Source: Health Products and Food Branch (CA) Revision Year: 2019
Flonase Allergy Relief (fluticasone propionate aqueous nasal spray) is contraindicated in:
Patients should be informed that the full effect of Flonase Allergy Relief (fluticasone propionate aqueous nasal spray) therapy is not achieved until 2 to 3 days of treatment have been completed. Treatment of seasonal rhinitis should, if possible, start before the exposure to allergens.
Although Flonase Allergy Relief will control seasonal allergic rhinitis in most cases, an abnormally heavy challenge of summer allergens may in certain instances necessitate appropriate additional therapy.
Under most circumstances, treatment with corticosteroids should not be stopped abruptly but tapered off gradually. Patients should be advised to inform subsequent physicians of prior use of corticosteroids.
(see PART III PATIENT MEDICATION INFORMATION).
See TOXICOLOGY.
In clinical trials of 2 weeks to 1 year in duration, epistaxis was observed more frequently in subjects treated with Flonase Allergy Relief Nasal Spray than those who received placebo (see ADVERSE REACTIONS).
Postmarketing cases of nasal ulceration have been reported in patients treated with Flonase Allergy Relief (see ADVERSE REACTIONS).
In clinical trials with fluticasone propionate 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 therapy and discontinuation of Flonase Allergy Relief. Patients using Flonase Allergy Relief over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.
Postmarketing cases of nasal septal perforation have been reported in patients treated with Flonase Allergy Relief (see ADVERSE REACTIONS).
Monitor patients periodically for signs of adverse effects on the nasal mucosa. Avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma, because of the inhibitory effect of corticosteroids on wound healing (see Immune, Effect of Corticosteroids on Wound Healing).
Although systemic effects have been minimal with recommended doses of Flonase Allergy Relief aqueous nasal spray, potential risk increases with larger doses. Therefore, larger then recommended doses of Flonase Allergy Relief aqueous nasal spray should be avoided.
When intranasal steroids are used at higher than recommended dosages in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism (Cushing’s syndrome, Cushingoid features) and suppression of HPA function may occur. These effects are much less likely to occur with intranasal corticosteroids than with oral corticosteroids.
In patients previously on systemic steroids, either over prolonged periods or in high doses, the replacement with a topical (i.e. intranasal) corticosteroid can be accompanied by symptoms of withdrawal, e.g. joint and/or muscular pain, lassitude and depression and, in severe cases, adrenal insufficiency may occur, necessitating the temporary resumption of systemic steroid therapy.
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.
Reduced growth velocity has been observed in children treated with intranasal corticosteroids. Therefore, children and adolescents should be maintained on the lowest dose which achieves adequate symptom control. Physicians should closely follow the growth of children and adolescents taking corticosteroids, by any route, and weigh the benefits of corticosteroid therapy against the possibility of growth suppression if growth appears slowed.
There is an enhanced effect of corticosteroids in patients with hypothyroidism.
Acetylsalicylic acid should be used cautiously in conjunction with corticosteroids in hypothrombinemia (see DRUG INTERACTIONS).
A drug interaction study of intranasal fluticasone propionate in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving intranasal or inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
There is an enhanced effect of corticosteroids in patients with cirrhosis.
Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, and rash) have been reported after administration of Flonase Allergy Relief. Discontinue Flonase Allergy Relief if such reactions occur (see CONTRAINDICATIONS). Rarely, immediate hypersensitivity reactions may occur after the administration of Flonase Allergy Relief.
The long term effects of fluticasone propionate in humans are still unknown, in particular, its local effects; the possibility of atrophic rhinitis and/or pharyngeal candidiasis should be kept in mind. As with all medications containing a corticosteroid, Flonase Allergy Relief should be administered with caution, and only if necessary, in patients with active or quiescent tuberculosis infections of the respiratory tract; chronic or untreated infections such as systemic fungal, bacterial, viral, or parasitic; or ocular herpes simplex.
Corticosteroids may mask some signs of infection and new infections may appear. A decreased resistance to localized infections has been observed during corticosteroid therapy; this may require treatment with appropriate therapy or stopping the administration of fluticasone propionate.
