Showing posts with label HCV agents/drug interactions. Show all posts
Showing posts with label HCV agents/drug interactions. Show all posts

Saturday, November 3, 2018

Minireview - Era of direct acting anti-viral agents for the treatment of hepatitis C

World J Hepatol. Oct 27, 2018; 10(10): 670-684
Published online Oct 27, 2018. doi: 10.4254/wjh.v10.i10.670

The different DAAs with their dose, efficacy, side effects, drug-drug interactions as well as specific treatment against different genotypes of HCV will be discussed.

Era of direct acting anti-viral agents for the treatment of hepatitis C 
Monjur Ahmed 

Core Tip: Treatment of hepatitis C has now become much easy and simple with the advent of direct acting anti-viral agents (DAAs) against hepatitis C virus (HCV). Although the DAAs are highly effective in eradicating HCV infection, they have different mechanisms of action, side effects, resistance factors and drug-drug interactions. The treatment also varies in special situations like HCV/ human immunodeficiency virus co-infection and post-liver transplant patients. Physicians treating patients with HCV infection should have a clear knowledge about the DAAs as well as the current guidelines.

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Friday, October 26, 2018

Hepatitis C - Potential drug‐drug interactions between DAAs and concomitant medications

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

First published: 25 October 2018

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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.

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

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.

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.

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.

Friday, September 28, 2018

Cardiovascular Risk Management and Hepatitis C: Combining Drugs

Cardiovascular Risk Management and Hepatitis C: Combining Drugs
Elise J. SmoldersPeter J. G. ter HorstSharon WoltersDavid M. Burger Elise J. Smolders

Article First Online: 27 September 2018

Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug–drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs. Therefore, the aim of this review was to describe DDIs between cardiovascular drugs (CVDs) and DAAs. An extensive literature search was performed containing search terms for the marketed DAAs and CVDs (β-blocking agents, ACE inhibitors, angiotensin II antagonists, renin inhibitors, diuretics, calcium channel blockers, statins/ezetimibe, fibrates, platelet aggregation inhibitors, vitamin K antagonists, heparins, direct Xa inhibitors, nitrates, amiodarone, and digoxin). In particular, the drug labels from the European Medicines Agency and the US Food and Drug Administration were used. A main finding of this review is that CVDs are mostly victims of DDIs with DAAs. Therefore, when possible, monitoring of pharmacodynamics is recommended when coadministering these drugs with DAAs. Nevertheless, it is sometimes better to discontinue a drug on a temporary basis (statins, ezetimide). The DAAs are victims of DDIs in combination with bisoprolol, carvedilol, labetalol, verapamil, and gemfibrozil. Despite there are many DDIs predicted in this review, most of these DDIs can be managed by monitoring the efficacy and toxicity of the victim drug or by switching to another CVD/DAA.

Key Points
Drug-drug interactions (DDIs) can be of major concern in hepatitis C patients with cardiovascular issues as there are many potential DDIs.

Especially clopidogrel and ticagrelor are drugs of which the potential drug-interactions are complex and hard to manage.

With increasing number of new direct-acting antivirals (DAAs) available the number clinical relevant DDIs are decreasing.

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Tuesday, February 6, 2018

Podcast - Referring, and Managing Patients with HCV

Published - January 26, 2018
Dr. Jorge Herrera, director of the Section of Hepatology and professor of Internal Medicine at the University of South Alabama, discusses screening, referring, and managing patients with hepatitis C virus.

Hepatitis C Risk Factors
Primary Care Physicians Treating HCV
Referral Process
Drug interactions
Define Cure
Treat Early
Quality of life after SVR
Treat All

Find more hepatitis-related content at our specialty site here.

Thursday, November 30, 2017

Drug-drug interactions in hepatitis C virus treatment: Do they really matter?

Clinical Liver Disease
Clinical Liver Disease is an official digital educational learning resource from the American Association for the Study of Liver Diseases. Visitors are able to view videos, access full text articles, and download files in either HTML or PDF formats.

November 2017 Volume 10, Issue 5 Pages 107–133

Controversies in HCV Management
Drug-drug interactions in hepatitis C virus treatment: Do they really matter? (pages 111–115)
Aijaz Ahmed, Glen A. Lutchman and Paul Y. Kwo
Version of Record online: 30 NOV 2017 | DOI: 10.1002/cld.668

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Begin here.....

Clinical Liver Disease

Monday, November 13, 2017

Labeling for Several HCV Drugs Updated With New Drug Interactions


Labeling for Several HCV Drugs Updated With New Drug Interactions
Specifically, the prescribing information for Viekira Pak (ombitasvir, paritaprevir, ritonavir, with dasabuvir; AbbVie), Viekira XR (dasabuvir, ombitasvir, paritaprevir, ritonavir; AbbVie), Technivie (ombitasvir, paritaprevir, ritonavir; AbbVie), Sovaldi (sofosbuvir; Gilead), Harvoni (ledipasvir, sofosbuvir; Gilead), Epclusa (sofosbuvir, velpatasvir; Gilead), Vosevi (sofosbuvir, velpatasvir, voxilaprevir; Gilead), Olysio (simeprevir; Janssen), Daklinza (daclatasvir; Bristol-Myers Squibb), and Zepatier (elbasvir, grazoprevir; Merck) has been updated to include information pertaining to changes in International Normalized Ratio (INR) values in patients receiving warfarin. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment. 

