What is the effect of nasal fluticasone (Flonase) on serum cortisol levels?

From the Guidelines

Intranasal fluticasone propionate causes minimal elevation of serum steroid levels when used as directed, with less than 2% systemic bioavailability, and is not generally associated with clinically significant systemic side effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression 1. The medication achieves its therapeutic effect primarily through local anti-inflammatory action in the nasal passages. Studies have shown that intranasal corticosteroids, including fluticasone propionate, have a low risk of systemic side effects, including effects on the HPA axis, ocular pressure, cataract formation, and bone density 1. However, higher doses, prolonged use, or concurrent use with other corticosteroid formulations (inhaled, topical, or oral) may potentially increase systemic exposure. Patients with liver disease may experience slightly higher serum levels due to reduced metabolism of the drug. For most patients using standard doses, the risk of clinically significant systemic effects remains very low, making intranasal fluticasone a safe option for long-term management of allergic rhinitis. Some key points to consider when using intranasal fluticasone propionate include:

• Typical intranasal doses (50-200 mcg daily) result in minimal systemic bioavailability
• The medication is not generally associated with clinically significant systemic side effects, including HPA axis suppression
• Higher doses or prolonged use may increase systemic exposure
• Patients with liver disease may experience higher serum levels due to reduced metabolism of the drug
• The risk of clinically significant systemic effects remains very low for most patients using standard doses.

From the FDA Drug Label

Plasma levels were undetectable in the majority of patients after intranasal dosing, but present at low levels in the majority after oral dosing Plasma fluticasone propionate concentrations following fluticasone propionate aqueous nasal spray alone were undetectable (<10 pg/mL) in most subjects, and when concentrations were detectable, peak levels (C ) averaged 11.9 pg/mL (range, 10.8 to 14. 1 pg/mL) and AUC averaged 8.43 pg•hr/mL (range, 4.2 to 18.8 pg•hr/mL).

The nasal fluticasone does not significantly raise serum steroid levels in the majority of patients, as plasma levels are often undetectable after intranasal dosing. When detectable, the peak levels and AUC are very low, averaging 11.9 pg/mL and 8.43 pg•hr/mL, respectively 2.

From the Research

Nasal Fluticasone and Serum Steroid Levels

• The effect of nasal fluticasone on serum steroid levels has been studied in several research papers 3, 4, 5, 6, 7.
• According to a study published in 1996, intranasal fluticasone propionate does not significantly affect serum steroid levels, as evidenced by the lack of impact on bone mineral density, biochemical markers of bone turnover, and hypothalamic-pituitary-adrenal axis function 3.
• Another study from 2009 found that intranasal corticosteroids, including fluticasone propionate, have a minimal effect on the hypothalamic-pituitary-adrenal axis, which regulates serum steroid levels 4.
• A 2012 review of fluticasone furoate, a novel intranasal corticosteroid, noted that it has low systemic bioavailability (<0.5%), suggesting that it is unlikely to significantly raise serum steroid levels 5.
• A study published in 1998 compared the effects of fluticasone propionate aqueous nasal spray and oral prednisone on the hypothalamic-pituitary-adrenal axis and found that fluticasone propionate did not suppress adrenal function, even at four times the recommended dose 6.
• Overall, the evidence suggests that nasal fluticasone is unlikely to significantly raise serum steroid levels, due to its low systemic bioavailability and minimal impact on the hypothalamic-pituitary-adrenal axis 3, 4, 5, 6.

Key Findings

• Fluticasone propionate aqueous nasal spray does not significantly affect serum steroid levels 3.
• Intranasal corticosteroids, including fluticasone propionate, have a minimal effect on the hypothalamic-pituitary-adrenal axis 4.
• Fluticasone furoate has low systemic bioavailability (<0.5%) and is unlikely to significantly raise serum steroid levels 5.
• Fluticasone propionate does not suppress adrenal function, even at four times the recommended dose 6.