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 |