Megan Brooks

March 26, 2013

For patients with hepatitis C virus receiving triple therapy, once-daily ribavirin dosing does not increase gastrointestinal adverse effects, and most patients prefer it over twice-daily dosing.

This finding comes from a study presented at the International Conference on Viral Hepatitis (ICVH) 2013 in New York City, which was sponsored by the International Association of Providers of AIDS Care and the Icahn School of Medicine at Mount Sinai.

Ribavirin is approved for twice-daily or divided dosing, but many of the new antivirals in the pipeline for hepatitis C will be taken once daily. "For convenience, we were interested in looking at once-daily ribavirin dosing," said presenter Kian Bichoupan, who is a graduate student at the Icahn School of Medicine at Mount Sinai in New York City.

"The half-life of ribavirin is 2 weeks," he explained, "so there is no reason to suspect there is any difference between taking it once a day or twice a day. Any opportunity that we have to make it easier for patients to take ribavirin would be attractive."

Bichoupan and colleagues conducted a study to assess adverse effects associated with twice-daily and once-daily weight-based ribavirin.

They used a structured interview and reviewed patient medical records to examine ribavirin dosing, changes in dosing over time, dosing preferences, and gastrointestinal (GI) adverse effects such as nausea, diarrhea, and vomiting. "We chose GI side effects because they are known to be more related to ribavirin," Bichoupan explained.

The study cohort consisted of 58 patients receiving telaprevir-based triple therapy and 16 receiving boceprevir-based triple therapy. Mean age was 59 years and time on treatment was about 25 weeks.

Patients can potentially take once-daily ribavirin and have fewer side effects and better adherence.

Adverse events were fairly common; 46% of patients required epoetin alfa for anemia, 9% received transfusions, and 14% visited the emergency department — mostly for anemia-related issues.

However, there was no statistical difference between once-daily and twice-daily ribavirin dosing in the frequency or percentage of patients with GI adverse effects, the investigators report.

GI symptoms were no worse in the once-daily group than they were in the twice-daily group, and most patients preferred taking ribavirin only once a day.

In patients who switched from twice-daily dosing to a lower once-daily dose, the prevalence of nausea, vomiting, and diarrhea was lower, which was "interesting," Bichoupan said.

In addition, this trial confirms what other trials have shown — "that ribavirin dose reductions do not have an impact on sustained virologic response," he noted.

"These results are promising. Patients can potentially take once-daily ribavirin and have fewer side effects and potentially better adherence," Bichoupan said. This is a small observational study, he acknowledged, and a randomized controlled trial is needed to confirm the findings.

Mark Nelson, MD, from Chelsea and Westminster Hospital, London, the United Kingdom, who is also ICVH 2013 conference cochair, told Medscape Medical News that "with the advent of new once-daily therapies, both with and without interferon, and the potential necessity of ribavirin as part of the regimen, the potential for using ribavirin once daily without increase in toxicity should lead to improvements in adherence and the potential, therefore, of even better results than currently seen in clinical practice."

This study was funded by Kadmon Pharmaceuticals. Mr. Bichoupan has disclosed no relevant financial relationships. Coauthor Valérie Martel-Laferrière, MD, from the Icahn School of Medicine at Mount Sinai, was funded by the 2011 AMMI Canada/Pfizer Post Residency Fellowship and the 2012 Grant of the CHUM Foundation. Coauthor Douglas Dieterich, MD, also from the Icahn School of Medicine, reports relationships with Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe & Dohme, ViiV Healthcare, and AbbVie.

International Conference on Viral Hepatitis (ICVH) 2013: Abstract 30. Presented March 25, 2013.