Co-morbidities and risk for drug-drug-interactions in HCV GT 1 patients treated with elbasvir/grazoprevir from the German Hepatitis C Registry (DHC-R)

Background:

Recently, it was reported that due to intake of concomitant medications up to 66% of HCV patients may be at risk for clinically relevant drug-drug-interactions (DDIs) if treated with different currently approved direct-acting antiviral therapies (Clin Infect Dis 2016; 62: 561 – 567). The present analysis of the DHC-R real-world cohort was aimed to assess the frequency of co-morbidities and the potential for clinically relevant DDIs in patients (pts) with chronic HCV GT1 infection selected for EBR/GZR therapy.

Methods:

From 09/20/2016 until 08/09/2017, co-morbidities and co-medications were documented at start of HCV GT1 treatment with EBR/GZR from 535 pts by 110 medical practices and hospital outpatient departments in the DHC-R. The risk for clinically relevant DDIs (co-administration of drugs contraindicated or requiring dose adjustment/closer monitoring) was assessed based on information available at www.hep-druginteractions.org and the prescribing information for each drug by 09/12/2017.

Results:

The mean age of 535 enrolled pts was 53 years, 62% male, 12% were under opioid substitution, 4% had HIV co-infection, 18% had cirrhosis and 24% had failed prior antiviral therapy. 92% were treated with EBR/GZR and 8% with EBR/GZR plus ribavirin. Co-morbidities were reported for 414 of 535 pts (77%), most frequently cardiovascular diseases (35% of all patients), drug addiction (21%), metabolic disorders (12%), psychiatric disorders (12%), renal dysfunction (11%, under dialysis 8%), and thyroid dysfunctions (8%). 330 of 535 pts (62%) reported the regular intake of drugs. Most frequent co-medications were agents acting on the renin-angiotensin system (24% of all patients), beta blocking agents (22%), drugs for psychiatric diseases (16%), drugs for acid related disorders (13%), diuretics (12%), opioid agonists (12%), analgesics (11%), calcium channel blockers (11%), antithrombotic agents (10%), thyroid drugs (9%) and antidiabetics (7%). In 1 of 535 pts (0.2%) the co-medication was formally contraindicated with EBR/GZR (regular use of cyclosporine). Co-medications requiring closer monitoring or dose adjustments were observed in 44 of 535 pts (8%): mainly use of simvastatin (N = 18) and metamizole (n = 11). Co-medications with a potential to interact with ribavirin were noted in 5 patients.

Conclusions:

Co-morbidities are a frequent problem in pts undergoing treatment of HCV GT1 infection with EBR/GZR in German real-world. As a consequence, there is a high rate of co-medications that require attention. However, in most cases (> 99%) either no significant interactions are expected or potential DDI can be managed by closer monitoring or dose adjustments.