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 eliglustat. Please also consult the relevant specialist information.
|Eliglustat||1 [0.41,5.35] 1||1|
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 eliglustat (100%). We do not expect any change in exposure for eliglustat, when combined with abarelix (100%). The AUC is between 41% and 535% depending on the CYP2D6
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.
Eliglustat has a low oral bioavailability [ F ] of 5%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is 6.5 hours and constant plasma levels [ Css ] are reached after approximately 26 hours. The protein binding [ Pb ] is moderately strong at 79.5%. which is why, with a mean hepatic extraction rate of 0.63, both liver blood flow [Q] and a change in protein binding [Pb] are relevant. The metabolism takes place via CYP2D6 and CYP3A4, among others and the active transport takes place in particular via PGP.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor eliglustat increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor eliglustat increase anticholinergic activity.
QT time prolongation
Rating: In combination, abarelix and eliglustat can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||eli|
|Musculoskeletal pain||11.0 %||n.a.||11.0|
|Abdominal pain||10.0 %||n.a.||10.0|
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: Gaucher disease (GD) is a lysosomal storage disorder caused by the deficient activity of acid beta glucosidase, with consequent accumulation of glucosylceramide in the spleen, liver, bone marrow, and various organs and tissues. Currently, the gold standard for GD treatment is enzyme replacement therapy (ERT). The efficacy of ERT in improving or stabilizing the visceral and hematological symptoms of GD is well-proven. However, since ERT has to be administered by frequent intravenous infusions, this therapeutic approach has an important impact on the patient's quality of life. Eliglustat tartrate is a new substrate reduction therapy for GD, which acts as a specific and potent inhibitor of glucosylceramide synthase and can be administered orally. This review summarizes the results of the preclinical and clinical trials, which experimented with eliglustat, and discusses its possible role in the management of GD, when compared to the currently available treatments and the new experimental approaches.
Abstract: Eliglustat is an oral glucosylceramide synthase inhibitor indicated for the long-term treatment of adults with Gaucher disease type 1 and CYP2D6 extensive, intermediate, or poor metabolizer phenotypes. Eliglustat is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4 and is a substrate of P-glycoprotein (P-gp). Three studies evaluated the effects of paroxetine (strong CYP2D6 inhibitor), ketoconazole (strong CYP3A4 and P-gp inhibitor), and rifampin (strong CYP3A4/P-gp inducer; OATP inhibitor) on the pharmacokinetics of orally administered eliglustat in healthy adults. An 8.9-fold increase in eliglustat exposure following co-administration of multiple-dose eliglustat and paroxetine is attributed to inhibition of CYP2D6-mediated metabolism of eliglustat by paroxetine. A 4.3-fold increase in eliglustat exposure following co-administration of multiple-dose eliglustat and ketoconazole is attributed to inhibition of CYP3A4-mediated metabolism and/or P-gp-mediated transport of eliglustat by ketoconazole. Co-administration of eliglustat with oral doses of rifampin reduced eliglustat exposure by >85% due to induction of CYP3A4/P-gp by rifampin, while a single intravenous dose of rifampin had no effect on eliglustat, confirming that eliglustat is not an OATP substrate. Depending on CYP2D6 metabolizer phenotype, co-administration of eliglustat with CYP2D6 and/or CYP3A inhibitors or CYP3A inducers may alter eliglustat exposure, warrant dosage adjustment or use with caution, or be contraindicated.