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Table 1 Medication in women with CKD in relation to conception, pregnancy and lactation. Adapted from Wiles et al. [(268])

From: Clinical practice guideline on pregnancy and renal disease

Drug Conception (see Section 3.3) Pregnancy Lactation References
Overall Maternal considerations Fetal considerations
Antihypertensive drugs (see section 4.4)
 Labetalol Safe Safe License for pregnancy. Avoid if asthmatic. No association with congenital abnormalities.
Reduced birth weight in unadjusted observational data.
Neonatal bradycardia (2%) and hypoglycaemia (5%).
Safe [11,11,12,13,14,15,16]
 Nifedipine Safe Safe None No association with congenital abnormalities. Safe [14, 15]
 Amlodipine Safe Limited data. None Limited data. No adverse effects reported. Safe [17, 18]
 Methyldopa Safe Safe Avoid in depression or if risk of depression. No association with congenital abnormalities. Avoid in all due to risk of postnatal depression. [14, 15]
 Doxazosin Safe Limited data None No evidence of harm in animal studies < 1% maternal dose detected. [15]
 Hydralazine Safe Safe Risk of hypotension, tachycardia No association with congenital abnormalities Safe [15]
 Beta-blockers Safe Limited data on individual drugs Avoid if asthmatic. Use in pregnancy determined by maternal indication. No association with congenital abnormalities.
Reduced birth weight, clinical significance unclear.
Neonatal bradycardia (1%) and hypoglycaemia (3%).
No adverse effects reported [15, 16, 19,20,21,22]
 Angiotensin converting enzyme inhibitors No apparent increase in risk with first trimester use when data are corrected for underlying hypertension. Continue until conception if required for nephroprotection. Unsafe None Fetotoxic in second and third trimesters leading to fetal and neonatal renal failure, bone and aortic arch malformations, oligohydramnios, and pulmonary hypoplasia. Safety data available for captopril and enalapril. [14, 15, 23,24,25]
 Angiotensin receptor antagonists Insufficient data on exposure in early pregnancy. Discontinue in advance of pregnancy. Unsafe None Fetotoxicity in second and third trimesters comparable to angiotensin converting enzyme inhibitors. No data. [14, 15]
 Thiazide diuretics Insufficient data on exposure in early pregnancy. No evidence of harm. Unsafe Reduced plasma volume expansion in pregnancy (n = 10) No evidence of thrombocytopenia, jaundice, hypokalaemia or hyponatraemia in meta-analysis (n = 5292) but advised to avoid. Potential suppression of lactation. Avoid. [15, 26, 27]
Immunosuppressant drugs (see Section 5.1 and 5.3)
 Corticosteroids Safe Safe Potential risks: diabetes, hypertension, pre-eclampsia, infection, preterm rupture of membranes. Aim for minimum maintenance dose. Fetus exposed to < 10% maternal dose due to placental deactivation. No evidence of increase in congenital abnormalities. Safe. Small amounts in breast milk. Consider timing feeds to 4 h post administration if high dose given (e.g. methylprednisolone induction) and monitor neonate. [15, 28,29,30,31]
 Hydroxychloroquine Safe Safe Withdrawal may precipitate lupus flare. Indicated throughout pregnancy if patient has a history of lupus nephritis. Placental transfer. No increase in miscarriage or congenital abnormality. May reduce risk of congenital heart block if maternal anti-SSA and or anti-SSB antibodies. Safe [15, 32,33,34,35,36,37]
 Azathioprine Safe Safe Recommend check TPMT status before dosing. Placental transfer. No association with congenital abnormalities. Safe. Low concentration in breast milk [7, 15, 38,39,40]
 Ciclosporin Safe Safe Monitor pre-dose levels more frequently in pregnancy and immediately post partum. May need higher dose in pregnancy.
