Vancenase

Because the consequences of uncontrolled asthma during pregnancy can be so devastating, drug therapy, which is aimed at maintaining control of the chronic condition and preventing 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 have been found to be 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 have been reassuring. These data include a surveillance study of Michigan Medicaid recipients, which included 1,090 newborns exposed to albuterol in the first trimester.

The older agents are preferable to a newer drug, inhaled salmeterol (Serevent), a 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 indicating that inhaled nonselective [beta]-agonists--which include epinephrine, ephedrine, and isoproterenol--are teratogenic. The concern with epinephrine is that it has fairly pronounced [alpha]-adrenergic effects, so it can reduce placental perfusion with consistent use. Ephedrine has mostly [beta]-activity and doesn't seem to have that effect.

There are solid human data showing a possible association between oral steroid use during the first trimester and some birth defects and toxic effects. Still, if an oral corticosteroid is indicated, it should be given, avoiding the first trimester if possible.

But inhaled corticosteroids, the most common drugs used in asthma, appear to be safe, particularly older ones like beclomethasone. When an inhaled steroid is indicated, beclomethasone (Beconase or Vancenase) or budesonide (Pulmicott) are recommended. In general, continue any inhaled steroid if the woman has been well controlled with it before pregnancy. If therapy is initiated during pregnancy budesonide may be the best choice because of its greater potency.

There are so few human data on the other inhaled corticosteroids--flunisolide (Aerobid), fluticasone (Flovent), and triamcinolone (Azmacort)--that the risk, if any, they present during pregnancy cannot be evaluated.

Inhaled cromolyn sodium (Intal), the treatment of choice for mild persistent disease, is safe in animals and appears to be safe in humans. There are not enough reported cases of women taking the drug during pregnancy but the few such case reports that are available have not revealed any problems.

Nedocromil (Tilade) is not teratogenic in animals, but there are no published human data on this drug.

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 would probably not be a problem at lower doses. There are no published human data on this drug.

Theophylline, used for moderate to severe disease, is terarogenic 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. These side effects have to be weighed against the fact that treatment can prevent a patient from progressing to life-threatening disease.

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.

Antihistamines, also used in asthma therapy will be the topic of a future column.

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. He is also coauthor of the textbook "Drugs in Pregnancy and Lactation."

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