Salbutamol Pregnancy Category
Salbutamol (albuterol) is classified as FDA Pregnancy Category C, meaning animal studies have shown adverse effects but there are no adequate controlled studies in pregnant women, and the drug should only be used if potential benefits justify potential risks to the fetus. 1, 2, 3
Understanding the Category C Classification
The FDA Category C designation for salbutamol specifically applies to the oral formulation and reflects the following evidence 1, 2:
Animal teratogenicity data: Studies in CD-1 mice showed cleft palate formation in 4.5% of fetuses at 0.25 mg/kg subcutaneously and 9.3% at 2.5 mg/kg (approximately 8 times the maximum recommended daily inhalation dose for adults). Cranioschisis occurred in 37% of rabbit fetuses at oral doses of 50 mg/kg. 3
Lack of adequate human studies: There are no adequate and well-controlled studies of salbutamol in pregnant women, though drug-related material does transfer from maternal circulation to the fetus. 3
Postmarketing surveillance: Various congenital anomalies including cleft palate and limb defects have been reported in offspring of patients treated with albuterol, though no consistent pattern has been established and mothers were often taking multiple medications. 3
Critical Distinction: Route of Administration Changes Risk Profile
Inhaled salbutamol has substantially more favorable safety data than oral formulations and is classified as Category A by the Australian Therapeutic Goods Administration, indicating extensive use without increased fetal malformations. 2, 4
Why Inhaled Route is Preferred:
Lower systemic exposure: Inhaled administration results in minimal plasma levels compared to oral/systemic routes. 3
Extensive safety evidence: Data from 6,667 pregnant women, including 1,929 with asthma and 1,599 who took beta2-agonists, provide reassuring safety data specifically for inhaled albuterol. 2, 4
Risk of structural anomalies similar to general population: Clinical studies show no increased baseline risk with inhaled salbutamol. 4
Decades of clinical use: Inhaled asthma medications including salbutamol have been used for many years without documentation of adverse fetal effects. 4
Clinical Context: Untreated Disease Poses Greater Risk
The risk-benefit calculation strongly favors treatment because uncontrolled respiratory disease poses substantially greater risks to the fetus than the medication itself 2, 4:
It is preferable to maintain asthma control during pregnancy rather than withholding medication, as the consequences of maternal hypoxia and uncontrolled asthma far outweigh theoretical medication risks. 2, 4
Practical Prescribing Guidance
For Inhaled Salbutamol (Preferred):
First-line short-acting beta-agonist during pregnancy due to most extensive safety evidence compared to other bronchodilators. 4
Dosing: 2-4 puffs via metered-dose inhaler as needed for acute symptoms. 4
Monitoring threshold: If needed more than twice weekly, this signals inadequate asthma control requiring controller therapy escalation (preferably inhaled budesonide). 4
Monthly evaluation of asthma control and lung function during prenatal visits is recommended. 4
For Systemic Administration (Oral/IV):
Should be avoided when possible due to Category C classification and higher systemic exposure. 2
Adverse effects with systemic use include maternal and fetal tachycardia, maternal hyperglycemia, and neonatal hypoglycemia. 4
Use in labor: Should be restricted to patients where benefits clearly outweigh risks due to potential interference with uterine contractility. 3
Important Caveats
FDA replaced the ABCDX system in 2015 with descriptive labeling under the Pregnancy and Lactation Labeling Rule, but Category C remains the historical classification. 2
Short-acting beta-agonists are preferred over long-acting formulations during pregnancy due to more extensive safety data. 4
Recent research (2011) found no increased risk of major malformations with SABA use (adjusted OR 0.93,95% CI 0.80-1.08), further supporting safety of inhaled salbutamol. 5