Drug–drug interactions with direct‐acting antivirals: when do we need to care?

Abstract Background With the introduction of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, drug–drug interactions (DDIs) emerged as significant challenge. Since then, HCV therapy and the infected population have rapidly changed. So far, very limited data are available regarding the clinical relevance of DDIs when using most modern DAA regimens. We aimed to assess how the importance of DDIs has evolved over time. Methods From January 2014 to July 2018, 668 consecutive HCV patients were evaluated for their outpatient medication and assessed for DDIs with DAAs. Different time periods were defined based on market approval of key DAAs: A (01/2014–11/2014), B (11/2014–08/2016), and C (08/2016–07/2018). Results The frequency of patients with real-world DDIs was highest in period B (A: 37.1%, B: 49.6%, C: 38.8%). The recently approved DAAs (period C) theoretically showed a lower DDI risk profile. However, real-world DDIs were still comparable to period A, as HCV patients’ characteristics changed (eg, age ≥75 years: A: 3.1%, B: 9.8%, C: 5.6%; polypharmacy/patients with ≥8 drugs: A: 11.1%, B: 15.2%, C: 17.2%). Furthermore, although DDIs via CYP 3A4 became less important for some modern regimens, other mechanisms like an altered pH value in the stomach, causing reduced bioavailability, evolved. Relevant DDIs most frequently occurred with proton pump inhibitors, metamizole, statins, and carvedilol. Conclusions DDIs during antiviral treatment still affect about 40% of HCV patients. The lower DDI potential of modern DAA regimens is partly counteracted by changing patient characteristics. Therefore, DDIs should not be underestimated.

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Drug Interactions of Hepatitis C Direct-Acting Antivirals in the HIV-Infected Person

Current HIV/AIDS Reports ◽

10.1007/s11904-015-0277-5 ◽

2015 ◽

Vol 12 (3) ◽

pp. 336-343 ◽

Cited By ~ 5

Author(s):

O. El-Sherif ◽

D. Back

Keyword(s):

Hepatitis C ◽

Drug Interactions ◽

Infected Person ◽

Direct Acting Antivirals ◽

Direct Acting

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Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0180 ◽

2021 ◽

Vol 27 (1) ◽

pp. 186-196

Author(s):

Po-Yao Hsu ◽

Yu-Ju Wei ◽

Jia-Jung Lee ◽

Sheng-Wen Niu ◽

Jiun-Chi Huang ◽

...

Keyword(s):

Hepatitis C ◽

Drug Interactions ◽

Median Number ◽

Lipid Lowering ◽

Hcv Rna ◽

Close Monitoring ◽

Potential Drug ◽

Direct Acting Antivirals ◽

Potential Ddis ◽

Direct Acting

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

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