Safety of Topical Medications for Scabies and Lice in Pregnancy

Abstract

Medications should be employed with caution in women of childbearing age. Topical medications have little systemic absorption. Therefore, they are considered safer than oral or parenteral agents and less likely to be embryotoxic or fetotoxic. However, their safety profile must be assessed cautiously as the available data are limited. In this article, we aggregate human and animal studies to provide recommendations on using topical anti-scabies and anti-lice therapy in pregnancy.

Introduction

What was known?

Topical medications are typically considered safer than oral or parenteral agents during pregnancy. However, topical medications may still cause embryotoxicity or fetotoxicity.

The old FDA pregnancy categories (A,B,C,D,X) do not accurately reflect the risks of drug use in pregnancy.

Scabies is an intensely pruritic dermatosis caused by the mite Sarcoptes scabiei var. hominis.[1] It is highly contagious and may have the pathognomonic sign of burrows in addition to nocturnal pruritus and erythematous papules.[2] Numerous medications are available for treatment such as permethrin, ivermectin, lindane, benzyl benzoate, malathion, crotamiton, and sulfur. Pediculosis capitis, also known as head lice, is caused by the head louse Pediculus humanus capitis.[3] Scalp pruritus is the cardinal symptom although patients can be asymptomatic.[4] Treatment should be considered if active lice or viable eggs are observed. Three treatment modalities include wet combing, topical pediculicides, and oral therapy.[5]

Although numerous medications are available, caution must be utilized in pregnant patients as several medications act as toxins that can cause significant fetal harm. This article aggregates human and animal studies and provides recommendations on the safe use of topical anti-scabies and anti-lice therapy in pregnancy. Table 1 provides Food and Drug Administration (FDA) pregnancy category ratings and their interpretation. Table 2 provides the summary of recommendations on using topical anti-scabies and anti-lice medications in pregnancy.

Table 1.

Food and Drug Administration pregnancy category interpretation

Table 2.

Recommendations on topical anti-scabies and anti-lice medications

In December 2014, the FDA published the pregnancy and lactation labeling rule, which eliminated the pregnancy letter categories. Instead, narrative summaries of the risks of drug use in pregnancy and discussion of the data supporting those summaries will be provided in the new label. The old label was criticized as confusing, overly simplistic, and as poorly communicating the risks of drug use during pregnancy and lactation. This rule is effective as of June 30, 2015. All new prescription drug submissions will utilize the new labeling format, while drugs approved after June 30, 2001, will gradually switch to the new format. Since the medications discussed herein may not have switched to the new labeling format, we still present the FDA pregnancy category ratings, along with a description of available studies and recommendations on their use in pregnancy [Table 1].

Topical Anti-scabies and Lice Medications

Benzyl benzoate (Category C, not available in the USA)

Benzyl benzoate was banned in the United States because its metabolite, benzyl alcohol was associated with neonatal fatal intoxication (“gasping syndrome,” with encephalopathy, metabolic acidosis, bone marrow suppression, and multiple organ failure).[6] However, intoxication only occurred when benzyl alcohol itself was used to rinse central vein catheters. Products containing benzyl alcohol are still available in over the counter products in the USA. Except for local skin irritation, no reports of toxicity in animals or humans have been reported after topical application of benzyl benzoate.[7] A Thai study examined 444 pregnant women in their second and third trimester who utilized 25% benzyl benzoate preparation topically. No increased risk for birth defects was reported.[8] The use of topical benzyl benzoate is likely safe.[9,10]

Camphor (Category C)

Topical camphor has a cooling and local anesthetic effect which makes it suitable for pruritic skin conditions. In animal studies, there is no evidence of embryotoxicity or teratogenicity even at maternally toxic doses.[11,12] Since camphor can cross the placental barrier, ingesting it can potentially cause fetal demise and neonatal respiratory failure.[13] In the Collaborative Perinatal Project, 168 women with first trimester exposure to topical camphor were followed throughout their pregnancy. No evidence of congenital malformations was reported.[14] Furthermore, in 763 women who utilized camphor at any time in their pregnancies, no congenital defects were found.[14] To date, there have been no reported adverse fetal outcomes as a result of camphor use.[15] Therefore, the use of topical camphor is permitted.[9,10,16,17]

Corticosteroids (Category C)

A 2015 Cochrane review analyzed five cohort and nine case–controlled studies and concluded that regardless of potency, topical corticosteroids are safe in pregnancy. They do not lead to increased risks of fetal malformations, congenital anomalies, and adverse perinatal outcomes such as mode of delivery, preterm birth, stillbirths, low Apgar scores, or fetal death.[18] However, an association was found between the use of very potent topical corticosteroids and low birth weights, especially when the cumulative dose is very high throughout pregnancy.[18] It is important to note that topical corticosteroid absorption varies not only among individuals but also with respect to anatomic location as well. It is the lowest on the soles of the feet (0.14%), ankle (0.42%), palms (0.83%), forearm (1%), and back (1.7%), while scalp (3.5%), face, neck, axilla (3.6%), forehead (6%), eyelids (42%), and groin (42%) absorb increased amounts.[19] The current recommendation is that topical mild or moderate potency corticosteroids are safe in pregnancy. Potent topical corticosteroids should be utilized for the shortest time possible with appropriate obstetrics care given due to the possible risk of fetal growth restriction.[20,21]

