What are the risks of prolonged exposure to intranasal corticosteroids (INCS)?

Risks of Prolonged Intranasal Corticosteroid Exposure

Intranasal corticosteroids (INCS) are remarkably safe for long-term use at recommended doses, with minimal systemic effects and primarily local side effects that are generally mild and manageable. 1

Systemic Effects: Minimal at Recommended Doses

The evidence strongly supports that prolonged INCS use does not cause clinically significant systemic complications when used appropriately:

Hypothalamic-Pituitary-Adrenal (HPA) Axis

• Studies demonstrate no clinically significant HPA axis suppression with standard doses of INCS in both children and adults. 1, 2
• Morning cortisol concentrations, cosyntropin stimulation tests, and 24-hour urinary-free cortisol excretion remain normal with once-daily dosing at recommended doses. 1
• Individual patient variability exists, but clinically relevant suppression is not observed with appropriate dosing. 1

Ocular Effects

• Patients receiving standard doses of INCS are not at increased risk for glaucoma or posterior subcapsular cataracts. 1
• Prospective studies of 24 weeks showed no lenticular changes consistent with cataracts. 1
• However, one study found statistically significant IOP elevation (15.24 vs 13.91 mm Hg) with >2 years of use, though without glaucomatous disc changes, suggesting yearly eye examinations may be prudent for long-term users. 3
• Individual patient variability may allow for ocular effects, especially in older patients. 1

Bone Health

• Limited data exist on long-term INCS effects on bone mineral density, but short-term studies show no suppression of plasma osteocalcin levels at 200 mcg/day doses. 1
• The concern about bone effects comes primarily from inhaled corticosteroid data in asthma patients, not INCS-specific studies. 1
• Harmful effects on bone metabolism would not be expected with doses that don't suppress basal HPA function. 2

Growth in Children

• Fluticasone propionate, mometasone furoate, and budesonide show no effects on growth at recommended doses compared with placebo, even at twice recommended doses. 1, 4
• Growth suppression was detected only with beclomethasone dipropionate at twice the recommended dose for 1 year, or in toddlers. 1, 4
• Growth suppression can occur with twice-daily administration of certain INCS but does not appear with once-daily dosing or agents with complete first-pass hepatic inactivation. 2
• Growth effects may occur without HPA axis suppression, making growth a more sensitive indicator of excessive corticosteroid effect in children. 1

Local Side Effects: Common but Generally Mild

Nasal Irritation and Bleeding

• The most common side effects are nasal irritation and epistaxis (blood-tinged secretions), occurring in 4-8% over short periods and up to 20% over one year. 1, 4, 5
• Burning or stinging is most often associated with propylene glycol-containing solutions. 1
• These effects can be minimized by directing the spray away from the nasal septum. 1, 4, 5

Nasal Septal Perforation

• Nasal septal perforation is rarely reported with long-term use. 1, 5
• The nasal septum should be periodically examined to ensure no mucosal erosions are present, as these may precede perforation. 1, 4, 5

Mucosal Integrity

• Nasal biopsies in patients with perennial allergic rhinitis show no evidence of atrophy or tissue change after 1 to 5 years of therapy. 1, 4
• Histologic and macroscopic appearance of nasal mucosa shows no deleterious pathological changes compared to placebo or antihistamines. 1

Critical Factors Affecting Safety

Dosing Frequency and Formulation

• The primary factors influencing the relationship between therapeutic and adverse systemic effects are dosing frequency and efficiency of hepatic inactivation of swallowed drug. 2
• Once-daily dosing is safer than twice-daily dosing for minimizing systemic effects. 2
• Agents with more complete first-pass hepatic inactivation have better safety profiles. 2, 6

Concomitant Corticosteroid Use

• The risk of adverse effects is increased by excessive dosing or concomitant inhaled corticosteroid or other topical corticosteroid therapy. 2
• Patients on multiple corticosteroid therapies should use INCS with low systemic exposure to reduce total systemic burden. 6

Monitoring Recommendations for Long-Term Use

For patients using INCS beyond 6 months (adults) or 2 months per year (children ages 4-11), the following monitoring is appropriate:

• Periodic nasal septum examination to detect mucosal erosions. 1, 4, 5
• Yearly eye examinations for patients with additional glaucoma risk factors or very prolonged use (>2 years). 3, 4
• Growth monitoring in children using stadiometer height measurements. 1, 4
• Use the lowest effective dose to maintain symptom control. 4, 5

Comparison to Systemic Corticosteroids

The safety profile of INCS is vastly superior to systemic corticosteroids, which carry risks of hypertension, hyperglycemia, sleep and mood disturbances, gastric ulceration, glaucoma, myopathy, and osteoporosis even with short courses. 1 Courses of systemic corticosteroids should not exceed 6 weeks due to these substantial risks. 1

Common Pitfalls to Avoid

• Do not discontinue INCS when symptoms improve—continued daily use maintains symptom control as long as allergen exposure persists. 4, 7, 8
• Do not confuse INCS with topical decongestants—unlike decongestants (limited to 3 days), INCS can be used long-term without causing rhinitis medicamentosa. 4, 7, 5
• Ensure proper administration technique is taught—improper use increases local side effects and reduces efficacy. 1, 4, 5
• Do not assume all INCS formulations are equivalent—differences in topical potency and systemic bioavailability exist, though clinical significance is debated. 6