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 inotuzumab 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 inotuzumab, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with inotuzumab (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 inotuzumab is unknown. The terminal half-life [ t12 ] is rather long at 295.2 hours and constant plasma levels [ Css ] are only reached after more than 1180.8 hours. The protein binding [ Pb ] is 97% strong. The metabolism does not take place via the common cytochromes and the active transport takes place in particular via PGP.
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 inotuzumab nor abarelix increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither inotuzumab nor abarelix increase anticholinergic activity.
QT time prolongation
Rating: In combination, inotuzumab and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||ino||aba|
|Abdominal pain||23.0 %||23.0||n.a.|
Elevated GGT (21%): inotuzumab
Hyperbilirubinemia (21%): inotuzumab
Veno occlusive disease of the liver (14%): inotuzumab
Elevated ALT: inotuzumab
Elevated AST: inotuzumab
Lymphocytopenia (18%): inotuzumab
Hemorrhage (5%): inotuzumab
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: AIM: The aim of this study was to characterize the effect of inotuzumab ozogamicin on QT interval in patients with B-cell malignancies. METHODS: Data were pooled from three clinical studies including 250 patients (n = 2743) who received inotuzumab ozogamicin monotherapy. Patients with relapsed/refractory acute lymphoblastic leukaemia (NCT01564784 and NCT01363297) received 1.8 mg m,per cycle in divided doses (mean C,371 ng ml,; considered therapeutic) and patients with relapsed/refractory non-Hodgkin lymphoma (NCT00868608) received 1.8 mg m,per cycle as a single dose (mean C,569 ng ml,; considered supratherapeutic). Triplicate 12-lead electrocardiograms were performed at baseline and predefined time points postdose with paired pharmacokinetic collections. The exposure-response relationship between corrected QT interval (QTc: QT interval corrected using population-specific formula [QTcS] or QT interval corrected using Fridericia's formula [QTcF]) and inotuzumab ozogamicin concentration was characterized using a linear mixed-effects model, and simulations were performed using the final validated model. Full model development involved testing for covariates that may account for part of the identified variability. RESULTS: QTc intervals had a small but positive correlation with inotuzumab ozogamicin concentration. Based on 1000 simulations, median (upper 95% CI) QTcS and QTcF changes from baseline were <10 ms at both therapeutic (2.70 ms [5.40 ms] and 2.53 ms [4.92 ms], respectively) and supratherapeutic (4.14 ms [8.28 ms] and 3.87 ms [7.54 ms], respectively) concentrations. CONCLUSIONS: Inotuzumab ozogamicin (1.8 mg m,per cycle) is not predicted to pose a clinically significant safety risk for QT prolongation in patients with acute lymphoblastic leukaemia or non-Hodgkin lymphoma.