Predictors of adverse drug reactions associated with ribavirin in direct‐acting antiviral therapies for chronic hepatitis C

Abstract

Purpose To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens. Methods A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow‐up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors. Results A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08‐3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38‐4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78‐18.30]). Treatment efficacy was 98.1%. Conclusions Direct‐acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.

Sex‐related difference analyses of efficacy and safety in clinical trials of direct‐acting antivirals to treat chronic HCV genotype 1 and 3 infections

“…Several published studies show fatigue, headache and GI events are common with DAA treatment 47–49 . Female sex and ribavirin use were the only two predictors of having at least one adverse event in a logistic regression analysis among HCV patients treated with DAAs 50 . A pharmacovigilance study on DAAs revealed that significantly more females reported GI side effects than males 51 .…”

“…[47][48][49] Female sex and ribavirin use were the only two predictors of having at least one adverse event in a logistic regression analysis among HCV patients treated with DAAs. 50 A pharmacovigilance study on DAAs revealed that significantly more females reported GI side effects than males. 51 Our findings were similar to published studies in that females had a higher incidence of certain adverse events 14 and some events and laboratory findings were driven in part by ribavirin-related toxicities.…”