Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes

Anastrozole is a selective non-steroidal aromatase inhibitor that blocks the conversion of androgens to estrogens in peripheral tissues. It is used as adjuvant therapy for early-stage hormone-sensitive breast cancer in postmenopausal women. Significant side effects of anastrozole include osteoporosi...

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Main Authors: Petr Potmešil, Radka Szotkowská
Format: Article
Language:English
Published: SAGE Publishing 2020-11-01
Series:Therapeutic Advances in Chronic Disease
Online Access:https://doi.org/10.1177/2040622320964152
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author Petr Potmešil
Radka Szotkowská
author_facet Petr Potmešil
Radka Szotkowská
author_sort Petr Potmešil
collection DOAJ
description Anastrozole is a selective non-steroidal aromatase inhibitor that blocks the conversion of androgens to estrogens in peripheral tissues. It is used as adjuvant therapy for early-stage hormone-sensitive breast cancer in postmenopausal women. Significant side effects of anastrozole include osteoporosis and increased levels of cholesterol. To date, seven case reports on anastrozole hepatotoxicity have been published. We report the case of an 81-year-old woman with a history of breast cancer, arterial hypertension, type 2 diabetes mellitus, hyperlipidemia, and chronic renal insufficiency. Four days after switching hormone therapy from tamoxifen to anastrozole, icterus developed along with a significant increase in liver enzymes (measured in the blood). The patient was admitted to hospital, where a differential diagnosis of jaundice was made and anastrozole was withdrawn. Subsequently, hepatic functions quickly normalized. The observed liver injury was attributed to anastrozole since other possible causes of jaundice were excluded. However, concomitant pharmacotherapy could have contributed to the development of jaundice and hepatotoxicity, after switching from tamoxifen to anastrozole since several the patient’s medications were capable of inhibiting hepatobiliary transport of bilirubin, bile acids, and metabolized drugs through inhibition of ATP-binding cassette proteins. Telmisartan, tamoxifen, and metformin all block bile salt efflux pumps. The efflux function of multidrug resistance protein 2 is known to be reduced by telmisartan and tamoxifen and breast cancer resistance protein is known to be inhibited by telmisartan and amlodipine. Moreover, the activity of P-glycoprotein transporters are known to be decreased by telmisartan, amlodipine, gliquidone, as well as the previously administered tamoxifen. Finally, the role of genetic polymorphisms of cytochrome P450 enzymes and/or drug transporters cannot be ruled out since the patient was not tested for polymorphisms.
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spelling doaj.art-e7e14248d8104b198f4894a1a4069e782022-12-21T21:26:45ZengSAGE PublishingTherapeutic Advances in Chronic Disease2040-62312020-11-011110.1177/2040622320964152Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetesPetr PotmešilRadka SzotkowskáAnastrozole is a selective non-steroidal aromatase inhibitor that blocks the conversion of androgens to estrogens in peripheral tissues. It is used as adjuvant therapy for early-stage hormone-sensitive breast cancer in postmenopausal women. Significant side effects of anastrozole include osteoporosis and increased levels of cholesterol. To date, seven case reports on anastrozole hepatotoxicity have been published. We report the case of an 81-year-old woman with a history of breast cancer, arterial hypertension, type 2 diabetes mellitus, hyperlipidemia, and chronic renal insufficiency. Four days after switching hormone therapy from tamoxifen to anastrozole, icterus developed along with a significant increase in liver enzymes (measured in the blood). The patient was admitted to hospital, where a differential diagnosis of jaundice was made and anastrozole was withdrawn. Subsequently, hepatic functions quickly normalized. The observed liver injury was attributed to anastrozole since other possible causes of jaundice were excluded. However, concomitant pharmacotherapy could have contributed to the development of jaundice and hepatotoxicity, after switching from tamoxifen to anastrozole since several the patient’s medications were capable of inhibiting hepatobiliary transport of bilirubin, bile acids, and metabolized drugs through inhibition of ATP-binding cassette proteins. Telmisartan, tamoxifen, and metformin all block bile salt efflux pumps. The efflux function of multidrug resistance protein 2 is known to be reduced by telmisartan and tamoxifen and breast cancer resistance protein is known to be inhibited by telmisartan and amlodipine. Moreover, the activity of P-glycoprotein transporters are known to be decreased by telmisartan, amlodipine, gliquidone, as well as the previously administered tamoxifen. Finally, the role of genetic polymorphisms of cytochrome P450 enzymes and/or drug transporters cannot be ruled out since the patient was not tested for polymorphisms.https://doi.org/10.1177/2040622320964152
spellingShingle Petr Potmešil
Radka Szotkowská
Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes
Therapeutic Advances in Chronic Disease
title Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes
title_full Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes
title_fullStr Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes
title_full_unstemmed Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes
title_short Drug-induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes
title_sort drug induced liver injury after switching from tamoxifen to anastrozole in a patient with a history of breast cancer being treated for hypertension and diabetes
url https://doi.org/10.1177/2040622320964152
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