Read more.....

Tuesday, April 11, 2017

Toxicity and risks from drug-to-drug interactions of new antivirals for chronic hepatitis C

European Review for Medical and Pharmacological Sciences

Toxicity and risks from drug-to-drug interactions of new antivirals for chronic hepatitis C
2017; 21 (1 Suppl): 102-111 C.

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Abstract. – The new direct acting antivirals (DAAs), defined as those drugs that are effective in combinations without interferon, have totally changed HCV treatment and probably in few years will also totally change global landscape of advanced liver diseases. The advantage of DAAs is a low-risk/high-benefit ratio. Although overall adverse events during DAAs treatment are limited in frequency and severity, some toxicity issues emerged during the first years of real-life experience with these drugs. Another peculiar characteristic of present DAAs is a high probability of interaction with other “common-use” drugs, such as anti-hypertensive, anti-platelet, antiarrhythmic and cholesterol lowering agents. Above all, special attention should be paid in older patients and in those belonging to special populations, who more frequently require the concomitant use of polytherapy.

Table II. Side effects reported in real-life.

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Wednesday, March 1, 2017

Hepatitis C - Real-life data on potential drug-drug interactions in patients undergoing interferon-free DAAs

Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study
Loreta A. Kondili , Giovanni Battista Gaeta, Donatella Ieluzzi, Anna Linda Zignego, Monica Monti, Andrea Gori, Alessandro Soria, Giovanni Raimondo, Roberto Filomia, Alfredo Di Leo, Andrea Iannone, Marco Massari, Romina Corsini,
Published: February 28, 2017

There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.

To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.

Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (

Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI.

Based on these results, we can estimate that 30–44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from “dose adjustment/closer monitoring”, in mild to moderate liver disease, to “the use is contraindicated” in severe liver disease.

Discussion Only

Polypharmacy has become an important issue among patients with HCV mono-infection, and DDIs are one of the challenges in the DAA-based treatment of these patients [9,10]. The most frequently reported drug interactions modify drug metabolism by inducing or inhibiting the cytochrome P450, leading to abnormal drug exposure [10].

Many of the DDI studies have been performed in healthy volunteers, yet HCV-infected patients with cirrhosis may have impaired CYP450 capacity and higher plasma concentrations of CYP450 substrates compared to healthy individuals. This would mean that they are at even more risk for drug toxicity when a DDI occurs. In light of this, different profiles of potential drug-drug interactions have been hypothesized in patients with moderate-to-severe liver disease, however, few data are available for real-life patients [1113].

Our real-life data stress that potential DDIs are an important clinical issue for individuals treated with DAAs for chronic HCV infection. We found that a wide variety of drugs belonging to different classes were used, even wider than that reported by Siederdissen et al. [6], who conducted a single center survey and whose patients were around 10 years younger, presumably with fewer comorbidities than those in our cohort.

The profile of the patients in our study mirrored the epidemiology of HCV infection in Italy, whose prevalence is greatest among the elderly [14]. As a consequence, in our cohort, polypharmacy was relatively common in patients with mild liver disease as in those with moderate-to-severe liver disease. Of the patients with mild liver disease, 30% reported a potential Category 2 DDI, for which the most suitable approach is monitoring for the early detection of adverse events [6,15]. These data indicate that in patients with mild liver disease, through careful pre-treatment assessment of concomitant medications and monitoring or dose-modifications, significant DDIs can be avoided even in elderly patients who generally take multiple comedications for different comorbidities [10,1619]. However, the use of contraindicated comedications (Category 3 of DDI) should always be checked and, if present, an alternative comedication should be provided, regardless of the severity of liver impairment. Our data showed that none of the patients with mild liver disease were taking contraindicated comedications during DAA treatment, whereas 10% of the comedications were contraindicated in patients with moderate-to-severe liver disease. Patients with moderate-to-severe liver disease were a group of particular interest, due to the intersection between older age, comorbidities and severity of liver disease. In this study, 44% of patients with severe liver disease were affected by more than one DDI. Of these patients, 17% used comedications that are contraindicated in cases of severe liver damage, mainly because of the possible deterioration of liver disease. That these drugs were prescribed and the lack of important clinical outcomes during ongoing DAA therapy could be explained by the fact that all were classified with Child-Pugh A liver cirrhosis, which indicated that the liver impairment was not very severe. However, clinicians should be aware of the possible interactions reported for different comedications and DAAs, in particular in patients with severe liver impairment [20].

