Escitalopram co-prescription in anastrozole-treated breast cancer patients

OBJECTIVE: The purpose of the study was to evaluate the impact of escitalopram co-prescription on plasma anastrozole levels in post-menopausal breast cancer patients. METHODS: A total of 24 post-menopausal operated breast cancer patients co-prescribed with escitalopram and anastrozole were included. Blood samples were collected, before and 1-month after the onset of escitalopram to analyze plasma anastrozole and estradiol levels. RESULTS: No significant difference was noted in basal plasma anastrozole levels with respect to age, body mass index (BMI), tumor stage, previous antineoplastic treatments, concomitant medications, and serum estradiol levels. Overall, 17 patients completed the 1-month escitalopram treatment, while 7 patients discontinued escitalopram within the 1st week of the treatment. Basal anastrozole levels of 24 patients were 26.1±2.4 ng/mL. Among 17 patients who continued 1-month escitalopram treatment was associated with significant increase in plasma anastrozole levels (24.5±2.3 ng/mL to 32.2±3.2 ng/mL, p<0.05). Notably, 1-month escitalopram use was associated with significant increase in plasma anastrozole levels only in the subgroup of obese (BMI >29 kg/m2 ) patients (23.1±2.8 to 35.9±4.7 ng/mL, p<0.01), while no such interaction was noted among non-obese patients. The estradiol levels of the patients were below ≤10 pg/mL in 75% of patients and no change occurred after escitalopram administration. CONCLUSION: Escitalopram co-prescription resulted in significant increase in plasma anastrozole levels without affecting the serum estradiol levels. Our findings emphasize the need for close monitoring in case of concomitant use of anastrozole and escitalopram, especially in obese patients and the potential role of therapeutic drug monitoring.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Abubakar MB, Wei K, Gan SH. The influence of genetic polymorphisms on the efficacy and side effects of anastrozole in postmenopausal breast cancer patients. Pharmacogenet Genomics 2014;24:575–81.
2. Ponzone R, Mininanni P, Cassina E, Pastorino F, Sismondi P. Aromatase inhibitors for breast cancer: different structures, same effects? Endocr Relat Cancer 2008;15:27–36.
3. Files JA, Ko MG, Pruthi S. Managing aromatase inhibitors in breast cancer survivors: not just for oncologists. Mayo Clin Proc 2010;85:560–6.
4. Ingle JN, Dowsett M, Cuzick J, Davies C. Aromatase inhibitors versus tamoxifen as adjuvant therapy for postmenopausal women with estrogen receptor positive breast cancer: meta-analyses of randomized trials of monotherapy and switching strategies. Cancer Res 2009;69:66.
5. Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group, Forbes JF, Cuzick J, Buzdar A, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008;9:45–53.
6. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr 2004;:57–71.
7. Cvetković J, Nenadović M. Depression in breast cancer patients. Psychiatry Res 2016;240:343–7.
8. Deshields T, Tibbs T, Fan MY, Taylor M. Differences in patterns of depression after treatment for breast cancer. Psychooncology 2006;15:398–406.
9. Hjerl K, Andersen EW, Keiding N, Mouridsen HT, Mortensen PB, Jørgensen T. Depression as a prognostic factor for breast cancer mortality. Psychosomatics 2003;44:24–30.
10. Spiegel D, Giese-Davis J. Depression and cancer: mechanisms and disease progression. Biol Psychiatry 2003;54:269–82.
11. Park HY, Lee BJ, Kim JH, Bae JN, Hahm BJ. Rapid improvement of depression and quality of life with escitalopram treatment in outpatients with breast cancer: a 12-week, open-label prospective trial. Prog Neuropsychopharmacol Biol Psychiatry 2012;36:318–23.
12. Miguel C, Albuquerque E. Drug interaction in psycho-oncology: antidepressants and antineoplastics. Pharmacology 2011;88:333–9.
13. Mannheimer B, Wettermark B, Lundberg M, Pettersson H, von Bahr C, Eliasson E. Nationwide drug-dispensing data reveal important differences in adherence to drug label recommendations on CYP2D6-dependent drug interactions. Br J Clin Pharmacol 2010;69:411–7.
14. Binkhorst L, Bannink M, de Bruijn P, Ruit J, Droogendijk H, van Alphen RJ, et al. Augmentation of endoxifen exposure in tamoxifen-treated women following SSRI switch. Clin Pharmacokinet 2016;55:249–55.
15. Turkistani A, Marsh S. Pharmacogenomics of third-generation aromatase inhibitors. Expert Opin Pharmacother 2012;13:1299–307.
