Clinical assessment of potential drug interactions of faldaprevir, a hepatitis C virus protease inhibitor, with darunavir/ritonavir, efavirenz, and tenofovir.
- Sabo JP Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.
- Kort J Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.
- Ballow C Buffalo Clinical Research Center, New York.
- Haschke M University Hospital Basel, Switzerland.
- Battegay M University Hospital Basel, Switzerland.
- Fuhr R PAREXEL International GmbH, Berlin, Germany.
- Girlich B Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland.
- Schobelock M Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.
- Feifel U Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim.
- Lang B Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany.
- Li Y Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.
- Elgadi M Boehringer Ingelheim Ltd, Burlington, Ontario, Canada.
- 2014-08-06
Published in:
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - 2014
HCV
HIV
antiretrovirals
drug–drug interactions
faldaprevir
Adenine
Adult
Anti-HIV Agents
Antiretroviral Therapy, Highly Active
Benzoxazines
Coinfection
Darunavir
Drug Interactions
Female
HIV Infections
HIV-1
Healthy Volunteers
Hepacivirus
Hepatitis C
Humans
Male
Middle Aged
Oligopeptides
Organophosphonates
Protease Inhibitors
Ritonavir
Sulfonamides
Tenofovir
Thiazoles
Young Adult
English
BACKGROUND
Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. Studies were performed to investigate potential drug interactions between faldaprevir and the commonly used antiretrovirals darunavir/ritonavir, efavirenz, and tenofovir to guide the coadministration of faldaprevir with these agents in human immunodeficiency virus/HCV-coinfected patients.
METHODS
In 3 open-label, phase 1 pharmacokinetic (PK) studies, healthy adult volunteers received (1) darunavir/ritonavir (800 mg/100 mg once daily) with and without faldaprevir (240 mg once daily); (2) faldaprevir (240 mg twice daily) with and without efavirenz (600 mg once daily); or (3) faldaprevir (240 mg twice daily) or tenofovir (300 mg once daily) alone and in combination. To assess potential drug interactions, geometric mean ratios and 90% confidence intervals for PK parameters were calculated. Safety was evaluated.
RESULTS
Efavirenz decreased faldaprevir area under the concentration-time curve (AUC) by 35%, Cmax by 28%, and Cmin by 46%, consistent with induction of CYP3A by efavirenz. Tenofovir decreased faldaprevir AUC by 22%, which was not considered to be clinically relevant. Faldaprevir had no clinically relevant effects on darunavir or tenofovir PK (15% and 22% AUC increase, respectively). Adverse events were consistent with the known safety profiles of faldaprevir and the antiretrovirals being examined.
CONCLUSIONS
No clinically significant interactions were observed between faldaprevir and darunavir/ritonavir or tenofovir. A potentially clinically relevant decrease in faldaprevir exposure was observed when coadministered with efavirenz; this decrease can be managed using the higher of the 2 faldaprevir doses tested in phase 3 trials (240 mg once daily as opposed to 120 mg once daily).
Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. Studies were performed to investigate potential drug interactions between faldaprevir and the commonly used antiretrovirals darunavir/ritonavir, efavirenz, and tenofovir to guide the coadministration of faldaprevir with these agents in human immunodeficiency virus/HCV-coinfected patients.
METHODS
In 3 open-label, phase 1 pharmacokinetic (PK) studies, healthy adult volunteers received (1) darunavir/ritonavir (800 mg/100 mg once daily) with and without faldaprevir (240 mg once daily); (2) faldaprevir (240 mg twice daily) with and without efavirenz (600 mg once daily); or (3) faldaprevir (240 mg twice daily) or tenofovir (300 mg once daily) alone and in combination. To assess potential drug interactions, geometric mean ratios and 90% confidence intervals for PK parameters were calculated. Safety was evaluated.
RESULTS
Efavirenz decreased faldaprevir area under the concentration-time curve (AUC) by 35%, Cmax by 28%, and Cmin by 46%, consistent with induction of CYP3A by efavirenz. Tenofovir decreased faldaprevir AUC by 22%, which was not considered to be clinically relevant. Faldaprevir had no clinically relevant effects on darunavir or tenofovir PK (15% and 22% AUC increase, respectively). Adverse events were consistent with the known safety profiles of faldaprevir and the antiretrovirals being examined.
CONCLUSIONS
No clinically significant interactions were observed between faldaprevir and darunavir/ritonavir or tenofovir. A potentially clinically relevant decrease in faldaprevir exposure was observed when coadministered with efavirenz; this decrease can be managed using the higher of the 2 faldaprevir doses tested in phase 3 trials (240 mg once daily as opposed to 120 mg once daily).
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1093/cid/ciu616
- PMID 25091302
- Persistent URL
- https://sonar.ch/global/documents/232342
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