Use with caution.
Potential for decreased daclatasvir concentrations; clinical significance unknown. May be more relevant with high amounts of chronic garlic intake.
Daclatasvir primarily undergoes biotransformation by CYP3A4. Metabolites were present at minimal levels in the plasma (<5%). While BMS-805215 is an active metabolite, it is also 100-fold less potent than the parent compound. In the plasma, BMS-805215 accounts for only trace amounts to 2% of the drug.
In vitro studies demonstrate that daclatasvir is also a substrate of P-glycoprotein. Daclatasvir is actively transported into hepatocytes by OCT1 and other unidentified uptake transporters, but not by OAT2, NTCP, or OATPs.
Effect of Daclatasvir on Pharmacokinetics of Other Drugs
Daclatasvir is a weak CYP3A4 inducer. In general, dose adjustment of concomitantly administered CYP3A4 substrates is not necessary. Daclatasvir does not inhibit (IC50 >40 μM) CYP enzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 2D6.
Daclatasvir is an inhibitor of P-gp, organic anion transporting polypeptide (OATP) 1B1, organic cation transporter (OCT)1 and breast cancer resistance protein (BCRP). Co-administration of daclatasvir with substrates of P-gp, OATP 1B1, OCT1 or BCRP may produce an increase in their systemic exposure, potentially prolonging their therapeutic effect and risk of adverse reactions. Therefore, caution and regular monitoring for toxicity is recommended when daclatasvir is coadministered with the following agents with a narrow therapeutic range:
In vitro studies suggest that daclatasvir also inhibits renal uptake transporters, organic anion transporters (OAT) 1 and 3, but the inhibitory effects are not expected to be clinically relevant.
Effect of Other Drugs on Daclatasvir’s Pharmacokinetics
Strong CYP3A4 and P-gp inducers may lead to lower exposures of daclatasvir. Therefore, coadministration with the following agents is contraindicated.
Moderate CYP3A4 and P-gp inducers may decrease the plasma levels and therapeutic effect of daclatasvir.
Strong CYP3A4 inhibitors may increase plasma levels of daclatasvir. Therefore, dose adjustment of daclatasvir (i.e., decrease to 30mg daily) is recommended when coadministered with the following agents:
P-gp and OCT1 inhibitors are likely to a have limited effect on daclatasvir exposure. No dose adjustment is recommended.
Other Drug-Drug Interactions
Cardiac arrhythmias such as severe bradycardia has been reported in patients receiving amiodarone in combination with daclatasvir and sofosbuvir. An alternate antiarrhythmic agent should be considered. If amiodarone is administered with daclatasvir and sofosbuvir, close monitoring is required.
The usual dose of daclatasvir is 60 mg once daily with or without meals. Monotherapy with daclatasvir is not recommended.
Indication:
Treatment of chronic hepatitis C virus (HCV) infection in adults with HCV genotypes 1, 2, or 3* and compensate liver disease, including cirrhosis, in combination with other agents (as below).
Note 1: The safety and efficacy of daclatasvir have not been established for the following patient populations:
Note 2: Use of daclatasvir in patients with HCV genotype 3 infections has been issued marketing authorization with conditions, pending the results of a trial to confirm its clinical benefit.
