Many patients on new HCV medications at risk of drug-drug interactions

Last Updated: 2015-12-17

By Anne Harding

NEW YORK (Reuters Health) - Many patients taking direct acting antivirals (DAA) to treat hepatitis C virus (HCV) are at risk of clinically significant drug-drug interactions (DDIs), new research shows.

These interactions have the potential to cause treatment failure, which is especially problematic given that it's currently unclear how to treat patients who fail DAA treatment, Dr. Heiner Wedemeyer of Hannover Medical School in Germany, one of the study's authors, told Reuters Health in a telephone interview.

Boceprevir and telaprevir, the first DAA to be approved for HCV, are known to carry a risk of DDI, Dr. Wedemeyer and his colleagues note in their report online November 26 in Clinical Infectious Diseases.

Now that several more DAA have been released, they add, they have become the standard of care for HCV in the U.S. and much of Europe. While newer DAAs are generally considered to carry a lower risk of DDIs, the researchers add, "the actual risk of DDI with these newer DAA regimens and the patients' concomitant medication remains unclear."

To investigate the "real-world" potential of clinically significant DDI, the researchers looked at 261 patients monoinfected with HCV, including 115 consecutive patients enrolled after the approval of boceprevir and telaprevir in 2011, and 146 consecutive patients recruited after sofosbuvir was approved in 2014. They asked patients about medications they took, and then assessed the potential for DDI between these medications and several types of DDA therapy.

Patients were on a median of two drugs, while 20% were not on any other medication. The four most commonly used drugs among the study participants were pantoprazole (18.8%), spironolactone (16.5%), levothyroxine (16.5%), and hydrochlorothiazide (10%).

The risk of clinically significant DDIs was lowest for patients on sofosbuvir/ribavirin, with 9.6% at risk of a DDI that would require either closer monitoring or dose adjustment. Patients on ombitasvir/paritaprevir/ritonavir with or without dasabusvir were at the highest potential risk of serious DDIs, at 66.3%.

Among patients on sofosbuvir/simeprevir, sofusbivir/daclatasvir, and sofosbuvir/ledipasvir, the researchers estimated a 31.4%, 36.8%, and 40.2% risk of clinically significant DDI, respectively.

The type of concomitant medications most often involved with DDIs varied by the DAA regimen patients were taking, Dr. Wedemeyer and colleagues found.

"Many physicians are simply not aware about potential drug-drug interactions," Dr. Wedemeyer told Reuters Health. "We must be aware of all potential issues leading to treatment failure, simply for cost reasons."

Dr. Wedemeyer said he and his colleagues will continue the study for the next wave of HCV drugs, expected to be approved this year or next. They will also look at registries of patients already on DAAs to investigate how often clinically significant DDIs actually occur. "You need real-world data to identify safety signals, which is extremely important in this field," he said.

The German Federal Ministry of Education and Research partially supported this research. Eight coauthors reported disclosures.

SOURCE: http://bit.ly/1IWPbIx

Clin Infect Dis 2015.