A significant number of patients treated with recently approved direct-acting antivirals for hepatitis C virus infection are at risk for drug-drug interactions, according to a study published in Clinical Infectious Diseases.
“The majority of recently approved [direct-acting antivirals (DAAs)] are considered to have a reduced impact on cytochrome P450 enzymes and/or [p-glycoprotein] compared with [Victrelis (boceprevir, Merck)] and [Incivek (telaprevir, Vertex)],” Heiner Wedemeyer, MD, managing senior physician and assistant professor in the department for gastroenterology, hepatology and endocrinology at Hannover Medical School in Germany, and colleagues wrote. “However, the actual risk of [drug-drug interactions] with these newer DAA regimens and the patients’ concomitant medication remains unclear.”
To analyze the clinical significance of drug-drug interactions between regular outpatient medications and DAA therapies in a large, real-world cohort, the researchers selected 261 patients with HCV monoinfection who had been chosen for DAA therapy at two intervals between 2011 and 2014.
The patients were asked to provide their regular outpatient medications. Using the website www.hep-druginteractions.org, the researchers assessed the potential for drug-drug interactions between these drugs and Sovaldi (sofosbuvir, Gilead Sciences )/ribavirin; Harvoni (ledipasvir/sofosbuvir, Gilead Sciences); sofosbuvir/Daklinza (daclatasvir, Bristol-Myers Squibb); sofosbuvir/Olysio (simeprevir, Janssen Therapeutics); and Viekira Pak (ombitasvir/paritaprevir/ritonavir with or without dasabuvir, AbbVie), and boceprevir- and telaprevir-based triple therapy.
According to the researchers, the median number of drugs taken by the patients was two, while 20% did not take any medication. Sofosbuvir/ribavirin carried the lowest risk for causing a potentially significant drug-drug interaction, which was expected in 9.6% of patients, while ombitasvir/paritaprevir/ritonavir with or without dasabuvir carried a significant risk, expected in 66.3%. Significant drug-drug interactions associated with sofosbuvir/simeprevir were anticipated in 31.4% of patients. Meanwhile, significant interactions for sofosbuvir/daclatasvir were expected in 36.8%, and for ledipasvir/sofosbuvir in 40.2%.
In addition, proton pump inhibitors, thyroid hormones and dihydropyridine derivatives were frequently associated with drug-drug interactions, depending on the DAA regimen, according to the researchers.
“Our findings have important clinical implications for the management of [drug-drug interactions] during HCV therapy,” Siederdissen and his colleagues wrote. “Drugs most frequently involved in [drug-drug interactions] varied between the different DAA regimens. Thus, no list of drugs can be provided that should be avoided or preferred across all DAA classes. Instead, a careful individual assessment of the patient’s regular medication and a subsequent individual evaluation of potential [drug-drug interactions] is required.” – by Jason Laday
Disclosures: Siederdissen reports receiving speaker fees from Gilead Sciences, Merck and Roche. Wedemeyer reports receiving grants and lecture and/or consulting fees from AbbVie, Gilead Sciences, Janssen-Cilag, Merck and Roche. Please see the full study for a list of all other authors’ relevant financial disclosures.