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Table 2 Commonly used drugs in inflammatory rheumatological diseases, their fetal effects, and recommendations during pregnancy

From: Managing pregnancy in inflammatory rheumatological diseases

Class Drug Fetal effects Recommendation
Analgesic Paracetamol Not known to be harmful Can be used during pregnancy
Analgesic (high dose) and antiplatelet agent (low dose) Aspirin Low dose (antithrombotic dose) 75 mg daily is safe and lowers risk of premature delivery and pre-eclampsia. At higher doses (analgesic doses), there is potential risk of impaired renal function, pulmonary hypertension, or clotting ability in newborn. Can be continued throughout pregnancy
Anti-inflammatory (analgesic) drugs NSAIDs If given within 14 days of delivery, premature closure of ductus arteriosus, which can lead to pulmonary hypertension. Possible risk of cardiac septal defects and gastroschisis Discontinue at 32 weeks of gestation earlier if premature delivery suspected. Need 2-week gap between stopping
NSAIDs and delivery. If needs to be used, ibuprofen preferred to
diclofenac as shorter half-life.
Analgesic Codeine Respiratory depression and withdrawal symptoms in neonate if opioid used during delivery Use at lowest effective dose, but avoid during labor.
Analgesic Pethidine Respiratory depression and withdrawal symptoms in neonate if opioid used during delivery Can be used during pregnancy
Analgesic Tramadol Embryotoxicity in animals Avoid during pregnancy
Analgesic Morphine Respiratory depression and withdrawal symptoms in neonate if opioid used during delivery Avoid during pregnancy
Anti-infl ammatory (analgesic) agent Cyclo-oxygenase inhibitors (COX inhibitors) Impaired renal function, decreased fetal urine output, development of oligohydramnios. Teratogenic in animal studies. Should be avoided
Immunosuppressive agents Corticosteroids Prolonged treatment >15 mg/day increases risk of premature rupture of membranes and preterm labor. Increased risk of oral cleft and palate at high doses. Can be continued in pregnancy but should be lowest effective dose. (See 'Drugs' subsection of 'Management of pregnancy' section.)
Disease-modifying agent Hydroxycholoquine No associated congenital abnormalities or malformations Can be continued throughout pregnancy
Disease-modifying agent Sulphasalazine Folic acid antagonist. Associated with two- to threefold increased risk of oral clefts and cardiovascular anomalies Risk diminished by concomitant use of folic acid throughout pregnancy. Can be continued in pregnancy but requires folic acid supplementation throughout pregnancy
Disease-modifying agent Azathioprine Small risk of depressed hematopoiesis in infant in doses of >2 mg/kg per day Can be continued in pregnancy, not more than 2 mg/kg per day
Disease-modifying agent Ciclosporin No increase in rate of birth defects but risk of maternal hypertension and intrauterine growth restriction Can be continued in pregnancy up to dose of 2.5 mg/kg per day
Disease-modifying agent Cyclophosphamide Embryopathy with growth defects, developmental delay, craniofacial defects, or distal limb defects Discontinue at least 3 months prior to conception. Effective contraception vital during this time
Disease-modifying agent Methotrexate Increased risk of congenital abnormalities in central nervous system, cranial ossification, limbs, palate, and growth retardation. Discontinue 3 months prior to conception. Wait at least one menstrual cycle after stopping drug before trying to conceive.
Disease-modifying agent Leflunomide Inhibits de novo synthesis of pyramidine in activated lymphocytes, leads to increased risk of embryotoxicity and teratogenicity in animals. Stop 2 years before conception or use washout procedure with cholestyramine.
Disease-modifying agent Mycophenolate mofetil Recently identified phenotype of craniofacial malformations affecting oral cavity and ears as well as ocular anomalies. Less frequently, limb abnormalities, with congenital cardiovascular, renal, or central nervous system malformations Discontinue and switch to azathioprine at least 3 months prior to conception.
Disease-modifying agent Gold salts Cross placenta, found in fetal liver and kidneys, no evidence of increase in neonatal malformations in small number of reports available May be continued
Biological agent Tumor necrosis factor- alpha inhibitors (for example, infliximab etanercept, adalimumab) No toxic effects in animals, sporadic adverse events in humans but insufficient to determine toxicity or safety Discontinue at missed period or positive pregnancy test.
Biological agent Abatacept Crosses placenta in animals, no data in human pregnancies Discontinue at least 10 weeks prior to conception.
Biological agent Anakinra No evidence with human pregnancy Discontinue use prior to conception.
Biological agent Rituximab Actively transported across placenta, with neonatal levels being higher than maternal levels. Can lead to transient B-cell depletion in neonate, no infections reported Discontinue 1 year prior to conception.
Prevention or treatment of osteoporosis Bisphosphonates Cross placenta and accumulate in fetal bone, causing bone abnormalities in animals. Discontinue 2 years before planned pregnancy as retained in human skeleton and released in circulation for at least 2 years after stopping drug
Prevention or treatment of osteomalacia and osteoporosis Calcium and vitamin D supplements Therapeutic doses unlikely to be harmful. Can be continued in pregnancy
H2 blocker to reduce gastric acid production Ranitidine Not known to be harmful Can be continued in pregnancy (extensive experience)
Proton pump inhibitors Omeprazole (lansoprazole) Not known to be harmful May be continued (less experience)
Anti-hypertensive agent Angiotensin- converting enzyme inhibitors Adversely affect fetal and neonatal blood pressure control and renal function. Skull defects and oligohydramnios have been reported. Discontinue 3 months prior to conception. Contraindicated in pregnancy except possibly in scleroderma renal crisis.
Anti-hypertensive agent and vasodilator Calcium channel blockers No significant abnormalities Can be continued in pregnancy (more experience with nifedipine than amlodipine or others)
Anticoagulant Heparin Does not cross placenta and is not associated with congenital defects Can be continued in pregnancy, but owing to heparin-induced osteopenia, calcium and vitamin D supplements are needed
Anticoagulant Warfarin Risk of fetal warfarin syndrome Contraindicated in first and third trimesters of pregnancy but can be used in postpartum period