Antirheumatic drugs and risk during pregnancy (modified and updated from Hazes et al23)
| Drug class | FDA category | Effects on pregnancy or exposed babies | Clinical recommendations in female patients |
|---|---|---|---|
| NSAIDs | B (in early stage of pregnancy) C (after week 30) | Late in pregnancy can cause premature closure of the ductus arteriosus, increase the risk of neonatal bleeding, impairment of fetal renal function and development of oligohydramnios | Compatible with pregnancy in first half of the pregnancy23 |
| STEROIDS | C | In doses >10 mg/day during pregnancy they can have adverse side effects both on mothers (diabetes, hypertension, osteopaenia, infections) and fetuses (prematurity, low birth weight, IUGR, infections, adrenal suppression, oral cleft) | Compatible with pregnancy in doses up to 10–15 mg/day (prednisolone equivalent)23 24 |
| METHOTREXATE | X | Potential embryotoxicity and teratogenicity in animal and human pregnancy | Discontinuation 3–6 months before conception23 |
| LEFLUNOMIDE | X | Potential embryotoxicity and teratogenicity in animal and human pregnancy | Discontinue 2 years before pregnancy or use cholestyramine washout procedure23 |
| SULFASALAZYNE | B | No increase in malformation in human pregnancy | Compatible with pregnancy;Folate supplements needed23 |
| ANTIMALARIALS | C | Malformations of the inner ear after treatment with higher than the recommended dose of chloroquine25 | Hydroxychloroquine compatible with pregnancy23 |
| CYCLOSPORIN A | C | Increase in premature delivery and low birth weight, but no increase of congenital malformations | Compatible with pregnancy in patients with autoimmune disease refractory to other immunosuppressive treatment26 |
| AZATHIOPRINE | D | No increase in malformation in human pregnancy; potential teratogenicity in animal models | Compatible with pregnancy23 |
| TNFa INHIBITORS | B | No increase in miscarriage or birth defects | Discontinuation after pregnancy detection. If used during pregnancy, they should be discontinued before gestational week 3024 |
| ABATACEPT | C | No conclusive human data | Discontinuation 3 months before conception24 |
| TOCILIZUMAB | C | No conclusive human data | Discontinuation 3 months before conception24 |
| RITUXIMAB | C | No increase in miscarriage or malformation. Exposure during the second and third trimesters possibly causes B cell depletion in the fetus | Discontinuation 12 months before conception27 |
| ANAKINRA | B | Animal data: no harm in offspring. No conclusive human data | Discontinuation after pregnancy detection24 |
The US FDA pregnancy risk categories are as follows: A, no risk in controlled clinical studies in humans; B, animal studies show no risk and human data is reassuring even if well-controlled studies of pregnant women have not been conducted; C, human data are lacking and animal studies show risk (or have not been undertaken); D, positive evidence of human fetal risk: use only if potential benefit outweighs the risk; X, studies in animals or reports of adverse reactions show positive evidence of risk: contraindication during pregnancy.
FDA, Food and Drug Administration; NSAIDs, nonsteroidal anti-inflammatory drugs; TNF, tumour necrosis factor.