Is Deriphyllin (theophylline) safe to use during pregnancy?

Deriphyllin (Theophylline) Safety During Pregnancy

Inhaled medications should be preferred over theophylline (Deriphyllin) during pregnancy for respiratory conditions like asthma, as theophylline is FDA Pregnancy Category C and carries potential risks to both mother and fetus. 1, 2

Safety Profile and Recommendations

• Theophylline crosses the placenta and has no adequate, well-controlled studies in pregnant women, earning it an FDA Pregnancy Category C classification 2
• For women with asthma, inhaled medications (such as inhaled corticosteroids and bronchodilators) should be considered first-line therapy during pregnancy as they have been used for many years without documented adverse effects on the fetus 1
• Maintaining adequate asthma control remains essential during pregnancy, as undertreated asthma resulting in severe exacerbation with maternal hypoxia has well-documented adverse effects on the fetus 1

Maternal Considerations

• Theophylline clearance is frequently reduced during pregnancy (by 20-53% in some patients), potentially resulting in excessive serum levels and increased risk of toxicity, particularly during the third trimester 3
• Pregnant women on theophylline require more frequent monitoring of serum levels during the last half of pregnancy to avoid toxicity 3
• Patients receiving theophylline during pregnancy have shown a higher incidence of preeclampsia (15.6%) compared to non-asthmatic controls (6.4%) 4

Fetal and Neonatal Considerations

• Animal studies have shown potential embryotoxicity at high doses, with one study in rabbits demonstrating teratogenic effects including cleft palate at high maternal plasma concentrations 5
• Newborns of mothers treated with theophylline have shown a higher incidence of jaundice requiring phototherapy (15.0%) compared to control groups (7.8%) 4
• Theophylline is excreted into breast milk at concentrations equivalent to maternal serum levels, potentially causing irritability or mild toxicity in nursing infants 2

Comparative Efficacy

• A randomized controlled trial comparing inhaled beclomethasone to oral theophylline for moderate asthma during pregnancy found:
  • Similar rates of asthma exacerbations between the two treatments 6
  • Better lung function (FEV1) in the inhaled corticosteroid group 6
  • Significantly fewer side effects leading to medication discontinuation with inhaled corticosteroids compared to theophylline 6

Clinical Approach

• When selecting medications for use during pregnancy, clinicians should balance:
  • Maternal risk of therapy versus no therapy
  • Fetal risk of uncontrolled maternal disease versus risk of therapy on the newborn 1
• If theophylline must be used during pregnancy:
  • Monitor serum theophylline levels more frequently, especially in the third trimester 3
  • Watch for signs of toxicity as clearance may be reduced 3
  • Consider using moderate doses during the second and third trimesters, which appears relatively safe based on available data 4

Common Pitfalls and Caveats

• Failing to recognize that theophylline clearance decreases during pregnancy, potentially leading to toxicity if doses aren't adjusted 3
• Not monitoring serum theophylline levels frequently enough during pregnancy, especially in the third trimester 3
• Using theophylline as first-line therapy when safer alternatives (inhaled medications) are available 1, 6
• Discontinuing necessary asthma medications during pregnancy, which can lead to poor asthma control and adverse fetal outcomes due to maternal hypoxia 1