1.1 Treatment of Seasonal or Perennial Allergic Rhinitis

RHINOCORT AQUA Nasal Spray is indicated for the treatment of nasal symptoms of seasonal or perennial allergic rhinitis in adults and children six years of age and older.

5.1 Local Nasal Effects

Epistaxis

In clinical studies of 3 to 52 weeks’ duration epistaxis was observed more frequently in patients treated with RHINOCORT AQUA Nasal Spray than those who received placebo [see Adverse Reactions (6.1)].

Candida Infection

In clinical studies with budesonide administered intranasally, the development of localized infections of the nose and pharynx with Candida albicans has occurred. When such an infection develops, it may require treatment with appropriate local or systemic therapy and discontinuation of treatment with RHINOCORT AQUA Nasal Spray. Patients using RHINOCORT AQUA Nasal Spray over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.

Nasal Septal Perforation

Instances of nasal septum perforation have been reported following the intranasal application of corticosteroids, including budesonide [see Adverse Reactions (6.2)].

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 a nasal corticosteroid until healing has occurred.

5.2 Hypersensitivity Reactions Including Anaphylaxis

Hypersensitivity reactions including anaphylactic reaction, urticaria, rash, dermatitis, angioedema and pruritus may occur [see Contraindications (4) and Adverse Reactions, Post-marketing Experience (6.2)].

5.3 Immunosuppression

Patients who are on drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such 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 exposed to chicken pox, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If 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 chicken pox develops, treatment with antiviral agents may be considered.

The clinical course of chicken pox or measles infection in patients on intranasal or inhaled corticosteroids has not been studied. While there is no data with intranasal corticosteroids, a clinical study has examined the immune responsiveness to the varicella vaccine in asthma patients 12 months to 8 years of age who were treated with budesonide inhalation suspension.

An open-label, nonrandomized clinical study examined the immune responsiveness to varicella vaccine in 243 asthma patients 12 months to 8 years of age who were treated with budesonide inhalation suspension 0.25 mg to 1 mg daily (n=151) or non-corticosteroid asthma therapy (n=92) (i.e., beta2-agonists, leukotriene receptor antagonists, or cromones). The percentage of patients developing a seroprotective antibody titer ≥ 5.0 (gpELISA value) in response to the vaccination was similar in patients treated with budesonide inhalation suspension (85%) compared to patients treated with non-corticosteroids asthma therapy (90%). No patient treated with budesonide inhalation suspension developed chicken pox as a result of vaccination.

Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection, untreated fungal, bacterial, systemic viral or parasitic infections; or ocular herpes simplex.

5.4 Hypothalamic-Pituitary-Adrenal Axis Effects

Hypercorticism and Adrenal Suppression: 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 RHINOCORT AQUA Nasal Spray 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, and in addition some patients may experience symptoms of corticosteroid withdrawal, e.g., joint and/or muscular pain, fatigue, weakness, nausea, vomiting, hypotension, lassitude, and depression. Patients previously treated for prolonged periods with systemic corticosteroids should be weaned off slowly when transferred to topical corticosteroids and carefully monitored for acute adrenal insufficiency in response to stress. In those patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms.

5.5 Interactions with Strong Cytochrome P450 3A4 Inhibitors

Caution should be exercised when considering the co-administration of RHINOCORT AQUA Nasal Spray with ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systemic exposure to budesonide may occur [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

5.6 Effect on Growth

Intranasal corticosteroids, including budesonide may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth routinely of pediatric patients receiving long-term treatment with RHINOCORT AQUA Nasal Spray. To minimize the systemic effects of intranasal corticosteroids, including RHINOCORT AQUA Nasal Spray, titrate each patient’s dosage to the lowest one that effectively controls his/her symptoms [see Use in Specific Populations, Pediatric Use (8.4)].

5.7 Glaucoma and Cataracts

Glaucoma, increased intraocular pressure and cataracts have been reported following the intranasal application of corticosteroids, including budesonide. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts [see Adverse Reactions (6.2)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The incidence of common adverse reactions in Table 1 is based upon two U.S. and five non-U.S. controlled clinical trials in 1,526 patients with seasonal or perennial rhinitis in adults and children ≥ 6 years treated with RHINOCORT AQUA Nasal Spray at doses up to 400 mcg once daily for 3-6 weeks. This population included 745 females and 781 males with a mean age of 31 years (range of 6-85 years, 349 were 6 < 18 years). The racial distribution of patients receiving RHINOCORT AQUA Nasal Spray was 93% white, 3% black and 4% other. Table 1 describes adverse reactions occurring at an incidence of 2% or greater and more commonly among RHINOCORT AQUA Nasal Spray-treated patients than in placebo-treated patients in controlled clinical trials.

A similar adverse reaction profile was observed in the subgroup of pediatric patients 6 to 12 years of age. These patients are included in Table 1.

Two to three percent (2-3%) of patients in clinical trials discontinued because of adverse reactions. Systemic corticosteroid side effects were not reported during controlled clinical studies with RHINOCORT AQUA Nasal Spray.

If recommended doses are exceeded, or if individuals are particularly sensitive, symptoms of hypercorticism, ie, Cushing’s Syndrome, and adrenal suppression could occur.

6.2 Post-marketing Experience

The following adverse reactions have been reported during post-approval use of RHINOCORT AQUA Nasal Spray. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders: immediate and delayed hypersensitivity reactions (including anaphylactic reaction, urticaria, rash, dermatitis, angioedema and pruritus), [see Warnings and Precautions (5.2) and Contraindications (4)]

Eye disorders: glaucoma, increased intraocular pressure, cataracts [see Warnings and Precautions (5.7)]

Respiratory, thoracic, and mediastinal disorders: nasal septum perforation, anosmia, pharynx disorders (throat irritation, throat pain, swollen throat, burning throat, and itchy throat), and wheezing

Cardiac disorders: palpitations

Musculoskeletal and connective tissue disorders: growth suppression [see Warnings and Precautions (5.6) and Use in Specific Populations (8.4)]

7.1 Inhibitors of Cytochrome P450 3A4

The main route of metabolism of corticosteroids, including budesonide, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased. Concomitant administration of CYP3A4 may inhibit the metabolism of, and increase the systemic exposure to, budesonide. Caution should be exercised when considering the co-administration of RHINOCORT AQUA Nasal Spray with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].