OPTIMIZATION OF ANTIRHEUMATIC DRUG-TREATMENT IN PREGNANCY

Authors
Citation
M. Ostensen, OPTIMIZATION OF ANTIRHEUMATIC DRUG-TREATMENT IN PREGNANCY, Clinical pharmacokinetics, 27(6), 1994, pp. 486-503
Citations number
153
Categorie Soggetti
Pharmacology & Pharmacy
Journal title
ISSN journal
03125963
Volume
27
Issue
6
Year of publication
1994
Pages
486 - 503
Database
ISI
SICI code
0312-5963(1994)27:6<486:OOADIP>2.0.ZU;2-Y
Abstract
Active rheumatic disease during pregnancy may require drug treatment t o ensure the mother's health is maintained and that there is a good ou tcome for the fetus. However, knowledge on the use of antirheumatic dr ugs during pregnancy is limited, rendering decision making difficult b oth for the patient and the physician. The effect of nonsteroidal anti -inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis has been investigated in depth for aspirin (acetylsalicylic acid) and indomethacin only. Information about the use of ibuprofen, sulindac, k etoprofen and diclofenac during pregnancy is scanty and there is no su ch information for newer agents such as the fenemates and oxicams. The re is no evidence for teratogenicity of any NSAID in humans. However, due to the shared property of inhibition of prostaglandin synthesis, a dverse effects such as constriction of the ductus arteriosus in utero, persistent pulmonary hypertension in the neonate and prolongation of pregnancy and labour are possible. When administered to pregnant patie nts, NSAIDs should be given in the lowest effective dose, and should b e withdrawn within the 8 weeks prior to expected delivery. Transplacen tal passage varies for different corticosteroids. Because of the inabi lity of the fetal liver to convert prednisone to its active metabolite and the ability of the placenta to convert prednisolone to the inacti ve prednisone, both prednisolone and prednisone are drugs of choice in pregnant patients requiring corticosteroid treatment. Corticosteroids do not increase the risk of congenital malformations. Possible advers e effects are perinatal infection and adrenal insufficiency in the new born. Both events are only rarely reported in the literature, which co mprises information on more than 1000 pregnancies. The clinical experi ence on the effect of slow-acting antirheumatic drugs (SAARDs) on preg nancy is insufficient to draw substantial conclusions. Available data from the literature give no clear evidence of an increased risk of ter atogenicity for any of these drugs. Rheumatologists differ in their vi ew on the advisability of using SAARDs during pregnancy. Hydroxychloro quine, which is regarded as less toxic than chloroquine, is recommende d by some rheumatologists far the treatment of pregnant patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis. Sul fasalazine can be continued during pregnancy. Data on gold compounds a nd penicillamine are sparse and inconclusive. A reasonable approach is to stop these agents as soon as pregnancy is confirmed. The limited e xperience with cyclosporin has been obtained when the drug was used to prevent allograft rejection. Further data regarding the use of this d rug in pregnant patients with rheumatic diseases are needed. With the exception of azathioprine, which is not teratogenic in humans, the alk ylating antitumour agents and methotrexate increase the risk of congen ital malformations when given during the early stages of pregnancy. Cy clophosphamide, chlorambucil and methotrexate should not be prescribed to women of childbearing potential, unless effective birth control is being practised.