Our series showed that DAA regimens containing a protease inhibitor (3D combination with ritonavir or SOF/SIM) was associated with a higher risk for DDIs (38% and 32%, respectively), compared to other SOF-containing regimens (11–23%). Furthermore, these regimens were contraindicated in patients with advanced/decompensated liver cirrhosis. The mechanism of DDIs in patients receiving the 3D regimen can primarily be attributed to the ritonavir component of 3D, whose mechanism of action is to modify the metabolism of concomitant drugs, mainly increasing concomitant drug concentrations [16].

Warnings on the administration of comedications with the DAA regimens that include protease inhibitors (3D and Simeprevir regimens) were released in 2015, when our data were being collected, which, over time, may have increased the awareness of possible DDIs related to these regimens [15,21,22].

In general, regimens with the NS5B inhibitor sofosbuvir plus an HCV NS5A inhibitor (i.e., ledipasvir, daclatasvir), which do not affect CYP450, were relatively free of significant pharmacokinetic interactions, even in patients with moderate to severe liver impairment.
PPIs were the most frequently used comedication in our study (used in 19% and 34% of patients with mild and moderate-to-severe liver disease, respectively). The possible DDIs between PPIs and DAAs has been emphasized recently, given that gastric pH could affect DAA bioavailability due to increased or decreased pharmacokinetics, as reported for 3D and SOF/LDV and in other DAA regimens containing NS3/4A protease inhibitors, such as grazoprevir, and the NS5A inhibitor elbasvir [2326]. However, the finding of a post-hoc analysis provides reassurance that the co-administration of 3D and PPI does not negatively affect the chance of viral eradication [27].
In conclusion, hundreds of thousands of patients are currently being treated with DAAs, and, based on our real-life data, 30–44% of those taking comedications are at risk of a DDI. For several drugs, the recommendation related to a potential DDI depends on the severity of liver disease, and a careful evaluation of DDIs is required, particularly in patients with severe liver impairment. This stresses the need for increased awareness of this issue and for additional extensive research.

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Monday, September 26, 2016

A Review of Daclatasvir Drug-Drug Interactions

Review article
A Review of Daclatasvir Drug-Drug Interactions.
Garimella T, et al. Adv Ther. 2016

Adv Ther. 2016 Sep 23. [Epub ahead of print]

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The treatment of hepatitis C virus (HCV) infection has been revolutionized in recent years by the development of direct-acting antiviral regimens that do not contain peginterferon (pegIFN) and/or ribavirin (RBV). While direct-acting antiviral-based regimens have been shown to be greatly superior to pegIFN/RBV-based regimens in terms of efficacy and safety, they have a greater susceptibility to drug–drug interactions (DDIs).

Daclatasvir (DCV)—the benchmark pangenotypic nonstructural protein 5A inhibitor—has been shown to be efficacious and generally well tolerated in partnership with other HCV direct-acting antivirals, including sofosbuvir, asunaprevir (ASV), and ASV plus beclabuvir. DCV may be the object of a DDI via the induction or inhibition of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) by the concomitant medication, or the precipitant of a DDI via DCV-based induction/inhibition of CYP 3A4 or inhibition of P-gp, organic anion transporting polypeptide 1B1/B3, and/or breast cancer resistance protein.

This article presents an overview of the drug interaction studies conducted during the clinical development of DCV, the findings of these studies that led to the guidance on concomitant medication use and dosage along with any required DCV dose modifications, and the use of the known metabolic pathway of DCV to guide concomitant dosing where direct drug–drug studies have not been conducted. The robust characterization of the DCV clinical pharmacology program has demonstrated that DCV has few or no clinically relevant DDIs with medications with which it is likely to be co-administered, and the majority of DDIs that do occur can be predicted and easily managed.

Funding: Bristol-Myers Squibb.

KeywordsConcomitant medications Daclatasvir Drug–drug interactions Hepatitis C virus Infectious diseases

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Sunday, July 14, 2013

Meeting Report - 8th Hepatitis Pharmacology Workshop

Produced by

Meeting Report - 8th Hepatitis Pharmacology Workshop, Cambridge, USA.

Posted Thursday 11 July 2013

The objective of this workshop was to provide a platform for presentation and discussion of the latest developments in the field, to map all current studies and results, to translate new data to treatment guideline and to educate clinicians on how to best implement current and new drugs.

There were several presentations in Wednesday’s session on drug interactions with new HCV agents in development and one survey on drug interactions with the currently licensed DAAs, boceprevir and telaprevir. The session on Thursday saw presentations on the management of drug interactions in transplant patients and the challenge of treating HIV/HCV coinfected patients.

The meeting report below summarises the presentations relating to drug interactions and pharmacology. The abstract book and slides from the presentations are available to view on line on
the Virology Education website.

Click here for the meeting report (pdf format)

Simeprevir & TMC647055/r
Asunaprevir & Ketoconazole or Rifampicin
Daclatasvir & Midazolam
Daclatasvir and Sofosbuvir
MK ‐ 5172 & Methadone or Buprenorphine
Boceprevir & Telaprevir
BMS ‐ 791325, Daclatasvir & Asunaprevir
Pharmacology of Ledipasvir
Simeprevir & Food