Dataset Information

Frequency of Potential Drug-Drug Interactions in the Changing Field of HCV Therapy.

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.

SUBMITTER: Schulte B

PROVIDER: S-EPMC7033915 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Frequency of Potential Drug-Drug Interactions in the Changing Field of HCV Therapy.

Schulte Benjamin B Wübbolding Maximilian M Marra Fiona F Port Kerstin K Manns Michael P MP Back David D Cornberg Markus M Stichtenoth Dirk O DO Höner Zu Siederdissen Christoph C Maasoumy Benjamin B

Open forum infectious diseases 20200203 2

<h4>Background</h4>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.<h4>Methods</h4>From January 2014 to July 2018, 668 consecuti ...[more]

PMID: 32104719

Similar Datasets

Project description:ObjectivesDevelopment of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients.MethodsCross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed.ResultsOf 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%), sofosbuvir/ledipasvir (0.2%/67.6%), daclatasvir (0%/49.4%), ombitasvir/boosted paritaprevir (with or without dasabuvir) (34.4%/52.2%) and simeprevir (78.8%/0%).ConclusionsSignificant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

Project description:ImportanceSuboptimal adherence to endocrine therapy (ET) among patients with hormone-receptor-positive breast cancer significantly affects survival outcomes and is associated with higher hospitalization rates and health care costs. Weak adherence to long-term treatments has multiple determinants, including disease characteristics, treatment adverse effects, and patients' attributes, such as age and comorbidities.ObjectiveTo examine whether potential drug-drug interactions (PDDI) with tamoxifen or aromatase inhibitor were associated with adherence to ET in patients with early and advanced breast cancer.Design, setting, and participantsThis cohort study used anonymized health record data of women with breast cancer who received ET in a private observational primary care database. Patients eligible for analysis included women aged 18 years or older who had a reported diagnosis of breast cancer and received ET with tamoxifen or aromatase inhibitor between 1994 and 2021. Data were analyzed 2021.ExposuresAdherence to ET during a given year was defined by a medication possession ratio of 80% or greater over 1-year prescription periods. PDDI were categorized into absent, minor (a combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended), and contraindicated according to guidelines in the Claude Bernard Drug Database.Main outcomes and measuresWe used regression models to estimate odds ratios (ORs) and 95% CIs for the associations between adherence and age, baseline comorbidities, PDDI, and adherence to ET during the previous year.ResultsA total of 10 863 patients who were prescribed ET for breast cancer were eligible for the analysis (age 70 years or older, 3509 patients [32.3%]). In the tamoxifen cohort (3564 patients), PDDI were reported in 497 of 3670 patients (13.5%) at baseline (moderate, 254 patients [51.1%]; major, 227 patients [45.7%]), 2047 of 4831 patients (42.4%) at year 1, 1127 of 2751 patients (41.0%) at year 2, 761 of 1861 patients (40.9%) at year 3, 376 of 1058 patients (35.5%) at year 4, and 201 of 593 patients (33.9%) at year 5. In the aromatase inhibitor cohort (7299 patients), PDDI were reported in 592 of 7437 patients (8.0%) at baseline (moderate in 588 of 592 patients [99.3%]), which reached 2875 of 9031 patients (31.8%) at year 1 and ranged between 31.4% (1802 of 5730 patients in year 2) and 32.8% (791 of 2411 in year 4) throughout the study period. No association between adherence and PDDI was found in the tamoxifen (OR, 0.99; 95% CI, 0.91-1.08) or aromatase inhibitor (OR, 1.05; 95% CI, 0.95-1.15) cohort.Conclusions and relevanceIn this cohort of patients with hormone-receptor-positive breast cancer, PDDI with tamoxifen and aromatase inhibitors were not associated with adherence to ET.

