*8.3.1 Biologic agents*

There is no sufficient data regarding biologic agents during pregnancy, so their use cannot be encouraged. Rituximab (RTX) is a B-cell depleting chimeric monoclonal antibody and is recommended to be stopped 6 months before conception. However, it has not been shown to be teratogenic [60, 64].

Belimumab (BEL) is BAFF inhibitor human monoclonal antibody and there is no sufficient data to recommend it during pregnancy. Until 12th week, IgG does not across placenta in significant amounts; so, accidental exposure to RTX or BEL during the first trimester is unlikely to be harmful. On the other hand, second/third trimester exposure will be associated with neonatal B-cell depletion [65].

**97**

*Systemic Lupus Erythematosus Pregnancy DOI: http://dx.doi.org/10.5772/intechopen.99008*

*8.4.1 Cyclophosphamide (CYC)*

*8.4.2 Mycophenolate mofetil*

*8.4.3 Methotrexate*

place [67].

*8.4.4 Leflunomide*

3 times a day, for 11 days).

**8.4 Drugs contraindicated during pregnancy**

Cyclophosphamide (CYC) is an alkylating drug used in SLE, to treat severe organ or life-threatening manifestations [60]. Due to its teratogenic effects, its use in pregnancy is contraindicated, especially during the first trimester, when the fetus is more susceptible to congenital malformations. Nevertheless, it can be considered in exceptional circumstances, when mother faces an organ- or life-threatening disease complication. Embryotoxicity varies according to the stage of gestation. The use of this drug in fertile women should always be carefully evaluated and counseling about fertility preservation strategies should be advised prior to its use [66].

Mycophenolate mofetil (MMF) is an inhibitor of purine biosynthesis, commonly used in LN, as both in induction and maintenance therapy, and is also used in severe to refractory non-renal manifestations, with the exception of neuropsychiatric lupus [60]. Due to its teratogenic effects, its use in pregnancy is contraindicated. MMF exposure can cause lip and cleft palate, abnormalities of distal limbs and malformations of multiple internal organs, such as heart, esophagus and kidneys [67]. For these reasons, it should be avoided. Alternative options are azathioprine, tacrolimus or low dose of glucocorticoids, which can be used to control disease

Methotrexate (MTX) is a folate antagonist – it inhibits the enzyme dihydrofolate

Leflunomide (LEF) is another drug that, although it may not be teratogenic, it is strongly advised to be avoided during pregnancy [68, 69]. It's an antimetabolite that inhibits dihydroorotate dehydrogenase, the catalyst enzyme responsible for the limiting step in pyrimidine biosynthesis. Despite its short half-life (approximately 15 days), its major metabolite follows a long path through enterohepatic circulation remaining detectable for more than 2 years. It is essential to complete its washout until undetectable levels before switching to alternative medication compatible with pregnancy and trying to conceive. For accelerate elimination of this drug, for example if an accidental pregnancy occurs, it is used cholestyramine (8 g orally,

reductase which impairs purine and pyrimidine synthesis. It is contraindicated during pregnancy, due to its teratogenic effects. MTX exposure *in utero* can induce multiple congenital abnormalities, such as cleft palate, hydrocephalus, anencephaly and meningoencephalocele, delayed ossification and multiple facial deformities. It is strongly advised contraceptive use in patients taking MTX. This medication should be discontinued 3 months before attempting to conceive. If a woman is being treated with a low dose of MTX within 3 months prior to conception, or an accidental pregnancy occurs, the drug should be stopped immediately and the mother should continue to take folate supplementation (5 mg daily) throughout pregnancy. In the last case, a careful evaluation of fetal risk at an experienced center must take

activity. They should be started, ideally, 6 months prior conception.
