Keywords
glecaprevir, pibrentasvir, HCV, HIV, chronic hepatitis C, direct-acting antiviral, adverse drug reaction.
Abstract
Glecaprevir (GLE)/pibrentasvir (PIB) is a pangenotypic direct- acting antiviral regimen approved for treating chronic hepatitis C virus. Primary treatment and re-treatment with GLE/PIB are effective and safe for patients without decompensated liver cirrhosis and chronic hepatitis C in a real-world clinical setting. However, in the context of compensated cirrhosis and concomitant adminis- tration of inhibitors of cytochromes, a careful monitoring of liver biomarkers, as well as therapeutic drug monitoring (TDM), may be advisable during GLE/PIB therapy. The GLE / PIB combination is very effective and safe in achieving a sustained virological response, but it can be associated with the development of severe hepatic adverse events, which require virological and serum con- centration monitoring of the two drugs to prevent a serious liver damage. The possible onset of hyperbilirubinemia must not neces- sarily lead to the suspension of therapy, because the phenomenon may be transient. We report what is likely the first known case of severe jaundice after treatment with GLE/PIB in Italy in a patient with compensated chronic hepatitis in the context of HIV disease.
References
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[11] Kosloski MP, Wang H, Pugatch D, Mensa FJ, Gane E, Lawitz E, Marbury TC, Preston RA, Kort J, Liu W. Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment. Eur J Clin Pharmacol 2019;75:217-226. doi: 10.1007/s00228-018-2576-4. Epub 2018 Oct 19. PMID: 30341499..
[12]https://ec.europa.eu/health/documents/communityregister/2017/20170726138539/anx_138539_en.pdf. ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS.
[13] Kosloski MP, Oberoi R, Wang S, et al. Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered With Human Immunodeficiency Virus Antiretrovirals. J Infect Dis 2020;221:223-31
[14] Jinyu Zhang, MD, Randeep Kaur, MD, Mahmoud Isseh, MD, Mouhanna K. Abu Ghanimeh, MD, Syed-Mohammed Jafri, MD. Potential complications of hyperbilirubinemia on therapy with glecaprevir and pibrentasvir for therapy of hepatitis C in complex real worlds patients. Program No. P0642. ACG 2018 Annual Scientific Meeting Abstracts. Philadelphia, Pennsylvania: American College of Gastroenterology.
[15] Yoon JH, Kim SM, Kang G, Kim HJ, Jun CH, Choi SK. A case report of glecaprevir/pibrentasvir-induced severe hyperbilirubinemia in a patient with compensated liver cirrhosis. Medicine (Baltimore). 2019;98:e17343. doi:10.1097/MD.0000000000017343
[16] Hsu SJ, Chiu MC, Fang YJ, et al. Real-world effectiveness and safety of glecaprevir/pibrentasvir in Asian patients with chronic hepatitis C. J Formos Med Assoc. 2019;118:1187-1192. doi:10.1016/j.jfma.2019.06.014.
[17].Chayama, K., Suzuki, F., Karino, Y. et al. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis. J Gastroenterol 2018;53:557–565. https://doi.org/10.1007/s00535-017-1391-5.
[18] Toyota H, Chayama K, Suzuki F, Sato K, Atarashi T, Watanabe T, et al. efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection. Hepatology 2018;67:505-513.
[19] Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, et al. Glecaprevir-pibrentasvir for 8 or 12 Weeks in HCV genotype 1 or 3 infection. N Engl J Med 2018;378:354-369.
[20] US Food and Drug Administration. FDA warns about rare occurrence of serious liver injury with use of hepatitis C medicines Mavyret, Zepatier, and Vosevi in some patients with advanced liver disease. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrence-serious-liver-injury-use-hepatitis-c-medicines-mavyret-zepatier-and Published August 28, 2019. Accessed September 9, 2019.
[2] Suleiman AA, Lin CW, Liu W, et al. Population Pharmacokinetics of Glecaprevir/Pibrentasvir in HCV-infected Japanese Subjects in Phase 3 CERTAIN-1 and CERTAIN-2 Trials. J Clin Pharmacol 2020;60:331-339. doi:10.1002/jcph.1524.
[3] Lin CW, Dutta S, Ding B, Wang T, Zadeikis N, Asatryan A, Kort J, Campbell A, Podsadecki T, Liu W. Pharmacokinetics, Safety, and Tolerability of Glecaprevir and Pibrentasvir in Healthy White, Chinese, and Japanese Adult Subjects. J Clin Pharmacol 2017;57:1616-1624.
