What is the pregnancy category of salbutamol (albuterol) oral tablets during the 1st trimester?

Salbutamol Oral Tablet Pregnancy Category for 1st Trimester

Salbutamol oral tablets are classified as FDA Pregnancy Category C, meaning animal studies have shown adverse effects and there are no adequate controlled studies in pregnant women, but the drug may be used if potential benefits justify potential risks to the fetus. 1

FDA Classification and Regulatory Context

• The FDA classifies oral albuterol (salbutamol) as Pregnancy Category C based on animal teratogenicity data showing cleft palate formation in mice at doses corresponding to 1.25 times the human nebulization dose, and cranioschisis in rabbits at 250 times the human dose 1
• The FDA replaced the ABCDX pregnancy category system in 2015 with descriptive labeling under the Pregnancy and Lactation Labeling Rule, but Category C remains the historical classification for oral salbutamol 2
• Category C indicates that animal reproduction studies have revealed adverse effects on the fetus, and studies in women and animals are not available, so drugs should be given only if potential benefit justifies potential risk 2

Important Distinction: Route of Administration Matters

• Inhaled salbutamol has a more favorable safety profile and is classified as Category A by the Australian Therapeutic Goods Administration, indicating it has been taken by a large number of pregnant women without increase in fetal malformations 3
• The oral formulation carries greater systemic exposure and different risk considerations compared to inhaled forms 3, 1
• Systemic (oral or intravenous) salbutamol can cause adverse cardiovascular and metabolic effects including maternal and fetal tachycardia, maternal hyperglycemia, and neonatal hypoglycemia 3

Clinical Safety Data and Real-World Experience

• Despite the Category C classification, there is reassuring safety data for albuterol use in pregnancy from 6,667 pregnant women, including 1,929 with asthma and 1,599 who took beta2-agonists 3
• During worldwide marketing experience, various congenital anomalies including cleft palate and limb defects have been rarely reported, but no consistent pattern of defects has been discerned and a relationship between albuterol use and congenital anomalies has not been established 1
• Prescription drug use studies show salbutamol was among the most frequently filled prescriptions in pregnancy, though evidence on safety remains limited 4

Critical Clinical Considerations for Oral Formulation

• Oral salbutamol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 1
• Oral administration results in higher systemic concentrations (mean 12 ng/ml during oral treatment vs. inhaled routes) and greater metabolic side effects 5
• Tolerance develops to metabolic and cardiovascular effects with chronic oral use (4 mg four times daily for 12-33 days), with significantly less pronounced effects after long-term treatment 6
• Oral albuterol has been shown to delay preterm labor in some reports, requiring cautious use to avoid interference with uterine contractility when given near term 1

Preferred Alternative: Inhaled Route

• Inhaled salbutamol is strongly preferred over oral formulation during pregnancy because it has more extensive safety evidence and lower systemic exposure 3
• Inhaled asthma medications including salbutamol have been used for many years without documentation of adverse effects on the fetus 3
• The risk of structural anomalies with inhaled salbutamol is similar to that of the general population 3

Risk-Benefit Framework for First Trimester

• Uncontrolled respiratory disease poses greater risk to the fetus than asthma medications, including risks of perinatal mortality, preeclampsia, and low birth weight 3
• It is preferable to keep asthma controlled during pregnancy rather than suspending medication 3
• The first trimester is the period of organogenesis when teratogenic risk is theoretically highest, making the Category C classification particularly relevant for oral formulations 1

Common Pitfalls to Avoid

• Do not assume all salbutamol formulations have the same pregnancy classification—oral tablets are Category C while inhaled forms have more favorable safety profiles 3, 1
• Do not withhold necessary bronchodilator therapy due to pregnancy category concerns when maternal respiratory compromise threatens fetal oxygenation 3
• Do not prescribe oral salbutamol when inhaled formulations would be equally effective, as the inhaled route minimizes systemic exposure and fetal risk 3
• Be aware that oral contraceptives and other Category X drugs are sometimes inadvertently continued into early pregnancy before pregnancy recognition 4, 7