Drug Treatment of Osteoarthritis During Breastfeeding

Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the drugs of choice in osteoarthritis. Some sources recommend that topical NSAIDs should be considered before oral NSAIDs for hand or knee osteoarthritis pain. Topical NSAIDs, such as diclofenac gel, are good choices during breastfeeding because of their virtual lack of systemic effects.

Oral NSAIDs are generally acceptable to use during breastfeeding. They are weak acids that are highly protein bound in maternal plasma, so little reaches the breast milk. A few adverse effects have been reported in breastfed infants. Urticaria occurred in the newborn infant of a mother taking diclofenac and a few case reports of adverse effects in infants with antiarthritic dosages of maternal aspirin use have been reported, so aspirin is generally not recommended. While nursing a newborn, it is probably best to avoid long-acting drugs such as naproxen, because they might accumulate in the infant.

A concern with conventional NSAIDs such as naproxen is their antiplatelet effect. One case of severe gastrointestinal bleeding was reported in a newborn whose mother was taking naproxen. The cyclooxygenase II inhibitors, such as celecoxib, do not have antiplatelet activity and might be preferable to conventional NSAIDs. Ibuprofen, which has very low levels in breast milk, is also a good choice.

Some guidelines recommend that a proton-pump inhibitor (PPI) be given concomitantly with long-term NSAIDs. Only esomeprazole, omeprazole, and pantoprazole have information on their excretion into breast milk. Pantoprazole has the most published breast milk excretion data. In 12 mothers who were studied, it was undetectable for 80% of the day. After 7 days of therapy, the highest milk concentration averaged only 150 mcg/L. Omeprazole data consist of one case in which the peak milk level was 20 mcg/L. Esomeprazole had a peak milk level of 19.6 mcg/L in a woman taking 10 mg/day, which translates to an infant dose of only 3 mcg/kg daily.

The newer strontium salt of esomeprazole should probably be avoided because strontium is taken up into bone. Although none of the PPIs are officially approved in the United States for use in infants, they have been given directly to neonates and infants. The amounts of pantoprazole and omeprazole excreted into milk are 300–600 times less than doses reportedly given to neonates. In addition to their low excretion into breast milk, stomach acid degrades PPIs, which is why they are marketed as enteric-coated products. Therefore, any drug in breast milk may be destroyed in the infant's stomach and not systemically absorbed, at least in older infants.

Acetaminophen

Although not as effective in osteoarthritis as the NSAIDs, acetaminophen is a good choice for nursing mothers. Amounts in milk are much less than doses usually given to infants. Adverse effects in breastfed infants appear to be rare. Only one case report of an infant rash occurred with maternal use. It disappeared on drug discontinuation and reappeared on rechallenge.

Capsaicin

Topical capsaicin is used for local treatment of osteoarthritis of the knee. No information is available on the clinical use of topical capsaicin during breastfeeding. However, capsaicin is poorly absorbed after topical application, so it is not likely to reach the breast milk. Application of capsaicin to the mother's skin should not affect the infant as long as the infant's skin does not come into direct contact with the areas of maternal skin that have been treated. Signs of severe pain have been reported in an infant who ingested capsaicin from the mother's skin, so it should not be applied to parts of the body, such as the hand, that the infant might contact. A glove should be used to apply capsaicin.

Opioids

Pure opiate agonists are generally contraindicated in the treatment of osteoarthritis because of the risk of addiction with long-term use. However, tramadol is considered to be acceptable, although as a last-line therapy. The excretion of tramadol into milk is low and even lower amounts of the active metabolite, O-desmethyltramadol, are excreted. With usual maternal dosage, the amount excreted into breast milk is much less than the dose that has been given to newborn infants for analgesia. Studies in breastfed newborn infants found no adverse effects attributable to tramadol.

Although tramadol is unlikely to adversely affect nursing infants with usual maternal dosages, the U.S. Food and Drug Administration and the manufacturer recommend against the use of tramadol during breastfeeding because of its metabolic pathway, which is subject to genetic variability. If tramadol is used, infants should be monitored for increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, and a physician should be contacted immediately if any of these occur. A death occurred in the 8-month-old breastfed infant of a woman addicted to tramadol, although breastfeeding exposure alone might not have been the cause of death.