HCV Genotype | Regimen | Duration |
Genotype 1 | ||
Treatment-naïve (a) or treatment-experienced (b) without cirrhosis | Daclatasvir + sofosbuvir | 12 weeks (e) |
Treatment-naïve or treatment-experienced with compensated cirrhosis (g) | 24 weeks (f) | |
Genotype 2 | ||
Treatment-naïve with or without compensated cirrhosis (d) | Daclatasvir + sofosbuvir | 24 weeks |
Treatment-experienced (c) without cirrhosis (d) | 24 weeks | |
Genotype 3 | ||
Treatment-naïve or treatment-experienced (c) without cirrhosis | Daclatasvir + sofosbuvir | 12 weeks |
Treatment-naïve or treatment-experienced (c) with compensated cirrhosis (d) | Daclatasvir + sofosbuvir | 24 weeks |
Genotype 4 (use is based on extrapolation from genotype 1 studies, per manufacturer) | ||
Without cirrhosis | Daclatasvir + sofosbuvir | 12 weeks (e) |
Compensated cirrhosis (d) | 24 weeks (f) | |
| Daclatasvir + peginterferon + ribavirin (weight-based) | 24 weeks of daclatasvir in combination w/ 24-48 weeks of peginterferon alfa and ribavirin (g) |
a. No prior exposure to any interferon, ribavirin, or other HCV-specific direct-acting antiviral agent. b. Prior null or partial response to an interferon- or protease inhibitor-based treatment. c. For the treatment of HCV genotype 2 and 3 infections, daclatasvir-sofosbuvir combination has only been studied in treatment-naïve patients with a treatment duration of 24 weeks. Clinical trial experience has been extrapolated to treatment-experienced patients. d. The addition of ribavirin to daclatasvir-sofosbuvir can be considered in patients with compensated cirrhosis. e. In patients with prior treatment (including NS3/4A inhibitor), consider treatment duration of 24 weeks f. In treatment-naïve patients with cirrhosis and positive prognostic factors (i.e., IL28B CC genotype, low baseline viral load), can consider treatment duration of 12 weeks g. Per SPC: · If the patient has HCV RNA undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for a total duration of 24 weeks. · If the patient achieves HCV RNA undetectable, but not at both treatment weeks 4 and 12, daclatasvir should be discontinued at 24 weeks and peginterferon alfa and ribavirin continued for a total duration of 48 weeks. · Refer to Summary of Product Characteristics regarding virologic treatment stopping rules. |
Dose Adjustment and Treatment Interruptions
Discontinuation
Dosage Adjustments when use with concomitant agents
Missed Doses
If the missed dose is remembered MORE than 20 hours after the scheduled dose, the dose should be skipped and the next dose should be taken at the appropriate time
The pharmacokinetic properties of daclatasvir were evaluated in healthy and HCV-infected adult subjects. Therapeutic drug concentrations of daclatasvir were achieved after 4 days of once-daily administration. At steady state, exposure to daclatasvir (at the 60 mg dose) was comparable between both groups (as below). Daclatasvir Cmax, AUC, and Cmin increased in a near dose-proportional manner.
Following multiple oral doses of daclatasvir 60 mg once daily in combination with peginterferon alfa and ribavirin:
Although data from clinical trials on patients greater than 65 years of age are limited, population pharmacokinetic analyses suggest that age had no apparent effect on daclatasvir exposures. Gender and race were identified as statistically significant covariates in these analyses; however, the magnitude of the effect on the pharmacokinetics of daclatasvir was not found to be clinically meaningful.
Induces CYP3A4.
Note: The web app has been optimized for the following browsers: Google Chrome, Apple Safari. Other web browsers (e.g. Mozilla Firefox, Internet Explorer, Opera, etc) may experience performance issues. Please use one of the optimized browser versions, or download our mobile application.
The information in this website/app is intended for use by and with experienced physicians and pharmacists. The information is not intended to replace sound professional judgment in individual situations, and should be used in conjunction with other reliable sources of information. Due to the rapidly changing nature of information about HIV treatment and therapies, users are advised to recheck the information contained herein with the original source before applying it to patient care. Decisions about particular medical treatments should always be made in consultation with a qualified medical practitioner knowledgeable about HIV-related illness and the treatments in question.
Neither Toronto General Hospital, Alberta Health Services, the Ottawa Hospital, nor the authors and contributors are responsible for deletions or inaccuracies in information or for claims of injury resulting from any such deletions or inaccuracies. Mention of specific drugs, drug doses or drug combinations within this website does not constitute endorsement by the authors, Toronto General Hospital, Alberta Health Services or the Ottawa Hospital.
The opinions expressed herein are those of its authors and do not necessarily reflect the views and opinions of Abbvie, Gilead Canada, Merck Canada Inc., and ViiV Healthcare.