[4] Lin CW, Dutta S, Asatryan A, Wang H, Clifton J 2nd, Campbell A, Liu W. Pharmacokinetics, Safety, and Tolerability Following Single and Multiple Doses of Pibrentasvir in a First-in-Human Study. Clin Pharmacol Drug Dev 2018;7:44-52. doi: 10.1002/cpdd.350. Epub 2017 May 2. PMID: 28464496.
[5] European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol. 2018;69:461-511. doi:10.1016/j.jhep.2018.03.026].
[6] https://ec.europa.eu/health/documents/community-register/2017/20170726138539/anx_138539_en.pdf. Annex I summary of product characteristics.
[7] Lin CW, Dutta S, Zhao W, Asatryan A, Campbell A, Liu W. Pharmacokinetic Interactions and Safety of Coadministration of Glecaprevir and Pibrentasvir in Healthy Volunteers. Eur J Drug Metab Pharmacokinet. 2018;43:81-90. doi:10.1007/s13318-017-0428-8.
[8] Product monograph. Including patient medication information. PrMAVIRET® glecaprevir/pibrentasvir tablets (100/40 mg) MAVIRET Product Monograph Page 1-67. Date of Revision: June 12, 2020 and Control No. 229422. AbbVie Corporation, https://www.abbvie.ca/content/dam/abbviedotcom/ca/en/documents/products/MAVIRET_PM_EN.pdf
[9] Forns X, Lee SS, Valdes J, Lens S, Ghalib R, Aguilar H, Felizarta F, Hassanein T, Hinrichsen H, Rincon D, Morillas R, Zeuzem S, Horsmans Y, Nelson DR, Yu Y, Krishnan P, Lin CW, Kort JJ, Mensa FJ. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis 2017;17:1062-1068.
[10] Gane E, Poordad F, Zadeikis N, et al. Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease. Clin Infect Dis. 2019;69:1657-1664. doi:10.1093/cid/ciz022
[11] Kosloski MP, Wang H, Pugatch D, Mensa FJ, Gane E, Lawitz E, Marbury TC, Preston RA, Kort J, Liu W. Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment. Eur J Clin Pharmacol 2019;75:217-226. doi: 10.1007/s00228-018-2576-4. Epub 2018 Oct 19. PMID: 30341499..
[12]https://ec.europa.eu/health/documents/communityregister/2017/20170726138539/anx_138539_en.pdf. ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS.
[13] Kosloski MP, Oberoi R, Wang S, et al. Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered With Human Immunodeficiency Virus Antiretrovirals. J Infect Dis 2020;221:223-31
[14] Jinyu Zhang, MD, Randeep Kaur, MD, Mahmoud Isseh, MD, Mouhanna K. Abu Ghanimeh, MD, Syed-Mohammed Jafri, MD. Potential complications of hyperbilirubinemia on therapy with glecaprevir and pibrentasvir for therapy of hepatitis C in complex real worlds patients. Program No. P0642. ACG 2018 Annual Scientific Meeting Abstracts. Philadelphia, Pennsylvania: American College of Gastroenterology.
[15] Yoon JH, Kim SM, Kang G, Kim HJ, Jun CH, Choi SK. A case report of glecaprevir/pibrentasvir-induced severe hyperbilirubinemia in a patient with compensated liver cirrhosis. Medicine (Baltimore). 2019;98:e17343. doi:10.1097/MD.0000000000017343
[16] Hsu SJ, Chiu MC, Fang YJ, et al. Real-world effectiveness and safety of glecaprevir/pibrentasvir in Asian patients with chronic hepatitis C. J Formos Med Assoc. 2019;118:1187-1192. doi:10.1016/j.jfma.2019.06.014.
[17].Chayama, K., Suzuki, F., Karino, Y. et al. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis. J Gastroenterol 2018;53:557–565. https://doi.org/10.1007/s00535-017-1391-5.
[18] Toyota H, Chayama K, Suzuki F, Sato K, Atarashi T, Watanabe T, et al. efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection. Hepatology 2018;67:505-513.
[19] Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, et al. Glecaprevir-pibrentasvir for 8 or 12 Weeks in HCV genotype 1 or 3 infection. N Engl J Med 2018;378:354-369.
[20] US Food and Drug Administration. FDA warns about rare occurrence of serious liver injury with use of hepatitis C medicines Mavyret, Zepatier, and Vosevi in some patients with advanced liver disease. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrence-serious-liver-injury-use-hepatitis-c-medicines-mavyret-zepatier-and Published August 28, 2019. Accessed September 9, 2019.