Drug Safety

, Volume 34, Issue 2, pp 97–115 | Cite as

Mammalian Target of Rapamycin (mTOR) Inhibitors

Potential Uses and a Review of Haematological Adverse Effects
  • Sofia Sofroniadou
  • David GoldsmithEmail author
Review Article


Mammalian target of rapamycin (mTOR) inhibitors (mTORis) constitute a relatively new category of immunosuppressive and antineoplastic drugs. These share a unique mechanism of action that is focused on the inhibition of the mTOR. Their clinical applications have recently expanded significantly to cover a wide spectrum of immune and non-immune-mediated disorders, including, apart from solid organ transplantation, various solid organ and haematological malignancies, rheumatological and auto-immune diseases such as rheumatoid arthritis, systemic lupus erythematosus, fibrotic conditions, e.g. pulmonary and hepatic fibrosis, and even metabolic problems such as diabetes mellitus and obesity. The most challenging and frequent adverse effects of the mTORis are the haematological ones, especially anaemia, leukopenia and thrombocytopenia. A unique characteristic of mTORi-induced anaemia is concurrent marked microcytosis. Recently, mechanisms have been proposed to explain the microcytic appearance of this anaemia; these include globin production defect, erythropoietin resistance, chronic inflammation, dysregulation of cellular iron metabolism and hepcidin-mediated iron homeostasis interference. As the differential diagnosis of microcytic anaemia includes pure iron deficiency, functional iron deficiency and haemoglobinopathies, characterization of the anaemia requires significant investigation, time and costs. Therefore, understanding of the likely interaction between mTORis and patients is valuable in clinical practice. Moreover, this could expand the drugs’ therapeutic applications to other disorders, and suggest novel targets for further research.


Everolimus Sirolimus Mycophenolate Mofetil Temsirolimus Mean Corpuscular Volume 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to prepare this manuscript. David Goldsmith has received consultancy fees from Wyeth and Novartis, and honoraria from Novartis. Sofia Sofroniadou has no conflicts of interest to declare.


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Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Department of Renal Medicine and Transplantation, Guy’s and St Thomas’ NHS Foundation TrustKing’s Health Partners Academic Health Science Centre (AHSC)LondonUK

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