1.Ledipasvir/sofosbuvir in chronic hepatitis C: a guide to its use in the EU    Drugs & Therapy Perspectives    2015
Abstract：A single-tablet regimen of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir; Harvoni®) was recently approved in the EU. The phase 3 ION trials included treatment-naïve (ION-1 and -3) or treatment-experienced (ION-2) patients with chronic hepatitis C virus (HCV) genotype 1 infection; ≈20% of patients in ION-1 and -2 had cirrhosis, whereas none of the patients in ION-3 had cirrhosis. In ION-1, a 12-week regimen of ledipasvir/sofosbuvir achieved high rates of sustained virological response 12 weeks' post-treatment (SVR12) in treatment-naïve patients, with no additional benefit conferred by the addition of ribavirin or extending the treatment duration to 24 weeks. An 8-week regimen also achieved high SVR12 rates in patients with a baseline HCV RNA level of <6 million IU/mL in ION-3. High SVR12 rates were seen in treatment-experienced patients who received ledipasvir/sofosbuvir for 12 or 24 weeks in ION-2. Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 infecti on, in HCV and HIV co-infection and, in combination with ribavirin, in patients with chronic HCV genotype 1 or 4 infection who have decompensated cirrhosis or are liver transplant recipients and in chronic HCV genotype 3 infection. Oral ledipasvir/sofosbuvir was generally well tolerated.
2.Drug–Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen Ledipasvir/Sofosbuvir    Clinical Pharmacokinetics    2018
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 u sed 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 .