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 vardenafil. 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 vardenafil (100%). We do not expect any change in exposure for vardenafil, 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.
Vardenafil has a low oral bioavailability [ F ] of 15%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is rather short at 4.5 hours and constant plasma levels [ Css ] are reached quickly. The protein binding [ Pb ] is moderately strong at 95%. The metabolism takes place via CYP2C9 and CYP3A4, among others.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor vardenafil increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor vardenafil increase anticholinergic activity.
QT time prolongation
Rating: In combination, abarelix and vardenafil can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||var|
|Hearing loss||1.9 %||n.a.||1.9|
|Chest pain||1.9 %||n.a.||1.9|
|Myocardial infarction||1.9 %||n.a.||1.9|
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: QT correction factors (QTc) can cause errors in the interpretation of drug effects on cardiac repolarization because they do not adequately differentiate changes when heart rate or autonomic state deviates from the baseline QT/RR interval relationship. The purpose of our study was to determine whether the new method of QT interval dynamic beat-to-beat (QTbtb) analysis could better discriminate between impaired repolarization caused by moxifloxacin and normal autonomic changes induced by subtle reflex tachycardia after vardenafil. Moxifloxacin produced maximum mean increases of 13-14 ms in QTbtb, QTcF, and QTcI after 4 h. After vardenafil administration, a 10-ms effect could be excluded at all time points with QTbtb but not with QTcF or QTcI. Subset analysis of the vardenafil upper pharmacokinetic quartile showed that the upper bound of QTcF and QTcI was >10 ms, whereas that of QTbtb was <8 ms. This study demonstrated that newer methods of electrocardiogram (ECG) analysis can differentiate changes in the QT interval to improve identification of proarrhythmia risk.
Abstract: OBJECTIVES: This study was conducted to compare the effect of CYP3A5*3 genotype on the disposition of three phosphodiesterase type 5 inhibitors (PDE5Is), vardenafil, sildenafil, and udenafil, because our previous in-vitro microsomal incubation study showed that the relative contribution of CYP3A5 enzyme to their metabolism was different among these PDE5Is. METHODS: An open-label three-way crossover study was performed with a single oral dose of PDE5Is (20 mg vardenafil, 100 mg sildenafil, or 200 mg udenafil) in 21 healthy men carrying CYP3A5*1/*1, *1/*3, or *3/*3. After each dose, plasma concentrations of the parents and their major metabolites were measured up to 24 or 48 h. RESULTS: The AUC(∞) and C(max) of vardenafil were 2.9-fold and 3.1-fold higher in CYP3A5*3/*3 carriers than in individuals with CYP3A5*1/*1 (P=0.003 and 0.002, respectively). The AUC(∞) and C(max) of sildenafil were 1.5-fold and 1.7-fold higher in CYP3A5*3/*3 carriers compared with individuals with CYP3A5*1/*1, but the statistical difference of both parameters among genotype groups was not observed. The disposition of udenafil differed little among groups in relation to the CYP3A5*3 allelic variant. CONCLUSION: These results suggest that the disposition of these PDE5Is are differently influenced by the CYP3A5*3 genotype of individual participants. The CYP3A5*3 genotype affects the oral disposition of vardenafil significantly. The pharmacokinetic diversity of PDE5Is in relation to CYP3A5 genotype may lead to the clinical response variation and remains to be evaluated.
Abstract: No Abstract available