We emphasize that program only checks for interactions between HIV or HCV drugs and other drugs, it will NOT check for interactions between sets of non-HIV or HCV drugs.
Also, program content focuses primarily on pharmacokinetic based interactions, and will not include comprehensive data on pharmacodynamics interactions, including QT prolongation.
Last updated: January 10, 2016
Please read these Terms, Conditions & Disclaimer carefully before using the www.hivclinic.ca website (the "Service") operated by Immunodeficiency Clinic ("us", "we", or "our").
By using this site, you signify your assent to these Terms and Conditions. If you do not agree to all of these Terms and Conditions of use, do not use this site. The Immunodeficiency Clinic may revise and update these Terms and Conditions without notice at any time. Your continued usage of the Immunodeficiency Clinic Web site (the "site") will mean you accept those changes.
Any Web sites linked from the site are created by organizations outside the Immunodeficiency Clinic. Those organizations are responsible for the information contained within their sites. We do not recommend and do not endorse the content on any third-party websites. We are not responsible for the content of linked third-party sites or third-party advertisements and do not make any representations regarding their content or accuracy. Your use of third-party websites is at your own risk and subject to the terms and conditions of use for such sites. Any specific comments regarding these sites should be directed to that individual organization.
These Terms shall be governed and construed in accordance with the laws of Ontario, Canada, without regard to its conflict of law provisions. Our failure to enforce any right or provision of these Terms will not be considered a waiver of those rights. If any provision of these Terms is held to be invalid or unenforceable by a court, the remaining provisions of these Terms will remain in effect. These Terms constitute the entire agreement between us regarding our Service, and supersede and replace any prior agreements we might have between us regarding the Service.
We reserve the right, at our sole discretion, to modify or replace these Terms at any time. If a revision is material we will try to provide at least 30 days notice prior to any new terms taking effect. What constitutes a material change will be determined at our sole discretion. By continuing to access or use our Service after those revisions become effective, you agree to be bound by the revised terms. If you do not agree to the new terms, please stop using the Service.
Thank you for visiting the HIV/HCV Drug Therapy Guide housed on the Toronto General Hospital Immunodeficiency Clinic Web site. General aggregate user data that will be tracked for both the web-based and mobile applications includes country of origin, new vs. returning visitor to the site, browsers used and sections of the guide that are used most frequently. Any identifying personal information will not be collected.
Accessing information from the HIV/HCV Drug Therapy Guide: This web-based application is housed on the Toronto General Hospital Immunodeficiency Clinic Web site at app.hivclinic.ca. Future updates will include an application for mobile devices also.
The Toronto General Hospital website has been in operation since 2000. The main objectives of the drug information portion of the website/app are to provide a comprehensive and centralized repository of current data on HIV/HCV drug therapy for health care professionals with a main focus on drug interactions, and to promote safe and rational prescribing of antiretrovirals and directly acting antivirals. The website/app content is updated regularly, and includes information from key international HIV/HCV conferences and recent publications in the medical/pharmacy literature.
The primary editors of the website/app content are:
The ongoing contributions of Michelle Foisy, PharmD, founding co-editor, as well as the following people are also gratefully acknowledged: Michelle Bender, Alison Wong, Bill Cornish, Margaret Ackman, Tony Antoniou, Cara Hills-Nieminen, Natalie Dayneka, Dominic Martel, Denise Kreutzwiser, Cherry Hui, Sanjeev Sockalingham.
Contact us at: app@hivclinic.ca
HIV/HCV Drug Therapy Guide. UHN- Toronto General Hospital, Immunodeficiency Clinic; 2022 [insert date cited e.g. cited 2022 Jan 10]. Available from: https://app.hivclinic.ca/
Thank you for visiting. We hope you find your visit to be worthwhile and useful.
Please submit application error reports here for correction by webmaster Tom Tranmer.
Please select below to enable or disable visible sections for print output. Your printout will also depend on what you have opened on the screen when you click the print button.