Fluticasone

What it is

Fluticasone is a synthetic corticosteroid delivered by inhaler (for asthma and, combined with a long-acting bronchodilator, COPD) or nasal spray (for allergic rhinitis and nasal polyps). The label describes fluticasone propionate as a synthetic trifluorinated corticosteroid with anti-inflammatory activity.

What the research says

For asthma, a Cochrane review found fluticasone effective compared with placebo, even at low doses, with more thrush, sore throat and hoarseness. In COPD, inhaled steroids reduce flare-ups but do not reduce deaths and raise pneumonia risk (with fluticasone, 18 more hospital-admitted pneumonias per 1,000 people over 18 months; the budesonide estimate was six per 1,000 over nine months). In children, inhaled steroids slow growth by about half a centimetre in the first year. Nasal steroids help nasal symptoms and increase nosebleeds.

Evidence grade: Well established.

How it works

Drug class: Corticosteroid (inhaled and intranasal glucocorticoid)

Fluticasone is a man-made steroid that calms inflammation in the airways or nose. Inhaled or sprayed, most of it acts locally, but some reaches the bloodstream, which is why high doses or certain drug combinations can cause whole-body steroid effects. (Source 1)

What it is used for

• Cochrane (2008) found fluticasone 100-1000 mcg/day effective against placebo, with low doses nearly as good as high doses, and more oropharyngeal side effects. Evidence: established. (Source 2)
• Inhaled steroids reduce exacerbations and probably slow FEV1 decline (of uncertain clinical relevance) but probably do not reduce deaths, and fluticasone raises serious pneumonia risk. Evidence: disputed. (Source 3)
• Cochrane (2016) on intranasal steroids as a class: symptom improvement (low to moderate quality evidence) with increased nosebleeds (high quality evidence). Not fluticasone-specific. Evidence: limited. (Source 4)
• Approved and widely used; we could not reach an allergic-rhinitis systematic review in this run, so the evidence rating is left unassessed here. Evidence: unknown. (Source 4)
• In one small 6-week RCT, swallowed fluticasone cleared esophageal eosinophils far more often than placebo but did not significantly improve swallowing difficulty, and esophageal thrush occurred only with fluticasone. The abstract copy read has inconsistent numbers, so exact rates are not given. Evidence: limited. (Source 5)

Interactions

• Ritonavir and other strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin) (pharmacokinetic study): These block fluticasone's breakdown, so much more reaches the blood. In a label-cited interaction trial in healthy volunteers using the nasal spray form of fluticasone, ritonavir significantly raised fluticasone levels and significantly lowered the body's own cortisol. (Source 1)
• Ritonavir (clinical cases) (case reports): Published case reports describe severe Cushing's syndrome and adrenal insufficiency from this combination. (Source 6)

Stopping it

• In adults with well-controlled asthma, stepping down the inhaled steroid dose showed no clear difference in attacks, control or side effects, but the evidence was too weak to say whether stepping down brings net benefit or harm. (Source 7)
• In COPD, withdrawing the inhaled steroid while keeping long-acting bronchodilators showed no consistent change in exacerbations or lung function across trials. (Source 8)
• The label warns that people moving from oral steroid tablets to the inhaler need a slow taper of the tablets because of adrenal suppression. (Source 1)

What goes wrong

Fluticasone for asthma increases thrush, sore throat and hoarseness, which get worse with higher doses. (Source 2)

• Systematic review, Moderate certainty.
• Size: Not stated on the page read.
• Who: Adults and children with asthma.
• How long: Varied.
• Result: More oropharyngeal side effects, dose-related.
• Funding: Not stated on the page read.

This drug is associated with symptoms such a thrush, sore throat and hoarseness and these get worse with higher doses.

In COPD, fluticasone increased non-fatal serious pneumonia needing hospital admission by 18 per 1,000 people treated over 18 months (high quality evidence); the 18 per 1,000 figure is for fluticasone only. (Source 9)

• Systematic review, High certainty.
• Size: Not stated on the page read.
• Who: People with COPD.
• How long: Up to about 18 months.
• Result: Fluticasone: OR 1.78 (95% CI 1.50 to 2.12), 18 more per 1000 treated over 18 months for non-fatal serious pneumonia requiring hospital admission. Budesonide (separate estimate): six more per 1000 treated over nine months (moderate quality). No significant difference in overall mortality for either.
• Funding: Not stated on the page read.

Fluticasone increased non-fatal serious adverse pneumonia events (requiring hospital admission) (odds ratio (OR) 1.78, 95% confidence interval (CI) 1.50 to 2.12; 18 more per 1000 treated over 18 months; high quality)

For budesonide, a different inhaled steroid, the same review estimated a smaller rise in serious pneumonia (six more per 1,000 over nine months, moderate quality); the review's comparison of the two found fluticasone linked to more of the less serious, community-treated pneumonias. (Source 9)

• Systematic review, Moderate certainty.
• Size: Not stated on the page read.
• Who: People with COPD.
• How long: About nine months (budesonide trials)
• Result: Budesonide: six more per 1000 treated over nine months; fluticasone vs budesonide higher risk of any (less serious) pneumonia.
• Funding: Not stated on the page read.

