Drugs during pregnancy: an issue of risk classification and information to prescribers.

The Swedish system for the classification of fetal risk of drugs was the first of its kind and was implemented in 1978. Drugs for use in pregnant women are classified in 4 general categories--A to D. The US Food and Drug Administration (FDA) introduced a system in 1979 also using the letters A to D, together with an X category. However, the definitions differ considerably between the FDA system and the Swedish system, resulting in a very different allocation of drugs to the respective categories. In the Swedish system, category A includes drugs that have been extensively used and/or for which there are reliable clinical data indicating no evidence of disturbance of the reproductive process. Category B includes drugs for which data from pregnant women are insufficient for making any solid estimation of human teratogenic risk, and classification is therefore based on animal data, with allocation to 3 subgroups. For products in category C, the pharmacological action of the drug may have undesirable effects on the human fetus or newborn infant. Finally, category D contains drugs for which human data indicate an increased incidence of malformations. The categorisation statement is always followed by a short explanatory text. In contrast to the FDA system, the Swedish system has been well accepted, as judged by an interview study including 934 physicians and pharmacists. We believe that much of the American dissatisfaction may be a consequence of shortcomings in the category definitions of the FDA system. The FDA system requires an unrealistically high quality of data, e.g. the availability of controlled studies in pregnant women that fail to demonstrate a risk to the fetus are needed for a drug to be assigned to category A. Consequently, the majority of drugs on the US market are allocated to category C, interpreted as 'risk cannot be ruled out'. The distribution of drugs into the various categories is thus very different between the Swedish and FDA systems. We think that the issue of this debate reflects a fundamental problem related to public health information: how should a large, compounded, changing and difficult to evaluate databank be organised before it is made available to professionals and secondarily to lay people?

Drug use during pregnancy and breast-feeding. A classification system for drug information.

Since 1978 the Swedish catalogue of registered pharmaceutical specialties (FASS) has carried a special section entitled "Pregnancy and breast-feeding" in each product presentation, intended to form an aid for the prescription of drugs to women during childbearing and lactation. After a brief review of transplacental transport and milk secretion, reproduction-toxicology studies in animals, and methods for clinical evaluation of drugs for use during pregnancy, the classification system is presented. On the basis of available data with regard to effects on early and late stages of pregnancy and labour, all the pharmaceutical specialties concerned are assigned to one of the following pregnancy categories: A, B 1, B 2, B 3, C or D. The letters refer to information based on findings in man, and the figures to information based on animal data. For drugs in categories B 3, C or D any harmful effects observed or likely to occur in man or animals are to be specified. The pregnancy categories are defined as follows: Category A. Drugs which may be assumed to have been used by a large number of pregnant women and women of child-bearing age, without any form of definite disturbance in the reproductive process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus. Category B. Drugs which may be assumed to have been used by only a limited number of pregnant women and women of child-bearing age, without any form of definite disturbance in the reproduction process having been noted so far, e.g. an increased incidence of malformations or other direct or indirect harmful effects on the fetus. Category C. Drugs which by their pharmacological effects have caused, or must be suspected of causing disturbances in the reproduction process that may involve risk to the fetus without being directly teratogenic. Category D. Drugs which have caused an increased incidence of fetal malformations or other permanent damage in man or which on the basis of e.g. reproduction-toxicology studies must be suspected of doing so. This category comprises drugs with primary teratogenic effects. If the drug also has pharmacological effects that may directly or indirectly have a harmful effect on the fetus, this must also be stated. As experience of effects of drugs in Category B is limited, results of reproduction-toxicology studies in animals are indicated by allocation to one of three subgroups according to the following definitions: Category B 1.(ABSTRACT TRUNCATED AT 400 WORDS)

PIP: Since 1978, the Swedish catalogue of registered pharmaceutical preparations (FASS) has classified drugs in terms of their effects on reproduction and breastfeeding. On the basis of available data concerning effects on pregnancy and labor, pharmaceutical specialties are asigned to 1 of the following pregnancy categories: A--drugs that have been used by large numbers of pregnant women and women of childbearing age with no evidence of any disturbance in the reproductive process; B--drugs that have been used by only a limited number of pregnant and reproductive age women, yet have not been noted to cause any harmful effects on fetal development; C--drugs whose pharmacological effects are suspected to cause disturbances in the reproductive process that may involve risk to the fetus without being directly teratogenic; and D--drugs that, on the basis of reproduction-toxicology studies, are suspected to have caused an increased incidence of fetal malformations. Of the 675 active substances identified in the drugs included in FASS 1984, 205 have been allocated to Category A, 183 to Category A, 183 to Category B, 118 to Category C, and 70 to Category D. Category C includes beta-adrenoceptor blocking agents, benzothiadiazines and related diuretics, dicoumarl, sufonamides, rifampicin, chloramphenicol, glucocorticoids, antithyroid substances, benzodiazepines, narcotic analgetics, ergotamine, and inhibitors of prostglandin synthesis; Category D includes ethanol, quinine and quinidine, chloroquine and hydroxycloroquine, warfarin, cytostatic drugs, tetracyclines, aminoglycosides, androgens and other anabolic steriods, gestagens, diethylstilbestrol, penicillamine, phenobarbital, and anticonvulsants. With respect to use during breastfeeding, drugs are allocated to the following 4 groups: Group I--does not enter breast milk; Group II--enters breast milk but is unlikely to affect the infant; Group III--enters breast milk in such quantities that there is risk of affecting the infant; and Group IV--not known whether it enters breast milk. Group IV comprises over 50% of the drugs listed.