BECLOMETHASONE

Fetal Risk Summary

Beclomethasone dipropionate is given by inhalation for the chronic treatment of bronchial asthma in patients requiring corticosteroid therapy for the control of symptoms. It is also available for intranasal use and, outside of the United States, for topical application.

Beclomethasone was embryocidal (increased fetal resorption) and teratogenic when administered by SC injection to mice and rabbits at approximately 10 times the human dose (1,2). Congenital malformations observed included cleft palate, agnathia, microstomia, absence of the tongue, delayed ossification, and agenesis of the thymus. Similar toxic effects in both species were observed with SC injections that were approximately one-half the maximum recommended adult daily inhalation dose on a mg/m2 basis (3). In the rat, no embryo or fetal harm was found with inhaled (at 10 times the human dose) or oral (at 1,000 times the human dose) beclomethasone (1,2).

No human reports associating the use of beclomethasone with human congenital anomalies have been found. A 1975 report briefly mentioned seven healthy babies born from mothers who had used beclomethasone aerosol for over 6 months (4). In another report, beclomethasone was used during 45 pregnancies in 40 women (5). Dosage ranged between 4 and 16 inhalations/day (mean 9.5), with each inhalation delivering 42mg of drug. Three of the 33 prospectively studied pregnancies ended in abortion that was not thought to be caused by the maternal asthma. Forty-three living infants resulted from the remaining 42 pregnancies. Six infants had low birth weights, including two of the three premature newborns (less than 37 weeks' gestation). There was no evidence of neonatal adrenal insufficiency. One full-term infant had cardiac malformations (double ventricular septal defect, patent ductus arteriosus, and subaortic stenosis). However, the mother's asthma was also treated with prednisone, theophylline, and epinephrine. In addition, she had schizophrenia and diabetes mellitus for which she took fluphenazine and insulin. Cardiac malformations are known to occur with diabetes mellitus (see Insulin).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 395 newborns had been exposed to beclomethasone during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 16 (4.1%) major birth defects were observed (16 expected). Specific information was not available on the defects, but no anomalies were observed in six categories (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias). These data do not support an association between the drug and congenital defects.

Breast Feeding Summary

It is not known whether beclomethasone is excreted into breast milk. Other corticosteroids are excreted into milk in low concentrations (see Prednisone) and the passage of beclomethasone into milk should be expected. One report has been located that notes three cases of maternal beclomethasone use during breast feeding (4). Effects on the nursing infants were not mentioned.

References

1. Product information. Beconase. Glaxo Wellcome, 2000.
2. Product information. Vancenase; Vanceril. Schering, 2000.
3. Product information. Beclovent. Glaxo Wellcome, 2000.
4. Brown HM, Storey G. Treatment of allergy of the respiratory tract with beclomethasone dipropionate steroid aerosol. Postgrad Med J 1975;51(Suppl 4):59–64.
5. Greenberger PA, Patterson R. Beclomethasone dipropionate for severe asthma during pregnancy. Ann Intern Med 1983;98:478–80.