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 flupentixol 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 flupentixol, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with flupentixol (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.
Flupentixol has a mean oral bioavailability [ F ] of 48%, which is why the maximum plasma levels [Cmax] tend to change with an interaction. The terminal half-life [ t12 ] is rather long at 35 hours and constant plasma levels [ Css ] are only reached after more than 140 hours. The protein binding [ Pb ] is very strong at 99%. 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 flupentixol nor abarelix increase serotonergic activity.
|Kiesel & Durán b||1||+||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: Flupentixol only has a mild effect on the anticholinergic system. 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, flupentixol and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||flu||aba|
|Weight gain||1.0 %||+||n.a.|
|Disturbance of attention||1.0 %||+||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: The clinical pharmacokinetics of the 4 depot antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol decanoate, clopenthixol decanoate and flupenthixol decanoate) are reviewed. The proper study of these agents has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma. Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to injectable therapy are discussed. The depot antipsychotics are synthesised by esterification of the active drug to a long chain fatty acid and the resultant compound is then dissolved in a vegetable oil. The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate. Fluphenazine is available as both an enanthate and decanoate ester (both dissolved in sesame oil), although the decanoate is more commonly used clinically. The enanthate produces peak plasma concentrations on days 2 to 3 and declines with an apparent elimination half-life (i.e. the half-time of the apparent first-order decline of plasma concentrations) of 3.5 to 4 days after a single injection. The decanoate produces an early high peak which occurs during the first day and then declines with an apparent half-life ranging from 6.8 to 9.6 days following a single injection. After multiple injections of fluphenazine decanoate, however, the mean apparent half-life increases to 14.3 days, and the time to reach steady-state is 4 to 6 weeks. Withdrawal studies with fluphenazine decanoate suggest that relapsing patients have a more rapid plasma concentration decline than non-relapsing patients, and that the plasma concentrations do not decline smoothly but may exhibit 'lumps' due to residual release from previous injection sites or multicompartment redistribution. Cigarette smoking has been found to be associated with a 2.33-fold increase in the clearance of fluphenazine decanoate. In 3 different studies, fluphenazine has been proposed to have a therapeutic range from less than 0.15 to 0.5 ng/ml with an upper therapeutic range of 4.0 ng/ml. Plasma concentrations following the decanoate injection are generally lower than, but clinically equivalent to, those attained with the oral form of the drug. Haloperidol decanoate plasma concentrations peak on the seventh day following injection although, in some patients, this peak may occur on the first day.(ABSTRACT TRUNCATED AT 400 WORDS)
Abstract: Antipsychotic drugs (neuroleptics) are candidates for plasma concentration monitoring, but not all agents have the same potential in this respect. The present review analyses the available data on the kinetics and metabolism of fluphenazine, perphenazine, thiothixene, flupenthixol, clopenthixol, haloperidol, pimozide, penfluridol, sulpiride and clozapine. Although some of the drugs described in this review have been in use for many years, knowledge of their pharmacokinetics is still only approximate. This is primarily because determination in biological fluids is not always feasible. Accordingly, analytical methods useful for pharmacokinetic studies or plasma concentration monitoring of these antipsychotic drugs are discussed. With the exception of sulpiride, all the neuroleptics reviewed share some basic pharmacokinetic properties: good gastrointestinal absorption but reduced systemic availability because of hepatic first-pass metabolism, high hepatic clearance and a large apparent volume of distribution leading to an apparent elimination half-life of about 24 hours for most of these compounds. The renal elimination is negligible and it seems that these drugs do not possess active metabolites. The pharmacokinetic properties of antipsychotic drugs are important for the inclusion of a set of drugs in a psychiatric institution where there is a possibility of drug concentration monitoring. In addition, the availability of a depot preparation is of importance. These factors are discussed in view of the experience made during the last years in the University Psychiatric Institutions of Geneva.
Abstract: 1 The binding of some antidepressant drugs, including some new drugs of atypical structure (flupenthixol, iprindole, maprotiline, mianserin, nomifensine, tofenacine and viloxazine) to muscarinic acetylcholine receptors in the brain has been studied by displacement of [3H]-atropine. 2 Many of the drugs are potent muscarinic antagonists. 3 Some correlation can be made between the affinity for binding to the muscarinic acetylcholine receptor and the incidence of anticholinergic side effects in clinical usage.
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.