Contraindicated Drug-Drug Interactions Between Hepatitis C Virus Treatment Regimens

Combination therapy effective after bipolar episode
Combination therapy effective after bipolar episode
Researchers found data that showed drug interactions were most likely with glecapravir/pibrentasvir combination treatment for the hepatitis C virus.

Clinicians need to consider the significant differences in the frequency of contraindicated drug-drug interactions (XXDIs) between various hepatitis C virus (HCV) treatment regimens, with a greater number of medications and longer duration of HCV infection being predictors of XXDIs, according to a cross-sectional study published in the Annals of Hepatology.1

There are currently 4 regimens that are recommended for treating HCV infection, including glecapravir/pibrentasvir (GLE/PIB), grazoprevir/elbasvir (GZR/EBR), lediprasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL).2-6 While each has demonstrated impressive rates of sustained virologic response in treatment recipients with low toxicity,7-11 limited comparative data exist evaluating the potential risk for XXDIs between these regimens. Therefore, researchers in the Upstate New York Veterans Healthcare Administration compared the frequencies of XXDIs when each HCV regimen is added to the medication profiles of 4047 patients who were HCV monoinfected, quantified the proportion of patients with XXDIs to all 4 regimens, and determined the covariates that are independently associated with having a XXDI to all 4 regimens.1 They found that the prevalence of XXDIs was highest for GLE/PIB (17.8%), followed by LDV/SOF (4.4%), and the remaining 2 regimens (2.8%). Ninety-five (2.3%) patients had XXDIs to all 4 regimens. In addition, predictors of having XXDIs to all 4 regimens were 6 or more medications and HCV infection for 10 or more years.

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“In summary, there were significant differences in the frequency of XDDIs between various HCV treatment regimens,” stated the authors.1 Therefore, “Clinicians prescribing HCV treatment should include drug interactions in the multiple considerations that are involved in selecting an HCV treatment regimen.”


1. Ahmeda A, Schriever C, Britt N, et al. Comparing drug interaction frequencies of various hepatitis C treatment regimens among monoinfected patients [published online May 4, 2019]. Ann Hepatol. doi:10.1016/j.aohep.2019.01.005

2. American Association for the Study of Liver Diseases (AASLD) – Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. Accessed December 22, 2018.

3. Gilead Sciences. Harvoni (ledipasvir/sofosbuvir) tablet package insert. Foster City, CA; 2017.

4. Gilead Sciences. Epclusa (velpatasvir/sofosbuvir) tablet package insert. Foster City, CA; 2017.

5. AbbVie Inc. Mavyret (glecaprevir/pibrentasvir) tablet package insert. North Chicago, IL; 2017.

6. Merck & Co., Inc. Zepatier (elbasvir/grazoprevir) tablet package insert. Whitehouse Station, NJ; 2017.

7. Forns X, Lee SS, Valdes J, et al. 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(10):1062-1068.

8. Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370(16):1483-1493.

9. Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014;370:1889-1898.

10. Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373(27):2599-26607.

11. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis c virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med 2015;163(1):1-13.