QT time prolongation
Adverse drug events
|Hand foot syndrome|
Variants ✨For the computationally intensive evaluation of the variants, please choose the paid standard subscription.
Explanations of the substances for patients
We have no additional warnings for the combination of capecitabine 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 capecitabine, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with capecitabine (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.
Capecitabine has a mean oral bioavailability [ F ] of 60%, which is why the maximum plasma levels [Cmax] tend to change with an interaction. The terminal half-life [ t12 ] is rather short at 0.69166667 hours and constant plasma levels [ Css ] are reached quickly. The protein binding [ Pb ] is rather weak at 60%. 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 capecitabine nor abarelix increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither capecitabine nor abarelix increase anticholinergic activity.
QT time prolongation
Rating: In combination, capecitabine and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||cap||aba|
|Hand foot syndrome||58.5 %||58.5||n.a.|
|Peripheral edema||33.0 %||33.0||n.a.|
Vomiting (26%): capecitabine
Abdominal pain (24.5%): capecitabine
Loss of appetite (17.5%): capecitabine
Constipation (14.5%): capecitabine
Gastrointestinal hemorrhage (6%): capecitabine
Dermatitis (22.5%): capecitabine
Stevens johnson syndrome: capecitabine
Toxic epidermal necrolysis: capecitabine
Fever (17.5%): capecitabine
Paresthesia (16.5%): capecitabine
Hyperbilirubinemia (11%): capecitabine
Anemia (9.6%): capecitabine
Myocardial infarction: capecitabine
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: PURPOSE: The primary objective of this study was to investigate the influence of renal impairment on the pharmacokinetics of capecitabine and its metabolites in cancer patients. Capecitabine (Xeloda) is an orally administered precursor of 5'-deoxy-5-fluorouridine (5'-DFUR), which is preferentially activated to 5-fluorouracil (5-FU) in tumors. METHODS: A total of 27 patients were enrolled, of whom 24 were evaluable for pharmacokinetics (6 with normal renal function, 8 with mild, 6 with moderate, and 4 with severe renal impairment at baseline). Patients received capecitabine orally at the standard dosing regimen (1250 mg/m(2) capecitabine twice daily for 2 weeks followed by a 1-week rest period). On study days 1 and 14, blood samples were collected to evaluate the pharmacokinetics of capecitabine and its metabolites. The relationship between the area under the plasma concentration-time curve (AUC) and creatinine clearance (CL(CR)) was assessed by log-linear regression analysis. RESULTS: The primary pharmacokinetic parameter with respect to the effect of renal dysfunction was systemic exposure to 5'-DFUR, 5-FU and FBAL determined on study day 14. Renal impairment led to an increase in the systemic exposure to 5'-DFUR and FBAL (23% and 109% increase in AUC, respectively) for a 50% reduction in CL(CR). By contrast, renal impairment may lead to decreased exposure to 5'-DFCR. There was no evidence for an effect of renal impairment on systemic exposure to 5-FU or capecitabine. Renal impairment did not have a major effect on peak concentration (C(max)) or elimination half-life (t(1/2)) of capecitabine, 5'-DFCR, 5'-DFUR, and 5-FU. However, in the case of FBAL, moderate or severe renal impairment caused up to a twofold increase in C(max) and prolongation of t(1/2). All patients with severe renal impairment (four patients) had drug-related grade 3 or 4 adverse-events (AEs) and serious AEs. Patients with moderate renal impairment experienced a similar number of grade 3 or 4 AEs (six of nine patients) but had a higher incidence of serious AEs (three of nine patients) when compared with those with normal renal function (four of six patients and one of six patients, respectively). A similar effect was seen in patients with mild renal dysfunction (grade 3 or 4 AEs in four of eight patients; serious AEs in three of eight patients). The relationship between systemic exposure to capecitabine or its metabolites and safety was investigated using logistic regression. This exploratory analysis showed a strong positive relationship between AUC of 5'-DFUR and treatment-related grade 3 or 4 AEs, whereas there was no relationship with exposure to capecitabine, 5'-DFCR, 5-FU or FBAL. CONCLUSIONS: Renal impairment has no effect on the pharmacokinetics of capecitabine or 5-FU, but leads to an increase in the systemic exposure to 5'-DFUR and FBAL. However, only the AUC of 5'-DFUR is correlated with safety. Based on the safety results in patients with severe renal impairment, a dose modification cannot be recommended for these patients and they should not be treated with capecitabine. Additional data from the clinical safety database and pharmacokinetic results from the present study support the recommendation that patients with moderate renal impairment should be treated with 75% of the recommended standard starting dose to achieve systemic exposure comparable to that in patients with normal renal function.
Abstract: AIMS: The aim of the present study is to investigate the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemoradiotherapy. MATERIALS AND METHODS: One hundred ten males suffering from locally advanced head and neck squamous cell carcinoma and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs) by PCR-based RFLP. Each case was assessed thoroughly for treatment response following WHO criteria. RESULTS: The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.3%) and CYP2C9FNx013 (20.1%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several fold increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (134) carrying variant alleles of both CYP2C9FNx012 (65.3%) or CYP2C9FNx013 (70.58%) were found to respond poorly to the radio-chemotherapy. CONCLUSIONS: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment schedule.
Abstract: Capecitabine is an oral fluoropyrimidine which can prolong QT interval. However, there have been no reports that capecitabine induced ventricular fibrillation (VF) due to secondary QT prolongation in patients with no structural heart disease. A 39-year-old woman developed VF during the chemotherapy of capecitabine for colon cancer. At the administration, corrected QT interval (QTc) was prolonged to 559 ms despite no evidence of organic heart disease. Discontinuation of capecitabline normalized the QTc (414 ms). During the follow-up of eight years, neither the QTc prolongation nor the recurrent VF has been detected. We report the rare case of capecitabine-related VF without any organic heart disease. <Capecitabine is an oral fluoropyrimidine carbamate commonly used to treat colorectal and breast cancer. Capecitabine has been reported to be associated with VF due to vasospasm. However, capecitabine is also associated with QT elongation. This is the first report to describe VF due to capecitabine-related secondary long QT syndrome in a patient with no cardiac heart disease. Physicians must carefully follow up patients during capecitabine chemotherapy with serial electrocardiograms.>.