Breast-feeding & Rheumatoid Arthritis

Dr Nick Sheehan MBChB MD FRCP
Original article: 01/08/2001
Reviewed: 03/03/2009
Next review due: 03/03/2012

Introduction

Rheumatoid arthritis (RA) is more than twice as common in women as in men and its incidence in women increases steadily up to their mid forties. Women of childbearing age therefore constitute a substantial percentage of people with rheumatoid arthritis. This raises the important question of which of the drugs prescribed for rheumatoid arthritis are safe to take during pregnancy and breast-feeding.

Firstly, there is no reason why the majority of women with rheumatoid arthritis should not have children and breast-feed them if they want to. The long-term outcome of rheumatoid arthritis is not adversely affected by pregnancy. Obstetric complications are infrequent and successful pregnancy, a normal delivery and a healthy infant are the rule.

About three quarters of women find that their arthritis becomes less active or even goes into remission during pregnancy. The improvement usually begins in the first trimester and it normally continues throughout the pregnancy. A major bonus of this is that it allows their medication to be reduced to a minimum.

The downside is that the majority of women relapse after giving birth, sometimes within a matter of hours of delivery and usually within three months. The maximum rate of relapse occurs between four and six weeks after the birth of the baby. The flare-up can persist for six months but disease activity usually settles to pre-pregnancy levels within a year.

This post-partum flare has particular implications for the choice of suitable anti-arthritic drugs in women who wish to breast-feed. Breast-feeding does not delay the relapse nor influence its severity but careful attention must be given to the choice of medication as some drugs taken by nursing mothers can pass through the milk to the infant. Thus it is advisable that mothers take only essential medications for their arthritis while breast-feeding in order to minimise the risk of harm to their baby. Clear guidance as to which drugs can be taken safely and which should be avoided is given in the British National Formulary (BNF), a prescribing handbook used widely by doctors. However, as there is a lack of information on the transfer of many drugs to breast milk and their possible effects on the suckling infant, as a general principle, it is advisable to reduce medication to a minimum during lactation, aiming to control disease activity and symptoms using the least hazardous drugs in the smallest possible dose. It is important to remember that the benefits associated with breast-feeding may outweigh the risks of a carefully chosen drug or drugs.

Painkillers (Analgesics)

As can be seen from the Table, codeine and paracetamol can be taken safely by nursing mothers. Generally, there is little risk with non-steroidal anti-inflammatory drugs (NSAIDs) either. However, where insufficient information is available about the secretion of a drug into maternal milk or its possible untoward effects on the infant are unknown, the manufacturer will usually advise that the drug be avoided during breast-feeding. This is the situation for two thirds of the NSAIDs and even in the cases of ibuprofen and ketoprofen where the amount of drug reaching the breast milk is probably too small to be harmful, the manufacturers of some brands recommend that they should be avoided unless essential. Nevertheless, there are still plenty of safe NSAIDs to meet the needs of most nursing mothers.

Acceptability of painkilling drugs during breast-feeding

Acceptable	Insufficient data–preferably avoid	Avoid
NSAIDs: Dexibuprofen Diclofenac Fenoprofen Flurbioprofen Ibuprofen Piroxicam Tiaprofenic acid	Ketoprofen Sulindac Tenoxicam	Aceclofenac Acemetacin Aspirin Azapropazone Celecoxib Dexketoprofen Etodolac Etoricoxib Fenbufen Indometacin Mefanamic acid Meloxicam Nabumetone Naproxen
Other analgesics: Codeine Paracetamol	Tramadol

Because individual drugs may have several different brand names, only the approved name is given in the table. The approved name, or generic name as it is otherwise known, is normally shown somewhere on the tablet bottle or packet.