Project description:ObjectivesWe sought to determine the prevalence of phosphodiesterase type 5 inhibitor (PDE-5) mediated drug-drug interactions (DDIs) in males with HIV infection receiving antiretroviral therapy (ART) and identify factors associated with PDE-5-mediated DDIs.MethodsMale US Military HIV Natural History Study participants diagnosed with erectile dysfunction (ED) and having a PDE-5 inhibitor and potentially-interacting ART co-dispensed within 30 days were included. DDIs were defined according to criteria found in published guidelines and drug information resources. The primary outcome of interest was overall PDE-5 inhibitor-mediated DDI prevalence and episode duration. A secondary logistic regression analysis was performed on those with and without DDIs to identify factors associated with initial DDI episode.ResultsA total of 235 male participants with ED met inclusion criteria. The majority were White (50.6%) or African American (40.4%). Median age at medication co-dispensing (45 years), duration of HIV infection (14 years), and duration of ED (1 year) did not differ between the two groups (p>0.05 for all). PDE-5 inhibitors included sildenafil (n = 124), vardenafil (n = 99), and tadalafil (n = 14). ART regimens included RTV-boosted protease inhibitors (PIs) atazanavir (n = 83) or darunavir (n = 34), and COBI-boosted elvitegravir (n = 43). Potential DDIs occurred in 181 (77.0%) participants, of whom 122 (67.4%) had multiple DDI episodes. The median DDI duration was 8 (IQR 1-12) months. In multivariate analyses, non-statistically significant higher odds of DDIs were observed with RTV-boosted PIs or PI-based ART (OR 2.13, 95% CI 0.85-5.37) and in those with a diagnosis of major depressive disorder (OR 1.74, 95% CI 0.83-3.64).ConclusionsPDE-5-mediated DDIs were observed in the majority of males with HIV infection on RTV- or COBI-boosted ART in our cohort. This study highlights the importance of assessing for DDIs among individuals on ART, especially those on boosted regimens.

Project description:Identifying and understanding potential drug-drug interactions (DDIs) are vital for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This article discusses DDIs between doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), and cytochrome P450 3A (CYP3A) substrates and drugs that modulate CYP3A activity. Consistent with previously published in vitro data and DDI trials with the CYP3A substrates midazolam and atorvastatin, doravirine did not have any meaningful impact on the pharmacokinetics of the CYP3A substrates ethinyl estradiol and levonorgestrel. Coadministration of doravirine with CYP3A inhibitors (ritonavir or ketoconazole) increased doravirine exposure approximately 3-fold. However, these increases were not considered clinically meaningful. Conversely, previously published trials showed that coadministered CYP3A inducers (rifampin and rifabutin) decreased doravirine exposure by 88% and 50%, respectively (K. L. Yee, S. G. Khalilieh, R. I. Sanchez, R. Liu, et al., Clin Drug Investig 37:659-667, 2017 [https://doi.org/10.1007/s40261-017-0513-4]; S. G. Khalilieh, K. L. Yee, R. I. Sanchez, R. Liu, et al., J Clin Pharmacol 58:1044-1052, 2018 [https://doi.org/10.1002/jcph.1103]), while doravirine exposure following prior efavirenz administration led to an initial reduction in doravirine exposure of 62%, but the reduction became less pronounced with time (K. L. Yee, R. I. Sanchez, P. Auger, R. Liu, et al., Antimicrob Agents Chemother 61:e01757-16, 2017 [https://doi.org/10.1128/AAC.01757-16]). Overall, the coadministration of doravirine with CYP3A inhibitors and substrates is, therefore, supported by these data together with efficacy and safety data from clinical trials, while coadministration with strong CYP3A inducers, such as rifampin, cannot be recommended. Concomitant dosing with rifabutin (a CYP3A inducer less potent than rifampin) is acceptable if doravirine dosing is adjusted from once to twice daily; however, the effect of other moderate inducers on doravirine pharmacokinetics is unknown.

Dataset Information

Frequency of Potential Drug-Drug Interactions in the Changing Field of HCV Therapy.

Publications

Frequency of Potential Drug-Drug Interactions in the Changing Field of HCV Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets