Masterstudiengang "Drug Regulatory Affairs"
Master-Thesis
Medicinal products during pregnancy and lactation an issue of risk management ***
Dr. Anita Jörg (Abschlußjahr: 2007)
Language: English
Women who discover they are pregnant after exposure to a medicinal product and pregnant women who require continued treatment during pregnancy are told to balance the benefits and risks of exposure to justify continuation of treatment, discontinuation of treatment or even terminate the pregnancy. The profound effects that drugs and other chemicals can have on the fetus were brought into clear focus with the thalidomide disaster in the early 60ies (Dally 1998). Many babies were born with severe deformities of arms, legs and other malformations.
This finding brought attention to the possibility that other medicinal products could have similar effects on the fetus. It has been shown that any medicinal product or chemical substance administered to the mother is able to cross the placenta to some extent, unless it is destroyed or altered during passage, or its molecular size and low solubility limit transplacental transfer (Syme et al. 2004).
When a new medicinal product is approved the risk assessment is based on animals reproductive toxicology studies and clinical studies done on male and nonpregnant women leading to a lack of scientific knowledge of the clinical pharmacology, pharmacokinetics and pharmacodynamics of the medications administered during pregnancy. Unless a product is intended specifically for use during pregnancy, pregnant women are actively excluded from clinical trials. If pregnancy occurs during a trial, the usual procedure is to discontinue treatment and drop the patient from the study.
Missing or insufficient human data are reflected in a restricted labelling of new medicinal products with contraindications, special warnings and strictly benefit/risk assessment causing physicians to avoid therapeutic regimen. Especially for expecting mothers with chronic diseases as bronchial asthma, psychiatric disorders, epilepsy or hypertension, therapeutic nihilism may lead to a dramatic deterioration of the disease, and this may also induce a higher risk for the fetal development. On the other hand numerous abortions without profound indications are carried out due to insufficient information of patients and medical staff concerning the real risk of a medicinal product used during early pregnancy.
To determine the relationship between exposure to a medicinal product and fetal outcome the collection of post-authorisation data is needed and the responsible marketing authorisation holder is obliged to introduce a pro-active monitoring. The limitation of this approach is that first of all the physician or the pregnant woman must report any medicinal product exposure. This takes place more or less only after an adverse outcome of pregnancy occured. If the medicinal product in question has a strong teratogenic potential or causes rare malformation then a reasonable suspicion arises early. The more difficult scenario is given if the medicinal product acts as moderate or low-risk teratogen, then a broad range of data is necessary to determine whether the medicinal product has an adverse effect on the embryo/fetus. Since there is no systematic post-marketing surveillance of all exposed pregnancies after approval of a medicinal product, the observations result in an overrepresentation of recorded adverse outcomes.
The decision whether to treat or not to treat a pregnant woman with medicinal product(s) is an issue of risk management. In situations in which a normal patient is administered the necessary medicinal product without any doubts, pregnant women or potentially pregnant women may be treated after thorough consideration of all pros and cons. The cons are mainly due to potential teratogenic effects on the fetus after medicinal product exposure. On the other hand reluctant therapeutically intervention may also have serious consequences for both - mother and fetus.
Pages: 53