TABLE 3.
Summary of safety profile of topical products used in acne vulgaris during pregnancy
| TOPICAL PRODUCTS | SYSTEMIC ABSORPTION | ANIMAL STUDY | HUMAN STUDY | UNITED STATES FOOD AND DRUG ADMINISTRATION5 | RECOMMENDATIONS IN PREGNANCY |
|---|---|---|---|---|---|
| Tretinoin | 1 – 2 % in normal skin,23 Facial application of 2 g tretinoin 0.05% cream, the rate of transdermal absorption is 2 – 6%.40 No appreciable increase of the endogenous plasma retinoid concentrations (2–5 μg/L) were observed after treatment.25 |
There is an increase risk of congenital malformation, with higher dose poses higher risk.31 | Five case reports have raised the suspicion that birth defects cannot be ruled out after topical use of tretinoin.25 Two prospective studies during first trimester on 96 and 106 pregnant women, which reported neither congenital malformation nor evidence of retinoid embryopathy.41,42 | C | Topical use of all topical retinoids should be strictly avoided during pregnancy. In the case of inadvertent exposure, termination of pregnancy is not necessary, but consultation and fetal investigation should take place.25 |
| Adapalene | Trace amounts23 | No teratogenicity from animal studies after high dose dermal application.43 | A case report of adapalene usage until the thirteenth week of pregnancy revealed incidence of anophthalmia and agenesis of the chiasma opticum and led to termination of pregnancy. However, it is concluded not related to adapalene.44 | C | |
| Tazarotene | Up to 5 – 6% in normal skin23,25 | Teratogenic effects and post-implantation fetal loss have been observed in rats and rabbits at doses producing 0.7 and 13 times, respectively, the systemic exposure for topical treatment of 20% of body surface area.45 | Healthy children were reported after treatment during pregnancy; however, details on the duration of therapy and the dose were not presented.45 | X | |
| Erythromycin | No data23 | No teratogenic effect23 | Surveillance study on clindamycin either oral or topical in pregnant women during third trimester reported that there was no increase of congenital marformation risk. However, there was a report about pseudomembranous colitis after topical clindamycin application.47 | B | Considered safe in pregnancy and use with caution in patient with history of gastrointestinal disturbance.47 |
| Clindamycin | 4 – 5 %23 | No teratogenic effect23 | Surveillance study on clindamycin either oral or topical in pregnant women during third trimester reported that there was no increase of congenital marformation risk. However, there was a report about pseudomembranous colitis after topical clindamycin application47 | B | Considered safe in pregnancy and use with caution in patient with history of gastrointestinal disturbance.47 |
| Benzoyl peroxide (BPO) | There is only 5% of the compound, which can be systemically absorbed and undergone complete metabolism into benzoic acid, also known as food additive substance.23,25 It undergoes rapid excretion in the kidney without any estimated systemic toxicities and it has low risk in causing congenital malformation.48 | Rodent teratogen studies have apparently not been conducted.4 | There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether BPO crosses the human placenta. Considering the dose and route, it is unlikely the maternal systemic concentration will reach a clinically relevant level.49 | C | Although it is classified as category C by US FDA, BPO generally is still considered to be safe during pregnancy.48 |
| Dapsone | Twice-daily application to 22.5% body surface area for 2 weeks resulted in a steady-state exposure 126 times lower than that achieved with a single 100 mg oral dose. The half-life of topical dapsone is 48 hours versus 20.6 hours for oral dapsone.50 | There was no teratogenic effect with high dose usage.51 | Controlled study on human is not available yet. Until present, the use of topical dapsone did not increase the risk of congenital malformation. There was very minimal risk of maternal hemolytic anemia in patient with glucose-6-phosphatase dehydrogenase (G6PD) deficiency.52,53 | C | Use with caution, might be prescribed if there is more benefit than its risk. |
| Azelaic acid | Summarized in Table 2 | ||||
| Salicylic acid | Various systemic absorptions, depend on vehicle and occlusion.54 | Embryo malformation is associated with systemic administration of salicylic acid.54 | Most of the studies revealed that low dose of asetylsalicylic acid which administered during pregnancy was not associated with the increase of side effects, such as malformation, prematurity, and low birthweight.39 | C | Risk during pregnancy is low if use is restricted to local areas for a limited duration. Broad use of salicylic acid, either with high concentration or under occlusion, should be avoided due to the increase risk of salicylic toxicity.55 |
| Glycolic acid | Very minimal56 | Side effect on reproduction system has been reported after the use of high dose.56 | Study of glycolic acid usage in pregnant woman is not available yet. No adverse effects observed in this population ever reported.39 | - | Considered safe for use during pregnancy due to its minimal absorption.48 |