Patients who are on drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in nonimmune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects 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 chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
In patients who have had recent nasal surgery or trauma, a nasal corticosteroid should be used with caution until healing has occurred, because of the inhibitory effect of corticosteroids on wound healing.
Nasal and inhaled corticosteroids may result in the development of glaucoma, cataracts and/or central serous chorioretinopathy (CSCR). CSCR is a posterior segment disease characterized by localized, limited serous detachments of the neurosensory retina often associated with focal detachments of an altered retinal pigment epithelium (RPE). Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure (IOP), glaucoma, and/or cataracts (see ADVERSE REACTIONS).
Although rare, there is a potential of psychological and behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression which have been reported.
Careful attention must be given to patients with asthma or other clinical conditions in whom a rapid decrease in systemic steroids may cause a severe exacerbation of their symptoms.
The safety of fluticasone propionate in pregnancy has not been established. If used, the expected benefits should be weighed against the potential hazard to the fetus, particularly during the first trimester of pregnancy.
Like other glucocorticosteroids, fluticasone propionate is teratogenic to rodent species (see TOXICOLOGY). Adverse effects typical of potent corticosteroids are only seen at high systemic exposure levels; direct intranasal application ensures minimal systemic exposure. The relevance of these findings to humans has not yet been established. Infants born of mothers who have received substantial doses of glucocorticosteroids during pregnancy should be carefully observed for hypoadrenalism.
Glucocorticosteroids are excreted in human milk. It is not known whether fluticasone propionate is excreted in human milk. When measurable plasma levels were obtained in lactating laboratory rats following subcutaneous administration there was evidence of fluticasone propionate in the breast milk. However, following intranasal administration to primates, no drug was detected in the plasma, and it is therefore unlikely that the drug would be detectable in milk. The use of fluticasone propionate in nursing mothers, requires that the possible benefits of the drug be weighed against the potential hazards to the infant.
Flonase Allergy Relief is not recommended for children and adolescents younger than 18 years of age.
A limited number of patients 65 years of age and older have been treated with Flonase Allergy Relief in clinical trials. The adverse events reported in this population were similar to those reported in younger patients.
During long term therapy, HPA axis function and haematological status should be assessed.
Systemic and local corticosteroid use may result in the following:
Because clinical trials are conducted under very specific conditions the adverse drug reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
Adverse reactions in controlled clinical studies with Flonase Allergy Relief (fluticasone propionate aqueous nasal spray) have been primarily associated with irritation of the nasal mucous membranes, and are consistent with those expected from application of a topical medication to an already inflamed membrane. The adverse reactions reported by patients treated with Flonase Allergy Relief were similar to those reported by patients receiving placebo.
The most frequently reported adverse reactions (≥1% in any treatment group) considered by the investigator to be potentially related to Flonase Allergy Relief or placebo in trials of seasonal allergic rhinitis are listed below (Table 1). These studies conducted in 948 adults and in 499 children evaluated 14-28 days of treatment with recommended doses of Flonase Allergy Relief compared with placebo.
Table 1. Adverse Reactions Reported Most Frequently in Clinical Trials of Seasonal Allergic Rhinitis:
| Adults (age ≥12 years) | Children (age 4-11 years) | |||||
|---|---|---|---|---|---|---|
| Flonase Allergy Relief 100 mcg BID (n=312) % | Flonase Allergy Relief 200 mcg QD (n=322) % | Placebo (n=314) % | Flonase Allergy Relief 100 mcg QD (n=167) % | Flonase Allergy Relief 200 mcg QD (n=164) % | Placebo (n=168) % | |
| Nasal burning | 2.2 | 3.4 | 2.5 | 1.8 | 2.4 | 1.2 |
| Pharyngitis | 1.3 | 1.6 | <1 | <1 | 0 | 0 |
| Runny nose | <1 | 1.6 | <1 | <1 | <1 | <1 |
| Blood in nasal mucus | 0 | 1.6 | <1 | 0 | <1 | 0 |
| Epistaxis | 1.6 | 2.8 | 2.2 | 3.0 | 3.7 | 3.6 |
| Sneezing | <1 | 1.2 | 2.2 | 0 | <1 | 0 |
| Crusting in nostrils | 0 | 0 | 0 | 1.2 | 0 | 0 |
| Nasal congestion | 0 | 0 | 0 | 0 | 1.2 | 0 |
| Nasal ulcer | <1 | 0 | 0 | 1.2 | 1.2 | 1.2 |
| Headache | 1.3 | 2.5 | 1.9 | 1.2 | 1.2 | 1.2 |
Includes studies FLN203, FLN204, FLN305, FLN306, FLN320, FLN321.
