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 tamoxifen 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 tamoxifen, when combined with abarelix (100%). We do not expect any change in exposure for abarelix, when combined with tamoxifen (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.
Tamoxifen has a high oral bioavailability [ F ] of 100%, which is why the maximum plasma level [Cmax] tends to change little during an interaction. The terminal half-life [ t12 ] is rather long at 144 hours and constant plasma levels [ Css ] are only reached after more than 576 hours. The protein binding [ Pb ] is very strong at 99%. The metabolism takes place via CYP2B6, CYP2C19, CYP2C9, CYP2D6 and CYP3A4, among others and the active transport takes place in particular via PGP.
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 tamoxifen nor abarelix increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither tamoxifen nor abarelix increase anticholinergic activity.
QT time prolongation
Rating: In combination, tamoxifen and abarelix can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||tam||aba|
|Vaginal discharge||13.2 %||13.2||n.a.|
|Peripheral edema||11.1 %||11.1||n.a.|
|Abnormal vaginal bleeding||10.2 %||10.2||n.a.|
Steatosis of liver: tamoxifen
Endometrial hyperplasia: tamoxifen
Thromboembolic disorder: tamoxifen
Pulmonary embolism: tamoxifen
Erythema multiforme: tamoxifen
Stevens johnson syndrome: tamoxifen
Interstitial pneumonia: tamoxifen
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: Selective estrogen receptor modulators (SERMs) are a class of compounds used to treat and prevent breast cancer and osteoporosis. SERMs currently approved for use in patients include tamoxifen, toremifene and raloxifene. These compounds are well tolerated in patients, and the most common adverse effects experienced in patients undergoing SERM therapy include vasomotor symptoms such as hot flashes and vaginal discharge. New SERMs currently under development for use in the treatment and prevention of osteoporosis and breast cancer include ospemifene, a derivative of toremifene, and arzoxifene, a compound very similar in structure to raloxifene. SERMs are administered orally at doses ranging from 20 to 60 mg/day. Tamoxifen and toremifene have a bioavailability of approximately 100%, whereas that of raloxifene is only 2%. SERMs are very highly bound to plasma proteins (>95%). Tamoxifen and toremifene are metabolised by the cytochrome p450 enzyme system, and raloxifene is metabolised by glucuronide conjugation. The terminal elimination half-lives of these drugs range from 27.7 hours to 7 days. The pharmacokinetics of these compounds are affected in hepatically impaired patients, but not in renally impaired patients. SERMs have several potential drug interactions with other agents, such as warfarin, rifampicin (rifampin), cholestyramine and aromatase inhibitors.
Abstract: We report on a case of tamoxifen-induced QT interval prolongation in a 56-year-old-female patient with hormone-dependent carcinoma of the right breast, stage T2N0M0, grade 3 and HER-2 negative. Partial mastectomy with axillary lymph node excision was performed in July 2007 with adjuvant hormonal and radiation therapy. This case highlights the risk of tamoxifen causing depression of electrical impulse in the sino-atrial node, leading to symptomatic sinus bradycardia with prolonged QT interval. It indicates the necessity of regular monitoring of patients undergoing tamoxifen treatment. ECG should be performed not only before and after, but also during treatment. with an average duration of treatment of 5 years, we would advise an annual ECG for asymptomatic patients. In the presence of symptomatic sinus bradycardia, constant monitoring is necessary. We also highlight potential drug interactions, between tamoxifen and acitretin and the need to be aware of drugs which may induce QT interval prolongation.
Abstract: BACKGROUND: Anticholinergic drugs are often involved in explicit criteria for inappropriate prescribing in older adults. Several scales were developed for screening of anticholinergic drugs and estimation of the anticholinergic burden. However, variation exists in scale development, in the selection of anticholinergic drugs, and the evaluation of their anticholinergic load. This study aims to systematically review existing anticholinergic risk scales, and to develop a uniform list of anticholinergic drugs differentiating for anticholinergic potency. METHODS: We performed a systematic search in MEDLINE. Studies were included if provided (1) a finite list of anticholinergic drugs; (2) a grading score of anticholinergic potency and, (3) a validation in a clinical or experimental setting. We listed anticholinergic drugs for which there was agreement in the different scales. In case of discrepancies between scores we used a reputed reference source (Martindale: The Complete Drug Reference®) to take a final decision about the anticholinergic activity of the drug. RESULTS: We included seven risk scales, and evaluated 225 different drugs. Hundred drugs were listed as having clinically relevant anticholinergic properties (47 high potency and 53 low potency), to be included in screening software for anticholinergic burden. CONCLUSION: Considerable variation exists among anticholinergic risk scales, in terms of selection of specific drugs, as well as of grading of anticholinergic potency. Our selection of 100 drugs with clinically relevant anticholinergic properties needs to be supplemented with validated information on dosing and route of administration for a full estimation of the anticholinergic burden in poly-medicated older adults.
Abstract: : Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30-100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, sincegenotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functionalgenotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.