Recent letter by ENTIS members question the EMA warning on Paternal Use of Mycophenolate Mofetil
Damkier P, Passier A, Petersen LB, Havnen G, Petersen AJT.
Birth Defects Res A Clin Mol Teratol. 2016 Sep 28. doi: 10.1002/bdra.23556
In this commentary, we strongly argue against the changes to the Summary of Product Characteristics (SmPC) made by European Medicines Agency (EMA) for mycophenolate mofetil (MMF) in 2015. This change specifically addressed pregnancy related issues in SmPC sections 4.4 (Special warnings and precautions for use) and 4.6 (Pregnancy and lactation). The SmPC now specifically warns against paternal exposure: ”Sexually active men are recommended to use condoms during treatment and for at least 90 days after cessation of treatment”
This warning has widespread consequences as – if recommendations are followed -male renal transplant recipients are basically precluded from fathering a child while receiving mycophenolate treatment. Similar warnings are not featured in the FDA approved label, and we have received many calls from worried patients and confused clinicians in different TIS/DIS in Denmark, The Nederlands and Norway.
We argue that the scientific data necessary to substantiate and justify such strong precautions are not presented by the EMA; on the contrary, we argue that the available data does not suggest any reproductive risk increase following paternal exposure. In vitro and preclinical data does not suggest a teratogenic risk be present at relevant concentrations. Human data from the United States National Transplantation Registry and a large Norwegian study does not suggest any such risk either.
We urge the EMA to reconsider these specific changes to the SmPC or bring forward evidence that substantiate and justify their case.