Avoid medications which interfere with calcineurin inhibitor metabolism (e.g. erythromycin, clarithromycin). Increased risk of gestational diabetes
Placental transfer. No association with congenital abnormalities. Safe [15, 41, 42]
 Tacrolimus Safe Safe Monitor pre-dose levels more frequently in pregnancy and immediately post-partum. May need a higher dose in pregnancy.
Avoid medications which interfere with calcineurin inhibitor metabolism (e.g. erythromycin, clarithromycin). Increased risk of gestational diabetes
Placental transfer. No association with congenital abnormalities. Safe [15, 43,44,45]
 Mycophenolate mofetil Unsafe. Effective contraception during treatment and for 6 weeks after treatment. Ensure disease/transplant stability prior to conception. Unsafe None Placental transfer. Teratogenic causing ear, heart, eye, lip/palate, kidney, and bone abnormalities, tracheoesophageal fistula, congenital diaphragmatic hernia. Increased miscarriage. Avoid use during lactation due to insufficient data. [7, 15, 39, 46]
 Cyclophosphamide Unsafe. Effective contraception during and for 3 months after treatment. Dose- and age-related risk of infertility. Unsafe None Placental transfer. Teratogenic. Congenital abnormalities of the skull, ear, face, limb and visceral organs. Increased risk of miscarriage. Excreted in breast milk. Discontinue breast-feeding during and for 36 h after treatment. [7, 15, 34, 47, 48]
 Rituximab Unclear (limited data available). Treatment decision depends on indication and alternative options. Unclear (limited data available) If indicated for severe disease, aim to give dose before, or in early, pregnancy to minimise the risk of neonatal B-cell depletion. Active placental transfer in 2nd and 3rd trimester. Potential risk of neonatal B-cell depletion. Avoid unless potential benefit to woman outweighs risk. Long term effects unknown. Unclear (limited data available). Possible excretion of trace amounts but neonatal absorption unlikely. [7, 15, 39, 49, 50]
 Sirolimus / Everolimus Unsafe – fetal toxicity in rats. Effective contraception during and for 3 months after treatment. Unsafe Impaired wound healing. Proteinuria. Likely placental transfer. Toxicity in animal studies Limited data available Avoid. [15, 51, 52]
 Eculizumab Unclear (limited data available). Treatment decision depends on indication and alternative options. Unclear (limited data available) Morbidity of underlying condition may mean treatment in pregnancy is required. Monitor for increased dosage requirements. Active placental transfer in 2nd and 3rd trimester. No congenital abnormality reported in 20 infants. Long-term effects unknown. Limited data available. Possible excretion of trace amounts but neonatal absorption unlikely. [15, 53, 54]
Other drugs
 Aspirin (75–150 mg) (see Section 4.3) Safe Safe Decreases risk of pre-eclampsia in general obstetric population. No evidence of maternal haemorrhagic complications. Insufficient data on optimum dose (i.e. 75 mg versus 150 mg). No association with congenital abnormalities. Safe [8, 9, 14, 15]
 Iron (see Section 4.6) Safe Safe Intravenous preparations may offer better bioavailability in CKD Safety data available in 2nd and 3rd trimesters but limited data on exposure on the first trimester. Expert consensus is not to withhold IV iron if indicated in the first trimester. Safe [15, 55,56,57,58,59]
 Low-molecular- weight heparin Safe Safe Level of proteinuria which confers a significant risk of VTE in pregnancy is unclear. All pregnant women should be risk assessed for VTE. No placental transfer. Safe [10, 15]
 Erythropoietin (see section 4.6) Safe Safe Monitor blood pressure. No placental transfer. Safe [15, 60,61,62]
 Metformin (see Section 5.4) Safe Safe Use contraindicated outside of pregnancy if eGFR < 30 ml/min/1.73m2 (approximates to serum creatinine > 150 μmol/L in pregnancy). None Levels in milk are low, infants receive < 0.5% of maternal weight-adjusted dosage. No reported adverse effects. [2, 15]