Is the fixed‑dose combination budesonide/formoterol safe for use in pregnant women with moderate to severe persistent asthma?

Safety of Budesonide/Formoterol in Pregnancy

The fixed-dose combination budesonide/formoterol is safe for use in pregnant women with moderate to severe persistent asthma and should be continued if the patient was well-controlled on this regimen before pregnancy. 1

Evidence Supporting Safety of Individual Components

Budesonide Safety Profile

• Budesonide is the preferred inhaled corticosteroid during pregnancy with the most extensive safety data and FDA Pregnancy Category B classification. 1
• At usual doses, budesonide has not been associated with increased risk of major malformations, intrauterine growth restriction, preterm delivery, or low birth weight. 1
• Safety data from over 2,500 infants exposed to budesonide show no increase in congenital malformations (3.6% observed versus 3.5% background rate). 2
• Low to moderate doses of inhaled corticosteroids should be continued throughout pregnancy to control symptoms and prevent exacerbations, though caution is warranted with doses exceeding 1000 µg/day (beclomethasone equivalent). 3

Formoterol Safety Profile

• Limited human data exists on formoterol use during pregnancy, but animal data suggest low risk. 1
• The pharmacologic and toxicologic profiles of long-acting beta-agonists (including formoterol) are similar to short-acting beta-agonists like albuterol, which have extensive reassuring pregnancy safety data from over 6,600 pregnant women showing no evidence of fetal harm. 4, 2
• If a woman was well-controlled on formoterol before pregnancy, it is acceptable to continue with the same medication during pregnancy. 1

Clinical Algorithm for Management

For Patients Already on Budesonide/Formoterol

• Continue the medication without switching if asthma is well-controlled, as maintaining stable disease control takes priority over theoretical concerns about formoterol's limited pregnancy data. 1
• Avoid unnecessarily switching from formoterol to salmeterol, as this can destabilize asthma control without clear benefit. 1

For Patients Requiring Initiation During Pregnancy

• Consider budesonide as the preferred inhaled corticosteroid component due to its extensive pregnancy safety data. 1
• For moderate persistent asthma, combination therapy with low-dose inhaled corticosteroid plus long-acting beta-agonist is a preferred treatment option. 1
• While salmeterol has historically been preferred due to longer experience during pregnancy, formoterol is acceptable if needed for optimal control. 1

Dosing Considerations

• Use the lowest effective dose necessary to maintain asthma control. 1
• High-dose budesonide/formoterol (320/9 µg, two inhalations twice daily) is effective and well-tolerated in patients with persistent symptomatic asthma, with a safety profile comparable to lower doses. 5

Rationale: Risks of Uncontrolled Asthma Outweigh Medication Risks

Poorly controlled asthma poses substantially greater risks to mother and fetus than potential medication risks. 1

Maternal and Fetal Risks of Uncontrolled Asthma

• Uncontrolled asthma increases risk of perinatal mortality, preeclampsia, preterm birth, and low birth weight infants. 2
• Asthma exacerbations during pregnancy have the potential to lead to severe problems for the fetus and should be managed aggressively. 4
• Maternal hypoxia from poorly controlled asthma can lead to adverse fetal outcomes. 1

Evidence Supporting Combination Therapy

• Strong evidence from randomized controlled trials in non-pregnant adults shows that adding a long-acting beta-agonist to low-dose inhaled corticosteroid provides greater asthma control than only increasing the corticosteroid dose. 4
• In patients already receiving inhaled corticosteroids, adding formoterol reduced the risk for severe exacerbations and poorly controlled days by 43% and 30%, respectively, compared to doubling the corticosteroid dose. 6

Monitoring Requirements Throughout Pregnancy

• Regular monitoring of asthma symptoms is recommended throughout pregnancy, as asthma course changes in approximately two-thirds of pregnant women (improves in one-third, worsens in one-third). 1, 2
• Monthly evaluation of asthma control and lung function is essential during prenatal visits. 2
• Serial fetal ultrasound examinations should commence at 32 weeks gestation for women with moderate-to-severe asthma, suboptimally controlled asthma, or after recovery from severe exacerbations. 2

Critical Pitfalls to Avoid

• Never discontinue asthma medications during pregnancy due to unfounded safety concerns, as this leads to poor asthma control and increased risks to both mother and fetus. 1
• Do not fail to aggressively manage asthma exacerbations during pregnancy, as maternal hypoxia poses immediate danger to fetal well-being. 1
• Avoid switching from formoterol to salmeterol unnecessarily if the patient was previously well-controlled on formoterol, as medication changes can destabilize asthma control. 1
• Do not reduce inhaled corticosteroid doses below the level required for stable asthma control in an attempt to minimize fetal exposure, as uncontrolled asthma is more dangerous than medication exposure. 1

Additional Context on Safety and Tolerability

• Budesonide/formoterol maintenance and reliever therapy is well-tolerated with an incidence of adverse events similar to conventional regimens. 7
• All treatments with budesonide/formoterol are well-tolerated, and the incidence of class-related adverse events is similarly low across dosing regimens. 5
• Changes in serum potassium and plasma cortisol with high-dose budesonide/formoterol are comparable to other treatment regimens, indicating no additional systemic effects. 5