Comorbidities, Concomitant Medications and Potential Drug-Drug Interactions With Interferon-free Direct-acting Antiviral Agents in Hepatitis C Patients in Taiwan

Chen-Hua Liu; Ming-Lung Yu; Cheng-Yuan Peng; Tsai-Yuan Hsieh; Yi-Hsiang Huang; Wei-Wen Su; Pin-Nan Cheng; Chih-Lin Lin; Ching-Chu Lo; Chi-Yi Chen; Jyh-Jou Chen; Qian Ma; Craig Brooks-Rooney; Jia-Horng Kao


Aliment Pharmacol Ther. 2018;48(11-12):1290-1300. 

In This Article

Abstract and Introduction


Background: While direct-acting antivirals have been approved for treating hepatitis C, the guidelines highlight the importance of considering potential drug-drug interactions between DAAs and concomitant medications.

Aim: To assess comorbidity prevalence, concomitant medication use and potential drug-drug interactions between DAAs and concomitant medications for hepatitis C patients in Taiwan.

Methods: This cross-sectional study enrolled 822 patients from May to August 2016 in Taiwan. Patient demographics, comorbidities and concomitant medications were evaluated by physician surveys.

Results: A total of 709 (86.3%) patients had ≥1 comorbidity; the most prevalent comorbidity categories were diseases of the digestive system (40.1%), circulatory system (38.7%) and endocrine/nutritional/metabolic diseases (35.2%). Elderly patients had more comorbidities. A total of 622 (75.7%) patients received ≥1 concomitant medication; the average number of concomitant medications was 3.2. The most common concomitant medication classes were cardiovascular (34.4%), gastrointestinal (25.7%) and central nervous system drugs (22.7%). Among patients without cirrhosis or with compensated cirrhosis, contraindications were most prevalent with paritaprevir/ritonavir/ombitasvir plus dasabuvir, daclatasvir/asunaprevir and glecaprevir/pibrentasvir (13.3%, 6.0% and 5.4% respectively), and least prevalent with sofosbuvir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir and sofosbuvir/velpatasvir (0.8%, 1.3%, 1.4% and 2.1% respectively). Sofosbuvir-based regimens had no contraindications in patients with decompensated cirrhosis.

Conclusion: Our population represented an elderly demographic, with a high prevalence of comorbidities and widespread use of concomitant medications. The potential drug-drug interactions between these concomitant medications and DAA regimens differed, with the fewest potential interactions with sofosbuvir-based regimens.


Given that chronic hepatitis C virus (HCV) infection may lead to cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC), it is considered a global health issue.[1,2] It is estimated that approximately 71.1 million people globally have chronic HCV infections.[3] In Taiwan, HCV infection is prevalent in 1.8%-5.5% of the population, and inflicts substantial clinical and economic burden.[2,4,5] It has been shown that viral eradication would improve the long-term adverse hepatic outcomes and extra-hepatic manifestations associated with chronic HCV infection, and therefore, effective treatment is crucial for all patients.[6–10]

Interferon (IFN)-free direct-acting antivirals (DAAs) have now been recommended as first-line treatment for HCV-infected patients by American, European and Asian-Pacific guidelines.[11–13] Compared to IFN-based therapies, IFN-free DAA regimens have higher rates of efficacy and patient acceptance, and are associated with fewer adverse events and a lower pill burden.[11–14] However, the guidelines also highlight the importance of considering potential drug-drug interactions (DDIs) between DAAs and concomitant medications.[11–13] A comprehensive assessment of potential DDIs prior to DAA therapy initiation is thus paramount in optimising patient safety and treatment efficacy.[15]

Given the large number of potential concomitant medications and limited pharmacokinetic data, DDIs have become a challenge in the era of DAAs, particularly for patients with multiple comorbidities who use a number of concomitant medications.[16] Several studies in the USA, Spain, Germany, France, Japan and Taiwan have examined potential DDIs in HCV-infected patients receiving DAAs in clinical practice.[17–25] The US and German studies showed that patients with cirrhosis received a higher number of concomitant medications compared with patients with no cirrhosis, and a higher number of concomitant medications was also associated with higher rates of potential DDIs.[17,20] In Japan, 39% of patients with chronic HCV infection were taking at least one medication contraindicated to DAA regimens, and the percentage increased from 21% in patients aged 18–34 years to 44% in patients aged 65–74 years.[23] Careful evaluation of concomitant medications is therefore critical in choosing a suitable DAA regimen in clinical practice, and is particularly important for cirrhotic and/or elderly patients.[17,19,20,23] Since several novel DAA regimens have recently been approved for the treatment of HCV infection, updated information regarding the potential DDIs associated with these regimens is essential.

This study aimed to assess the prevalence of comorbidities in chronic HCV-infected patients in Taiwan, as well as the potential DDIs between DAA regimens and concomitant medications taken by patients.