Safety of Topical Dermatologic Medications in Pregnancy

complications include preeclampsia, hypertension, infections, and miscarriages.^11,12 Fetal and neonatal complications include preterm birth, low birth weights, stillbirths, hyperkalemia, and diabetes mellitus, although tacrolimus has not been linked to congenital malformations.^11-13 When used topically, it is poorly absorbed systemically due to its large molecular size. Therefore, topical use on small surfaces is permissible, especially when no alternatives exist.¹⁴

In animal studies, topical pimecrolimus has not shown maternal or fetal toxicity.¹⁵ Unlike tacrolimus however, there is no data on pimecrolimus safety in pregnant women so it should be avoided. However, if no alternatives exist, it can be used if benefits outweigh risks.^14,16

5-fluorouracil is an antimetabolite that interferes with DNA synthesis, and is topically used for actinic keratosis and basal cell carcinoma. When used topically for actinic keratosis, about 6% of fluorouracil is absorbed systemically.¹⁷ Several cases of fetal malformations have been described in women who employed topical fluorouracil during pregnancy. One case of cleft lip and palate was reported in a pregnant female who used fluorouracil on skin and another case of ventricular septal defect was reported in a woman who used fluorouracil on mucous membranes.¹⁷ Miscarriages have been observed in women who used fluorouracil on mucous membranes.¹⁷ Due to the risk of fetal harm, use of topical fluorouracil in pregnancy is contraindicated.

Topical calcipotriene is an important treatment option for psoriasis in pregnancy.^16,18 Following contact with psoriatic plaque, about 6% of calcipotriene is absorbed systemically while 5% is absorbed if applied on normal skin.¹⁹ Animal studies have shown increased incidence of skeletal abnormalities such as enlarged Lambertfontanelles, extra ribs, incomplete ossification of pubic bones, and forelimb phalanges of fetus, but no human studies have been conducted and data is thus limited.^20,21 Some articles recommend^22,23 while another did not favor²⁴ topical calcipotriene therapy for psoriasis in pregnancy, instead opting for narrowband UVB therapy. Most consider topical calcipotriene safe in pregnancy.^25-27

There are no published studies regarding anthralin safety in pregnancy in either animals or humans.^24,28 One manufacturer of this drug states that anthralin metabolites are not detected in urine, while another manufacturer cites a limited study that concluded systemic absorption is negligible.^14,29 Theoretical risk of using an anti-mitotic agent in pregnancy always exists and when combined with lack of data on safety, it is best avoided in pregnancy. But if it must be used as third or fourth line therapy, avoid using large amounts on inflamed skin as systemic absorption can be increased.^14,24

Animal studies using high dose coal tar have shown increased risk of cleft palate, small lungs and thymus, and reduced fetal growth rates.^30,31 However, several studies in humans have not shown any adverse effects. A large cohort study and a small retrospective study did not reveal significant increase in spontaneous abortions or fetal abnormalities.^32,33 Due to concerns raised by animal studies, many authorities recommend avoiding coal tar products in pregnancy, although accidental use does not require any action.^14,16,25,34

About 6% of tazarotene is absorbed systemically after topical applications and its metabolites are water soluble so they are not stored in adipose tissues.^14,35 Water soluble metabolites are highly bound to plasma proteins (>99%) so placental transfer is unlikely