16. von Moltke LL, Greenblatt DJ, Giancarlo GM, Granda BW, Harmatz JS, Shader RI. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab Dispos 2001;29:1102–9.
17. Rao N. The clinical pharmacokinetics of escitalopram. Clin Pharmacokinet 2007;46:281–90.
18. Shavi GV, Nayak UY, Maliyakkal N, Deshpande PB, Raghavendra R, Kumar AR, et al. Nanomedicine of anastrozole for breast cancer: Physicochemical evaluation, in vitro cytotoxicity on BT-549 and MCF-7 cell lines and preclinical study on rat model. Life Sci 2015;141:143–55.
19. Hubalek M, Oberguggenberger A, Beer B, Meraner V, Sztankay M, Oberacher H, et al. Does obesity interfere with anastrozole treatment? Positive association between body mass index and anastrozole plasma levels. Clin Breast Cancer 2014;14:291–6.
20. Pfeiler G, Königsberg R, Hadji P, Fitzal F, Maroske M, Dressel-Ban G, et al. Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer. Br J Cancer 2013;109:1522–7.
21. Brill MJ, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CA. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet 2012;51:277–304.
22. Caraco Y, Zylber-Katz E, Berry EM, Levy M. Carbamazepine pharmacokinetics in obese and lean subjects. Ann Pharmacother 1995;29:843–7.
23. Caraco Y, Zylber-Katz E, Berry EM, Levy M. Significant weight reduction in obese subjects enhances carbamazepine elimination. Clin Pharmacol Ther 1992;51:501–6.
24. Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet 2010;49:71–87.
25. Goodwin PJ. Commentary on: “Effect of obesity on survival in women with breast cancer: systematic review and meta-analysis” (Melinda Protani, Michael Coory, Jennifer H. Martin). Breast Cancer Res Treat 2010;123:637–40.
26. Pop A, Lupu DI, Cherfan J, Kiss B, Loghin F. Estrogenic/antiestrogenic activity of selected selective serotonin reuptake inhibitors. Clujul Med 2015;88:381–5.
27. Arimidex: Non-Steroidal Aromatase Inhibitor [product monograph]. AstraZeneca; 2011.
28. Dowsett M, Cuzick J, Howell A, Jackson I; ATAC Trialists’ Group. Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the ‘Arimidex and tamoxifen alone or in combination’ (ATAC) trial. Br J Cancer 2001;85:317– 24.
29. Ingle JN, Buzdar AU, Schaid DJ, Goetz MP, Batzler A, Robson ME, et al. Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer. Cancer Res 2010;70:3278–86.
30. Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, et al. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 2003;95:1758–64.
31. Grimm SW, Dyroff MC. Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos 1997;25:598–602.
32. Li X, Yang J, Qiao Y, Duan Y, Xin Y, Nian Y, et al. Effects of radiation on drug metabolism: a review. Curr Drug Metab 2019;20:350–60.
33. Pasanen M, Lang S, Kojo A, Kosma VM. Effects of simulated nuclear fuel particles on the histopathology and CYP enzymes in the rat lung and liver. Environ Res 1995;70:126–33.
34. Murdoch D, Keam SJ. Escitalopram: a review of its use in the management of major depressive disorder. Drugs 2005;65:2379–404.
35. Biglia N, Sgandurra P, Peano E, Sgandurra P, Sismondi P, Spatola M, et al. Duloxetine and escitalopram for treatment of hot flushes in breast cancer survivors. Maturitas 2009;63:34.
36. Boeddinghaus IM, Dowsett M. Comparative clinical pharmacology and pharmacokinetic interactions of aromatase inhibitors. J Steroid Biochem Mol Biol 2001;79:85–91.

