International Journal of Clinical Pharmacy

, Volume 41, Issue 2, pp 555–562 | Cite as

Off-label use of tamoxifen in a Chinese tertiary care hospital

  • Jianhui YangEmail author
  • Wubin Lin
  • Yao Chen
Research Article


Background Tamoxifen is an estrogen receptor modulator used for the treatment of breast cancer; however, currently, it is used in many off-label indications. Objective To investigate the prevalence of tamoxifen off-label prescribing and explore available scientific evidence that supports those uses in outpatients. Setting Xiamen maternity and child health care hospital in Xiamen city of China. Method All the prescriptions of outpatients receiving tamoxifen were exported from an electronic prescribing system during a 1-year period. Tamoxifen use was then classified as either on- or off-label according to the criteria we established previously, and the details of the off-label prescriptions were collected. Logistic regression was applied to explore predictive variables. Evidence search was limited to Up-To-Date, the Micromedex database and PubMed. Main outcome measure The rate of off-label use, risk factors identified by logistic regression and evidence exhibition. Results A total of 75% of all the prescriptions available were classified as off-label use. Hyperplasia of the breast was the most frequently prescribed off-label indication. According to the analysis of logistic regression, male patients, patients less than 34 years old, and physicians with a higher professional title were more likely associated with off-label prescribing. After a search in Up-To-Date, the Micromedex database and PubMed, only male infertility, atypical hyperplasia, mastodynia, peripheral precocious puberty and gynecomastia were found to have strong evidence supporting the use of tamoxifen off-label (22.75%). Conclusion Although the off-label use of tamoxifen was common in our hospital, there was a relative shortage of evidence available supporting those uses.


China Off-label use Tamoxifen 



We would like to thank engineer Xu Jianbao (Information Services Department), for her assistance in extracting data from the Hospital Information System and pharmacist Liao Yufang for screening and managing the eligible data.


No external funding was obtained for this study.

