QT time prolongation
Adverse drug events
Variants ✨For the computationally intensive evaluation of the variants, please choose the paid standard subscription.
Explanations of the substances for patients
We have no additional warnings for the combination of eribulin 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 eribulin, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with eribulin (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 eribulin is unknown. Protein binding [ Pb ] is not known. 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 eribulin nor abarelix increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither eribulin nor abarelix increase anticholinergic activity.
QT time prolongation
Rating: In combination, eribulin and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||eri||aba|
|Peripheral neuropathy||32.0 %||32.0||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: Several cancer therapies can prolong cardiac repolarization. This study assessed the potential of eribulin to affect cardiac repolarization in patients with advanced solid tumors. METHODS: In this Phase I, open-label, single-arm study, patients received eribulin mesylate (1.4 mg/m(2); Days 1 and 8 of a 21-day cycle). The primary objective was to assess the effect of eribulin on the QTcF pre- and post-infusion; QTcF and QTcNi were compared for ability to remove heart-rate dependence of the QT interval. Relationship between concentration of eribulin and ΔQTc was explored using linear mixed-effects analysis. Secondary objectives explored pharmacokinetics, safety, and tolerability. RESULTS: Twenty-six patients were enrolled. QTcNi was more effective than QTcF in correcting for heart-rate dependency of the QT interval. On Day 1, mean ΔQTcNi were ~0 at all timepoints. An apparent time-dependent increase in ΔQTc was observed: on Day 8, changes from baseline were larger and more variable, without clear relation to plasma levels of eribulin. Day 8 predose ΔQTcNi was 5 ms, post-infusion mean values ranged from 2 to 9 ms (largest mean ΔQTcNi at 6 h). No new or unexpected toxicities were reported. CONCLUSION: Eribulin demonstrated an acceptable safety profile and a minor prolongation of QTc not expected to be of clinical concern in oncology patients.
Abstract: PURPOSE: To evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors. METHODS: Patients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m(2) (except cycle 1 day 1, 1.4 mg/m(2)); severe, 0.7 mg/m(2); normal, 1.4 mg/m(2). RESULTS: Nineteen patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m(2) in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m(2) in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events. CONCLUSIONS: Renal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal impairment. CLINICALTRIALS. GOV IDENTIFIER: NCT01418677.