Fluticasone was associated with higher risk of any pneumonia when compared with budesonide (i.e. less serious cases dealt with in the community)

Regular low or medium dose inhaled steroids slow children's growth by a mean 0.48 cm per year in the first year of treatment. (Source 10)

• Systematic review, Moderate certainty.
• Size: Not stated on the page read.
• Who: Children with mild to moderate persistent asthma.
• How long: One year.
• Result: -0.48 cm/y growth velocity; -0.61 cm height change from baseline.
• Funding: Not stated on the page read.

Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma.

Case reports describe Cushing's syndrome and adrenal suppression when fluticasone is combined with ritonavir; one 2015 review counted 11 pediatric and 26 adult cases. (Source 6)

• Case series, Very low certainty.
• Size: 37 published cases.
• Who: People with HIV on ritonavir using inhaled or nasal fluticasone.
• How long: n/a.
• Result: Cushing's syndrome, adrenal insufficiency, osteoporosis.
• Funding: Not stated in the text read.

revealed a total of 11 pediatric and 26 adult cases of iatrogenic Cushing's syndrome and adrenal suppression from concomitant fluticasone and ritonavir therapy.

What the evidence supports

Fluticasone 100-1000 mcg/day is effective against placebo for chronic asthma, and low doses are only a little less effective than high doses. (Source 2)

• Systematic review, Moderate certainty.
• Size: Not stated on the page read.
• Who: Adults and children with chronic asthma.
• How long: Varied.
• Result: Dose-response small; high doses reduce oral steroid need.
• Funding: Not stated on the page read.

Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo.

Inhaled steroids in COPD likely reduce exacerbations of clinical relevance. (Source 3)

• Systematic review, Moderate certainty.
• Size: Not stated on the page read.
• Who: People with stable COPD.
• How long: Varied.
• Result: Exacerbation rate reduced (numbers not on the page read)
• Funding: Not stated on the page read.

likely results in a reduction of exacerbation rates of clinical relevance

What the evidence does not support

Inhaled steroids alone in stable COPD did not change death rates compared with placebo. (Source 3)

• Systematic review, Moderate certainty.
• Size: Not stated on the page read.
• Who: People with stable COPD.
• How long: 6 months or longer for long-term outcomes.
• Result: All-cause mortality unchanged; exacerbations reduced.
• Funding: Not stated on the page read.

Death rates from any cause were unchanged.

Where the evidence is mixed

Intranasal steroids improve nasal symptoms in chronic rhinosinusitis (low to moderate quality evidence) and increase nosebleeds (high quality evidence). (Source 4)

• Systematic review, Low certainty.
• Size: Not stated on the page read.
• Who: Mostly people with chronic rhinosinusitis with nasal polyps.
• How long: Varied.
• Result: Moderate benefit for blockage, small for runny nose; epistaxis risk increased.
• Funding: Not stated on the page read.

The risk of epistaxis is increased (high quality evidence), but these data included all levels of severity; small streaks of blood may not be a major concern for patients.

In one small 6-week trial, swallowed fluticasone for eosinophilic esophagitis improved the esophageal tissue findings but not swallowing symptoms, and esophageal thrush occurred in the fluticasone group only. (Source 5)

• Randomized trial, Low certainty.
• Size: 42 adults (small, single trial)
• Who: Adults with newly diagnosed eosinophilic esophagitis.
• How long: 6 weeks, 880 mcg twice daily swallowed.
• Result: Complete histologic response and candidiasis were more common with fluticasone; dysphagia improvement did not differ significantly (P = .22). Exact percentages and group sizes are withheld because the abstract copy read is internally inconsistent (see caveat).
• Funding: Not stated in the abstract read.

Limit of this finding: The copy of this abstract we could read (Mayo Clinic research portal) contradicts itself: it says the placebo group had 15 people in one place and counts "7 of 21" placebo patients in another; it reports 11 of 15 as 62% (11 of 15 is 73%; 13 of 21 would be 62%); and it reports thrush as 5 of 19 when the fluticasone group had 21. We could not check the published journal version (PubMed, Europe PMC and the journal page were blocked). Rely on the direction of the result (tissue improved, symptoms did not significantly improve, thrush occurred only with fluticasone), not on the exact percentages or group sizes.

Conclusions: Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE.

Where the research disagrees

Whether inhaled steroids belong in routine COPD treatment

• Cochrane (2023) review authors, systematic review of RCTs: against adverse events (likely to increase local oropharyngeal adverse effects and may increase the risk of pneumonia) and probably no reduction in mortality. (Source 3)
• Georgiou et al. (2024), systematic review of RCTs and observational studies: Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes. (Source 8)

How much

• Reference intake: Dosing is set by the prescriber and depends on the product (inhaler or nasal spray), condition and age. As a position, the Flovent HFA label (2023) is for asthma maintenance in people aged 4 and older. (Source 1)
• Upper limit: Label position (Flovent HFA, 2023): maximum 880 mcg twice daily for patients aged 12 years and older. (Source 1)
• Studied: Asthma trials pooled by Cochrane used fluticasone propionate 100-1000 mcg/day. (Source 2)
• Studied: Eosinophilic esophagitis RCT: 880 mcg swallowed twice daily for 6 weeks. (Source 5)

A common belief, and what the research shows

The belief: Because it is inhaled or sprayed, fluticasone has no whole-body effects.

