Abstract
Purpose
The aim of this study was to analyze the cases of gynecomastia associated with α1A-adrenergic receptor antagonists (α1-ARAs) in the Italian spontaneous reporting system database (Rete Nazionale di Farmacovigilanza or RNF) and in the World Health Organization ICSRs database (VigiBase™), focusing on tamsulosin use.
Methods
We analyzed the spontaneous reports of gynecomastia related to the use of α1-ARAs and collected from the RNF and from VigiBase™ up to December 2012. Cases of gynecomastia have been defined as reports associated with gynecomastia according with Medical Dictionary for Regulatory Activities (MedDRA). Reporting odds ratio (ROR) and Information Component (IC) were calculated as measures of disproportionality in RNF and VigiBase™, respectively.
Results
Up to December 2012, about 186,000 reports were recorded in the RNF. Among these, 902 reports of adverse drug reaction (ADR) have been associated with the use of at least one α1-ARAs. Of these, in 15 cases, gynecomastia was a listed ADR: in 10, the suspected drug was tamsulosin (in eight, it was the sole suspect); in two, doxazosin and alfuzosin, respectively; and in one, terazosin. ROR for tamsulosin was 5.3 (95 % CI 1.8, 15.7). In VigiBase™, 84 reports of gynecomastia indicated tamsulosin as suspected drug. Tamsulosin-associated gynecomastia showed the highest IC value within this class of drugs (IC 95 % 2.43).
Conclusion
In this study, we highlight a possible association between gynecomastia and tamsulosin use. To our knowledge, this association has not been described before and could represent a potential signal.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barros AC, Sampaio MC (2012) Gynecomastia: physiopathology, evaluation and treatment. Sao Paulo Med J 130(3):187–197
Eckman A, Dobs A (2008) Drug-induced gynecomastia. Expert Opin Drug Saf 7(6):691–702
Richardson CD, Donatucci CF, Page SO et al (1997) Pharmacology of tamsulosin: saturation-binding isotherms and competition analysis using cloned alpha 1-adrenergic receptor subtypes. Prostate 33(1):55–59
Summary Product Information of Pamsvax® XL 400 micrograms capsules (Arrow)
European Core Safety Profiles, Tamsulosin, http://www.infarmed.pt/portal/page/portal/INFARMED/MEDICAMENTOS_USO_HUMANO/FARMACOVIGILANCIA/INFORMACAO_SEGURANCA/Core%20Safety%20Profile%20(CSP)1/Tamsulosin_CSP_NL_H_0014_PSUR_002_20130523.doc
MICROMEDEX® 2.0 and MICROMEDEX® 1.0 [homepage on the Internet]. Tamsulosin, Drug: Detailed evidence-based information (DRUGDEX®) updated 2013 November 14; cited 2013 November 15]. Available from: http://www.micromedexsolutions.com
Naranjo CA, Busto U, Sellers EM et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30(2):239–245
Bate A, Lindquist M, Edwards IR, Olsson S, Orre S, Lansner A, De Freitas RM (1998) A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol 54:315–321
Bate A, Lindquist M, Orre R et al (2002) Data-mining analyses of pharmacovigilance signals in relation to relevant comparison drugs. Eur J Clin Pharmacol 58(7):483–490
Noren GN, Sundberg R, Bate A et al (2008) A statistical methodology for drug-drug interaction surveillance. Stat Med 27(16):3057–3070
Bowman J, Kim H, Bustamante J (2012) Drug-induced gynecomastia. Pharmacotherapy 32(12):1123–1140
Jeunemaitre X, Chatellier G, Kreft-Jais C et al (1987) Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 60:820–825
Dickson G (2012) Gynecomastia. Am Fam Physician 85(7):716–722
Deepinder F, Braunstein GD (2012) Drug-induced gynecomastia: an evidence-based review. Expert Opin Drug Saf 11(5):779–795
Krause W (2012) Drug-inducing gynaecomastia—a critical review. Andrologia 44(Suppl):621–626. doi:10.1111/j.1439-0272.2011.01240.x
Summary Product Information of Cardura® http://www.medicines.org.uk/emc/medicine/1456/spc#undesirable_effects. Accessed 28 August 2013
Roets E, Peeters G (1985) Identification and characterization of -Prazosin binding to α1-adrenergic receptors in bovine teat muscles. Arch Int Pharmacodyn Ther 275:189–198
Wellnitz O, Zurbriggen A, Friis RR, Blum JW, Bruckmaier RM (2001) α1C- and β2-adrenergic receptor mRNA distribution in the bovine mammary gland detected by competitive RT-PCR. J Dairy Res 68:699–704
Stojkov NJ, Janjic MM, Kostic TS, Andric SA (2013) Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats. Andrology 1(2):332–347
Disclosures
The opinions expressed by the authors in this article are personal and may not be construed or reported as those of AIFA and WHO.
Conflicts of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOCX 14 kb)
Rights and permissions
About this article
Cite this article
Viola, E., Opri, S., Moretti, U. et al. α1-Adrenergic receptor antagonists and gynecomastia. A case series from the Italian spontaneous reporting system and VigiBase™ . Eur J Clin Pharmacol 70, 1003–1009 (2014). https://doi.org/10.1007/s00228-014-1700-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-014-1700-3