Immunosuppressive drugs and fertility

Abstract

Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs.

Gravidez, Aleitamento e Fármacos em Dermatologia - Tratamento Sistémico

“…90 Um intervalo mínimo de um a três meses entre a interrupção do metotrexato e a conceção é recomendado. 5,91 O metotrexato é excretado no leite e, embora as concentrações aqui obtidas sejam baixas, pode acumular-se em recém-nascidos com função renal imatura, devendo por isso ser evitado durante a amamentação. 5,15,92 10.…”

“…93 Apesar de não ser comprovadamente teratogénica, associa-se a um maior risco de baixo peso ao nascimento e prematuridade. 91 Existem centenas de recém-nascidos expostos in utero à ciclosporina, que foram seguidos durante a infância, sem evidência de repercussões ao nível do desenvolvimento neurológico, renal ou imunológico a longo prazo. [94][95][96] Pelo risco acrescido de hipertensão arterial na gravidez, a ciclosporina deve ser reservada apenas como terapia de resgate por curtos períodos de tempo e na menor dose eficaz possível.…”

“…Há poucos dados sobre a exposição ao micofenolato de mofetilo em fases mais tardias da gravidez, mas pode resultar em alterações hematológicas nos recém--nascidos. 91 Desta forma, o micofenolato de mofetilo não deve ser usado durante a gravidez e a administração deve ser interrompida pelo menos um mês e meio antes da conceção. 5,102 Estudos com modelos animais mostram uma significativa transferência de micofenolato de mofetilo para o leite de ratos lactantes.…”

Preparation and in vitro/pharmacokinetic/pharmacodynamic evaluation of a slow-release nano-liposomal form of prednisolone

“…Glucocorticoids belong to one of the main important classes of immunosuppressive and anti-inflammatory drugs widely used in treatment of many diseases such as allergies, asthma, autoimmune diseases and sepsis (McDonough et al, 2008;Leroy et al, 2015). However, chronic use of these drugs often leads to severe systemic side effects like immunosuppression, thinning of the skin, osteoporosis, induction of diabetes and adrenal failure, thus decreasing patient's quality of life (Saag, 2002;Schiffelers et al, 2006;van den Hoven et al, 2011;Leroy et al, 2015).…”

“…However, chronic use of these drugs often leads to severe systemic side effects like immunosuppression, thinning of the skin, osteoporosis, induction of diabetes and adrenal failure, thus decreasing patient's quality of life (Saag, 2002;Schiffelers et al, 2006;van den Hoven et al, 2011;Leroy et al, 2015).…”