Dermatologic Drugs During Pregnancy and Lactation

Sources for Information—Drug Use in Pregnancy and Lactation

Q65.1 On June 30, 2015, The US Food and Drug Administration (FDA) made the Pregnancy and Lactation Labeling Rule (PLLR) effective for prescription drug labeling. The labeling change applied immediately to all drugs approved after implementation. It was phased in over 3 to 5 years, for drugs approved after June 30, 2001, and the change did not apply to pre-2001 or over-the-counter (OTC) medications. The final rule required the removal of the pregnancy categories A, B, C, D, and X from all human prescription drug and biologic product labeling. The new labeling included descriptive information regarding risks during pregnancy, lactation, and females and males of reproductive potential, as well as information on pregnancy exposure registries. The elimination of the pregnancy categories was because of concern that the pregnancy categories were “confusing and did not accurately and consistently communicate differences in degrees of fetal risk.” The FDA stated that a narrative structure for pregnancy labeling is better able to convey potential risks based on animal or human data.

Other pregnancy categories are also used, and these may not be entirely consistent with those listed by the manufacturer. One highly recommended source by Briggs, Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk , is one of the most comprehensive references for drugs in pregnancy and lactation. Briggs has categorized the FDA narrative ratings based on evaluation of human and animal data, route of administration, and risk of maternal disease, among other issues evaluated.

Additional sources of information on drug use during pregnancy and lactation are listed in Table 65.1 .

Risk Related to Time of Drug Consumption

Risks from drug intake during pregnancy may differ from those during the prenatal period or during lactation. Drug-related risks during pregnancy may also vary with the trimester of pregnancy. Drugs labeled as teratogenic may put a fetus at risk for only a few weeks of pregnancy: nevertheless, it is generally recommended that these drugs be avoided for the entire pregnancy. Drugs that place a neonate or mother at risk during lactation may be different from those that adversely affect a fetus during pregnancy.

Timing—Before Conception

Q65.2 Physicians prescribing a drug for women of childbearing potential should have several concerns:

• 1.

  Contraceptive failure because of medication interactions;

• 2.

  Potential risk to mother and fetus caused by the drug, should pregnancy occur;

• 3.

  Possible interference with conception;

• 4.

  Potential risk of spontaneous abortion; and

• 5.

  Preserving fertility.

Q65.3 Some medications have been associated with a possible risk of contraceptive failure ( Table 65.2 ). The efficacy of many oral contraceptives is dependent on increased estrogen levels that simulate pregnancy and prevent ovulation. Drugs that reduce concentrations of ethinyl estradiol and progestin may lead to breakthrough ovulation and place the patient at risk of oral contraceptive failure. Azathioprine and nonsteroidal anti-inflammatory drugs (NSAID), for example, have been associated with increased risk of contraceptive failure of the intrauterine device. Oral contraceptive failure may occur when the oral contraceptive is taken along with hepatic enzyme inducers, such as griseofulvin, which may increase the metabolism of estrogen because of induction of hepatic microsomal enzymes. Rifampin may stimulate estrogen metabolism or reduce enterohepatic circulation of estrogens, thereby reducing the effectiveness of oral contraception. Some controversy exists regarding the effect of commonly used systemic antibacterial agents on oral contraceptive effectiveness. It has been postulated that penicillins may reduce enterohepatic circulation of estrogens, and that tetracyclines alter the gut flora, which may in turn affect estrogen circulation. However, contraceptive failures rates of 1% to 3%, while on antibiotics, do not differ significantly from control groups and the American College of Obstetricians and Gynecologists (ACOG) cautions about lowered oral contraceptive levels for only rifampin and griseofulvin.

Medications with the capacity to mutate or kill germ cells should also be avoided. Both men and women should avoid methotrexate if pregnancy is anticipated. Although there are no published studies implicating thalidomide in the production of congenital anomalies, when men use the drug around the time of conception, the manufacturer of thalidomide recommend that men receiving thalidomide use a latex condom during intercourse.