EMEA/CHMP/313666/2005
EMEA 2005
5/21
2.
GENERAL CONSIDERATIONS REGARDING THE NEED TO COLLECT
INFORMATION
2.1
Background
The majority of medicinal products or chemical substances administered to a pregnant woman could
have effects on the foetus either before the placenta is fully developed or subsequently, if they can cross
the placenta to at least some extent. Substances used for therapeutic purposes in the mother have the
potential to reach the foetus with the consequential potential for harmful effects, depending on whether
the rate and extent of drug transfer results in sufficient concentrations within the foetus.
Medicinal products may have a different impact at different stages of pregnancy. The spectrum of
effects varies according to the period of exposure. For example, the exposure to a teratogenic agent
during the period of organogenesis may induce major malformation, growth retardation or death, while
exposure during the second or third trimester may induce growth retardation, renal insufficiency,
neurological disorders, stillbirth, etc. On the other hand, exposure to a teratogenic agent during the first
two weeks of pregnancy (3rd and 4th gestational week) may lead either to the death or to a normal
preembryo according to the "all or nothing rule"; at this period zygotes and blastocysts contain
omnipotent stem cells without any differentiation, therefore, teratogenic agents may lead to seriously
damaged preembryos, which will not survive, or to less seriously damaged preembryos, which will
survive with complete regeneration.
Drug treatment of male patients prior to or around the time of conception and/or during pregnancy could
affect the offspring due to a drug-induced defect in the spermatozoon itself such as an effect on the
DNA or chromosome or due to an effect caused by the presence of the drug in the seminal fluid.
Two important conclusions can be drawn from the above considerations:
In order to minimise the foetal risk of exposure, drug therapy of the mother should be restricted as much
as possible. This principle, however, cannot be applied in all cases. The mother may have a serious
illness which requires treatment, or a condition that untreated may pose significant risk to the foetus.
In order to optimise the knowledge about any potential teratogenic or embryotoxic/foetotoxic effects of
a medicinal product and the doses and concentrations at which such effects will develop, it is desirable
to gather information about all medicinal products taken by pregnant women.
2.2
Assessing the need for information on drug exposure
It is good practice to always try to collect information on medicinal exposure during pregnancy.
However, there are various situations in which an assessment of the foetal effects following exposure of
pregnant women to medicinal products is particularly important:
• Conditions and diseases where drug therapy is essential for maternal and/or foetal benefit and
where discontinuation or omission of treatment would result in increased risk for the mother
and/or the foetus.
In these situations, the potential harm posed by drug therapy to the foetus must be weighed
against the risk of lack of therapy both to the mother and the foetus. Examples of such
conditions and diseases include asthma, autoimmune disorders, diabetes mellitus, epilepsy,
high blood pressure, thyroid disorders, infections, intoxications, malignant diseases, severe
psychiatric disorders, thromboembolic events, as well as use of general anaesthetics and
treatments for prevention of transplant rejection.
There is a special need for information in situations when available treatment options are
already limited due to known or suspected risks established from animal studies or human
experience. Examples of these situations include: antiepileptic, antineoplastic, antithyroid
agents, antiretrovirals. This must not, however, be equated with a waiver for other products,
for which only limited or no information about their impact during pregnancy exists. The
database established for collecting information on antiretroviral therapy is a good example of a