Can fluticasone (fluticasone propionate) nasal spray cause systemic steroid effects?

Fluticasone Nasal Spray and Systemic Steroid Effects

Fluticasone nasal spray at recommended doses is not generally associated with clinically significant systemic steroid effects in adults, though individual patient variability exists and children may experience transient growth effects. 1

Systemic Effects in Adults

• It is unusual for adult patients to develop systemic corticosteroid side effects after administration of intranasal fluticasone propionate at recommended doses. 1
• Studies demonstrate minimal systemic corticosteroid effects on the HPA axis at recommended and moderate doses given once daily, as assessed by morning cortisol concentrations, cosyntropin stimulation, and 24-hour urinary-free cortisol excretion. 1
• The efficacy of fluticasone propionate nasal spray results from direct topical effects on the nasal mucosa rather than indirect systemic effects following absorption, as demonstrated in controlled trials comparing intranasal versus oral administration. 2, 3
• Fluticasone propionate has extremely low systemic bioavailability (<0.5% for fluticasone furoate formulation), which minimizes the risk of systemic effects. 4

Systemic Effects in Children

• In children, an effect of intranasal corticosteroids on growth has been demonstrated, although an effect on the HPA axis has not been demonstrated and no reduction in bone density or other systemic effects have been reported. 1
• Studies with intranasal fluticasone propionate at recommended doses show no effects on growth compared with placebo, though the effect is dependent on the specific product, dose, and concomitant use of other corticosteroids. 1
• Growth suppression is both a sensitive and relatively specific indicator of excessive corticosteroid effect and can occur without an effect on the HPA axis, representing a disparity between HPA axis assessment and transient growth effects. 1
• A 1-year placebo-controlled study in children ages 3-9 years found no statistically significant effect on growth with fluticasone propionate nasal spray 200 mcg daily, with no evidence of clinically relevant changes in HPA axis function or bone mineral density. 5

When Systemic Effects Can Occur

Use of excessive doses or concomitant use with potent CYP3A4 inhibitors can lead to clinically significant systemic effects. 5

• When used at higher than recommended doses or in rare individuals at recommended doses, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. 5
• Ritonavir (a highly potent CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations. 5
• During postmarketing surveillance, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. 5

Individual Patient Variability

• Individual patient variability may allow for the development of systemic effects from intranasal corticosteroids, especially in older patients, though this is uncommon at recommended doses. 1
• If signs or symptoms of hypercorticism and/or HPA axis suppression occur, the dosage should be discontinued slowly consistent with accepted procedures for discontinuing oral corticosteroid therapy. 5

Clinical Monitoring Recommendations

• Patients using fluticasone propionate nasal spray over several months or longer should be examined periodically for evidence of adverse effects on the nasal mucosa. 5
• The growth of pediatric patients receiving intranasal corticosteroids should be monitored routinely (e.g., via stadiometry), and each patient should be titrated to the lowest dose that effectively controls symptoms. 5
• Larger than recommended doses should be avoided to minimize the risk of systemic effects. 5