The consequences of uncontrolled asthma during pregnancy can be devastating, so drug therapy to control the chronic condition and prevent acute exacerbations is a lesser risk in almost all cases.
Commonly used inhaled short-acting [[beta].sub.2]-agonists include metaproterenol (Alupent), albuterol (Proventil, Ventolin), and terbutaline (Brethine). At high doses, several of these drugs are teratogenic in animals, but there is no evidence that the animal risk is predictive of human risk, based on the limited human data that are available.
Although most of the data are from cases exposed later in pregnancy the small amount of first-trimester human data for older agents are reassuring. These data include a surveillance study of Michigan Medicaid recipients; it included 1,090 newborns exposed to albuterol in the first trimester.
The older agents are preferable to inhaled salmeterol (Serevent), a newer long-acting [beta]-agonist used in moderate to severe persistent asthma. There are no published human reports on salmeterol use during pregnancy but if a pregnant woman has had a good therapeutic response to salmeterol before becoming pregnant and has been stabilized, the recommendation is to continue using it. This may be preferable to doubling the dose of an inhaled corticosteroid in such a patient and may be better tolerated than adding oral theophylline.
There are no data that inhaled nonselective [beta]-agonists--including epinephrine, ephedrine, and isoproterenol--are teratogenic. The concern with epinephrine is that its [alpha]-adrenergic effects can reduce placental perfusion with consistent use. Ephedrine has mostly [beta]-activity and does not seem to have that effect.
Solid human data show a possible link between oral steroids in the first trimester and some birth defects and toxicity. But if indicated, an oral corticosteroid should be given, avoiding the first trimester if possible.
But inhaled corticosteroids, the most common asthma drugs, appear to be safe, particularly older ones like beclomethasone. When an inhaled steroid is indicated, beclomethasone (Beconase or Vancenase) or budesonide (Pulmicort) are recommended. In general, continue any inhaled steroid if the woman has been well controlled with it before pregnancy. If therapy starts during pregnancy budesonide may be the best because of its high potency.
There are so few human data on the other inhaled corticosteroids--flunisolide (Aerobid), fluticasone (Flovent), and triamcinolone (Azmacort)--that the risk, if any during pregnancy cannot be evaluated.
Inhaled cromolyn sodium (Intal), the treatment of choice for mild persistent disease, is safe in animals and appears safe in humans based on limited case reports.
Montelukast (Singulair), a leukotriene modifier, is not teratogenic in animals. Case reports of six pregnancies in a Merck pregnancy registry, including two exposed to montelukast throughout pregnancy provide too few data to evaluate. There are no published data on zileuton (Zyflo) use in humans, but the drug should be avoided because it has been found to be teratogenic and fetotoxic in animals. Zafirlukast (Accolate) is not a teratogen, but is fetotoxic at high doses in rats and monkeys. This would be a concern if a woman overdosed, but probably not at lower doses. There are no published human data on this drug.
Theophylline, used for moderate to severe disease, is teratogenic in animals, but does not appear to have any fetal risk. When used near delivery theophylline, which readily crosses the placenta, can cause symptoms like jitteriness, tachycardia, and vomiting in the newborn.
In general, maternal administration of these drugs during lactation does not result in high levels in breast milk and does not appear to pose problems for healthy normal birthweight infants.
GERALD G. BRIGGS is clinical pharmacist, Women's Hospital, Long Beach Memorial Medical Center; clinical professor of pharmacy, University of California, San Francisco; and adjunct associate professor of pharmacy, University of Southern California, Los Angeles.
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