In two 6 month trials involving 831 patients aged 12-75 years with perennial rhinitis, the adverse reactions reported by patients treated with Flonase Allergy Relief were similar in type and incidence to those reported in seasonal trials, with the exception of epistaxis (≤13.3%) and blood in nasal mucous (≤8.3%). In addition to the events reported most frequently in the seasonal trials, patients receiving Flonase Allergy Relief in the 6 month trials reported nasal soreness (≤2.5%), nasal excoriation (≤2.0%), sinusitis (≤1.6%), and nasal dryness (≤1.3%).
Uncommon adverse reactions (incidence of 0.1-1% and greater than placebo) reported by patients receiving fluticasone propionate aqueous nasal spray at the recommended daily dose of 200 mcg (or 100 mcg per day for children 4-11 years of age) in the aforementioned clinical trials included: pharyngeal irritation, nasal stinging, nausea and vomiting, unpleasant smell and taste, and sinus headache (0.3%); lacrimation, eye irritation, xerostomia, cough, urticaria, and rash (0.2%); and nasal septum perforation (0.1%).
The following events have been identified during post-approval use of fluticasone propionate in clinical practice.
General: Headache and hypersensitivity reactions including angioedema, skin rash, edema of the face or tongue, pruritis, urticaria, bronchospasm, wheezing, dyspnea and anaphylaxis/anaphylactoid reactions have been reported. Particularly with previous or concurrent use of systemic steroids (e.g., IV or oral), there have also been very rare cases of osteonecrosis reported and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression.
Ear, Nose and Throat: Alteration or loss in sense of taste and/or smell and, rarely, nasal septal perforation, nasal ulcer, sore throat, throat irritation and dryness, cough, hoarseness and voice changes.
Eye: Dryness and irritation of the eyes, conjunctivitis, blurred vision, and very rarely, glaucoma, increased intraocular pressure and cataracts.
Fluticasone propionate is cleared by extensive first-pass metabolism mediated by cytochrome P450 3A4 in the gut and liver.
A drug interaction study of intranasal fluticasone propionate in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving intranasal or inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
This study has shown that other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. However, there have been a few case reports during world wide post-market use of adrenal cortisol suppression associated with concomitant use of azole anti-fungals and inhaled fluticasone propionate. Therefore, care is advised when coadministering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole) as there is potential for increased systemic exposure to fluticasone propionate.
Acetylsalicylic acid should be used cautiously in conjunction with corticosteroids in patients with hypothrombinemia.
Table 2. Established or Potential Drug-Drug Interactions:
| Proper name | Ref | Effect | Clinical comment |
|---|---|---|---|
| Ritonavir | CT CS | Systemic effects including Cushing’s syndrome and adrenal suppression. | Concomitant use of fluticasone propionate and ritonavir should be avoided. (See DRUG INTERACTIONS; Overview) |
| Other inhibitors of cytochrome P450 3A4 | CT CS | Potential increased systemic exposure to fluticasone propionate. | Care is advised when coadministering potent cytochrome P450 3A4 inhibitors. (See DRUG INTERACTIONS; Overview) |
| Acetylsalicylic acid | T | Acetylsalicylic acid should be used cautiously in conjunction with corticosteroids in hypothrombinemia. (See DRUG INTERACTIONS; Overview and WARNINGS AND PRECAUTIONS; Hematologic) |
CS – Class Statement
CT – Clinical Trial
T – Theoretical
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