Table 6: Open in new tab Non-oral...

Prevalence of glucocorticoid-induced adrenal insufficiency^a

Factors increasing the risk of glucocorticoid-induced adrenal insufficiency

Strategies to mitigate the risk of glucocorticoid-induced adrenal insufficiency^d

Inhaled glucocorticoids

Overall: 7.8% (CI 4.2-13.9)
Short-term use (<1 month): 1.4% (CI 0.3-7.4)
Medium-term use (1-12 months): 11.9% (CI 5.8-23.1)
Long-term use (>12 months): 27.4% (CI 17.7-39.8)
Low dose use: 2.4% (0.6-9.3)
Intermediate dose use: 8.5% (4.2-16.8)
High dose^b use: 21.5% (12.0-35.5)

Treatment with high doses^b for prolonged periods
Use of fluticasone propionate
Concomitant use of other glucocorticoid formulations (e.g., oral glucocorticoids in chronic obstructive pulmonary disease or nasal glucocorticoids for rhinitis/nasal polyposis)
Lower body mass index
Higher compliance with treatment
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c (e.g., medications containing ritonavir; antifungal drugs for acute allergic bronchopulmonary aspergillosis)

Use the lowest effective glucocorticoid dose for the shortest period
Use spacers and mouth rinsing
Consider alternative glucocorticoids to fluticasone propionate
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Intra-articular glucocorticoids

52.2% (40.5-63.6)

Repeated injections over a short period (<3 months)
Simultaneous injections of multiple joints
Use of high glucocorticoid doses
Inflammatory arthropathies
Concomitant use of other glucocorticoid formulations
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c

Reduce the number of injections, if possible
Space out injections by at least 3-4 months, if possible
Triamcinolone hexacetonide may carry a lower risk of systemic absorption than triamcinolone acetonide
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Percutaneous (topical) glucocorticoids

4.7% (CI 1.1-18.5)

Long-term use of high-potency glucocorticoids on large surface areas or areas of increased absorption (e.g. mucosa)
Prolonged use on inflamed skin with impaired barrier function
Occlusive dressings
Use on mucous membranes, eyelids, and scrotum
Concomitant use of other glucocorticoid formulations
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c

Use the smallest effective quantity for the shortest period
Use lower potency glucocorticoids, if possible
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Intra-nasal glucocorticoids

4.2% (CI 0.5-28.9)

Long-term use
Concomitant use of other glucocorticoid formulations
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c

Use the lowest effective glucocorticoid dose for the shortest period
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Prevalence of glucocorticoid-induced adrenal insufficiency^a

Factors increasing the risk of glucocorticoid-induced adrenal insufficiency

Strategies to mitigate the risk of glucocorticoid-induced adrenal insufficiency^d

Inhaled glucocorticoids

Overall: 7.8% (CI 4.2-13.9)
Short-term use (<1 month): 1.4% (CI 0.3-7.4)
Medium-term use (1-12 months): 11.9% (CI 5.8-23.1)
Long-term use (>12 months): 27.4% (CI 17.7-39.8)
Low dose use: 2.4% (0.6-9.3)
Intermediate dose use: 8.5% (4.2-16.8)
High dose^b use: 21.5% (12.0-35.5)

Treatment with high doses^b for prolonged periods
Use of fluticasone propionate
Concomitant use of other glucocorticoid formulations (e.g., oral glucocorticoids in chronic obstructive pulmonary disease or nasal glucocorticoids for rhinitis/nasal polyposis)
Lower body mass index
Higher compliance with treatment
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c (e.g., medications containing ritonavir; antifungal drugs for acute allergic bronchopulmonary aspergillosis)

Use the lowest effective glucocorticoid dose for the shortest period
Use spacers and mouth rinsing
Consider alternative glucocorticoids to fluticasone propionate
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Intra-articular glucocorticoids

52.2% (40.5-63.6)

Repeated injections over a short period (<3 months)
Simultaneous injections of multiple joints
Use of high glucocorticoid doses
Inflammatory arthropathies
Concomitant use of other glucocorticoid formulations
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c

Reduce the number of injections, if possible
Space out injections by at least 3-4 months, if possible
Triamcinolone hexacetonide may carry a lower risk of systemic absorption than triamcinolone acetonide
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Percutaneous (topical) glucocorticoids

4.7% (CI 1.1-18.5)

Long-term use of high-potency glucocorticoids on large surface areas or areas of increased absorption (e.g. mucosa)
Prolonged use on inflamed skin with impaired barrier function
Occlusive dressings
Use on mucous membranes, eyelids, and scrotum
Concomitant use of other glucocorticoid formulations
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c

Use the smallest effective quantity for the shortest period
Use lower potency glucocorticoids, if possible
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Intra-nasal glucocorticoids

4.2% (CI 0.5-28.9)

Long-term use
Concomitant use of other glucocorticoid formulations
Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c

Use the lowest effective glucocorticoid dose for the shortest period
Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

Table 6:

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Non-oral glucocorticoid formulations and risk of glucocorticoid-induced adrenal insufficiency

