Published: 20-08-2019 13:17 | Updated: 30-09-2019 12:38

Clinically important interactions associated with warfarin treatment

Researchers at Karolinska Institutet now quickly generate new knowledge on clinically important drug-drug interactions associated to the anticoagulant warfarin.

By a newly established register-based cohort, unique opportunities to study interactions associated to the anticoagulant warfarin in large groups of individuals has been created. The research is based on a cooperation between associate professors Buster Mannheimer, Department of Clinical Science and Education, Södersjukhuset and Jonatan D Lindh, Department of Laboratory Medicine.

Warfarin is used to treat patients with an increased risk of thromboembolism following for example an atrial fibrillation. Being prone for a narrow therapeutic window, small changes in warfarin concentrations for example due to codispensed drugs, may lead to an increased or decreased anticoagulation, potentially with devastating consequences.

The research has contributed to an increased knowledge on the effect due to several less well characterized interactions. Thus, the researchers were able to show that four of five warfarin-treated patients, in whom cotreatment with carbamazepine was initiated, faced an anticoagulation falling below the recommended effect (INR < 2), within 3–5 weeks [1].

In a project executed by PhD student Johan Holm, the initiation of amiodarone, an inhibitor of several enzymes of importance for the clearance of warfarin, instead resulted in an increased anticoagulant effect (INR > 3) in one individual out of three [2].

Recently the effect following two interactions where knowledge up to now has been essentially absent was investigated. By studying over 5000 individuals on warfarin initiating treatment with simvastatin it was clear that the anticuagulation subsequently was significantly increased. Even though the effect was moderate, the proportion of individuals above the recommended level doubled [3].

In the most recent project, the anticoagulative effect in almost 6000 individuals initiating flucloxacillin was investigated. One in three patients with 10 days flucloxacillin and almost two in three patients initiating long-term treatment, was exposed to a subsequent subtherapeutic anticoagulant effect [4].

Over the last few years, due to the introduction of new types of anticoagulants with other modes of action (NOAKs), the relative importance of warfarin has decreased. However, also in the future, large groups of patients will depend on a safe warfarin treatment. Therefore, the studies are important to avoid major unnecessary bleedings as well as thromboembolic events among a fragile group of individuals.


Buster Mannheimer Senior Lecturer