Abstract

INTRODUCTION: The development of new pangenotypic direct-acting antivirals (pDAA) against hepatitis C virus (HCV) is revolutionizing the treatment of chronic hepatitis C (CHC). The availability of pDAA provides the opportunity to maximize Sustained Virologic Response and minimize side effects and drug-drug interactions. Given the large number of potential concomitant medications and limited pharmacokinetic data, DDIs have become a challenge in the era of DAA, particularly for patients with multiple comorbidities who use concomitant medications. OBJECTIVE: To determine the comorbidity and potential drug-drug interactions (DDIs) among DAAs associated with HCV patients in the usual clinical practice.

METHODS: This is a retrospective observational study, designed from the medical records review (computerized database). The study population was obtained from health records of healthcare provider organizations from various centers in Spain (BIG-PAC dissociated database). Patients were ≥18 years diagnosed with HCV, who required medical attention during 2018. Two groups were differentiated according to age ranges (< 50 years and ≥ 50 years). The variables collected were demographic (age, gender); general and specific comorbidity; and pharmacological (DDIs). DAAs analyzed: a) Sofosbuvir (SOF), b) Ledipasvir/Sofosbuvir (LDV/SOF), c) Glecaprevir /Pibrentasvir (GLE/PIB), d) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) and e) Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir (PrOD). The concomitant medication administered during follow-up, Table 1. To determine the DDIs effect, the recommendations of the University of Liverpool (AASLD). Statistical-analysis: descriptive/bivariate, p-value<0.05.

RESULTS: Summary of results obtained 3,430 patients were recruited, the average age was 56.9 years and 60.3% were males. The distribution by age ranges was: <50 years (28.9%) and ≥50 years (71.1%). The average of drugs was: 3.1 per patient/year, Table 1. Most used medication: alimentary tract and metabolism (37.5%), cardiovascular system (35.7%) and nervous system (34.1%). By subgroups of drugs was the following: drugs for acid related disorders (23.1%), agents acting on the renin–angiotensin system (21.8%) and psycholeptics (21.7%). The total percentage of potential pharmacological interactions was: 8.3% weak; 38.3% clinically significant; 7.5% contraindicated medication. These interactions were greater in patients ≥50 years (8.1%, 42.2% and 10.2%, respectively, p <0.001). For all ages, SOF compared to SOF/LDV, GLE/PIB, SOF/VEL/VOX and PrOD showed a lower percentage of contraindications (1.1% vs. 3.1%, 6.5%, 8.5% and 11,4%, p<0.001). 

CONCLUSION: The subjects with HCV are associated with a high comorbidity and consumption of concomitant medication, especially in older patients (≥50 yrs), a circumstance that results in greater exposure to potential DDI. The use of SOF and LDV/SOF can produce a lower proportion of contraindications (DDIs).