uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Investigation of how Results of Clinical Drug- Drug Interaction Studies with Warfarin, Ethinylestradiol and Omeprazole Translate into Warning and Precaution Text in Drug Labels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2012 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Introduction: Warfarin, ethinylestradiol and omeprazole are among the most common drugs on the market worldwide. However, they are not faultless due to their great risk for interacting when coadministered with other drugs. A drug-drug interaction (DDI) is often described as an alternation in the mechanisms of a drugs pharmacokinetics (PK) or pharmacodynamics (PD).

Aim: The aim of this report was to investigate different DDI studies with warfarin, ethinylestradiol and omeprazole to understand how the results from these studies are translated into warning and precaution text in drug labels.

Materials and Methods: Published drug interaction studies and relevant drug labels were obtained from different databases. PK and PD parameters, such as AUC, Cmax, prothrombin time (PT) and/or international normalized ratio (INR) from published drug interaction studies with warfarin, ethinylestradiol (EE) and omeprazole are compiled in tables and presented as forest plots. In addition to the literature search a computer simulation with warfarin and fluconazole was conducted to see how, by means of adjusting the dose regimen can alter DDI.

Results: A total of 45 DDI studies with warfarin, EE and omeprazole were investigated. The majority of DDI were not considered clinically significant. However, warfarin dose adjustment is recommended when coadministered with fluconazole and amiodarone while coadministration of omeprazole with clopidogrel, raltegravir or saquinavir should be avoided. There is no data available saying how great the changes (%) in EE and warfarin could be, for when drug interactions become concerning. The simulation process showed that staggered administration and / or a 50 % reduction of the fluconazole dose resulted in a small reduction in the exposure of warfarin.

Conclusions: Even if studies and drug labels confirm presence of drug interactions, it doesn’t mean that all suffers from the consequences. Genetic factors, dose regimen and type of disease are factors and conditions that could enhance the risk for drug interactions.

Place, publisher, year, edition, pages
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-176608OAI: oai:DiVA.org:uu-176608DiVA: diva2:536046
External cooperation
AstraZeneca Mölndal
Subject / course
Drug Development
Available from: 2012-08-13 Created: 2012-06-21 Last updated: 2012-11-20Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Vojin, Sebastiana
By organisation
Department of Pharmaceutical Biosciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 247 hits
ReferencesLink to record
Permanent link

Direct link