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2012, Number 2

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Ann Hepatol 2012; 11 (2)

A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients

Wilby KJ, Greanya ED, Ford JE, Yoshida EM, Partovi N

Language: English
References: 26
Page: 179-185
PDF size: 89.28 Kb.


ABSTRACT

Purpose. Chronic hepatitis C virus (HCV) is a major problem affecting up to 170 million people worldwide. Two protease inhibitors have recently been approved that will revolutionize treatment. Our objective was to summarize and evaluate the literature pertaining to the pharmacokinetics of boceprevir and telaprevir, in order to provide clinicians with insight into the management of actual and potential drug interactions. Summary. A standardized search using MEDLINE (1948-November 2011), EMBASE (1980-November 2011), IPA (1970-November 2011), Google, and Google Scholar that combined the search terms boceprevir, telaprevir, pharmacokinetics, drug interaction, and drug metabolism was performed. Manual reference searches of chosen articles were completed. Monographs and articles, conference proceedings, and abstracts were evaluated. Boceprevir and telaprevir are both substrates and inhibitors of cytochrome P450 3A4 and telaprevir is a substrate of p-glycoprotein. Levels of boceprevir are decreased in patients taking efavirenz but effects with other antiretrovirals are minimal or unknown. Coadministration with efavirenz may compromise telaprevir levels and should be avoided. Telaprevir may increase levels of cyclosporine, tacrolimus, atorvastatin, and amlodipine, which may expose patients to increased adverse effects. Conclusions. Significant drug-drug interactions occur with both boceprevir and telaprevir. Until studies are reported and experience is gained with these agents, clinicians will need to be careful when administering in high-risk populations and those receiving chronic therapy with interacting agents. Studies are urgently needed in HIV patients taking antiretrovirals and patients taking chronic immunosuppresion as these populations are at increased risk of experiencing clinically significant interactions.


REFERENCES

  1. Hepatitis C. World Health Organization. www.who.org [Accessed 2011 Aug 18].

  2. Rosen HR. Chronic hepatitis C infection. N Eng J Med 2011; 364: 2429-38.

  3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, et al. Peginterferon alfa- 2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001; 358: 958-65.

  4. Hadziyannis SJ, Sette H Jr., Morgan TR, Vijayan B, Diago M, Marcellin P, Ramadori G, et al. Peginterferon alfa-2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribvirin dose. Ann Intern Med 2004; 140: 346-55.

  5. Yoshida EM, Sherman M, Bain VG, Cooper CL, Deschenes M, Marotta PJ, Lee SS, et al. Re-treatment with peginteferon alfa-2a and ribavirin in patients with chronic hepatitis C who have relapsed or not responded to a first course of pegylated interferon-based therapy. Can J Gastroenterol 2009; 23: 180-4.

  6. Di Martino V, Rufat P, Boyer N, Renard P, Degos F, Martinot- Peignoux M, Matheron S, et al. The influence of human immunodeficiency virus co-infection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study. Hepatology 2001; 34: 1193-9.

  7. Lai JC, Verna C, Brown RS Jr., O’Leary JG, Trotter JF, Forman LM, Durman JD, et al. Hepatitis C virus infected women have a higher risk of advanced fibrosis and graft loss after liver transplantation than men. Hepatology 2011; 54: 418-24.

  8. Gludd LL, Marchesini E, Lorio A. Peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus. Am J Gastroenterol 2009; 104: 2335-41.

  9. Wang CS, Ko HH, Yoshida EM, Marra CA, Richardson K. Interferon- based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis. Am J Transpl 2006; 6: 1586-99.

  10. Poordad F, McCone J, Bacon B, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Eng J Med 2011; 364: 1195-206.

  11. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Eng J Med 2011; 364: 1207-17.

  12. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Eng J M 2011; 364: 2405-16.

  13. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, et al. Telaprevir for retreatment of HCV infection. N Eng J Med 2011; 364: 2417-28.

  14. Merck & Co. Victrelis (boceprevir) Product Monograph [Internet]. Whitehouse Station, NJ 2011. Accessed August 5, 2011. Available from: http://www.merck.ca/assets/ en/pdf/products/VICTRELIS-PM_E.pdf

  15. Vertex Pharmaceuticals Inc. Incivek (telaprevir) Product Monograph. Cambridge, MA 2011.

  16. Kasserra C, Hughes E, Treitel M, Gupta S, O’Mara E. Clinical pharmacology of boceprevir: metabolism, excretion, and drug-drug interactions (abstract 118). 18th Conference on Retroviruses and Opportunistic Infections, Feb 27-Mar 2, 2011, Boston, USA [Accessed on 14 Aug 2011]. Available from: http://www.retroconference.org/2011/ Abstracts/41140.htm

  17. Ogu CC, Maxa JL. Drug interactions due to cytochrome P450. Proc (Bayl Univ Med Cent) 2000; 13: 421-3.

  18. Augustine JJ, Bodziak KA, Hricik DR. Use of sirolimus in solid organ transplantation. Drugs 2007; 67: 369-91.

  19. Van Heeswijk RPG, Vandevoorde A, Boogaerts G, Vangeneugden T, de Paepe E, Polo R, Van Solingen-Ristea R, et al. Pharmacokinetic interactions between ARV agents and the investigational HCV protease inhibitor TVR in healthy volunteers (abstract 119). 18th Conference on Retroviruses and Opportunistic Infections, Feb 27-Mar 2, 2011, Boston, USA [Accessed on 14 Aug 2011]. Available from: http://www.retroconference.org/2011/Abstracts/ 41437.htm

  20. Hariparsad N, Nallani S, Sane R, Buckley DJ, Buckley AR, Desai PB. Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and Phenobarbital. Clin Pharmacol 2004; 44: 1273-81.

  21. Kempf DJ, Klein C, Chen HJ, Klein LL, Yeung C, Randolph JT, Lau YY, et al. Pharmacokinetic enhancement of the hepatitis C virus protease inhibitors VX-950 and SCH 503034 by co-dosing with ritonavir. Antivir Chem Chemother 2007; 18: 163-7.

  22. Garg V, Luo X, McNair L, van Heeswijk R, Kauffman R. Low-dose ritonavir and the pharmacokinetics of the investigational HCV protease inhibitor telaprevir in healthy volunteers (abstract 629). 18th Conference on Retroviruses and Opportunistic Infections, Feb 27-Mar 2, 2011, Boston, USA [Accessed 14 Aug 2011]. Available from: http:// www.retroconference.org/2011/Abstracts/40192.htm

  23. Garg V, van Heeswijk R, Lee J, Alves K, Nadkarni P, Luo X. Effect of telaprevir on the pharmacokinetics of cyclosporine and tacrolimus. Hepatology 2011; 54: 20-17

  24. Lam S, Partovi N, Ting LSL, Ensom MH. Corticosteroid interactions with cyclosporine, tacrolimus, mycophenolate, and sirolimus: fact or fiction? Ann Pharmacother 2008; 42: 1037-47.

  25. Lee J, van Heeswijk R, Alves K, Smith F, Garg V. Effect of the hepatitis C protease inhibitor telaprevir on the pharmacokinetics of amlodipine and atorvastatin. Antimicrob Agents Chemother 2011; Epub 8 Aug 2011. DOI: 10.1128/ AAC.00653-11.

  26. Garg V, Yang Y, Smith F, et al. The pharmacokinetic interaction between an oral contraceptive containing ethinyl estradiol and norethindrone and telaprevir [abstract PK_17]. 6th International Workshop on Clinical Pharmacology of Hepatitis Therapy, June 22-23, 2011, Cambridge, MA.




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