Lactation data on non-steroidal anti-inflammatory drugs (NSAIDs), non-biologic and biologic drugs used to treat rheumatic diseases (publications 1970–2015)
| Drug | Number of cases* | Drug detected in breast milk† | Weight-adjusted dose‡, theurapeutic infant dose or milk:plasma ratio | Infant serum level | Reported side effects in breastfed children | Comments |
|---|---|---|---|---|---|---|
| Non-selective COX inhibitors (classical NSAIDs) | 28 | Not detected (n=20) Detected (n=14) | Weight-adjusted dose <0.1% (minimal). Dose <0.1–5% of therapeutic infant dose | No data | No adverse events (n=25) | Weak acids, with poor excretion in breast milk, but short half-life agents preferred in neonatal period |
| Selective COX II inhibitors | 25 | Not detected (n=9) Detected (n=16) | Weight-adjusted dose 0.1–1.2% (minimal) | Not detected (n=2) | No adverse events (n =2) | Data only for celecoxib |
| Prednisone | 24 | Detected(n=16) | Weight-adjusted dose < 1.5% (minimal) if maternal dose ≤ 50 mg | No data | No adverse events (n=7) | Consider a 4 h delay before breast feeding after prednisone dose >50 mg |
| Hydroxychloroquine | 18 | Detected (n=10) | Weight-adjusted dose < 2% (minimal) | No data | No adverse events (n=9) | Long half-life |
| Chloroquine | 61 | Detected (n= 61) | Weight-adjusted dose 0.6–14% (minimal–moderate) | No data | No data | Long half-life |
| Mepacrine (quinacrine) | 0 | No data | No data | No data | No data | |
| Sulfasalazine (SSZ) | 29 | Mesalamine not detected (n=1) Mesalamine detected low level (n=3) Sulfapyridine detected (n=7) | No data | SSZ not detected (n=5) SSZ detected (n=2) Sulfapyridine ≤ 10% of maternal serum level (n=6) | No adverse events (n=6) Bloody diarrhoea (n=1) | SSZ consists of sulfapyridine and mesalamine (5-aminosalicylic acid) which is considered to be the active component Caution in premature children,G6PD deficit and hyperbilirubinaemia |
| Leflunomide | 0 | No data | No data | No data | No data | Long half-life |
| Azathioprine§ | 72 | Not detected (n=14) Detected (n=11) | Weight-adjusted dose < 1% (minimal). Dose < 0.1% of paediatric transplant dose | Not detected (n=16) Detected low level (n=1) | No adverse events (n=56) Neutropenia (n=1) | Caution in thiopurine methyltransferase-deficient individuals |
| Methotrexate | 3 | Not detected (n=1) Detected low level (n=2) | No data | No data | No adverse events (n=1) | Limited excretion in breast milk due to mainly lipid insoluble form at physiological pH |
| Cyclophosphamide | 3 | Detected (n=1) | No data | No data | Neutropenia and bone marrow suppression (n=2) | Alkylating agent; risk for side effects in breastfed child |
| Ciclosporin | 76 | Detected; variable titres (n=19) | Weight-adjusted dose <2% (minimal). Dose <2% of paediatric transplant dose | Not detected (n=12) Detected (n=2) | No adverse events (n=68) | LipophilicTitres in milk dependent on fat content in sampled milk |
| Tacrolimus | 154 | Detected; variable titres (n=20) | Weight-adjusted dose <0,5% (minimal). Dose <0.5% of paediatric transplant dose | Not detected (n=15) Detected, level declining with time (n=4) | No adverse events (n=136) | LipophilicTitres in milk dependent on fat content in sampled milk |
| Mycophenolate mofetil | 7 | No data | No data | No data | No adverse events (n=7) | Blocks purine synthesis and inhibits lymphocyte proliferation |
| Colchicine | 154 | Detected (n=6) | Weight-adjusted dose < 10% (moderate) | Not detected (n=1) | No adverse events (n=149) | Reconsider breast feeding if infant has diarrhoeaDue to drug interaction, be aware of macrolide prescription in breastfed infants. |
| IVIG | 149 | IgG normal (n=1) IgG high (n=1) | No data | No data | No adverse events (n=146) Transient rash (n=1) | Normal component of breast milk |
| Tofacitinib | 0 | No data | No data | No data | No data | Low molecular weight might facilitate its passage into milk |
| Infliximab§ | 25 | Not detected (n=5) Detected low level (n=17) | Milk:plasma ratio 1:200 (minimal) | Detected low level (n=1) Not detected (n=2) | No adverse events (n=18) | Large protein molecule, absorption unlikely due to low bioavailability |
| Adalimumab§ | 10 | Not detected (n=6) Detected low level (n=3) | Milk:plasma ratio 1:100–1: 1000 (minimal) | Not detected (n=2) | No adverse events (n=7) | Large protein molecule, absorption unlikely due to low bioavailability |
| Golimumab§ | 0 | No data | No data | No data | No data | Large protein molecule, absorption unlikely due to low bioavailability |
| Etanercept§ | 4 | Detected low level (n=4) | Milk:plasma ratio 1:1000–1:2000 (minimal) | Detected at birth, but not during breastfeeding period (n=2) | No adverse events (n=1) | Large protein molecule, absorption unlikely due to low bioavailability |
| Certolizumab§ | 8 | Not detected (n=1) | No data | Not detected (n=1) | No adverse events (n=8) | Large protein molecule, absorption unlikely due to low bioavailability |
| Rituximab | 0 | No data | No data | No data | No data | Large protein molecule, absorption unlikely due to low bioavailability |
| Anakinra | 1 | No data | No data | No data | No adverse events (n=1) | IL-1Ra is a normal component of human milk |
| Ustekinumab | 0 | No data | No data | No data | No data | Large protein molecule, absorption unlikely due to low bioavailability |
| Tocilizumab | 0 | No data | No data | No data | No data | Large protein molecule, absorption unlikely due to low bioavailability |
| Abatacept | 0 | No data | No data | No data | No data | Large protein molecule, absorption unlikely due to low bioavailability |
| Belimumab | 0 | No data | No data | No data | No data | Large protein molecule, absorption unlikely due to low bioavailability |
*Publications on breast feeding including maternal drug levels, infant drug levels or reports on side effects in breastfed children. Publications may include one, two or all three parameters.
†The definition of detected or not detected agent in breast milk varies by method and chosen cut-off value.
‡Weight-adjusted dose is child dose (mg/kg in child) relative to mother dose (mg/kg in mother): <2%=minimal, 2–5%=low, 5–10%=moderate, 10–50%=high.70
§Caution with the use of TNF inhibitors + thiopurines. These combinations might increase the risk of infant infections.71
IVIG, intravenous immunoglobulin; TNF, tumour necrosis factor.