QT time prolongation
Adverse drug events
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Explanations of the substances for patients
We have no additional warnings for the combination of abarelix and betrixaban. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We do not expect any change in exposure for abarelix, when combined with betrixaban (100%). We do not expect any change in exposure for betrixaban, when combined with abarelix (100%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
The bioavailability of abarelix is unknown. The terminal half-life [ t12 ] is rather long at 316.8 hours and constant plasma levels [ Css ] are only reached after more than 1267.2 hours. The protein binding [ Pb ] is 97.5% strong. The metabolism via cytochromes is currently still being worked on.
Betrixaban has a low oral bioavailability [ F ] of 34%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is 23 hours and constant plasma levels [ Css ] are reached after approximately 92 hours. The protein binding [ Pb ] is rather weak at 60%. which is why, with a mean hepatic extraction rate of 0.38, both liver blood flow [Q] and a change in protein binding [Pb] are relevant. The metabolism does not take place via the common cytochromes and the active transport takes place in particular via PGP.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor betrixaban increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor betrixaban increase anticholinergic activity.
QT time prolongation
Rating: In combination, abarelix and betrixaban can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||bet|
|Gastrointestinal hemorrhage||0.0 %||n.a.||0.1|
|Intracranial hemorrhage||0.0 %||n.a.||0.1|
Based on your answers and scientific information, we assess the individual risk of undesirable side effects. These recommendations are intended to advise professionals and are not a substitute for consultation with a doctor. In the restricted test version (alpha), the risk of all substances has not yet been conclusively assessed.
Abstract: OBJECTIVE: To evaluate the effects of the anticoagulant betrixaban on individual heart rate-corrected QT (QTcI). RESEARCH DESIGN AND METHODS: Ninety-six healthy adults were randomly assigned to single-dose betrixaban 80 and 140 mg (therapeutic and supratherapeutic doses, respectively), placebo, and moxifloxacin 400 mg (positive control) in a four-period crossover study. Electrocardiograms were recorded at pre-dose and post-dose hours 1, 2, 3, 4, 5, 6, 8, 12, 16 and 24. MAIN OUTCOMES MEASURES: An analysis of covariance determined the placebo-corrected, time-matched mean change from baseline QTcI at the 95% upper confidence interval (UCI; one-sided). The pre-specified clinically significant change for betrixaban-treated groups was > 10 ms (95% UCI, one-sided). Subjects were monitored for safety and tolerability. RESULTS: Mean QTcI change was < 10 ms for both betrixaban groups at all time points; expected changes were observed for moxifloxacin, establishing assay sensitivity. Correlation between betrixaban plasma concentration and QTcI duration confirmed the absence of effect on QT. CONCLUSIONS: Betrixaban at therapeutic and supratherapeutic doses did not cause clinically relevant changes in QTcI intervals or other electrocardiographic parameters. Betrixaban was well tolerated.
Abstract: A recent survey on the use of direct oral anticoagulants (DOACs) revealed that 43% of patients with atrial fibrillation and renal impairment were potentially overdosed and had a hazard ratio for major bleeding of 2.19. In this review, we analyse and discuss the effect of renal failure on the pharmacokinetics and pharmacodynamics of DOACs and of strategies proposed to adjust doses according to the level of renal dysfunction. The pharmacokinetic characteristics of available DOACs (dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban) differ substantially as regards oral bioavailability, plasma protein binding and the relative involvement of renal and non-renal elimination. In this respect, 80% of dabigatran is excreted as an unchanged drug in urine, whereas edoxaban, rivaroxaban, apixaban and betrixiban are excreted unchanged by, respectively, 50, 33, 27 and 11% of the dose. Therefore, drug exposure (the area under the concentration-time curve, AUC) is expected to increase to differing extents, depending on the residual renal function and the contribution of the kidneys to the excretion of each drug. Our analysis found that the increased AUC in patients with severe renal dysfunction was greater than expected in the case of dabigatran, betrixaban and rivaroxaban, indicating that other pharmacokinetic parameters may be altered besides renal clearance. Although DAOC pharmacodynamics do not seem to be altered by renal diseases (the correlation between plasma levels and anticoagulant effects overlaps that of healthy subjects), renal failure per se is associated with an increased risk of bleeding and thromboembolism. Guidelines on dose adjustments in patients with renal dysfunction have been published by three National Drug Agencies (FDA, EMA, HC), but many of their items do not match one another, reflecting our substantial paucity of knowledge in advanced renal failure. Routine monitoring of DOAC anticoagulant effects or plasma concentrations is not recommended, since no validated therapeutic ranges have been established. However, this approach may be useful in emergency situations such as bleeding or thrombotic events, urgent surgery, pharmacokinetic interactions, etc. We conclude that more experimental work is needed to improve our knowledge of DOAC pharmacology in renal failure and to provide clinicians with valid tools to adjust therapy.