The FDA Center for Drug Evaluation and Research (CDER) has published a warning regarding the use of medicinal products containing nasal forms of mometasone furoate, associated with the risk of local nasal adverse reactions, hypercorticism and adrenal suppression, reduced growth velocity when used in children, and specifics of use in certain population groups.
Section “Warnings and precautions”
Subsection “Local nasal adverse reactions”
Subsection title revised
Additions and/or changes are underlined:
Nosebleed
Nosebleeds were observed more often in patients with allergic rhinitis and patients with chronic rhinosinusitis with nasal polyps who received mometasone furoate than in those who received placebo (see the "Adverse reactions" section).
Candida infection
Localized infections of the nose and pharynx caused by Candida albicans occurred as a result of nasal administration of mometasone furoate. If such an infection develops, the use of mometasone furoate should be discontinued and, if necessary, appropriate topical or systemic therapy prescribed.
Perforation of the nasal septum
Cases of nasal septum perforation have been observed in patients after nasal use of corticosteroids, including mometasone furoate. As with any long-term local treatment of the nasal cavity, patients who use mometasone furoate for several months or longer should be periodically examined for possible changes in the nasal mucosa.
Impaired wound healing
Due to the inhibitory effect of corticosteroids on wound healing, patients who have recently had nasal septum ulcers, nasal surgery, or nasal trauma should not use nasal corticosteroids until healing is complete.
Subdivision “Hypercortisolism and adrenal suppression”
Additions and/or changes are underlined:
Hypercorticism and adrenal suppression may occur when nasal corticosteroids, including mometasone furoate, are used at doses higher than recommended (see the section “Method of administration and dosage”), or in patients at risk of developing such effects. If such changes occur, the dose of mometasone furoate should be slowly discontinued, in accordance with accepted procedures for discontinuing oral corticosteroid therapy.
Subsection “Effect on growth”
Additions and/or changes are underlined:
Corticosteroids, including mometasone furoate, may cause a reduction in growth velocity when administered to children. Monitor regularly the growth of pediatric patients receiving mometasone furoate. To minimize the systemic effects of nasal corticosteroids, including mometasone furoate, titrate each patient’s dose to the lowest dose that effectively controls his/her symptoms (see the section “Use in Specific Populations”].
“Adverse reactions” section
Additions and/or changes are underlined:
The following clinically significant adverse reactions are described in other sections:
- Nosebleeds, ulcers, Candida albicans infection, impaired wound healing (see the section “Warnings and precautions”)
- Glaucoma and cataract (see section "Warnings and precautions")
- Immunosuppression and risk of infections (see the section “Warnings and precautions”)
- Hypercortisolism and adrenal suppression, including growth reduction (see the sections "Warnings and Precautions" and "Use in Specific Populations").
Subsection “Clinical trial experience”
Additions and/or changes are underlined:
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a medicinal product cannot be directly compared with the rates in the clinical trials of another medicinal product and may not reflect the rates observed in practice.
Allergic rhinitis
Adults and children aged 12 years and older
In controlled American and international clinical studies, a total of 3210 adults and children aged 12 years and older with allergic rhinitis were treated with mometasone furoate nasal spray at doses from 50 to 800 mcg/day. Most patients (n=2103) received 200 mcg/day. A total of 350 adults and children aged 12 years and older were treated for one year or longer. Adverse reactions did not differ significantly by age, sex or race. Four percent or fewer of patients in the clinical trials discontinued treatment because of adverse effects, and the discontinuation rate was the same for the medicinal product and the active comparators.
All adverse reactions (regardless of relationship to treatment) reported by 5% or more of adults and children aged 12 years and older who received mometasone furoate intranasally at a dose of 200 mcg/day compared with placebo and which were observed more frequently with mometasone furoate than with placebo. Adults and children aged 12 years and older – adverse reactions based on the results of controlled clinical studies in seasonal allergic and perennial allergic rhinitis (percentage of patients who reported them)
Other adverse reactions that occurred in less than 5% but more than or equal to 2% of adults and children (aged 12 years and older) who received mometasone furoate nasally at 200 mcg/day (regardless of relationship to treatment), and more often than in the placebo group, included: arthralgia, asthma, bronchitis, chest pain, conjunctivitis, diarrhea, dyspepsia, ear pain, flu-like symptoms, myalgia, nausea, and rhinitis.
