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 perphenazine. 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 perphenazine (100%). We do not expect any change in exposure for perphenazine, 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.
Perphenazine has a low oral bioavailability [ F ] of 40%, which is why the maximum plasma level [Cmax] tends to change strongly with an interaction. The terminal half-life [ t12 ] is 10 hours and constant plasma levels [ Css ] are reached after approximately 40 hours. Protein binding [ Pb ] is not known. The metabolism mainly takes place via CYP2D6 and the active transport takes place in particular via PGP.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor perphenazine 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: Perphenazine 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, abarelix and perphenazine can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||per|
|Orthostatic hypotension||1.0 %||n.a.||+|
Tardive dyskinesia: perphenazine
Ineffective thermoregulation: perphenazine
Neuroleptic malignant syndrome: perphenazine
Blurred vision: perphenazine
Epithelial keratopathy: perphenazine
Urinary retention: perphenazine
Nasal congestion: perphenazine
Paralytic ileus: perphenazine
Lupus erythematosus: perphenazine
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 pharmacokinetics of a single oral dose of 6 mg perphenazine was studied in a group of six slow and six rapid hydroxylators of debrisoquin. Peak serum concentrations of perphenazine were significantly higher in slow hydroxylators than they were in rapid hydroxylators (2.4 +/- 0.6 versus 0.7 +/- 0.3 nmol/L, p less than 0.001). The AUC(0-12) was also higher in slow hydroxylators than it was in rapid hydroxylators (18.5 +/- 6.2 versus 4.5 +/- 2.5 nmol.L-1.hr, p less than 0.001). The data suggest that the disposition of the antipsychotic drug perphenazine covaries with polymorphic debrisoquin hydroxylation.
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: Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers.
Abstract: BACKGROUND: Anticholinergic drugs put elderly patients at a higher risk for falls, cognitive decline, and delirium as well as peripheral adverse reactions like dry mouth or constipation. Prescribers are often unaware of the drug-based anticholinergic burden (ACB) of their patients. This study aimed to develop an anticholinergic burden score for drugs licensed in Germany to be used by clinicians at prescribing level. METHODS: A systematic literature search in pubmed assessed previously published ACB tools. Quantitative grading scores were extracted, reduced to drugs available in Germany, and reevaluated by expert discussion. Drugs were scored as having no, weak, moderate, or strong anticholinergic effects. Further drugs were identified in clinical routine and included as well. RESULTS: The literature search identified 692 different drugs, with 548 drugs available in Germany. After exclusion of drugs due to no systemic effect or scoring of drug combinations (n = 67) and evaluation of 26 additional identified drugs in clinical routine, 504 drugs were scored. Of those, 356 drugs were categorised as having no, 104 drugs were scored as weak, 18 as moderate and 29 as having strong anticholinergic effects. CONCLUSIONS: The newly created ACB score for drugs authorized in Germany can be used in daily clinical practice to reduce potentially inappropriate medications for elderly patients. Further clinical studies investigating its effect on reducing anticholinergic side effects are necessary for validation.