EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2015
NEW YORK (FRONTLINE MEDICAL NEWS) – Disease exacerbations during pregnancy can be more dangerous for the fetus than some of the medications used to treat them..
No one wants to take unnecessary drugs during pregnancy, Dr. Jenny Murase said at the American Academy of Dermatology summer meeting. But concern about medication safety should never override the need to treat new-onset disease or control existing disorders.
“Often, patients are so worried about the effects of medicines on the baby that they don’t think about the effects of the disease. This is a thing we need to address with each patient. What would happen to you, and your baby, if this disease is not treated?” said Dr. Murase of the Palo Alto Foundation Medical Group, San Francisco.
Primary herpes simplex infections are an excellent example of this dilemma, she said. “Primary HSV has up to a 50% transmission rate to the fetus. In utero infections are associated with microcephaly, hydrocephalus, and chorioretinitis. About a third of neonates have central nervous system disease, and a quarter are born with disseminated disease,” and the neonatal mortality rate is nearly 70%.
“On the other hand, acyclovir is very, very safe,” based on data on thousands of patients, Dr. Murase said. Famciclovir and valacyclovir are also likely safe but data on those drugs are more limited, she added.
Sometimes, ideas about a drug’s safety during pregnancy are based on old or confusing studies. The worries about the teratogenicity of systemic steroids, for example, stem from a 1951 report that cortisone caused orofacial cleft in prenatally exposed mice.
“Since then, no prospective studies have found any evidence of congenital malformations associated with systemic steroids,” Dr. Murase said. However, “epidemiologic studies have suggested a threefold increase, which, interestingly, is in line with the mouse findings.”
The drugs do, however, have an important place in the armamentarium; they should be used judiciously and as part of a careful risk-benefit analysis. Both betamethasone and dexamethasone pass the placental barrier well; prednisone is not as transferable.
Dr. Murase provided a list of some medications commonly employed in dermatologic practice, with considerations for their use during pregnancy.
• Topical steroids. A 2013 study found that pregnancy-long exposure to more than 300 g of a potent or superpotent topical corticosteroid did not increase risk of orofacial cleft in the newborn, but did increase risk of low birth weight. “So if you are giving more than five tubes of 60 g, there is a potential for low birth weight – although this could also be related to the actual severity of the disease. Still, you should discuss this risk with your patient.”
• Antihistamines. These should be avoided in the last month of pregnancy as they can stimulate uterine contractions, especially if they are given intravenously or in very high doses. There have been reports of a doubling of retinopathy in premature infants (22% vs. 11%) associated with antihistamines used within 2 weeks of delivery. Some infants can have withdrawal symptoms, including seizure, if the mother has been taking high doses of the drugs.
• Antibiotics. The first-line antibiotics are penicillin, cephalosporins, and dicloxacillin; all are safe. Of the macrolides, erythromycin is preferred. However, the estolate form of the drug has been associated with reversible abnormalities in liver enzymes; the base and ethylsuccinate forms don’t have this risk. Rifampin may be used, but vitamin K should be given with it. Sulfonamides are a second-line choice up until the third trimester. They shouldn’t be used after that, as they can cause anemia, hyperbilirubinemia, and kernicterus. Tetracycline can be used up to 14 weeks’ gestation but not after that, because of the risks of bone growth inhibition and tooth discoloration in the infant, and maternal hepatitis.
• Antifungals. Topical antifungals are not too concerning. Nystatin is safe, but not as effective as the later-generation medications. Clotrimazole is the first choice, followed by miconazole and ketoconazole. Data are limited, but topical terbinafine, naftifine, and ciclopirox are also probably safe, she said.
Systemic antifungals are a different matter. None of the imidazole derivatives are advised during pregnancy, as they have been associated with craniosynostosis, congenital heart defects, and skeletal anomalies. If they are used, a diagnostic ultrasound at 20 weeks is advisable.
• Light. Light therapy is generally considered safe, although there is some evidence that narrow-band ultraviolet can deplete folic acid levels. Despite that, there are no reports of neural tube or orofacial defects associated with light therapy. Nevertheless, make sure patients are supplementing with folic acid if they receive light therapy.
Light therapy should never be combined with oxsoralen in pregnant women; the drug is a known mutagen. Data on cyclosporine are more limited, but it’s a category C drug in pregnancy, so it’s best to avoid it.
• Biologics. Etanercept, adalimumab, infliximab, and alefacept are all category B drugs in pregnancy. There are some hints that they, as well as tumor necrosis factor (TNF)-inhibitors, may be associated with some fetal anomalies in the VACTERL association cluster (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities). A confirmation of the syndrome requires three signs to be present. Only two infants born to mothers taking a biologic have had three qualifying signs.
However, pregnancy outcome reports for the drugs have recorded malformations. Among the adalimumab cohorts totaling 256 pregnancies, there were 14 fetal anomalies (5.5%); of these, nine were VACTERL-related. In the etanercept cohorts totaling 204 pregnancies, there were 13 anomalies (6.4%); of these, six were VACTERL-related. In the infliximab cohorts totaling 112 pregnancies, there was only one anomaly, which was in the VACTERL cluster. Among the 407 pregnancies in the TNF-inhibitors, there were three anomalies, none of which were related to VACTERL.
Dr. Murase had no financial disclosures relevant to her talk.
The current system of using letter categories to denote risk of prescription drugs during pregnancy and breastfeeding is being replaced by the Food and Drug Administration, with the addition of subsections in drug labeling.
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