Drug–Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen Ledipasvir/Sofosbuvir

  • Polina German
  • Anita Mathias
  • Diana M. Brainard
  • Brian P. Kearney
Review Article

Abstract

Ledipasvir/sofosbuvir (Harvoni®), a fixed-dose combination tablet of an NS5A inhibitor ledipasvir and an NS5B polymerase inhibitor sofosbuvir, is approved for the treatment of chronic hepatitis C virus infection. Ledipasvir/sofosbuvir exhibits a favorable drug–drug interaction profile and can be administered with various medications that may be used by hepatitis C virus-infected patients, including patients with comorbidities, such as co-infection with human immunodeficiency virus or immunosuppression following liver transplantation. Ledipasvir/sofosbuvir is not expected to act as a victim or perpetrator of cytochrome P450- or UDP-glucuronosyltransferase 1A1-mediated drug–drug interactions. With the exception of strong inducers of P-glycoprotein, such as rifampin, ledipasvir/sofosbuvir is not expected to act as a victim of clinically relevant drug–drug interactions. As a perpetrator of pharmacokinetic drug–drug interactions via P-glycoprotein/BCRP, ledipasvir/sofosbuvir should not be used with rosuvastatin and elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, whereas its co-administration with amiodarone is not recommended because of a pharmacodynamic interaction. This review summarizes a number of drug interaction studies conducted in support of the clinical development of ledipasvir/sofosbuvir.

Notes

Compliance with Ethical Standards

Funding

Gilead Sciences, Inc. provided funding for the research presented in this article.

Conflict of interest

Polina German, Anita Mathias, Diana Brainard, and Brian P. Kearney are employees of Gilead, contributed significantly to the design, conduct, analyses, and interpretation of data, and were involved in the preparation, review, and approval of this article. Polina German, Anita Mathias, Diana Brainard, and Brian P. Kearney are stockholders of Gilead Sciences, Inc.

Ethics approval

The study protocol and informed consent documents were reviewed and approved by a duly constituted institutional review board before study initiation in accordance with the basic principles defined in the US 21 CFR Part 312.20 and the principles enunciated in the Declaration of Helsinki.

Consent to participate

Informed consent was obtained from each subject before the initiation of any screening procedures.

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Authors and Affiliations

  1. 1.Gilead Sciences, Inc.Foster CityUSA

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