warfarin and tibolone

To investigate the potential drug interaction between tibolone and warfarin in healthy postmenopausal women.. The study was designed as a double-blind, randomized, placebo-controlled, two-way crossover study in postmenopausal women. After stabilization of the International Normalized Ratio (INR; a standardized prothrombin time, PT) between 1.4 and 2.0 with warfarin, subjects were randomized to receive either tibolone (2.5mg/day) or placebo for 21 days. After a 7-day wash-out period (during which warfarin treatment was continued) the treatments were crossed over. Primary efficacy parameters were INR and coagulation Factors II, VII, VIIa and X (means of measurements at Days 18 and 20 and Days 46 and 48). Treatment with tibolone induced a statistically significant increase in INR (estimate of mean difference=0.40; P=0.002), and a statistically significant decrease in coagulation factors. Treatments were generally well tolerated and no clinically significant adverse events were observed.. Tibolone enhances warfarin-induced anticoagulation in postmenopausal women, as reflected by increases in INR and decreases in coagulation Factors II, VII, VIIa and X, compared to placebo. It is advisable to monitor for changes in coagulation status during (and after discontinuation of) simultaneous use of tibolone and warfarin.

Topics: Aged; Anticoagulants; Blood Coagulation Factors; Cross-Over Studies; Double-Blind Method; Drug Synergism; Estrogen Receptor Modulators; Female; Humans; International Normalized Ratio; Middle Aged; Norpregnenes; Postmenopause; Warfarin

There is limited information regarding the interaction of hormone replacement therapy (HRT) and oral anticoagulants. Following the acute over-anticoagulation of two women shortly after the initiation of tibolone, we have undertaken a retrospective review of anticoagulated women to determine if the dose of oral anticoagulants and quality of anticoagulant control are affected by the introduction of HRT. We demonstrate that acute over-anticoagulation consistently occurs following the commencement of tibolone and requires anticoagulant dose modification to re-establish target international normalised ratio (INR). In contrast, non-tibolone HRT preparations do not consistently alter anticoagulant control or dose requirements.

Topics: Administration, Oral; Anticoagulants; Contraindications; Dose-Response Relationship, Drug; Drug Interactions; Estrogen Receptor Modulators; Female; Hormone Replacement Therapy; Humans; International Normalized Ratio; Norpregnenes; Phenindione; Warfarin