Is deriphyllin (theophylline) safe to use during pregnancy?

Safety of Deriphyllin (Theophylline) During Pregnancy

Deriphyllin (theophylline) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as it is classified as FDA Pregnancy Category C. 1

Risk Classification and Safety Profile

• Theophylline has been designated as FDA Pregnancy Category C, indicating that animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in humans 1
• According to the FDA label, theophylline was not shown to be teratogenic in mice at oral doses up to 400 mg/kg or in rats at oral doses up to 260 mg/kg 1
• At a dose of 220 mg/kg in rats, embryotoxicity was observed in the absence of maternal toxicity 1

Clinical Evidence in Pregnancy

• Limited clinical data from a case-control study of 212 pregnant asthmatics on theophylline showed that during the second and third trimesters, moderate doses of theophylline can be considered relatively safe 2
• The safety of theophylline during the first trimester regarding teratogenicity remains less certain, as the study found 3 infants with malformations among 121 patients treated with theophylline during the first trimester 2
• Pregnant women on theophylline showed a higher incidence of preeclampsia (15.6%) compared to non-asthmatic controls (6.4%) 2
• Neonatal jaundice requiring phototherapy was more common in infants whose mothers received theophylline (15.0%) compared to control groups (7.8%) 2

Pharmacokinetic Considerations

• Theophylline clearance is frequently reduced during pregnancy, particularly in the third trimester, resulting in potentially higher serum levels 3
• In one study, five out of six patients displayed a reduction in theophylline clearance during pregnancy ranging between 20-53% compared to postpartum values 3
• Two patients in the study required dosage reductions due to symptoms of toxicity 3

Recommendations for Use

• Theophylline should be used in pregnancy only when clearly needed and when the benefits outweigh the potential risks 1
• If theophylline is required during pregnancy, serum theophylline concentrations should be monitored more frequently, especially during the third trimester 3
• For women with asthma, inhaled medications have been used for many years without documentation of adverse effects on the fetus and should be considered as first-line therapy 4
• The effect of undertreated asthma resulting in severe exacerbation with maternal hypoxia is well documented to have adverse effects on the fetus, so maintaining adequate asthma control remains essential 4

Breastfeeding Considerations

• Theophylline is excreted into breast milk at concentrations approximately equivalent to maternal serum concentration 1
• An infant ingesting a liter of breast milk containing 10-20 mcg/mL of theophylline per day is likely to receive 10-20 mg of theophylline per day 1
• Serious adverse effects in the infant are unlikely unless the mother has toxic serum theophylline concentrations 1
• Infants should be monitored for irritability or other signs of mild toxicity if the mother is taking theophylline while breastfeeding 1

Alternative Treatments

• For respiratory conditions like asthma, inhaled medications (such as inhaled corticosteroids and bronchodilators) are preferred during pregnancy as they have been used for many years without documentation of adverse effects on the fetus 4
• When selecting medications for use during pregnancy, the clinician should compare the benefits and risks of each medication, balancing maternal risk of therapy versus no therapy and the fetal risk of uncontrolled maternal disease with the risk of therapy on the newborn 4