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 zuclopenthixol 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 zuclopenthixol, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with zuclopenthixol (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.
Zuclopenthixol has a mean oral bioavailability [ F ] of 49%, which is why the maximum plasma levels [Cmax] tend to change with an interaction. The terminal half-life [ t12 ] is 20 hours and constant plasma levels [ Css ] are reached after approximately 80 hours. The protein binding [ Pb ] is 98% strong. The metabolism takes place via CYP2D6 and CYP3A4, among others.
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 zuclopenthixol nor abarelix increase serotonergic activity.
|Kiesel & Durán b||2||++||Ø|
Recommendation: As a precaution, attention should be paid to anticholinergic symptoms, especially after increasing the dose and at doses in the upper therapeutic range.
Rating: Zuclopenthixol modulates the anticholinergic system to a moderate extent. The risk of anticholinergic syndrome with this medication is rather low if the dosage is in the usual range. According to our knowledge, abarelix does not increase anticholinergic activity.
QT time prolongation
Rating: In combination, zuclopenthixol and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||zuc||aba|
|Tardive dyskinesia||0.2 %||0.2||n.a.|
|Cerebrovascular accident||0.0 %||0.0||n.a.|
|Neuroleptic malignant syndrome||0.0 %||0.0||n.a.|
|Abnormal ejaculation||0.0 %||0.0||n.a.|
|Erectile dysfunction||0.0 %||0.0||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 QT prolongation and associated arrhythmias, torsades de pointes (TdP), are considerable negative outcomes of many antipsychotic and antidepressant agents frequently used by psychiatric patients. Objective To identify the prevalence, levels, and predictors of QT prolonging drug-drug interactions (QT-DDIs), and AZCERT (Arizona Center for Education and Research on Therapeutics) classification of drugs involved in QT-DDIs. Setting Psychiatry wards of three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Method This was a multicenter cross-sectional study. Micromedex DrugReax was used for identification of QT-DDIs. TdP risks were identified by the AZCERT classification. Multivariate logistic regression analysis was performed to identify predictors of QT-DDIs. Main outcome measure Prevalence of QT-DDIs (overall, age-wise and gender-wise) and their levels of severity and documentation; AZCERT classes of drugs involved in QT-DDIs; and odds ratios for predictors of QT-DDIs. Results Of 600 patients, 58.5% were female. Median age was 25 years (IQR = 20-35). Overall 51.7% patients had QT-DDIs. Of total 698 identified QT-DDIs, most were of major-severity (98.4%) and fair-documentation (93.7%). According to the AZCERT classification, 36.4% of the interacting drugs were included in list-1 (known risk of TdP), 26.9% in list-2 (possible risk of TdP) and 27.5% in list-3 (conditional risk of TdP). Drugs commonly involved in QT-DDI were olanzapine (n = 146), haloperidol (138), escitalopram (122), risperidone (91), zuclopenthixol (87), quetiapine (n80) and fluoxetine (74). In multivariate logistic regression analysis, QT-DDIs were significantly associated with 6-7 prescribed medications (p = 0.04) and >7 medications (p = 0.03). Similarly, there was significant association of occurrence of QT-DDIs with 2-3 QT drugs (p < 0.001) and >3 QT drugs (p < 0.001). Conclusion A considerable number of patients are exposed to QT-DDIs in psychiatry. There is a need to implement protocol for monitoring the outcomes of QT-DDIs.