Pharmaceutical Medicine

, Volume 33, Issue 5, pp 395–406 | Cite as

Effectiveness of Risk Minimization Measures to Prevent Pregnancy Exposure to Mycophenolate-Containing Medicines in Europe

  • Terri MadisonEmail author
  • Barbara Donner
  • Roger Mutter
  • Roberto Mingrino
  • Giuseppe Alvaro
Original Research Article



In 2015, the European Medicines Agency (EMA) requested additional Risk Minimization Measures (RMM), consisting of a Direct Healthcare Professional Communication (DHPC), a Guide for Healthcare Professionals (HCPs), and a Guide for Patients, to prevent pregnancy exposure to mycophenolate-containing medicines.


This study assessed the effectiveness of the additional RMM for any mycophenolate-containing medicine among prescribers of these products in Europe.


A cross-sectional survey was conducted among prescribers of mycophenolate-containing medicines in five European countries via the administration of 19 questions checking knowledge levels for the key messages included in the additional RMM.


Of 79,783 invitations sent to potential prescribers of mycophenolate-containing medicines, 295 HCPs accessed the survey, giving an overall response rate of 0.4% (range 0.1–8.6%). A total of 231 prescribers were included in the primary analysis. Knowledge levels for 15 questions was fair (50 to < 70%) to high (≥ 70%), and for 4 questions was poor (< 50%). Highest knowledge (≥ 75%) was for knowing that mycophenolate is contraindicated in women of childbearing potential not using highly effective contraception (80.3%) and that mycophenolate should not be routinely prescribed during pregnancy (77.5%). Lowest knowledge (≤ 30%) was for knowing that no specific mechanism of teratogenicity and mutagenicity has been identified for mycophenolate (23.4%). Less than half of HCPs reported receipt of the DHPC (42.5%) or were aware of the Guide for HCPs (32.1%) and Guide for Patients (29.7%). The most frequently reported primary source from which HCPs learned about these risks was the Summary of Product Characteristics (SmPC; 33.8%), while only 9.9% indicated the Guide for HCPs.


Prescribers who participated in this survey appear to be reasonably well informed about the key messages of the RMM put in place in Europe for mycophenolate-containing medicines. The relatively high knowledge levels, in spite of the low proportion of HCPs reporting receipt of the additional RMM, suggest that the SmPC may be sufficiently informing prescribers about the pregnancy risks of mycophenolate-containing medicines and actions recommended to minimize pregnancy risk. Nevertheless, Roche in consultation with EMA will continue to distribute all additional RMM.



The Authors wish to acknowledge Dr. Alan Hochberg for his valuable comments during the review of the early manuscript.

Compliance with Ethical Standards


This study was sponsored by Hoffman-La Roche Ltd.

Conflict of interest

Terri Madison is an employee of Mapi, an ICON plc Company, who received funding from Hoffman-La Roche Ltd to conduct this study. Giuseppe Alvaro, Barbara Donner, Roger Mutter, and Roberto Mingrino are employees of Hoffman-La Roche Ltd which commercializes CellCept in Europe.

Ethical approval

Ethics approval for this healthcare professional survey was not required in the participating countries.

Informed consent

Although formal written informed consent was also not required, consent to participate in the survey was documented at the beginning of the survey questionnaire.

Supplementary material

40290_2019_304_MOESM1_ESM.pdf (213 kb)
Supplementary material 1 (PDF 212 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Terri Madison
    • 1
    Email author
  • Barbara Donner
    • 2
  • Roger Mutter
    • 2
  • Roberto Mingrino
    • 2
  • Giuseppe Alvaro
    • 2
  1. 1.Scientific Medical Affairs, Mapi, an ICON plc companyLexingtonUSA
  2. 2.Safety Risk Management, F. Hoffmann-La Roche LtdBaselSwitzerland

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