Drug-Drug Interactions Remain a Problem Among Patients With HCV

Hepatitis C virus (HCV) remains a substantial health burden in the United States, particularly in the wake of the ongoing opioid crisis. However, treatment options have evolved over the last decade including the introduction of direct-acting antivirals.

As direct-acting antivirals have been introduced, drug-drug interactions have emerged as a challenge among patients living with HCV. Currently, drug-drug interactions affect approximately 40% of HCV patients.

Investigators of a newly published study in Open Forum Infectious Diseases evaluated patients with HCV who were treated with direct-acting antivirals from 2014 to 2018. The investigators found that changing patient characteristics may counteract the lower drug-drug interaction potential of modern direct acting antiviral regimens.

The study population included 668 patients with chronic HCV infection treated with direct-acting antivirals at the hepatitis outpatient clinic of Hannover Medical School. Patients were seen between January 2014 and July 2018.

Three time intervals were established in order to compare the changing epidemiology of drug-drug interactions as new direct-acting antivirals were introduced.

Time period 1 initiated when the first patient was treated with sofosbuvir. Time period 2 begins as the first patients are treated with ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir and dasabuvir +/- ribavarin, marking the start of fixed-dose regimens. Time period 3 lines up with the first patients who are treated with velpatasivir, elbasvir/grazoprevir, or glecaprevir/pibrentasvir, marking the availability of pengenotypic therapies.

Drug-drug interactions were evaluated using the web resource hep-druginteractions.org. Clinical pharmacists and pharmacologists were consulted in the event of missing information.

The frequency of patients with drug-drug interactions was 37.1% in the first period, 49.6% in the second period, and 38.8% in the third period. While recently approved direct-acting antivirals had a theoretically lower drug-drug interaction risk profile, changes in patient profile such as a higher risk of polypharmacy mitigated these benefits in the real world.

The mean age of patients has decreased, but the proportion of patients >75 years of age has increased.

Drug-drug interactions most frequently occurred with proton pump inhibitors, metamizole, statins, and carvedilol.

The study team explained that their results point to the importance of not underestimating drug-drug interactions in patients with HCV, even with technical improvements in the risk profile of medications.

The investigators also pointed to a need for further research on drug-drug interaction in the upscaling of HCV treatments, particularly as treatment is expanded among high-risk populations such as people who use injection drugs.

“Careful assessment of patient's regular outpatient medication and individual evaluation for potential [drug-drug interaction] seems as important as ever,” study authors wrote.