Safety of Topical Dermatologic Medications in Pregnancy
July 2016 | Volume 15 | Issue 7 | Original Article | 830 | Copyright © July 2016
Viral M. Patel BS, Robert A. Schwartz MD MPH DSc (Hon), and W. Clark Lambert MD PhD
Rutgers New Jersey Medical School, Newark, NJ
Dermatologic drugs should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Topical drugs have little systemic absorption. Therefore, they are deemed safer than oral or parenteral agents and less likely to harm the fetus. However, their safety profile must be assessed cautiously, as there is limited available data. In this article, we aggregate human and animal studies and provide recommendations on using topical dermatologic medications in pregnancy. J Drugs Dermatol.
Pregnant women and those of childbearing age should be treated with caution as medications can adversely affect a fetus. Topical medications are preferred, as they have little systemic absorption and therefore are less likely to harm a fetus. Many skin disorders are treated topically before starting systemic therapy. Dermatologists must be aware of medications that are safe in pregnancy. In this article, we present FDA pregnancy category ratings (see Table 1 for interpretation), animal and human studies, and recommendations on safe use of topical dermatologic medications in pregnancy. Table 2 provides summary of recommendations on using topical dermatologic medications in pregnancy.
In December 2014, the FDA published the Pregnancy and Lactation Labeling Rule (PLLR), which eliminated the pregnancy letter categories and created descriptive subsections for drug use in pregnancy, lactation, and effects on human reproductive potential. The old label was viewed 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 submissions for prescription drugs will use the new labeling formation, while drugs approved on or after June 30, 2001 will switch gradually to the new format. Since the medications discussed in this article may not have switched to the new labeling format, we still present the FDA pregnancy category rating along with a description of available studies and recommendations on their use in pregnancy.
Anti-inflammatory, Immunosuppressants, Anti-neoplastics
Corticosteroids, Category C
A 2015 Cochrane review of 5 cohort and 9 case-controlled studies concluded that topical corticosteroids (regardless of potency) do not lead to increased risks of fetal malformations or anomalies, and perinatal outcomes such as mode of delivery, preterm birth, stillbirths, low APGAR scores, or fetal death.1 However, there does appear to be an association between use
of very potent topical corticosteroids and low birth weights, especially when cumulative dose is very high throughout pregnancy.1 Topical corticosteroid absorption is low on the forearm (1%) while eyelids, face, neck, axilla, and groin absorb increased amounts.2 The current recommendation is to use mild or moderate potency corticosteroids, and utilize potent topical corticosteroids for as short a time as possible with appropriate obstetrics care given possible risk of fetal growth restriction.3,4
Diclofenac, Category C (<30 weeks gestation);
Category D (≥30 weeks gestation)
Animal studies of oral diclofenac were associated with dystocia, prolonged gestation, low fetal weights, impaired fetal growth, and decreased fetal survival with some of these outcomes attributed to prostaglandin synthesis inhibition.5 Both animal and human studies indicate that topical diclofenac crosses the placenta.6,7 A prospective observational cohort study of 145 pregnant women exposed to diclofenac (median dose 109 mg/day; median treatment duration 3.8 weeks) between 5th and 14th gestation weeks did not report increased occurrence of abortions, premature births, or birth defects.8 A patient had reversible constriction of fetal ductus arteriosus due to topical diclofenac and methyl salicylate.9 As with other NSAIDs, use of diclofenac beyond 30 weeks should be avoided due to risk of premature closure of ductus arteriosus in the fetus. There are no studies of topical diclofenac use in pregnancy; however, given that oral diclofenac use in early pregnancy has not demonstrated increased risk of congenital malformations, it is recommended that topical diclofenac be used only in <30 weeks gestation and when benefits outweigh risks.8, 10
Tacrolimus, Category C
Topical tacrolimus has not been studied in pregnancy, so much of the data is extrapolated from systemic tacrolimus use and physical properties of tacrolimus. Increasing evidence is supporting successful pregnancies with systemic tacrolimus, although maternal and fetal complications are increased. Maternal