Apr 21, 2009 - Richmond, VA: Reckitt Benckiser Pharmaceuticals, Inc., June 2005. 3. Berson A, Gervais A, Cazals D, et al. Hepatitis after intravenous bupre-.
Hepatitis After Intravenous Injection of Sublingual Buprenorphine in Acute Hepatitis C Carriers: Report of Two Cases of Disappearance of Viral Replication After Acute Hepatitis Hélène Peyrière, Ludmilla Tatem, Camille Bories, Georges-Philippe Pageaux, Jean-Pierre Blayac, and Dominique Larrey
igh-dose buprenorphine, a long-acting, partial opioid agonist, is as effective as methadone in treatment of heroin dependence, with a better safety profile due to its antagonist activity.1 It is a partial opioid agonist at the µ-opioid receptors in the nervous system as well as a µ-opioid receptor antagonist. Its activity is usually sufficient to diminish craving for heroin and prevent or alleviate opioid withdrawal in dependent heroin users.1 High-dose buprenorphine must be administered sublingually, the only effective and well tolerated route of administration, with a single daily induction dose varying from 0.8 to 4 mg. The maintenance dose varies depending on the patient and should be increased gradually until the minimum effective dose is reached. The recommended daily dose ranges from 4 to 10 mg, with a maximum of 16 mg.2 At recommended sublingual doses, buprenorphine is well tolerated. However, rare cases of acute hepatitis have been reported following misuse,3 overdose,4 and even during the use of buprenorphine at therapeutic doses.5,6 Some addict patients inject buprenorphine intravenously. Injecting buprenorphine may have health-threatening consequences in
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OBJECTIVE: To report 2 cases of acute hepatitis related to intravenous administration of buprenorphine in hepatitis C–infected patients. CASE SUMMARY: Two patients, aged 33 and 50 years, respectively, who were hepatitis C virus (HCV) carriers were treated with sublingual buprenorphine 8 mg/day for addiction. Several years after initiation of buprenorphine, they were hospitalized because of clinical hepatitis with jaundice that developed after intravenous injection of buprenorphine. Serum alanine aminotransferase rose to 100 times the upper limit of normal (ULN) in the first patient and to 21 times the ULN in the second. As cofactors, the first patient had consumed alcohol, and the second patient took aspirin 600 mg in addition to the injection of buprenorphine 20 mg 4 days before the onset of jaundice. After stopping the intravenous injections, both patients continued sublingual buprenorphine therapy, with no relapse of hepatitis. Interestingly, in these 2 patients, buprenorphine-induced hepatitis was followed by the disappearance of HCV RNA. DISCUSSION: Most cases of hepatotoxicity related to buprenorphine have occurred in hepatitis C–infected patients. The main mechanism for buprenorphine-induced hepatitis is a mitochondrial defect, exacerbated by cofactors with additional potential to induce mitochondria dysfunction (eg, HCV, alcohol, concomitant medications). According to the Naranjo probability scale, buprenorphine was found to be the probable cause of acute hepatitis in both patients. In addition, we assessed the relationship between intravenous buprenorphine and acute hepatitis using 2 scales for causality assessment of hepatotoxicity (the Council for International Organizations of Medical Sciences scale and the Maria & Victorino scale). The diagnosis of intravenous buprenorphine-induced hepatitis was classified as probable in both cases. In addition, these 2 cases illustrate that acute hepatitis in a carrier of chronic HCV may occasionally facilitate the clearance of virus. CONCLUSIONS: Although buprenorphine is well tolerated when used at recommended sublingual doses, patients should be informed about the risk of acute hepatitis with misuse of the drug by the intravenous route. These cases illustrate that, in carriers of chronic HCV, acute hepatitis may modify the host’s immunotolerance and facilitate clearance of the virus. KEY WORDS: acute hepatitis, buprenorphine, hepatitis C, injection, misuse.
Ann Pharmacother 2009;43:973-7. Published Online, 21 Apr 2009, www.theannals.com, DOI 10.1345/aph.1L628
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The Annals of Pharmacotherapy
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drug users, as local complications (eg, abscess), infections, puffy hand syndrome, or acute hepatitis. We report 2 cases of hepatitis in HCV-infected patients using buprenorphine intravenously. What is particularly noteworthy in these 2 observations is the disappearance of viral replication after acute hepatitis. Case Reports
CASE 1
A 33-year-old man with a history of intravenous drug abuse had stopped taking heroin in 2000. Seropositivity for HCV genotype 1a was detected in 2002. Because of the predominant problem of drug addiction, hepatitis C was not considered a priority and he was never treated for it. He had been treated with sublingual buprenorphine 8 mg daily since 2000. He did not take other medications, but he regularly consumed alcohol and smoked. On February 16, 2007, he was hospitalized because of jaundice, with abdominal pain and fever of more than 24 hours’ duration. According to the patient, he had injected himself intravenously with 3–5 tablets of buprenorphine 8 mg. At admission, liver function tests, complete viral screening, and abdominal computed tomography scan were performed. Laboratory test results showed alanine aminotransferase (ALT) 4132 U/L (normal
