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Drug–drug interactions between direct-acting antivirals and co-medications: a territory-wide cohort study

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Abstract

Background

The increasing number of direct-acting antiviral (DAA) regimens along with limited number of subjects and co-medications involved in clinical trials results in drug–drug interactions (DDIs) with DAAs is to be determined. We aimed to examine the prevalence and degree of DDIs between DAAs and other co-medications in a territory-wide cohort of chronic hepatitis C virus (HCV) patients.

Methods

DDIs were assigned to three risk categories: Category 1—no clinically significant DDI; category 2—potential clinically significant interaction (monitoring and caution required); category 3—contraindicated (should not be co-administered).

Results

Of 2981 patients (mean age 59.3 ± 12.3 years; male 60.6%), 810 (48.8%) had genotype 1 and 552 (33.2%) genotype 6 HCV among the 1661 patients with HCV genotype tested; 769 (25.8%) received sofosbuvir/velpatasvir, 510 (17.1%) sofosbuvir/ledipasvir, and 865 (29.0%) glecaprevir/pibrentasvir. More than one-fourth (26.3%) of the patients have polypharmacy (≥ 3 co-medications) in all patients, 27.0% in patients received sofosbuvir/velpatasvir, 25.1% in elbasvir/grazoprevir, and 21.2% in glecaprevir/pibrentasvir. 2037 (68.3%) patient experienced DDI (Category 2: 53.1%; Category 3: 15.2%). The commonest drugs leading to DDIs were calcium channel blockers (31.5%) and proton pump inhibitors (23.0%) in category 2; statins (10.2%), antiplatelet/anticoagulants (3.0%) and antipsychotics (2.9%) in category 3. Changing medication was the most common response from physicians in both category 2 and 3 DDIs.

Conclusion

The commonest co-medications leading to contraindication during DAA treatment were statins and antipsychotics. Category 2 and 3 DDIs are often managed by appropriate dose adjustments or temporary discontinuation of relevant co-medications. Careful assessment for potential DDI before DAA use is mandatory to avoid potential harmful effects.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to regulations of the Hospital Authority, but are available from the corresponding author on reasonable request.

Abbreviations

anti-HCV:

HCV antibody

DAA:

Direct-acting antiviral

DDI:

Drug–drug interactions

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

IQR:

Interquartile range

PWID:

People who inject drugs

SD:

Standard deviation

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Funding

This work was supported by the Investigator Sponsored Research of Gilead Sciences (Reference: IN-HK-987-6069).

Author information

Author notes

  1. Vicki Wing-Ki Hui and Christopher Langjun Au have equal contributions to this study.

Authors and Affiliations

  1. Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong SAR, China

    Vicki Wing-Ki Hui, Christopher Langjun Au, Amy Shuk Man Lam, Terry Cheuk-Fung Yip, Yee-Kit Tse, Jimmy Che-To Lai, Vincent Wai-Sun Wong & Grace Lai-Hung Wong

  2. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong SAR, China

    Vicki Wing-Ki Hui, Amy Shuk Man Lam, Terry Cheuk-Fung Yip, Yee-Kit Tse, Jimmy Che-To Lai, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong & Grace Lai-Hung Wong

  3. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China

    Vicki Wing-Ki Hui, Terry Cheuk-Fung Yip, Yee-Kit Tse, Jimmy Che-To Lai, Vincent Wai-Sun Wong & Grace Lai-Hung Wong

  4. Union Hospital, Hong Kong SAR, China

    Henry Lik-Yuen Chan

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Contributions

All authors were responsible for the study concept and design. VW-KH, TC-FY, Y-KT, and GL-HW were responsible for the acquisition and analysis of data, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors were responsible for the interpretation of data, the drafting, and critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Grace Lai-Hung Wong.

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Conflict of interest

Terry Yip has served as an advisory committee member and a speaker for Gilead Sciences. Henry Chan is an advisor for AbbVie, Aligos, Aptorum, Arbutus, Hepion, Janssen, Gilead, GSK, Merck, Roche, Vaccitech, VenatoRx, Vir Biotechnology; and a speaker for Mylan, Gilead and Roche. Vincent Wong has served as an advisory committee member for 3 V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Janssen, Novartis, Novo Nordisk, Perspectum Diagnostics, Pfizer, TARGET-NASH and Terns; and a speaker for Bristol-Myers Squibb, Echosens, Gilead Sciences and Merck. He has also received a research grant from Gilead Sciences. Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Furui, Gilead Sciences, Janssen and Roche, and received research grant from Gilead Sciences. The other authors declare that they have no competing interests.

Ethical approval

The study protocol was approved by the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee.

Animal research (ethics)

Not applicable.

Consent to participate (ethics)

Because of the retrospective nature of this study and we will have no access to patient identifiers, written informed consent will be waived, subject to approval by the Joint CUHK-NTEC CREC.

Consent to publish (ethics)

All the authors are consent to publish the data.

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Not available.

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Hui, V.WK., Au, C.L., Lam, A.S.M. et al. Drug–drug interactions between direct-acting antivirals and co-medications: a territory-wide cohort study. Hepatol Int 16, 1318–1329 (2022). https://doi.org/10.1007/s12072-022-10402-y

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  • DOI: https://doi.org/10.1007/s12072-022-10402-y

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