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 lurasidone 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 lurasidone, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with lurasidone (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.
Lurasidone has a low oral bioavailability [ F ] of 14%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is rather long at 29 hours and constant plasma levels [ Css ] are only reached after more than 116 hours. The protein binding [ Pb ] is very strong at 99% and the volume of distribution [ Vd ] is very large at 7175 liters, which is why, with a mean hepatic extraction rate of 0.61, both liver blood flow [Q] and a change in protein binding [Pb] are relevant. The metabolism mainly takes place via CYP3A4.
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 lurasidone nor abarelix increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither lurasidone nor abarelix increase anticholinergic activity.
QT time prolongation
Rating: In combination, lurasidone and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||lur||aba|
|Weight gain||4.7 %||4.7||n.a.|
|Orthostatic hypotension||1.6 %||1.6||n.a.|
Cerebrovascular accident: lurasidone
Neuroleptic malignant syndrome: lurasidone
Tardive dyskinesia: lurasidone
Transient ischemic attack: lurasidone
Elevated serum creatinine: lurasidone
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 "atypical" antipsychotics are grouped together based on what they are not (i.e., not dopamine-2 selective antagonists like haloperidol). While sharing this characteristic, these agents differ substantially in pharmacokinetics and pharmacodynamics. The first two columns in this series reviewed the bioavailability, half-life, and metabolism of the 10 newer "atypical" antipsychotics, including the most recently marketed members of this class (asenapine, iloperidone, and lurasidone). This third column in the series discusses the effect hepatic and renal impairment has on the clearance and hence dosing recommendations for these agents. An understanding of the pharmacokinetic differences among the "atypical" antipsychotics discussed in this series of columns can help clinicians optimize drug selection and dose for specific patients under specific treatment conditions. A subsequent column in the series will review the substantial and clinically important pharmacodynamic differences among these agents.
Abstract: We review the literature on management of psychosis and agitation in medical-surgical patients who have or are at risk for prolonged QT interval, a risk factor for torsade de pointes (TdP), and we describe our protocols for treating these patients. We searched PubMed and PsycInfo for relevant studies and found few papers describing options for treating psychosis and agitation in these patients. Prolonged QTc interval has been more often associated with low-potency phenothiazines such as thioridazine; however, it may occur with high potency typical antipsychotics such as fluphenazine and haloperidol as well as with atypical antipsychotics such as quetiapine, risperidone, olanzapine, iloperidone, and particularly ziprasidone. Antipsychotics for which no association with prolonged QTc interval has been shown include lurasidone, clozapine, and aripiprazole. For patients who have risk factors for prolonged QTc interval but whose electrocardiograms do not show this, reasonable first choices include oral or intramuscular olanzapine or aripiprazole, followed by risperidone and quetiapine or oral or intramuscular haloperidol. For those who have prolonged QTc but that measures less than 500 ms, we limit the use of antipsychotics to aripiprazole, olanzapine, risperidone, or quetiapine. Finally, for patients who have a QTc of 500 ms or greater, we rely on aripiprazole, valproate, trazodone, and benzodiazepines.
Abstract: Lurasidone hydrochloride, a benzisothiazol derivative, is a second-generation (atypical) antipsychotic agent that has received regulatory approval for the treatment of schizophrenia in the US, Canada, the EU, Switzerland, and Australia, and also for bipolar depression in the US and Canada. In addition to its principal antagonist activity at dopamine Dand serotonin 5-HTreceptors, lurasidone has distinctive 5-HTantagonistic activity, and displays partial agonism at 5-HTreceptors, as well as modest antagonism at noradrenergic αand αreceptors. Lurasidone is devoid of antihistaminic and anticholinergic activities. It is administered once daily within the range of 40-160 mg/day for schizophrenia and 20-120 mg/day for bipolar depression, and its pharmacokinetic profile requires administration with food. In adult healthy subjects and patients, a 40 mg dose results in peak plasma concentrations in 1-3 h, a mean elimination half-life of 18 h (mostly eliminated in the feces), and apparent volume of distribution of 6173 L; it is approximately 99 % bound to serum plasma proteins. Lurasidone's pharmacokinetics are approximately dose proportional in healthy adults and clinical populations within the approved dosing range, and this was also found in a clinical study of children and adolescents. Lurasidone is principally metabolized by cytochrome P450 (CYP) 3A4 with minor metabolites and should not be coadministered with strong CYP3A4 inducers or inhibitors. Lurasidone does not significantly inhibit or induce CYP450 hepatic enzymes.
Abstract: Therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding side effects by maintaining long-term exposure to minimally effective blood concentrations. The rationale for using therapeutic drug monitoring in relation to second-generation antipsychotics is still being discussed at least with regard to the real clinical utility, but there is evidence that it can improve efficacy, especially when patients do not respond or develop side effects using therapeutic doses. Furthermore, drug plasma concentration determinations can be of some utility in medico-legal problems. This review concentrates on the clinical pharmacokinetic data related to clozapine, risperidone, paliperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole, sertindole, asenapine, iloperidone, lurasidone, brexpiprazole and cariprazine and briefly considers the main aspects of their pharmacodynamics. Optimal plasma concentration ranges are proposed for clozapine, risperidone, paliperidone and olanzapine because the studies of quetiapine, amisulpride, asenapine, iloperidone and lurasidone provide only limited information and there is no direct evidence concerning ziprasidone, aripiprazole, sertindole, brexpiprazole and cariprazine: the few reported investigations need to be confirmed and extended.