Gerald G. Briggs
Topical and systemic agents are used in the treatment and prevention of acne, ranging from those that have negligible risks during pregnancy to a drug that is a major teratogen.
Azelaic acid (Azelex, Finevin), a topical antimicrobial, agent, is rated pregnancy risk factor B. It is embryotoxic in animals, but only at maternal toxic doses. No teratogenic effects have been observed in animals. About 4% of the dose is absorbed systemically in humans. This substance is found naturally in whole grain cereals and animal products, so levels of endogenous plasma levels of azelaic acid vary, ranging from about 20 ng/mL to 80 ng/mL, depending on dietary intake.
Benzoyl peroxide, which has multiple trade names, is rated risk factor C because it has not been studied in animals. It has antimicrobial and mild keratolytic effects. Even though there have been no studies in human pregnancy and lactation, it is considered safe because the amount absorbed through the skin is so small.
There are five other topical agents: clindamycin, erythromycin, thiouslfate, sulfacetamide, and tetracyclines. These agents do not present a significant risk during pregnancy when used topically.
The antiseptics, keratolytics, protectants, and adsorhents are common ingredients in antiacne cleansers and topical acne preparations. The antiseptics ethanol, isopropyl alcohol, phenol, sulfur, and acetone pose no risk during pregnancy when used topically, because absorption is low. Similarly, the keratolytic agents salicylic acid, resorcinol, and sulfur are not well absorbed and are safe during pregnancy and lactation. Protectives and adsorbents like zinc oxide also pose no risk. The same applies to hydrocortisone, which is added to products for its antiinflammatory effect.
Acne treatments in the retinoid class are considered potent human teratogens, although a topical retinoidlike compound known as adapalene (Differin) is rated C. Plasma concentrations of adapalene are less than 0.25 ng/mL after chronic use. There are no teratogenic effects of oral or topical adapalene in pregnant rats or rabbits. There is one human report of an infant whose mother used adapalene during pregnancy; that child had a birth defect that was not typical of retinoid-induced malformations.
The topical retinoid tazarotene (Tazorac, Avage), rated category X, is contraindicated in women who are or may become pregnant. Typical treatment produces detectable plasma levels that are dependent upon the amount of surface area treated. In pregnant rats at a dose very close to the human dose, reduced fetal body weight and skeletal ossification were seen in exposed offspring. Skeletal ossification is not considered a full-blown birth defect, but is on the verge of one. In rabbits at 13-34 times the human dose, retinoidlike anomalies, such as spina bifida, hydrocephaly, and cardiac defects, were seen in exposed offspring. To date, there have been nine case reports of human pregnancies exposed to topical tazarotene, but the exact timing of the exposures was not given. One woman elected to terminate the pregnancy and the remaining eight reportedly gave birth to apparently normal babies.
Topical tretinoin (Renova, Retin-A, Altinac) has been considered safe in pregnancy, with a teratogenic risk considered close to zero. But during the 1990s, there were case reports of babies with congenital malformations born to women who used topical tretinoin in the first trimester. These malformations were very similar to those seen with other vitamin A derivatives.
Antimicrobials and retinoids are the two classes of oral drugs used to treat acne. The primary antimicrobials used are clindamycin and erythromycin–neither of which poses a risk to the fetus–tetracyclines and trimethoprimsulfamethoxazole. Tetracyclines pose risks in the second and third trimesters and should be avoided. Trimethoprimsulfamethoxazole poses risks in the first trimester but not later in pregnancy.
Isotretinoin (Accutane) may be the most potent teratogen available; the effects of exposure during pregnancy involve the central nervous system, the head and face, cardiovascular system, and thymus. In addition to the program currently in place to prevent pregnancies, the Organization of Teratology Information Services (OTIS) has a national hotline (866-626-6847) to register patients who have used Accutane during pregnancy. These women will be enrolled in a Centers for Disease Control and Prevention–sponsored study investigating why exposures occur.
GERALD G. BRIGGS, B. PHARM., is pharmacist clinical specialist, Women’s Hospital, Long Beach Memorial Medical Center; clinical professor of pharmacy University of California, San Francisco; and adjunct professor of pharmacy, University of Southern California, Los Angeles. He also a coauthor of the reference book “Drugs in Pregnancy and Lactation.”
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