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 melperon. 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 melperon (100%). We do not expect any change in exposure for melperon, 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.
The bioavailability of melperon is unknown. Protein binding [ Pb ] is not known. The metabolism does not take place via the common cytochromes.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor melperon increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor melperon increase anticholinergic activity.
QT time prolongation
Rating: In combination, abarelix and melperon can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||mel|
|Tardive dyskinesia||1.0 %||n.a.||+|
|Orthostatic hypotension||0.0 %||n.a.||0.1|
|Cholestatic hepatitis||0.0 %||n.a.||0.1|
Elevated transaminases: melperon
Neuroleptic malignant syndrome: melperon
Thromboembolic disorder: melperon
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: Antipsychotic drugs (AD) are effective and frequently prescribed to more females than males. AD may cause serious cardiovascular side-effects, including prolonged QT interval, eventually leading to torsades de pointes (TdP) and sudden death. Epidemiologic data and case-control studies indicate an increased rate of sudden death in psychiatric patients taking AD. This review summarizes current knowledge about the QT prolonging effects of AD and gives practical suggestions. Amisulpride, clozapine, flupenthixol, fluphenazine, haloperidol, melperone, olanzapine, perphenazine, pimozide, quetiapine, risperidone, sulpiride, thioridazine and ziprasidone cause a QT prolongation ranging from 4 ms for risperidone to 30 ms for thioridazine. Our knowledge about the QT-prolonging effects of many AD is still limited. Females are under-represented in most studies. Many studies were conducted or supported by pharmaceutical companies. To avoid prodysrhythmia caused by QT prolongation, other factors influencing QT interval have to be considered, such as other drugs affecting the same pathway, hypokalemia, hypomagnesemia, bradycardia, increased age, female sex, congestive heart failure and polymorphisms of genes coding ion channels or enzymes involved in drug metabolism. Because the response of a patient to AD is individual, an electrocardiogram recording the QT interval has to be performed at baseline, after AD introduction and after occurrence of any factor that might influence the QT interval.
Abstract: AIMS: Drug-induced long QT syndrome (diLQTS) leading to Torsade de Pointes (TdP) is a potentially lethal condition, which has led to several post-marketing drug withdrawals in the past decade. The true incidence of diLQTS/TdP is largely unknown. One explanation is under-reporting of this potentially life-threatening adverse event by physicians and other medical staff to pharmacovigilance agencies. To gain more insight into the incidence of diLQTS and TdP, the Berlin Pharmacovigilance Center (PVZ-FAKOS) has actively and prospectively identified patients who developed this particular type of drug-induced adverse event. Here, the basic characteristics of the affected patients are summarized and suspected drugs are discussed. Furthermore, an extrapolation of the Berlin incidence rates to the German Standard Population is presented. METHODS AND RESULTS: Using a Berlin-wide network of 51 collaborating hospitals (>180 clinical departments), adult patients presenting with long QT syndrome (LQTS/TdP) between 2008 and 2011 were identified by active surveillance of these hospitals. Drug exposures as well as other possible risk factors were obtained from the patient's files and in a face-to-face interview with the patient. One-hundred and seventy patients of possible LQTS/TdP were reported to the Pharmacovigilance Center of whom 58 cases were confirmed in a thorough validation process. The majority (66%) of these cases were female and 60% had developed LQTS/TdP in the outpatient setting. Thirty-five (60%) of 58 confirmed cases were assessed as drug-related based on a standardized causality assessment applying the criteria of the World Health Organization. Drugs assessed as related in more than two cases were metoclopramide, amiodarone, melperone, citalopram, and levomethadone. The age-standardized incidence of diLQTS/TdP in Berlin was estimated to be 2.5 per million per year for males and 4.0 per million per year for females. CONCLUSION: While European annual reporting rates based on spontaneous reports suggest an annual diLQTS/TdP incidence of 0.26 per million in Germany, we estimated a considerably higher incidence of diLQTS/TdP in an active surveillance approach. Further measures are warranted to better sensitize physicians against this potentially life-threatening drug-induced adverse event.