Conflicts of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Yang G, Nowsheen S, Aziz K, Georgakilas AG. Toxicity and adverse effects of Tamoxifen and other anti-estrogen drugs. Pharmacol Ther. 2013;139(3):392–404.CrossRefGoogle Scholar
  2. 2.
    Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.CrossRefGoogle Scholar
  3. 3.
    Dooms M, Killick J. Off-label use of medicines: the need for good practice guidelines. Int J Risk Saf Med. 2017;29(1–2):17–23.CrossRefGoogle Scholar
  4. 4.
    Koukkou E, Billa E, Kapolla N, Pappa A, Venaki E, Andreou L, et al. An empiric treatment for idiopathic oligozoospermia revisited: a 20-year investigative saga. Andrologia. 2012;44(5):337–42.CrossRefGoogle Scholar
  5. 5.
    Eugster EA, Rubin SD, Reiter EO, Plourde P, Jou HC, Pescovitz OH, et al. Tamoxifen treatment for precocious puberty in McCune–Albright syndrome: a multicenter trial. J Pediatr. 2003;143(1):60–6.CrossRefGoogle Scholar
  6. 6.
    Sawathiparnich P, Osuwanaratana P, Santiprabhob J, Likitmaskul S. Tamoxifen improved final height prediction in a girl with McCune–Albright syndrome: patient report and literature review. J Pediatr Endocr Met. 2006;19(1):81–6.Google Scholar
  7. 7.
    Lapid O, van Wingerden JJ, Perlemuter L. Tamoxifen therapy for the management of pubertal gynecomastia: a systematic review. J Pediatr Endocrinol Metab. 2013;26(9–10):803–7.PubMedGoogle Scholar
  8. 8.
    Davido B, Bouchand F, Calin R, Makhloufi S, Lagrange A, Senard O, et al. High rates of off-label use in antibiotic prescriptions in a context of dramatic resistance increase: a prospective study in a tertiary hospital. Int J Antimicrob Agents. 2016;47(6):490–4.CrossRefGoogle Scholar
  9. 9.
    Porta A, Esposito S, Menson E, Spyridis N, Tsolia M, Sharland M, et al. Off-label antibiotic use in children in three European countries. Eur J Clin Pharmacol. 2010;66(9):919–27.CrossRefGoogle Scholar
  10. 10.
    Mukattash TL, Hayajneh WA, Ibrahim SM, Ayoub A, Ayoub N, Jarab AS, et al. Prevalence and nature of off-label antibiotic prescribing for children in a tertiary setting: a descriptive study from Jordan. Pharm Pract. 2016;14(3):725.CrossRefGoogle Scholar
  11. 11.
    Kalis JA, Pence SJ, Mancini RS, Zuckerman DS, Ineck JR. Prevalence of off-label use of oral oncolytics at a community cancer center. J Oncol Pract. 2015;11(2):e139–43.CrossRefGoogle Scholar
  12. 12.
    Mellor JD, Van KP, Yip SW, Thakerar A, Kirsa SW, Michael M. Access to anticancer drugs: many evidence-based treatments are off-label and unfunded by the Pharmaceutical Benefits Scheme. Intern Med J. 2012;42(11):1224–9.CrossRefGoogle Scholar
  13. 13.
    Eguale T, Buckeridge DL, Verma A, Winslade NE, Benedetti A, Hanley JA, et al. Association of off-label drug use and adverse drug events in an adult population. JAMA Intern Med. 2016;176(1):55–63.CrossRefGoogle Scholar
  14. 14.
    Wibowo E, Pollock PA, Hollis N, Wassersug RJ. Tamoxifen in men: a review of adverse events. Andrology. 2016;4(5):776–88.CrossRefGoogle Scholar
  15. 15.
    Wolters Kluwer. UpToDate [database on the Internet]. 2017. Accessed: 30 Sept 2017.
  16. 16.
    Truven Health Analytics. Micromedexsolutions [database on the Internet]. 2017. Accessed: 30 Sept 2017.
  17. 17.
    Field MJ, Lohr KN, editors. Committee to advise the public health service on clinical practice guidelines, Institute of Medicine. Clinical Practice Guidelines: Directions for a New Program. Washington: National Academies Press (US); 1990.Google Scholar
  18. 18.
    National Center for Biotechnology Information. Pubmed [database on the Internet]. 2017. Accessed 30 Sept 2017.
  19. 19.
    Product Information: Tamoxifen oral tablets. Shanghai Forward Pharmaceutical Co, Ltd. 2015.Google Scholar
  20. 20.
    Eguale T, Buckeridge DL, Winslade NE, Benedetti A, Hanley JA, Tamblyn R. Drug, patient, and physician characteristics associated with off-label prescribing in primary care. Arch Intern Med. 2012;172(10):781–8.CrossRefGoogle Scholar
  21. 21.
    Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–88.CrossRefGoogle Scholar
  22. 22.
    Waters EA, Cronin KA, Graubard BI, Han PK, Freedman AN. Prevalence of tamoxifen use for breast cancer chemoprevention among U.S. women. Cancer Epidemiol Biomark Prev. 2010;19(2):443–6.CrossRefGoogle Scholar
  23. 23.
    Chay WY, Ong WS, Tan PH, Jie Leo NQ, Ho GH, Wong CS, et al. Validation of the Gail model for predicting individual breast cancer risk in a prospective nationwide study of 28,104 Singapore women. Breast Cancer Res. 2012;14(1):R19.CrossRefGoogle Scholar
  24. 24.
    Challa VR, Swamyvelu K, Shetty N. Assessment of the clinical utility of the Gail model in estimating the risk of breast cancer in women from the Indian population. Ecancermedicalscience. 2013;7:363.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Rungruang B, Kelley JL 3rd. Benign breast diseases: epidemiology, evaluation, and management. Clin Obstet Gynecol. 2011;54(1):110–24.CrossRefGoogle Scholar
  26. 26.
    American College of Obstetricians and Gynecologists’ Committee. Practice bulletin no. 164: diagnosis and management of benign breast disorders. Obstet Gynecol. 2016;127(6):e141–56.CrossRefGoogle Scholar
  27. 27.
    Ly D, Forman D, Ferlay J, Brinton LA, Cook MB. An international comparison of male and female breast cancer incidence rates. Int J Cancer. 2013;132(8):1918–26.CrossRefGoogle Scholar
  28. 28.
    Fan L, Strasserweippl K, Li JJ, St LJ, Finkelstein DM, Yu KD, et al. Breast cancer in China. Lancet Oncol. 2014;15(7):e279.CrossRefGoogle Scholar
  29. 29.
    Wazana A. Physicians and the pharmaceutical industry: is a gift ever just a gift? JAMA. 2000;283(3):373–80.CrossRefGoogle Scholar
  30. 30.
    Kahan NR, Waitman DA, Blackman S, Vardy DA. Drug use evaluation of tamoxifen focusing on off-label use in a managed care population in Israel. J Manag Care Pharm. 2010;16(5):355.PubMedGoogle Scholar
  31. 31.
    Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166(9):1021–6.CrossRefGoogle Scholar
  32. 32.
    Seetasith A, Holdford D, Shah A, Patterson J. On-label and off-label prescribing patterns of erythropoiesis-stimulating agents in inpatient hospital settings in the US during the period of major regulatory changes. Res Social Adm Pharm. 2017;13(4):778–88.CrossRefGoogle Scholar
  33. 33.
    Wong J, Motulsky A, Abrahamowicz M, Eguale T, Buckeridge DL, Tamblyn R. Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system. BMJ. 2017;356:j603.CrossRefGoogle Scholar
  34. 34.
    Erman A, Nugent A, Amir E, Coyte PC. Cost-effectiveness analysis of extended adjuvant endocrine therapy in the treatment of post-menopausal women with hormone receptor positive breast cancer. Breast Cancer Res Treat. 2014;145(2):267–79.CrossRefGoogle Scholar
  35. 35.
    Moyer VA. Medications to decrease the risk for breast cancer in women: recommendations from the U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(10):698–708.PubMedGoogle Scholar
  36. 36.
    Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, et al. American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol. 2009;27(19):3235–58.CrossRefGoogle Scholar
  37. 37.
    Levine M, Moutquin JM, Walton R, Feightner J. Chemoprevention of breast cancer. A joint guideline from the Canadian Task Force on Preventive Health Care and the Canadian Breast Cancer Initiative’s Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. CMAJ. 2001;164(12):1681–90.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Rosolowich V, Saettler E, Szuck B. Mastalgia. J Obstet Gynaecol Can. 2006;28(1):49–57.CrossRefGoogle Scholar
  39. 39.
    Jungwirth A, Giwercman A, Tournaye H, Diemer T, Kopa Z, Dohle G, et al. European association of urology guidelines on male infertility: the 2012 update. Eur Urol. 2012;62(2):324–32.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PharmacyXiamen Maternity and Child Health Care HospitalXiamenChina

Personalised recommendations