Introduction
Dermatophytosis is common in pregnancy and lactation, and early treatment, before it becomes chronic and extensive, should be the dictum. Pregnancy as well as lactation is a condition where the metabolisms of two individuals, i.e., the mother and the child, must be considered, so as to balance between mother's health and child's safety, and as a dictum, all drugs are considered unsafe unless proven otherwise.
Pregnancy
Pregnancy is a physiological condition prone to infections, especially fungal, due to the physiological immune tolerance, weight gain, and increased sweating due to hormonal changes, and drug administration during pregnancy involves consideration of two individuals. There have been many studies with conflicting data on the use of antifungals in pregnancy. The following is a recommendation taking into consideration all studies.[12345]
Topical antifungals
Clotrimazole[6] and miconazole have no embryotoxic potentials and can be safely used in pregnancy. The data on topical terbinafine and ciclopirox are more limited.[1] Topical antifungals are used twice daily till the lesions subside and continued for up to 2 more weeks. In general, topical antifungals can be considered safe since there is a negligible systemic absorption.
Oral antifungals
Griseofulvin is avoided in pregnancy owing to limited safety data. Although it is classified under pregnancy category B, oral terbinafine should be avoided until after delivery and even during lactation. Fluconazole, ketoconazole, and itraconazole increase the risk of cardiovascular, skeletal, craniofacial, and neurodevelopmental defects in the first trimester. These also have effect on estrogen and testosterone production. These can be used with caution in late pregnancy though, as a rule, ketoconazole is not recommended for use in superficial fungal infections in humans.
Lactation
Many topically absorbed as well as systemic drugs are excreted via breast milk; hence, care should be taken in administration of antifungals.[2]
Topical antifungal
All may be safely used though there is minimal secretion in breast milk, and there is a case of lactation suppression due to use of selenium sulfide as selenium is a natural constituent of breast milk and excess can inhibit milk secretion.
Oral antifungal
Griseofulvin is tumorigenic and should be avoided. Fluconazole is secreted in breast milk but is considered safe in neonates. Ketoconazole and itraconazole are absorbed poorly in milk but better avoided during lactation. Terbinafine is transferred through milk, and as there are no long-term data on infant toxicity, it has to be used for a prolonged time. The dosage in pregnancy and lactation is similar to that in nonpregnant adults.
Table 1[1] summarizes the use of antifungals in pregnancy and lactation.
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Table 1: Food and Drug Administration category, level of evidence, and recommendation of antifungal drugs in pregnancy and lactation (modified from: Murase et al.)
Over-the-counter products in pregnancy and lactation
Whitfield's ointment which contains salicylic acid and benzoic acid is a category C drug in pregnancy, due to risk of absorption of salicylic acid; however, WHO allows application, especially if benefits outweigh risks. Undecylenic acid has not been given pregnancy category and is considered “probably safe” and is moderately safe (L3) in lactation. There is no documented risk of using Castellani paint use in pregnancy and lactation, but there are no large-scale studies to assess the risk-benefit. Topical sulfur has also not been assigned any pregnancy and lactation risk category though is considered safe for use as a single application scabicidal.[7]
General measures in pregnancy and lactation
As therapeutic choices are limited, the patient should be counseled regarding general measures such as avoiding the following: sharing of towels and clothes, tight and synthetic clothing, and excessive sweating. Absorbent antifungal dusting powders may be used once the active infection is taken care of. Onychomycosis treatment may be attempted after lactation is stopped as it mostly requires oral antifungals for prolonged duration.
Children
Dermatophytoses, other than tinea capitis, is relatively uncommon in children, though tinea cruris, in young children, mimics diaper dermatitis and is probably missed. In children, tinea pedis and unguim should be considered only after ruling out dermatitis and onycodystrophy. Tinea capitis, which predominantly occurs in prepubertal boys, is the most common pediatric dermatophytic infection worldwide, which indicates need for early diagnosis as it may result in scarring alopecia if left untreated.[89]
Topical therapy (creams, lotions, powders)
Imidazoles (1% clotrimazole, 2% miconazole, 1% econazole, 2% ketoconazole), 1% tolnaftate, 1% ciclopirox olamine, Whitfield ointment (6% benzoic acid and 3% salicylic acid) are safe and given for 2–4 weeks or continued for a couple of weeks after clinical subsidence. Topical agents mixed with corticosteroids should be avoided.[10]
Oral antifungal agents
Griseofulvin is a very effective option for tinea capitis caused by Trichophyton and Microsporum spp., requires longer duration of therapy to achieve complete cure (clinical and mycological cure). The most common side effects associated with oral griseofulvin are headache, gastrointestinal (GI) upset, and rash. Microsized and ultramicrosized formulations are designed to reduce GI upset and to optimize absorption. The microsized form has liquid formulation, which is highly acceptable and convenient for infants and young children. With oral griseofulvin, mycological cure rates have been reported between 80% and 95% and effective therapy (mycological and clinical cure) rates between 88% and 100%.[11] The American Academy of Pediatrics suggests dosing of 10–20 mg/kg/day for microsized griseofulvin and 5–10 mg/kg/day for ultramicrosized in a single daily dose for 4–6 weeks with treatment continuation for 2 weeks beyond the resolution of clinical symptoms of tinea capitis.[12]
Itraconazole
Studies have demonstrated that both continuous and pulse therapy is safe, well tolerated with minimal relapse, making it a better alternative to griseofulvin in children.[13] The capsules can be opened and the beads placed in semisolid food for dose adjustment. Oral solution of itraconazole, if available, should be given at a lesser dose of 3 mg/kg/day as it is better absorbed.
Terbinafine
Oral terbinafine, which has marked lipophilicity, is a Food and Drug Administration-approved treatment for tinea capitis in children 4 years of age or older. It is less efficacious for ectothrix scalp infections in children due to lack of penetration into eccrine sweat and low levels of sebum before puberty.[14]
Fluconazole
Oral fluconazole once weekly for 8 weeks is effective in children in the treatment of tinea capitis.[15]
The extent to which an antifungal agent interacts with the hepatic P-450 enzyme system has potential to cause significant drug interactions, which should be kept in mind.[16]
Table 2 summarizes the use of antifungals in children.
Table 2: Oral antifungal agents for common fungal infections in children
Conclusion
Topical azoles may be considered for use in pregnancy, whereas all oral antifungals are better avoided, especially in the first two trimesters. Topical azoles and oral fluconazole may be used in lactation. In neonates, topical azoles and oral fluconazole are safely used, whereas in older children, all topical and oral antifungals are safe for use, provided accurate dose adjustment is done.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
Dr. Arun C Inaamdar, Chief Editor, Symposium on dermatophytoses Dr. Manjunath Shenoy. President, IADVL Karnataka.
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