Disease-modifying drugs for rheumatoid arthritis, including corticosteroids

Most disease-modifying anti-rheumatoid drugs (DMARDs) are stopped during pregnancy and their reintroduction can usually be postponed until after the mother has finished nursing. If her arthritis flares up severely and needs to be suppressed, the choices are normally between ceasing breast-feeding and reintroducing a DMARD or alternatively taking corticosteroids until the natural end of lactation. Doses of up to 40mg a day of prednisolone can be taken by the mother without any likely adverse effect on the infant.

Amongst the DMARDs, sulphasalazine and gold (by intramuscular injection as sodium aurothiomalate or in tablet form as auranofin) both pass into the breast milk in small amounts with a theoretical risk of causing side-effects in the baby. However, sulphasalazine is considered safe to take whereas gold should preferably be avoided. Of the antimalarial drugs, the amount of chloroquine in breast milk is probably too small to be harmful but, although this is also likely to be true for hydroxychloroquine, the general advice is that both should be avoided because of the risk of toxicity in the infant.

The immuno-suppressant drugs methotrexate and cyclophosphamide must not be taken during lactation. Cyclophosphomide is especially strongly contra-indicated as it is secreted in large amounts into breast milk. Leflunamide and ciclosporin are also both secreted into breast milk and should not be taken by nursing mothers.

The low concentrations reached by azathioprine are probably not harmful to the infant but it is usually avoided during breast-feeding.

As the excretion of penicillamine in human breast milk has not been studied, its use during lactation is contra-indicated. However, it is prescribed infrequently nowadays anyway.

If the introduction of a DMARD is unavoidable in a woman who is keen to continue breast-feeding, sulphasalazine, the antimalarials and azathioprine are probably the safest options.

Biologic Agents

Adalimumab, etanercept and infliximab suppress rheumatoid arthritis by blocking the actions of tumour necrosis factor-alpha (TNF α blockers), a chemical which plays a major part in joint inflammation. No information is available yet about the safety or otherwise of the TNF α blockers in breast-feeding and they should therefore be avoided. Indeed the manufacturers of adalimumab and infliximab advise that breast-feeding should not be permitted for at least five to six months after the last dose as the drugs are eliminated very slowly from the body. Anakinra inhibits interleukin-1, another chemical which promotes inflammation. Rituximab suppresses joint inflammation by reducing the numbers of B lymphocytes. They should also be avoided during lactation on account of their unknown effects on the infant.

Other drugs

Some people receiving treatment for rheumatoid arthritis also require other drugs, for example to prevent indigestion caused by their anti-inflammatory medication. Drugs prescribed for dyspepsia associated with NSAIDs include H2-receptor antagonists (cimetidine, famotidine, nizatidine, ranitidine), proton-pump inhibitors (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) and the prostaglandin analogue, misoprostol.

Cimetidine, famotidine and ranitidine pass into breast milk in significant amounts and, although they are not known to be harmful to the infant, the manufacturers of cimetidine and famotidine advise that they be avoided during breast-feeding. The amount of nizatidine which reaches the milk is too small to be harmful. Lansoprazole and pantoprazole have been found in breast milk in animal studies and should not be used unless essential. Omeprazole reaches the milk but is not known to be harmful. No information is available for esomeprazole or rabeprazole and both should be avoided. Misoprostol should be avoided for the same reason.

Because of the protective effect of their natural sex hormones, only a small minority of women of childbearing age with rheumatoid arthritis need to take medication to prevent osteoporosis. However it may be advisable if they have been on corticosteroids for a long period of time. Commonly prescribed drugs for this purpose are disodium etidronate (Didronel), alendronic acid (Fosamax) and risedronate sodium (Actonel). As there is no information about these drugs in lactation they should not be restarted until after the baby has been weaned.

Conclusion

Although there are considerable restrictions on the medication that it is advisable for a woman to take while breast-feeding, this should not deter a mother from nursing her baby if she wishes to. If her arthritis flares up after giving birth there are various safe ways in which it can be treated while avoiding drugs which are potentially harmful to the baby or the effects of which are simply unknown.

References

The recommendations contained here are based principally on the guidance given in the BNF (British National Formulary).