Qnasl

Treatment of Nasal Symptoms of Allergic Rhinitis

QNASL® Nasal Aerosol is indicated for the treatment of the nasal symptoms associated with seasonal and perennial allergic rhinitis in patients 4 years of age and older.

Allergic Rhinitis

Adults and Adolescents (12 Years of Age and Older): The recommended dose of QNASL Nasal Aerosol is 320 mcg per day administered as 2 actuations in each nostril (QNASL 80 mcg Nasal Aerosol) once daily (maximum total daily dose of 4 actuations per day).

Children (4 to 11 Years of Age): The recommended dose of QNASL Nasal Aerosol is 80 mcg per day administered as 1 actuation in each nostril (QNASL 40 mcg Nasal Aerosol) once daily (maximum total daily dose of 2 actuations per day).

Pregnancy

 Risk Summary

There are no adequate and well-controlled studies with QNASL Nasal Aerosol or beclomethasone dipropionate in pregnant women. No published studies, including studies of large birth registries, have to date related the use of inhaled corticosteroids (ICS) or intranasal corticosteroids to any increases in congenital malformations or other adverse perinatal outcomes.  Thus, available human data do not establish the presence or absence of drug‑associated risk to the fetus.  In animal reproduction studies, beclomethasone dipropionate resulted in adverse developmental effects in mice and rabbits at subcutaneous doses equal to or greater than approximately 1.5 times the maximum recommended human dose (MRHD) in adults (0.32 mg/day) (see Data).  In rats exposed to beclomethasone dipropionate by inhalation, dose‑related gross injury to the fetal adrenal glands was observed at doses greater than 350 times the MRHD, but there was no evidence of external or skeletal malformations or embryolethality at inhalation doses of up to 860 times the MRHD.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown.  In the US general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2‑4% and 15‑20%, respectively.

Clinical Considerations

Labor or Delivery

There are no specific human data regarding any adverse effects of intranasal beclomethasone dipropionate on labor and delivery.

Data

Animal Data

In an embryofetal development study in pregnant rats, beclomethasone dipropionate administration during organogenesis from gestation days 6 to 15 at inhaled doses 350 times the MRHD in adults and higher (on a mg/m2 basis at maternal doses of 11.5 and 28.3 mg/kg/day) produced dose‑dependent gross injury (characterized by red foci) of the adrenal glands in fetuses.  There were no findings in the adrenal glands of rat fetuses at an inhaled dose that was 75 times the MRHD in adults (on a mg/m2 basis at a maternal dose of 2.4 mg/kg/day).  There was no evidence of external or skeletal malformations or embryolethality in rats at inhaled doses up to 860 times the MRHD (on a mg/m2 basis at maternal doses up to 28.3 mg/kg/day).

In an embryofetal development study in pregnant mice, beclomethasone dipropionate administration from gestation days 1 to 18 at subcutaneous doses equal to and greater than 1.5 times the MRHD in adults (on a mg/m2 basis at maternal doses of 0.1 mg/kg/day and higher) produced adverse developmental effects (increased incidence of cleft palate).  A no-effect dose in mice was not identified. In a second embryofetal development study in pregnant mice, beclomethasone dipropionate administration from gestation days 1 to 13 at subcutaneous doses equal to and greater than 5 times the MRHD in adults (on a mg/m2 basis at a maternal dose of 0.3 mg/kg/day) produced embryolethal effects (increased fetal resorptions) and decreased pup survival.

In an embryofetal development study in pregnant rabbits, beclomethasone dipropionate administration during organogenesis from gestation days 7 to 16 at subcutaneous doses  equal to and greater than 1.5 times the MRHD in adults (on a mg/m2 basis at maternal doses of 0.025 mg/kg/day and higher) produced external and skeletal malformations and embryolethal effects (increased fetal resorptions).  There were no effects in fetuses of pregnant rabbits administered a subcutaneous dose 0.4 times the MRHD in adults (on a mg/m2 basis at a maternal dose of 0.006 mg/kg/day).

Lactation

Risk Summary

There are no data available on the presence of beclomethasone dipropionate in human milk, the effects on the breastfed child, or the effects on milk production. However, other corticosteroids have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for QNASL and any potential adverse effects on the breastfed child from beclomethasone dipropionate or from the underlying maternal condition.

Females and Males of Reproductive Potential

Impairment of fertility was observed in rats and dogs at oral doses of beclomethasone dipropionate corresponding to 500 and 50 times the MRHD for adults on a mg/m2 basis, respectively. [see Nonclinical Toxicology ].

Pediatric Use

The safety and effectiveness of QNASL Nasal Aerosol in children 4 years and older have been established [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14)]. The safety and effectiveness of QNASL Nasal Aerosol in children younger than 4 years of age have not been established. Controlled pediatric clinical trials with QNASL Nasal Aerosol included 909 children 4 to 11 years of age and 188 adolescent patients 12 to 17 years of age [see Clinical Studies (14)].

Controlled clinical trials have shown that intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting 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 reduction in growth velocity associated with intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for "catch-up" growth following discontinuation of treatment with intranasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving intranasal corticosteroids, including QNASL Nasal Aerosol, should be monitored routinely (e.g., via stadiometry).

