Treatment of Nail Fungus While Breastfeeding

Oral Therapy

Oral therapy of onychomycosis is more effective and has a shorter duration of treatment than topical therapy. However, side effects are more likely with oral therapy and little information is available on the use of these drugs during breastfeeding.

Terbinafine appears to be the most effective oral treatment for onychomycosis. Lactation information on terbinafine in humans is not published, but a study was reported by the original manufacturer. Two healthy women were not breastfeeding, but had some milk production. After an 8-hour fast, they were each given four 125 mg tablets of terbinafine, which is double the recommended daily dosage. All milk was collected at 6-hour intervals for 72 hours after the dose. The highest concentrations of terbinafine in milk occurred in the first 6-hour aliquots and were 7.3 and 7.9 mg/L.

Using the average milk concentration values over the 24-hour period in the two subjects, an exclusively breastfed infant would receive 3.8% of the maternal weight-adjusted dosage of terbinafine, which is below the typical acceptable cutoff of 10%. Some older U.S. package inserts for generic terbinafine state that milk concentrations of terbinafine are sevenfold the maternal plasma concentrations. Communication with the U.S. manufacturer indicates that this value was derived from an animal experiment. This value is not relevant to humans.

Fluconazole is an azole antifungal that has been studied in nursing mothers for use in Candida mastitis. Two case reports of mothers taking fluconazole found low levels in milk. Using peak milk level data from these two patients, an exclusively breastfed infant whose mother was taking 200 mg daily of fluconazole would receive a maximum of about 0.6 mg/kg daily, which is 60% of the recommended neonatal (<2 weeks) infant dosage and 20% of the dosage used in older infants for oral thrush.

In a study of fluconazole for treatment of lactation-associated thrush of the breasts, mothers took an average of 7.3 capsules (range 1 to 29 capsules) of 150 mg every other day until pain resolved. Seven of the 96 women reported side effects possibly caused by fluconazole in their breastfed infants. These included flushed cheeks, gastrointestinal upset, and runny or mucous stools.

Itraconazole is an azole that has no published information available on its use during breastfeeding. However, an unpublished study reported two healthy volunteers who each took two oral doses of itraconazole 200 mg 12 hours apart, which is half the recommended dose. Milk samples were obtained with a breast pump at 4, 24, and 48 hours after the second dose. Average milk concentrations of itraconazole were 70.2, 27.7, and 16.2 mcg/L, respectively. At 72 hours, the milk level was 20.1 mcg/L in one woman and not detectable (<5 mcg/L) in the other.

Using data reported in the literature, including their study, researchers estimated that fully breastfed infants between 3 and 12 months of age would receive 1.5% of the mother's weight-adjusted dosage of itraconazole and infants would attain a plasma concentration of 0.77% of the mother's plasma concentration. Treatment for toenail infections lasts for 12 weeks, and no data are available for this duration in nursing infants, but itraconazole is indicated for long-term treatment in infants at a dose of 5 mg/kg twice daily for fungal infections of the central nervous system. Monitoring of the nursing infant's liver enzymes should be considered during long courses of maternal therapy. Fluconazole is probably preferable to itraconazole.

Griseofulvin has been available for decades and is approved for treatment of onychomycosis. It is rarely used now because it is less effective, requires a longer duration of treatment, and causes more adverse effects than other antifungal drugs. No information is available on its use during nursing. Because of its toxicity and very long half-life, it should be avoided during breastfeeding.

Oteseconazole is a new azole antifungal with an exceptionally long half-life that is indicated for treating recurrent vulvovaginal candidiasis. It has been used investigationally for treating onychomycosis; however, it must be avoided in women of reproductive potential because of its possible fetal toxicity based on animal studies and its extraordinarily long half-life of 138 days. This means that the drug could persist in a nursing mother for >2 years, during which time she could become pregnant again. No information is available on the use of the drug during lactation.

Posaconazole, fosravuconazole, and ravuconazole are other azole antifungals that are being investigated for onychomycosis. None of these have been studied during lactation.

Topical Therapy

Because information is sparse, opinions vary on the acceptability of topical antifungals during breastfeeding, with many authors citing package inserts, older review articles or even the outmoded pregnancy categories as justification to contraindicate the drugs during nursing. ² In reality, so little drug is absorbed after application to the nails, topical drugs are not a great concern during breastfeeding.

Ciclopirox has not been studied during breastfeeding. Because only ∼1.3% is absorbed after topical application, it is considered a low risk to the nursing infant.

Efinaconazole has the highest cure rate of current topical products for onychomycosis, although it is only ∼50% effective as a mycological cure and <20% effective in creating a complete cure. Women with a short duration of disease are more likely to respond than others and experts recommend efinaconazole as the first-line agent for mild-to-moderate onychomycosis and as maintenance therapy to prevent relapse. ³

Efinaconazole and tavaborole have not been studied during breastfeeding. Because maternal blood levels are very low after topical application to the toenails, it is unlikely that a measurable amount of these drugs will enter the breast milk.

Phototherapy

Carbon dioxide or neodymium-doped:yttrium aluminum laser therapy have been used alone to treat onychomycosis. Some expert opinion considers phototherapy to be the treatment of choice during breastfeeding. However, laser therapy in combination with topical antifungals such as terbinafine appears to be considerably more effective than either used alone. ⁴

Photodynamic therapy using a topical solution of a photosensitizer such as aminolevulinic acid has been used to treat onychomycosis with some success.^1,5 No data are available regarding the presence of aminolevulinic acid in human milk, or the effects of aminolevulinic acid on the breastfed infant. However, breastfeeding is not expected to result in exposure of the child to the drug due to the negligible systemic absorption of aminolevulinic acid in humans after topical administration under maximal clinical use conditions.

Prophylaxis

Topical antifungal drugs applied twice weekly are sometimes used in patients with risk factors such as diabetes or immunosuppression. Prophylaxis with a topical antifungal after terbinafine therapy decreases the rate of recurrence from 76% to 33%. ¹ Efinaconazole and tavaborole may be the best options for prophylaxis because of their long duration in the nail. Because onychomycosis can recur years after the initial episode, prophylaxis should continue for at least 3 years. ⁵ Unfortunately, no information is available on the long-term use of these drugs during breastfeeding.

Summary

Maternal treatment of onychomycoses with topical drugs during breastfeeding poses little risk to the nursing infant, but might not be very effective. Oral drugs used to treat the condition are more effective, but have a minimal amount of safety information in nursing mothers. Oral fluconazole has the most experience for use in infants, so it might be preferred at this time. Phototherapy combined with topical treatment may be the safest effective therapy during breastfeeding, but this method is less convenient and more expensive than other modes of treatment.