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Dermatological Drug Use in Pregnancy

C. Zip, MD, FRCPC
Department of Medicine, University of Calgary, Calgary, Alberta, Canada

Background

It is well known that the developing fetus can potentially be affected by any medication given to the mother. However, despite this, the use of medications during pregnancy is common and pregnant women often present for treatment of dermatological disease. A recent multinational survey indicated that 86% of women took an average of 2.9 medications during their pregnancy [Collaborative Group on Drug Use in Pregnancy. Int J Gynaecol Obstet 39(3):185-96 (1992 Nov)]

US FDA Pregnancy Categories

During the 1950s diethylstilbestrol and thalidomide use in early pregnancy both led to disastrous consequences for the exposed offspring, which were not causally linked for years. These events led to the development of the US FDA Pregnancy Categories (Table 1) that are assigned before a drug is released.

A No fetal risk in controlled studies.
B No risk to human fetus despite possible animal risk or no risks in animal studies, but human studies lacking.
C Human risk cannot be ruled out. Animal studies may or may not show risk.
D Evidence of risk to human fetus.
X Contraindicated in pregnancy.

Table 1: US FDA pregnancy categories for drugs

Acne

Topical

  • Preferred during pregnancy
  • Topical erythromycin (category B), clindamycin (category B), and benzoyl peroxide (category C) are safe
  • Avoid topical retinoids
    • Case reports of congenital malformations with tretinoin (category C)
    • Use of adapalene (category C) and tazarotene (category X) are also not recommended.

Systemic

  • Tetracyclines (category D) are associated with deciduous tooth staining, decreased bony growth, and maternal liver toxicity when taken after the first trimester.
  • Erythromycin (category B) use in early pregnancy may be associated with a higher risk of cardiovascular malformations.
  • Oral isotretinoin (category X) is a well-known teratogen. However, it is safe for women to conceive 1 month after this medication is stopped.

Rosacea

Topical metronidazole and azelaic acid are both category B and considered safe to use during pregnancy.

Psoriasis

Topical

  • Topical corticosteroids (category C) are widely used in pregnancy, although intrauterine growth retardation has been reported.
  • Only 6% of calcipotriene ointment (category C) is absorbed through the skin and is likely safe for localized disease.

Phototherapy

  • Broadband UVB is considered the safest therapy for extensive psoriasis.
  • PUVA is a potential teratogen, but adverse outcomes have not been reported.

Systemic

  • Methotrexate (category X)
    • Can be used in women of childbearing potential who are using effective contraception.
    • Pregnancy should be avoided for at least one ovulatory cycle following cessation of the drug.
  • Acitretin (category X)
    • Should not be prescribed for women of childbearing potential.
  • Cyclosporin (category C) does not appear to pose a major risk to the fetus based on relatively small numbers.

Biologics

  • Limited data available.
  • Alefacept (category B) and efalizumab (category C)
  • No evidence of teratogenicity in animal reproduction studies or in offspring of women who inadvertently became pregnant while taking either of these drugs
  • Etanercept (category B)
  • OTIS data [Chambers C, et al. J Am Acad Dermatol 56(2):38 (2007)]
  • 35 pregnancies with first TM exposure
  • 17 pregnancies have resulted in live births
  • 3 congenital abnormalities - no consistent pattern
  • Infliximab (category B)
  • Multiple reports of exposure during pregnancy in women receiving treatment for rheumatoid arthritis and Crohn’s disease
  • Used intentionally during pregnancy for induction or maintenance of remission in Crohn’s disease
  • No evidence of embryotoxicity, teratogenicity or increased fetal loss
  • Placental transfer documented.

Systemic Corticosteroids (category C)

  • Have been associated with intrauterine growth retardation and a small increase in incidence of cleft lip with or without cleft palate with first trimester exposure.
  • When needed, the benefits of short courses of oral corticosteroids appear to outweigh the fetal risks, especially when given beyond the first trimester.

Topical Calcineurin Inhibitors

  • Tacrolimus and pimecrolimus (category C)
  • Oral tacrolimus has not been associated with fetal loss or teratogenicity.
  • To date there are no reports of adverse effects on pregnancy with topical use of tacrolimus or pimecrolimus.

Antihistamines

  • Chlorpheniramine and diphenhydramine (category B) are the antihistamines of choice for oral and parenteral use, respectively.
  • One case-control study associated use of diphenhydramine with cleft palate in first trimester [Saxen I. Lancet 1(7854):407-8 (1974 Mar)]
  • Linked to retrolental fibroplasia in premature infants when taken in last 2 weeks.

Antivirals

  • Topical imiquimod (category B) is minimally absorbed and limited data has not shown adverse fetal effects.
  • Podophyllin and podophyllotoxin (category C) have been associated with fetal abnormalities and deaths.
  • Acyclovir, famciclovir and valacyclovir (category B) are probably safe.

Antifungals

  • Topical antifungals are safe because of negligible percutaneous absorption.
  • Minimal data for oral terbinafine (category B).
  • Oral fluconazole (category C) 400 mg/d appears to be teratogenic.
  • Associated with a pattern of abnormalities involving the head and face, bones and heart.
  • Smaller doses are likely safe.
  • Itraconazole (category C)
  • No significant risk for major abnormalities.
  • Because of concern regarding the use of fluconazole, a structurally related triazole antifungal, avoidance of itraconazole is suggested in the first trimester.

Antibiotics (Systemic)

  • Penicillins, cephalosporins, and azithromycin (category B) are generally considered safe in pregnancy.
  • A large surveillance study observed a possible association between certain cephalosporins (cefaclor, cefalexin, ceftriaxone, and cephadrine) and congenital malformation with first TM exposure.[Briggs GG, et al. Drugs in Pregnancy and Lactation. 7th ed. Philadelphia (PA): Lippincott Williams and Wilkins (2005).]

Conclusion

Medications that are considered safe in pregnancy are available for the treatment of common dermatological disorders. Knowledge of these medications is important when considering treatment options for both pregnant patients, and women of childbearing potential.

Dermatologic Diagnostic Challenge

Question:

A 61 year old Caucasian male presents with chronic erythema of his cheeks and easy flushing. On questioning, he notes that he never gets any “bumps” on his face, but he occasionally gets styes on his eyelids. He has no problems with his blood pressure nor any history of diarrhea.

What is your diagnosis?

a. Systemic lupus erythematosus
b. Carcinoid syndrome
c. Erythematotelangiectatic rosacea
d. Periorificial dermatitis
e. Papulopustular rosacea

Case study submitted by Benjamin Barankin, MD, FRCPC

Go online to www.SkinTherapyLetter.ca/cases to view an image and learn the answer.