Duloxetine

Duloxetine is another last-line therapy for osteoarthritis, or as an alternative to weak opioids such as tramadol. Published information on the use of duloxetine during breastfeeding indicates that the dosage in milk is low (<1% of the maternal weight-adjusted dosage). Serum levels were low to undetectable in two breastfed infants. Expert opinion finds duloxetine acceptable to use during breastfeeding.

Dietary Supplements

Guidelines differ considerably in their recommendations on the use of dietary supplements, especially glucosamine and chondroitin for osteoarthritis. One even strongly recommends against their use in general.

Chondroitin sulfate consists of a mixture of large glycosaminoglycans and disaccharide polymers, usually derived from shark or bovine cartilage. It is most commonly used to treat osteoarthritis of the hand. Chondroitin sulfate is poorly absorbed orally with a bioavailability of ∼10%. It is well tolerated with occasional gastrointestinal upset reported.

Although no studies exist on the use of chondroitin supplements during breastfeeding, small amounts occur naturally in breast milk where it might have an inhibitory effect on microbial binding to cellular receptors in the infant, helping to prevent infections, or acting as an antioxidant to protect the infant from oxidative stress. Mothers of preterm infants excrete greater amounts of chondroitin into breast milk than mothers of full-term infants. The use of chondroitin by a nursing mother is unlikely to adversely affect the breastfed infant.

Glucosamine is an amino-monosaccharide that is either derived from shellfish or synthetically produced. Glucosamine sulfate is well tolerated with occasional gastrointestinal discomfort (e.g., diarrhea, heartburn, nausea, and vomiting) reported. Although no studies exist on the use of glucosamine during breastfeeding, its use by a nursing mother is unlikely to harm the breastfed infant.

Methylsulfonylmethane (MSM; dimethylsulfone) is used orally and topically to treat osteoarthritis. Adverse reactions after oral use are rare. MSM is also part of the normal human metabolome and can be found in breast milk in levels ranging from 0.9 to 1.2 mcg/L. No studies have been done on the use of MSM in nursing mothers, but its low toxicity indicates that it is unlikely to adversely affect the breastfed infant.

Turmeric (Curcuma longa) rhizome contains curcuminoids such as curcumin, which are considered to be the active components. Several meta-analyses on the use of turmeric in osteoarthritis of the knee found it to be about as effective as an NSAID.^4,5 No data exists on the excretion of any components of turmeric into breast milk. A small study found no adverse effects in infants exposed to turmeric in milk. In addition to being widely consumed in food, turmeric has been used as a galactogogue in India, although no scientific data support this use. In fact, curcumin suppresses milk production in lactating mammary epithelial cells in vitro.

Piperine is the main pungent compound in black pepper (Piper nigrum). Piperine is often incorporated into turmeric products because it enhances the oral bioavailability of curcumin. Piperine can be found in breast milk after maternal ingestion, but the levels appear to be far below the taste threshold after ingestion of typical amounts of pepper.

Intra-Articular Injections

Intra-articular injections of corticosteroids have not been studied during breastfeeding, but only small single doses are used and diffusion out of the joint space occurs slowly. In addition, only the highest doses of intravenous corticosteroids result in relevant doses in milk, so it is extremely unlikely that clinically important amounts enter breast milk after intrasynovial injection. A few cases of decreased breast milk production have been reported after injection of a corticosteroid into a joint space. Whether these occurrences are drug related or just coincidental is unknown.

Hyaluronic acid is a high molecular weight polysaccharide glycosaminoglycan that is found naturally in the synovial fluid and human milk. ⁶ It is injected into the knee joint for osteoarthritis. No studies have been done on its intrasynovial injection, but hyaluronic acid gel has been safely used vaginally in nursing mothers. ⁷ Because only small amounts are injected and it only slowly reaches the systemic circulation, it is unlikely that it enters the milk in clinically relevant amounts.

Summary

Many drugs are available for treating osteoarthritis in nursing mothers. Short-acting NSAIDs, acetaminophen, and topical agents are good choices. Turmeric may be a good choice for osteoarthritis of the knee.