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 degarelix and abarelix. 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 degarelix, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with degarelix (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.
Degarelix has a low oral bioavailability [ F ] of 35%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is rather long at 1008 hours and constant plasma levels [ Css ] are only reached after more than 4032 hours. The protein binding [ Pb ] is moderately strong at 90%. The metabolism does not take place via the common cytochromes.
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.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither degarelix nor abarelix increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither degarelix nor abarelix increase anticholinergic activity.
QT time prolongation
Rating: In combination, degarelix and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||deg||aba|
|Weight gain||9.0 %||9.0||n.a.|
|Elevated GGT||1.0 %||+||n.a.|
|Hypersensitivity reaction||0.0 %||0.01||n.a.|
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: BACKGROUND AND OBJECTIVES: Degarelix is a gonadotropin-releasing hormone antagonist registered for the treatment of advanced hormone-dependent prostate cancer. Treatment causing androgen deprivation is associated with QT prolongation and this study investigated whether degarelix at supratherapeutic concentrations has an intrinsic effect per se on cardiac repolarisation and the QT interval. METHODS: This was a single-centre, randomised, crossover study comparing the effect of degarelix, placebo, and the positive control moxifloxacin on the QT interval. Degarelix and placebo treatments were double-blind, whereas moxifloxacin treatment was open-label. Eighty healthy men, aged 18-45 years, received single intravenous doses of degarelix 2.8 mg, and placebo, as well as a single oral dose of moxifloxacin 400 mg. Electrocardiograms were collected up to 24 h after the start of administration, with the QT interval assessed and plasma concentrations of degarelix concomitantly analysed. RESULTS: Time-matched, one-sided 95% upper confidence boundaries for baseline-corrected average changes from placebo for the QT interval, corrected using the Fridericia method (ΔΔQTcF), did not exceed 10 ms at any timepoint, with maximum degarelix concentrations reaching approximately threefold the concentrations seen in the treatment of prostate cancer. Furthermore, concentration-exposure analysis indicated absence of any QT prolongation effects of degarelix. No significant effect on any other cardiac parameter was observed. The lower bound of the 98.3% confidence interval for moxifloxacin ΔΔQTcF exceeded 5 ms, thus verifying assay sensitivity. CONCLUSION: The results showed that the study was validated to detect a significant effect on the QT interval, and that degarelix by itself does not have any effect on the QT interval and cardiac repolarisation at supratherapeutic concentrations.