Chronic rhinosinusitis with nasal polyps
Adults aged 18 years and older
In controlled clinical studies, the types of adverse reactions observed in patients with chronic rhinosinusitis with nasal polyps were similar to those observed in patients with allergic rhinitis. In total, 594 adult patients (aged 18 to 86 years) received mometasone furoate nasally at doses of 200 mcg once or twice daily for 4 months for the treatment of chronic rhinosinusitis with nasal polyps. The overall incidence of adverse reactions in patients receiving nasal mometasone furoate was comparable to that in patients receiving placebo, except for nosebleeds, which were 9% for 200 mcg once daily, 13% for 200 mcg twice daily, and 5% for placebo.
Section “Use in specific population groups”
Subsection «Pregnancy»
Additions and/or changes are underlined:
Risk summary
Mometasone is minimally absorbed systemically after nasal administration, and maternal use of the medicinal product is not expected to result in fetal exposure. The available data from observational studies of mometasone furoate use in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies in pregnant mice, rats or rabbits (subcutaneous, subcutaneous/topical dermal/oral and topical dermal/oral, respectively), mometasone furoate caused increased fetal malformations and decreased fetal survival and growth after administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose on a mcg/m2 or AUC basis (see Results). However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry a background risk of birth defects, loss or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Results
Results of animal studies
In an embryo-fetal development study in pregnant mice dosed during the period of organogenesis, mometasone furoate caused cleft palate at a dose lower than the maximum recommended daily intranasal dose (MRDID) (based on mcg/m2 with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at approximately 2 times the MRDID (based on mcg/m2 with a maternal subcutaneous dose of 180 mcg/kg). Toxicity was not observed at a dose resulting in exposure lower than the MRDID (based on mcg/m2 with maternal topical dermal doses of 20 mcg/kg and above).
Subsection “Breastfeeding period”
Additions and/or changes are underlined:
Risk summary
There are no available data on the presence of mometasone furoate in human milk, its effects on the breastfed infant, or its effects on milk production. However, mometasone furoate is minimally systemically absorbed by the mother after nasal administration, and breastfeeding is not expected to result in infant exposure to mometasone. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mometasone and any potential adverse effects of mometasone furoate on the breastfed infant or from the underlying maternal condition.
Subsection “Use in the pediatric population”
Additions and/or changes are underlined:
The safety and efficacy of mometasone furoate for the prophylaxis of nasal symptoms of seasonal allergic rhinitis in pediatric patients aged 12 years and older have been established (see the sections “Adverse Reactions” and “Clinical Studies”). The use of mometasone furoate for this indication is supported by evidence from controlled studies involving adults and children aged 12 years and older (see the section “Clinical Studies”).
The safety and efficacy of mometasone furoate for the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients under 18 years of age have not been established. Efficacy was not demonstrated in one 4-month study conducted to evaluate the safety and efficacy of mometasone furoate in the treatment of chronic rhinosinusitis with nasal polyps in children aged 6 to 17 years. The primary objective of the study was to evaluate safety; efficacy parameters were collected as secondary endpoints. A total of 127 patients with chronic rhinosinusitis with nasal polyps were randomized to receive placebo or mometasone furoate 100 mcg once or twice daily (patients aged 6 to 11 years) or 200 mcg once or twice daily (patients aged 12 to 17 years). The results of this study do not support the efficacy of mometasone furoate in the treatment of chronic rhinosinusitis with nasal polyps in children. The adverse reactions reported in this study were similar to the adverse reactions reported in patients aged 18 years and older with chronic rhinosinusitis with nasal polyps.
Effect on growth
Controlled clinical studies have shown that nasal corticosteroids may cause a reduction in growth velocity in children. This effect was observed in the absence of laboratory evidence of suppression of the hypothalamic-pituitary-adrenal (HPA) axis, which suggests that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with nasal corticosteroids, including the effect on final adult height, are unknown. The potential for "catch-up" growth after discontinuation of treatment with nasal corticosteroids has not been adequately studied. The growth of children receiving nasal corticosteroids, including mometasone furoate, should be monitored regularly (for example, by stadiometry). The potential effect of long-term treatment on growth should be weighed against the clinical benefits obtained and the availability of safe and effective non-corticosteroid treatment alternatives. To minimize the systemic effects of nasal corticosteroids, including mometasone furoate, the lowest effective dose should be selected for each patient.
Subsection “Geriatric use”
Additions and/or changes are underlined:
In total, 280 patients aged 64 years and older with allergic rhinitis or chronic rhinosinusitis with nasal polyps (age range from 64 to 86 years) received mometasone furoate for 3 or 4 months, respectively. No differences in safety and/or efficacy were observed in elderly patients compared with younger adult patients.
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