Rx CARE

New guidelines advise albuterol use for pregnant asthmatics

Albuterol (Proventil, Schering, or Ventolin, GlaxoSmithKline) is the short-acting inhaled beta-2 agonist of choice for pregnant women with asthma. That's the latest recommendation from the National Asthma Education & Prevention Program. NAEPP released new guidelines for the treatment of asthma during pregnancy at the 2004 annual meeting of the American Academy of Allergy, Asthma & Immunology, held in San Francisco in March.

"The guidelines reflect new medications that have been introduced since the last recommendations of 2002 and updates them by considering the safety data," said Harold Nelson, M.D., professor of medicine at National Jewish Medical & Research Center in Denver. "Asthma drugs are generally safe in pregnancy. The worst that can happen is for a woman to discover that she's pregnant and throw out all her meds."

Asthmatics who abandon medications tend to get worse quickly. That's particularly bad news for pregnant women, said Michael Schatz, M.D., chief of allergy at Kaiser Permanente Medical Center in San Diego.

More severe asthma symptoms increase the risk of preterm birth, low birth weight, perinatal mortality, and preeclampsia. Complications are generally linked to maternal hypoxia and reduced uteroplacental blood flow. Better maternal pulmonary function is directly related to better fetal outcomes such as increased birth weight.

"Pregnant patients with asthma are at increased risk," Schatz said. "We can't do much about pathogenic and demographic factors, but we can do something about the medications we use and our patients' control of their asthma."

Asthma affects about 7% of pregnant women in the United States. "That makes it the most common potential complication of pregnancy," Schatz continued. "There is a lot to be gained by doing the right thing by these patients."

Doing the right thing includes frequent monitoring, Schatz continued. Asthmatics should be seen by a healthcare professional at least monthly, he cautioned. Medications and compliance should be reviewed along with clinical data and symptoms.

The severity of asthma tends to worsen during pregnancy, but the disease is also twice as likely to respond to drug therapy. In general, he explained, symptoms tend to remain quiet during the first trimester, worsen during the last half of the second trimester and the first half of the third trimester, then improve in the final weeks before delivery.

Women with intermittent asthma may be at more risk than women with persistent symptoms. Among persistent asthmatics, unscheduled hospital admissions increase 2.5-fold—from 8% to 20.3%— during pregnancy, Schatz said. But among intermittent asthmatics, the unscheduled admission rate jumps nearly 4.5 times, from 2.3% to 11.3%.

"Even intermittent patients need to be followed closely," Schatz noted. "Undertreatment seems to lead to even worse outcomes."

The need to continue and perhaps increase treatment colors the new guidelines. In some cases, the new recommendations in the guidelines are based on lack of data rather than negative data.

Lack of data lies behind the NAEPP expert panel's decision to recommend albuterol. Terbutaline is not necessarily less effective or less safe than albuterol, explained Stanley Szefler, M.D., head of pediatric clinical pharmacology at the National Jewish Medical. Terbutaline is just less studied.

The panel used similar reasoning to suggest that women who need a long-acting beta₂ agonist might do better on salmeterol (Serevent, GlaxoSmithKline) than on formoterol (Foradil, Novartis).

"Salmeterol has been available longer in the United States," Szefler said, which gives more data supporting efficacy and safety compared with formoterol.

The new guidelines are based on a literature review that included 226 articles appearing in peer-reviewed journals between 1990 and May 2003. Forty-two articles met criteria for inclusion in the evidence review. Two articles published after May 2003 were also reviewed.

The panel concluded that theophylline is an alternative for treatment during pregnancy, but not preferred. The recommendation is based on a combination of animal data associating high-dose theophylline and adverse pregnancy outcomes and human data showing higher levels of side effects.

Studies and clinical experience show that theophylline is safe during pregnancy when used at recommended doses of 5-12 mcg/ mL. In randomized human trials, there were no differences in asthma exacerbations, maternal outcomes, or perinatal outcomes compared with beclomethasone dipropionate treatment.

For patients with persistent asthma, inhaled corticosteroids are the preferred treatment. No studies have related inhaled corticosteroids to any increases in congenital malformations or other adverse perinatal outcomes.

Nearly all of the data are with budesonide (Pulmicort, AstraZeneca). The panel found few or no studies with other inhaled corticosteroids during pregnancy.

For women with mild persistent asthma, cromolyn is an alternative, but not preferred, therapy. Current evidence supports the safety of cromolyn during pregnancy.

Minimal data are available on leukotriene modifiers during pregnancy. The panel concluded that these agents comprise an alternative, but not preferred, treatment for persistent asthma during pregnancy.

Women with severe asthma can be given oral corticosteroids when indicated during pregnancy. The recommendation is based on the relative risks of uncontrolled asthma versus oral corticosteroid use. Oral steroid use during pregnancy is associated with increased incidence of preeclampsia and the delivery of both preterm and low-birthweight infants and the risk of maternal and fetal mortality, but the risks of uncontrolled asthma are greater still.

"Use with caution," Szefler said, but "the risk-benefit consideration favors oral steroid use in severe asthma."

Fred Gebhart