA in alcoholism is not understoodhoweverinvolvement of the endogenous opioid system is suggested by preclinical dataREVIAan opioid receptor antagonistcompetitively binds to such receptors and may block the effects of endogenous opioidsOpioid antagonists have been shown to reduce alcohol consumption by animalsand REVIA has been shown to reduce alcohol consumption in clinical studies.

REVIA has not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for the addictions.

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