A 12-month, randomized, controlled clinical trial evaluated the effects of QVAR®, an orally inhaled HFA beclomethasone dipropionate product, without spacer versus chlorofluorocarbon-propelled (CFC) beclomethasone dipropionate with large volume spacer on growth in children with asthma ages 5 to 11 years. A total of 520 patients were enrolled, of whom 394 received HFA-beclomethasone dipropionate (100 to 400 mcg/day ex-valve) and 126 received CFC-beclomethasone dipropionate (200 to 800 mcg/day ex-valve). When comparing results at month 12 to baseline, the mean growth velocity in children treated with HFA-beclomethasone dipropionate was approximately 0.5 cm/year less than that noted with children treated with CFC-beclomethasone dipropionate via large volume spacer. The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks/benefits of treatment alternatives.

The potential for QNASL Nasal Aerosol to cause reduction in growth velocity in susceptible patients or when given at higher than recommended dosages cannot be ruled out.

Geriatric Use

Clinical trials of QNASL Nasal Aerosol did not include sufficient numbers of subjects aged 65 years and older to determine whether they responded differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, administration to elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Local Nasal Effects

Nasal Discomfort, Epistaxis, and Nasal Ulceration: In clinical trials of 2 to 52 weeks duration, epistaxis and nasal ulcerations were observed more frequently and some epistaxis events were more severe in patients treated with QNASL Nasal Aerosol than those who received placebo. In the 52-week safety trial in patients with perennial allergic rhinitis, nasal erosions were identified in 4 of 415 patients and a nasal ulceration was identified in 1 of 415 patients treated with QNASL Nasal Aerosol. No nasal erosions or ulcerations were reported for patients who received placebo. In clinical trials conducted in pediatric patients ages 4 to 11 years, the local nasal effect was similar to those reported in patients 12 years of age and older. Patients using QNASL Nasal Aerosol over several months or longer should be examined periodically for possible changes in the nasal mucosa. If an adverse reaction (e.g., erosion, ulceration) is noted, discontinue QNASL Nasal Aerosol [see Adverse Reactions (6.1)].

Candida Infection: In previous clinical trials with an aqueous formulation of beclomethasone dipropionate administered intranasally, localized infections of the nose and pharynx with Candida albicans had been reported. There were no instances of similar infections observed in clinical trials with QNASL Nasal Aerosol. If such an infection develops, it may require treatment with appropriate local therapy and discontinuation of QNASL Nasal Aerosol treatment. Thus, patients using QNASL Nasal Aerosol over several months or longer should be examined periodically for evidence of Candida infection.

Nasal Septal Perforation: Instances of nasal septal perforation have been reported in patients following the intranasal application of beclomethasone dipropionate. There were no nasal septal perforations reported during clinical trials in the indicated dose of QNASL 80 mcg Nasal Aerosol administered as 320 mcg once daily in adults and adolescents. There was one report of nasal septal perforation observed in the dose-ranging pediatric clinical trial.

Impaired Wound Healing: Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal ulcers, nasal surgery, or nasal trauma should not use QNASL Nasal Aerosol until healing has occurred.

Eye Disorders

Use of intranasal and inhaled corticosteroids may result in the development of increased intraocular pressure, blurred vision, glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, blurred vision, glaucoma, and/or cataracts.

Glaucoma and cataract formation was evaluated with ocular assessments that included intraocular pressure measurements and slit lamp examinations in 245 adolescent and adult patients (12 years of age and older) with perennial allergic rhinitis who were treated with QNASL Nasal Aerosol 320 mcg daily (N=197) or placebo (N=48) for up to 52 weeks. In 94% of patients, intraocular pressure (IOP) remained within the normal range (<21 mmHg) during the treatment portion of the trial. There were 10 patients (5%) treated with QNASL Nasal Aerosol and 1 patient (2%) treated with placebo that had intraocular pressure that increased above normal levels (≥21 mmHg) and greater than baseline during the treatment portion of the trial. Two of these occurrences in patients treated with QNASL Nasal Aerosol were reported as adverse reactions, one serious. No instances of cataract formation or other clinically significant ocular incidents were reported in this 52-week safety trial [see Adverse Reactions (6.1)].

Hypersensitivity Reactions Including Anaphylaxis

Hypersensitivity reactions including anaphylaxis, angioedema, urticaria, and rash have been reported following administration of beclomethasone dipropionate nasally administered and inhalationally administered products. Angioedema, urticaria, and rash have been reported following administration of QNASL Nasal Aerosol. Discontinue QNASL Nasal Aerosol if any such reactions occur [see Contraindications (4)].

Immunosuppression

Persons who are using drugs that suppress the immune system (e.g., corticosteroids) are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated (see the respective package inserts for complete VZIG and IG prescribing information). If chickenpox or measles develops, treatment with antiviral agents may be considered.

Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract, untreated local or systemic fungal or bacterial infections, systemic viral or parasitic infections, or ocular herpes simplex because of the potential for worsening of these infections.

Hypothalamic-Pituitary-Adrenal Axis Effect

When intranasal steroids are used at higher-than-recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of QNASL Nasal Aerosol should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy.

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. In addition, some patients may experience symptoms of corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, and depression). Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause a severe exacerbation of their symptoms.

Effect on Growth

Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Routinely monitor the growth of pediatric patients receiving QNASL Nasal Aerosol [see Use in Specific Populations (8.4)].