Question 3. Are asthma medications safe to use during pregnancy?

From Chapter 8 of the Philippine Consensus Report on Asthma 2004 by the Philippine College of Chest Physicians.
This guideline starts below.

Are asthma medications safe to use during pregnancy?

Answer

Most asthma medications are safe to use during pregnancy.

Summary of Evidence

The use of inhaled beta-2-agonist, theophylline, cromolyn, antihistamins and inhaled steroids are not associated with major congenital malformations when used at anytime during gestation, including the first trimester. In a review of ten studies on asthmatic women during the first trimester of pregnancy, only three met the relevant quality criteria. There was no significant increase in the rate of congenital malformations with any of the exposures.

Because few safety studies on medication use during pregnancy are available, the US Food and Drug Administration (FDA) has published pregnancy risk categories for drugs. All commonly used asthma medications fall under safety categories B and C. This system was developed from animal exposure data and epidemiological data from population studies.

For mild intermittent asthma and acute exacerbations in all asthmatic patients, inhaled short-acting beta-2-agonists are the preferred treatment. These agents have not been shown to have any adverse effects on pregnancy outcomes or teratogenic effects on the fetus. Use of oral and parenteral beta-2-agonists should be avoided because of lack of safety data, the increased risk of side effects (e.g. tremor), and the potential to inhibit delivery.

Inhaled corticosteroids are the gold standard for controlling all forms of persistent asthma. These agents have been shown to decrease asthma exacerbations and mortality and improve overall quality of life. The 2000 position paper of the American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology states, "it would not be unreasonable to continue a different inhaled corticosteroid in a patient well-controlled by that drug prior to pregnancy."

Long-acting beta-2-agonists salmeterol and formoterol are the preferred adjunctive therapy to inhaled corticosteroids for managing moderate to severe persistent asthma. Although no adequate or well-controlled human data are available on salmeterol and formoterol use during pregnancy, there are also no reports of congenital defects. Use of an inhaled long-acting beta-2-agonist with an inhaled corticosteroid appears to be acceptable during pregnancy, especially if the patient has taken such agents without problems before the pregnancy.

Long-term safety data are available for inhaled cromolyn and it is a feasible option for use during pregnancy especially if there is a concern about prescribing inhaled corticosteroids. The leukotriene receptor antagonists, zafirlukast and montelukast sodium are classified as FDA category B because no human or animal teratogenic effects have been seen with these agents. Use of oral corticosteroids during pregnancy poses some risk.

Theophylline has not been shown to have teratogenic effects during pregnancy although its use has radically decreased because of possible toxicity with elevated serum levels and because of the development of newer, safe agents. When used during pregnancy, clearance of the agent decreases, therefore dosing should be carefully watched and adjusted. Theophylline crosses the placenta and the newborn may have jitterness, increased heart rate and even vomiting at birth.

Nebulized ipratropium can be used for acute asthma not responding well to inhaled beta-2-agonist. Ipratropium bromide is an inhaled anticholinergic agent that is used as an adjunctive therapy to short-acting beta-2-agonists for acute asthma exacerbations. Animal data have not demonstrated any birth defects, but human data are lacking.

Omalizumab, an IgG monoclonal antibody directed against IgE was recently approved in the United States for use in moderate to severe allergic asthma that has not responded to moderate to high doses of inhaled corticosteroids. The FDA gave this agent a pregnancy category B rating because no teratogenic effects were seen in animal studies. In clinical studies with omalizumab before FDA approval, several women became pregnant and delivered normal infants. Because of the newness of this agent, caution should be exercised when prescribing during pregnancy.