Drugs in Pregnancy and Lactation: Tenth Edition

MOMETASONE

Corticosteroid

PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible

BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible

PREGNANCY SUMMARY

No reports describing the use of mometasone in human pregnancy have been located. The animal data suggest risk, but the observed developmental toxicity is similar to that observed after systemic exposure to other corticosteroids (e.g., see Hydrocortisone). In addition, the animal reproduction studies were not conducted with the inhaled or nasal spray formulation of mometasone. These products are known to have very low systemic bioavailability. Moreover, several large studies involving asthma patients have found no association between inhaled corticosteroids and adverse pregnancy outcomes, such as congenital anomalies (1), intrauterine growth restriction (2), or preterm delivery, low birth weight, small size for gestational age, and major malformations (3). Although mometasone was not included in any of these studies, and allergic rhinitis was not a condition studied, there is no reason to believe that the use of this corticosteroid or the additional diagnosis would have resulted in different outcomes. Because asthma is known to cause maternal and fetal harm, the use of mometasone should not be withheld because of pregnancy. However, beclomethasone or budesonide have been considered the inhaled corticosteroids of choice for use during pregnancy (4).

FETAL RISK SUMMARY

Mometasone is a corticosteroid in inhaled and nasal spray formulations. The inhaled product is indicated for the maintenance treatment of asthma as prophylactic therapy. It also is used to reduce or eliminate the need for oral corticosteroids (5). The nasal spray is indicated for the treatment of the nasal symptoms of seasonal allergic and perennial allergic rhinitis and for prophylaxis in patients with a known seasonal allergen that precipitates nasal symptoms of seasonal allergic rhinitis (6).

The mean absolute systemic bioavailability of a single inhaled 400-mcg dose, compared with a similar IV dose, is less than 1% (5). Plasma concentrations in most subjects were near or below the lower limit of quantitation (50 pg/mL). After administration of the recommended highest inhaled dose (400 mcg twice daily) for 28 days, the mean peak plasma concentrations were 94–114 pg/mL (5). Systemic bioavailability after use of the nasal spray also is low, with concentrations virtually undetectable at the quantitation limit (6). Moreover, any of the drug that is swallowed and absorbed undergoes extensive metabolism in the liver.

Reproduction studies have been conducted in mice, rats, and rabbits but not with the inhaled or nasal spray formulations (5,6). In mice, SC doses less than the maximum recommended daily inhaled dose in humans based on BSA (MRDID-BSA) caused cleft palate. Fetal survival was reduced at doses about equal to the MRDID-BSA. The no-toxicity dose was one-third the dose causing cleft palate. In rats, a topical dermal dose about 6 times more than the MRDID-BSA or higher resulted in umbilical hernia. A dose about 3 times the MRDID-BSA produced delays in ossification, but no malformations. An SC dose about 6 times the maximum recommended daily inhalation dose based on AUC (MRDID-AUC) or less than the MRDID-BSA, given throughout pregnancy or during the later stages of pregnancy, caused prolonged and difficult labor. In addition, this dose reduced the number of live births, birth weight, and early pup survival. These effects were not observed when the dose was halved. In rabbits, topical dermal doses about 3 times the MRDID-BSA caused multiple anomalies including flexed front paws, gallbladder agenesis, umbilical hernia, and hydrocephaly. When given orally in a dose less than the MRDID-AUC, mometasone increased resorptions and caused cleft palate and/or head defects (hydrocephaly and domed head). When the dose was increased to about twice the MRDID-AUC, most litters were aborted or resorbed. The no-toxicity dose was 20% of the dose causing cleft palate and/or head defects (5,6).

It is not known if mometasone crosses the animal or human placenta. The molecular weight (about 513) is low enough for passage, but the very low systemic bioavailability suggests that little, if any, drug will reach the embryo or fetus.

BREASTFEEDING SUMMARY

No reports describing the use of mometasone during human lactation have been located. Other corticosteroids are excreted into breast milk in low concentrations. (See Prednisone.) The molecular weight (about 513) suggests that the drug, if it reached the plasma, would be excreted into breast milk. However, the very low systemic concentrations obtained after use of the inhaled or nasal spray formulations suggest that any excretion into milk will be clinically insignificant.

References

1.Schatz M, Zeiger RS, Harden K, Hoffman CC, Chilingar L, Petitti D. The safety of asthma and allergy medications during pregnancy. J Allergy Clin Immunol 1997;100:301–6.

2.Namazy J, Schatz M, Long L, Lipkowitz M, Lillie MA, Voss M, Deitz RJ, Petitti D. Use of inhaled steroids by pregnant women does not reduce intrauterine growth. J Allergy Clin Immunol 2004;113:427–32.

3.Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W, Newman RB, Hauth JC, Lindheimer M, Caritis SN, Leveno KJ, Meis P, Miodovnik M, Wapner RJ, Paul RH, Varner MW, O’Sullivan MJ, Thurnau GR, Conway DL, for The National Institute of Child Health and Development Maternal-Fetal Medicine Units Network and the National Heart, Lung, and Blood Institute. The relationship of asthma medication use to perinatal outcomes. J Allergy Clin Immunol 2004;113:1040–5.

4.Joint Committee of the American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology (ACAAI). Position statement. The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475–80.

5.Product information. Asmanex Twisthaler. Schering Corporation, 2005.

6.Product information. Nasonex. Schering Corporation, 2005.