What the research shows: Some reaches the blood. The label warns 'It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects', and children on inhaled steroids grow about half a centimetre less in the first year.

Questions and answers

What is it?

Fluticasone is a prescription or over-the-counter man-made steroid used as an inhaler for asthma and COPD or as a nasal spray for allergies and nasal polyps. (Source 1)

What does it do in the body?

It reduces inflammation in the airways or nose. In asthma this means fewer symptoms; in severe asthma it can cut the need for steroid tablets. (Source 2)

Is it good or bad for you?

Good for asthma control in trials. In COPD it reduces flare-ups but raises pneumonia risk without reducing deaths. Side effects include thrush, hoarseness, nosebleeds (nasal) and slower growth in children. (Source 9)

How do you get more of it?

Does not apply in the usual sense; dose is set by a prescriber or the product label. The Cochrane asthma review found low doses nearly as effective as high doses. (Source 2)

If it is harmful, what reduces it?

To reduce mouth thrush, the label advises rinsing the mouth after inhaling. Dose step-down in controlled asthma, and withdrawal in COPD while keeping bronchodilators, have been studied. (Source 1)

Why might someone be low in it or missing it?

Does not apply. Fluticasone is a medicine, not a nutrient or something the body makes. (Source 1)

We searched: Label and Cochrane summaries read; the question does not apply to a synthetic drug.

Which whole foods contain it or feed it?

No food contains fluticasone. We found no documented food or supplement interaction in the sources read; the documented interactions are with drugs that block CYP3A4. (Source 1)

We searched: Flovent HFA label (2023) drug interactions section; ritonavir case literature. Grapefruit was not addressed in any source read.

What happens if you do not have it?

Without an inhaled steroid, people with persistent asthma have more symptoms in trials; in COPD, withdrawing it while keeping bronchodilators showed no consistent worsening. (Source 8)

How can you test for it?

There is no routine test for fluticasone itself. Its whole-body effect can show as reduced cortisol levels, which is how the label's ritonavir interaction trial (nasal spray, healthy volunteers) measured it. (Source 1)

References

1. US National Library of Medicine DailyMed (FDA-approved labeling). FLOVENT HFA (fluticasone propionate) inhalation aerosol label (A-S Medication Solutions repackager of GSK NDC 0173-0720), DailyMed. 2023. Read the source
2. Cochrane. Fluticasone versus placebo for chronic asthma in adults and children (Adams NP et al.), Cochrane Database of Systematic Reviews, CD003135 - summary page. 2008. DOI 10.1002/14651858.CD003135.pub4. Read the source
3. Cochrane. Inhaled corticosteroids versus placebo for stable chronic obstructive pulmonary disease (Cochrane Database of Systematic Reviews 2023, CD002991) - summary page. 2023. DOI 10.1002/14651858.CD002991.pub4. Read the source
4. Cochrane. Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis (Chong LY et al.), Cochrane Database of Systematic Reviews 2016, CD011996 - summary page. 2016. DOI 10.1002/14651858.CD011996. Read the source
5. Clinical Gastroenterology and Hepatology (abstract via Mayo Clinic research portal). Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis (Alexander JA et al.). 2012. PMID 22475741, DOI 10.1016/j.cgh.2012.03.018. Read the source
6. SpringerPlus. Iatrogenic Cushing syndrome and adrenal insufficiency during concomitant therapy with ritonavir and fluticasone (Epperla N, McKiernan F). 2015. DOI 10.1186/s40064-015-1218-x. Read the source
7. Cochrane. Stepping down the dose of inhaled corticosteroids for adults with asthma (Crossingham I et al.), Cochrane Database of Systematic Reviews 2017, CD011802 - summary page. 2017. DOI 10.1002/14651858.CD011802.pub2. Read the source
8. International Journal of COPD (Dove Medical Press). Withdrawal of Inhaled Corticosteroids from Patients with COPD; Effect on Exacerbation Frequency and Lung Function: A Systematic Review (Georgiou A et al.). 2024. DOI 10.2147/COPD.S436525. Read the source
9. Cochrane. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease (Kew KM, Seniukovich A), Cochrane Database of Systematic Reviews 2014, CD010115 - summary page. 2014. DOI 10.1002/14651858.CD010115.pub2. Read the source
10. Cochrane. Inhaled corticosteroids in children with persistent asthma: effects on growth (Zhang L et al.), Cochrane Database of Systematic Reviews 2014, CD009471 - summary page. 2014. DOI 10.1002/14651858.CD009471.pub2. Read the source