Crotamiton (Category C)

About 1% of topically applied dose is absorbed systemically.[22] No animal or human studies have been conducted. No adverse pregnancy outcomes have been reported from the use of topical crotamiton.[23] Although it should not be used as the first line therapy due to lack of safety data, crotamiton is considered safe to use in pregnancy.[10,24,25,26]

Ivermectin (Category C)

In animal studies, at doses which produced maternal toxicity, fetal malformations were noted such as cleft palate, exencephaly, and clubbed forepaws in rabbits.[27] In a 3 year Liberian study, ivermectin was inadvertently distributed to pregnant women. Two hundred and three children born to exposed women did not have increased birth defects, compared to untreated mothers in the same population.[28] A 1993 study from Cameroon, in which 110 pregnant women inadvertently received ivermectin did not report an increased incidence of abortions, stillbirths, or congenital malformations. In a second analysis, 97 pregnant women treated with ivermectin were compared with untreated women, but no statistically significant difference in fetal outcomes was reported between the two groups.[29] Although these studies deem it safe, many authors are hesitant due to the data from animal studies. Therefore, topical ivermectin is best avoided as there are other alternatives, such as permethrin, that are safer.[9,26,30,31]

Lindane (Category C)

Lindane has been withdrawn from many countries but is available in the US. Animal studies in rats showed an altered motor activity, increased mortality, and decreased pup weight gain at concentrations twice estimated human exposure.[32,33] At three times the concentration, increased stillbirths were noted.[32,33] However, no teratogenic effects were noted in these animal studies.[32,33,34,35] A surveillance study of Michigan Medicaid recipients, where 1417 newborns were exposed to topical lindane during the first trimester, did not have an increased incidence of defects such as cardiovascular anomalies, oral clefts, spina bifida, polydactyly, and limb reduction defects although seven cases of hypospadias were seen (three were expected).[17] Further, there are several case reports of stillborn infants, neutral tube defects, and mental retardation after maternal exposure to lindane.[36] Due to potential toxicity associated with lindane, it should be avoided during pregnancy.[10,26,37]

Malathion (Category B)

Animal studies failed to show evidence of teratogenicity or gross fetal abnormalities.[38] A cohort of 22,465 infants born to mothers exposed to aerial malathion spraying in the first trimester did not have an increased risk of congenital malformations.[39] A case-cohort study of 7450 women exposed to malathion during the 1981–1982 aerial spraying of San Francisco Bay area did not report an increased risk of congenital malformations.[40] Moreover, in several other studies where mothers had detectable malathion concentrations in the urine did not have differences in birth weight, head circumference, or altered neurodevelopment compared to the nonexposed group.[41,42] Although it is likely safe to use in pregnancy, it should be used after other safer alternatives have been utilized (such as mechanical treatment for lice or permethrin).[10,43,44,45,46] If malathion is used, aqueous rather than alcoholic solutions should be used and women should be advised not to exceed the recommended dose.

Menthol (Category N)

Menthol is available in numerous over the counter products. Lotions containing menthol are utilized as topical analgesics. Teratogenic effects are not observed in offspring of numerous animal species receiving doses up to 106 times the acceptable daily intake in humans.[15] Although human studies are lacking, adverse effects in pregnancies have not been reported.[25] The use of topical menthol lotions is safe.[10,16,47]

Permethrin (Category B)

About 2% of the topically applied dose is absorbed systemically.[7] Animal studies have not demonstrated fetal harm.[48] In a prospective study of 113 pregnant women who used permethrin shampoo (31 in their first trimester) did not have any indication of embryotoxicity.[49] In another study, 196 pregnant women who utilized 4% permethrin did not have adverse fetal outcomes.[8] Often considered the first line for topical treatment of parasitic infections, permethrin is safe to use during pregnancy.[26,30,37,50]

Precipitated sulfur (Category C)

Although not a first line agent, sulfur has been utilized to treat initial and recurrent cases of scabies.[51] About 1% of topically applied sulfur is absorbed.[52] There is limited information on safe use in human pregnancies. Due to its low systemic absorption and no reported cases of adverse outcomes, topical sulfur is not expected to cause fetal harm. After the use of other first line medications such as permethrin, limited use of topical precipitated sulfur is considered safe.[10,53,54]

Spinosad (Category B)

Animal studies using oral spinosad were negative for teratogenic effects. After 10 min of topical application, plasma spinosad concentration was undetectable.[55] Long-term carcinogenesis studies in animals were negative.[55] Genotoxicity tests did not show evidence of mutagenic or clastogenic potential.[55] Spinosad is poorly absorbed through the skin and is rapidly metabolized and excreted.[56] Although the drug suspension contains unspecified amounts of benzyl alcohol, it is unclear if sufficient amounts of it would be absorbed to cause embryotoxicity or fetotoxicity.[55] Human studies are lacking, but negligible systemic absorption coupled with the lack of toxicity in animal studies indicates that limited topical use is likely safe [Table 2].[17,56]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Although there are many topical drugs available for treating scabies and lice in pregnancy, permethrin has greater evidence of safety in pregnancy.