APA	Özyurt H, Ozden S, Gemici C, ÜLER P, yaprak g, Tepetam H, Küçükibrahimoğlu E, Gören M, Odabas H, Neşetoğlu N, UNAL D, Gumus M (2022). Escitalopram co-prescription in anastrozole-treated breast cancer patients. , 248 - 255. 10.14744/nci.2022.48264
Chicago	Özyurt Hazan,Ozden Sevgi,Gemici Cengiz,ÜLER PINAR,yaprak gokhan,Tepetam Hüseyin,Küçükibrahimoğlu Elif Esra,Gören M. Zafer,Odabas Hatice,Neşetoğlu Neşet,UNAL DURİ SEHVAR,Gumus Mahmut Escitalopram co-prescription in anastrozole-treated breast cancer patients. (2022): 248 - 255. 10.14744/nci.2022.48264
MLA	Özyurt Hazan,Ozden Sevgi,Gemici Cengiz,ÜLER PINAR,yaprak gokhan,Tepetam Hüseyin,Küçükibrahimoğlu Elif Esra,Gören M. Zafer,Odabas Hatice,Neşetoğlu Neşet,UNAL DURİ SEHVAR,Gumus Mahmut Escitalopram co-prescription in anastrozole-treated breast cancer patients. , 2022, ss.248 - 255. 10.14744/nci.2022.48264
AMA	Özyurt H,Ozden S,Gemici C,ÜLER P,yaprak g,Tepetam H,Küçükibrahimoğlu E,Gören M,Odabas H,Neşetoğlu N,UNAL D,Gumus M Escitalopram co-prescription in anastrozole-treated breast cancer patients. . 2022; 248 - 255. 10.14744/nci.2022.48264
Vancouver	Özyurt H,Ozden S,Gemici C,ÜLER P,yaprak g,Tepetam H,Küçükibrahimoğlu E,Gören M,Odabas H,Neşetoğlu N,UNAL D,Gumus M Escitalopram co-prescription in anastrozole-treated breast cancer patients. . 2022; 248 - 255. 10.14744/nci.2022.48264
IEEE	Özyurt H,Ozden S,Gemici C,ÜLER P,yaprak g,Tepetam H,Küçükibrahimoğlu E,Gören M,Odabas H,Neşetoğlu N,UNAL D,Gumus M "Escitalopram co-prescription in anastrozole-treated breast cancer patients." , ss.248 - 255, 2022. 10.14744/nci.2022.48264
ISNAD	Özyurt, Hazan vd. "Escitalopram co-prescription in anastrozole-treated breast cancer patients". (2022), 248-255. https://doi.org/10.14744/nci.2022.48264

APA	Özyurt H, Ozden S, Gemici C, ÜLER P, yaprak g, Tepetam H, Küçükibrahimoğlu E, Gören M, Odabas H, Neşetoğlu N, UNAL D, Gumus M (2022). Escitalopram co-prescription in anastrozole-treated breast cancer patients. İstanbul Kuzey Klinikleri, 9(3), 248 - 255. 10.14744/nci.2022.48264
Chicago	Özyurt Hazan,Ozden Sevgi,Gemici Cengiz,ÜLER PINAR,yaprak gokhan,Tepetam Hüseyin,Küçükibrahimoğlu Elif Esra,Gören M. Zafer,Odabas Hatice,Neşetoğlu Neşet,UNAL DURİ SEHVAR,Gumus Mahmut Escitalopram co-prescription in anastrozole-treated breast cancer patients. İstanbul Kuzey Klinikleri 9, no.3 (2022): 248 - 255. 10.14744/nci.2022.48264
MLA	Özyurt Hazan,Ozden Sevgi,Gemici Cengiz,ÜLER PINAR,yaprak gokhan,Tepetam Hüseyin,Küçükibrahimoğlu Elif Esra,Gören M. Zafer,Odabas Hatice,Neşetoğlu Neşet,UNAL DURİ SEHVAR,Gumus Mahmut Escitalopram co-prescription in anastrozole-treated breast cancer patients. İstanbul Kuzey Klinikleri, vol.9, no.3, 2022, ss.248 - 255. 10.14744/nci.2022.48264
AMA	Özyurt H,Ozden S,Gemici C,ÜLER P,yaprak g,Tepetam H,Küçükibrahimoğlu E,Gören M,Odabas H,Neşetoğlu N,UNAL D,Gumus M Escitalopram co-prescription in anastrozole-treated breast cancer patients. İstanbul Kuzey Klinikleri. 2022; 9(3): 248 - 255. 10.14744/nci.2022.48264
Vancouver	Özyurt H,Ozden S,Gemici C,ÜLER P,yaprak g,Tepetam H,Küçükibrahimoğlu E,Gören M,Odabas H,Neşetoğlu N,UNAL D,Gumus M Escitalopram co-prescription in anastrozole-treated breast cancer patients. İstanbul Kuzey Klinikleri. 2022; 9(3): 248 - 255. 10.14744/nci.2022.48264
IEEE	Özyurt H,Ozden S,Gemici C,ÜLER P,yaprak g,Tepetam H,Küçükibrahimoğlu E,Gören M,Odabas H,Neşetoğlu N,UNAL D,Gumus M "Escitalopram co-prescription in anastrozole-treated breast cancer patients." İstanbul Kuzey Klinikleri, 9, ss.248 - 255, 2022. 10.14744/nci.2022.48264
ISNAD	Özyurt, Hazan vd. "Escitalopram co-prescription in anastrozole-treated breast cancer patients". İstanbul Kuzey Klinikleri 9/3 (2022), 248-255. https://doi.org/10.14744/nci.2022.48264