	Prevalence of glucocorticoid-induced adrenal insufficiency^a	Factors increasing the risk of glucocorticoid-induced adrenal insufficiency	Strategies to mitigate the risk of glucocorticoid-induced adrenal insufficiency^d
Inhaled glucocorticoids	Overall: 7.8% (CI 4.2-13.9) Short-term use (<1 month): 1.4% (CI 0.3-7.4) Medium-term use (1-12 months): 11.9% (CI 5.8-23.1) Long-term use (>12 months): 27.4% (CI 17.7-39.8) Low dose use: 2.4% (0.6-9.3) Intermediate dose use: 8.5% (4.2-16.8) High dose^b use: 21.5% (12.0-35.5)	Treatment with high doses^b for prolonged periods Use of fluticasone propionate Concomitant use of other glucocorticoid formulations (e.g., oral glucocorticoids in chronic obstructive pulmonary disease or nasal glucocorticoids for rhinitis/nasal polyposis) Lower body mass index Higher compliance with treatment Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c (e.g., medications containing ritonavir; antifungal drugs for acute allergic bronchopulmonary aspergillosis)	Use the lowest effective glucocorticoid dose for the shortest period Use spacers and mouth rinsing Consider alternative glucocorticoids to fluticasone propionate Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c
Intra-articular glucocorticoids	52.2% (40.5-63.6)	Repeated injections over a short period (<3 months) Simultaneous injections of multiple joints Use of high glucocorticoid doses Inflammatory arthropathies Concomitant use of other glucocorticoid formulations Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c	Reduce the number of injections, if possible Space out injections by at least 3-4 months, if possible Triamcinolone hexacetonide may carry a lower risk of systemic absorption than triamcinolone acetonide Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c
Percutaneous (topical) glucocorticoids	4.7% (CI 1.1-18.5)	Long-term use of high-potency glucocorticoids on large surface areas or areas of increased absorption (e.g. mucosa) Prolonged use on inflamed skin with impaired barrier function Occlusive dressings Use on mucous membranes, eyelids, and scrotum Concomitant use of other glucocorticoid formulations Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c	Use the smallest effective quantity for the shortest period Use lower potency glucocorticoids, if possible Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c
Intra-nasal glucocorticoids	4.2% (CI 0.5-28.9)	Long-term use Concomitant use of other glucocorticoid formulations Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c	Use the lowest effective glucocorticoid dose for the shortest period Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

	Prevalence of glucocorticoid-induced adrenal insufficiency^a	Factors increasing the risk of glucocorticoid-induced adrenal insufficiency	Strategies to mitigate the risk of glucocorticoid-induced adrenal insufficiency^d
Inhaled glucocorticoids	Overall: 7.8% (CI 4.2-13.9) Short-term use (<1 month): 1.4% (CI 0.3-7.4) Medium-term use (1-12 months): 11.9% (CI 5.8-23.1) Long-term use (>12 months): 27.4% (CI 17.7-39.8) Low dose use: 2.4% (0.6-9.3) Intermediate dose use: 8.5% (4.2-16.8) High dose^b use: 21.5% (12.0-35.5)	Treatment with high doses^b for prolonged periods Use of fluticasone propionate Concomitant use of other glucocorticoid formulations (e.g., oral glucocorticoids in chronic obstructive pulmonary disease or nasal glucocorticoids for rhinitis/nasal polyposis) Lower body mass index Higher compliance with treatment Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c (e.g., medications containing ritonavir; antifungal drugs for acute allergic bronchopulmonary aspergillosis)	Use the lowest effective glucocorticoid dose for the shortest period Use spacers and mouth rinsing Consider alternative glucocorticoids to fluticasone propionate Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c
Intra-articular glucocorticoids	52.2% (40.5-63.6)	Repeated injections over a short period (<3 months) Simultaneous injections of multiple joints Use of high glucocorticoid doses Inflammatory arthropathies Concomitant use of other glucocorticoid formulations Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c	Reduce the number of injections, if possible Space out injections by at least 3-4 months, if possible Triamcinolone hexacetonide may carry a lower risk of systemic absorption than triamcinolone acetonide Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c
Percutaneous (topical) glucocorticoids	4.7% (CI 1.1-18.5)	Long-term use of high-potency glucocorticoids on large surface areas or areas of increased absorption (e.g. mucosa) Prolonged use on inflamed skin with impaired barrier function Occlusive dressings Use on mucous membranes, eyelids, and scrotum Concomitant use of other glucocorticoid formulations Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c	Use the smallest effective quantity for the shortest period Use lower potency glucocorticoids, if possible Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c
Intra-nasal glucocorticoids	4.2% (CI 0.5-28.9)	Long-term use Concomitant use of other glucocorticoid formulations Concomitant treatment with strong cytochrome P450 3A4 inhibitors^c	Use the lowest effective glucocorticoid dose for the shortest period Avoid co-administration with strong cytochrome P450 3A4 inhibitors^c

^aBased on a systematic review and meta-analysis of studies assessing the prevalence of biochemical impairment of the HPA axis, regardless of clinical correlates.¹⁹ Systematic data on the prevalence of signs and symptoms of adrenal insufficiency are lacking.

^bHigh doses of commonly prescribed inhaled glucocorticoids in adults are:

Fluticasone propionate >500 μg/day
Beclometasone dipropionate (standard particle inhalers) > 1000 μg/day
Beclometasone dipropionate (extra fine particle inhalers) > 400 μg/day
Budesonide >800 μg/day
Ciclesonide >320 μg/day
Fluticasone furoate >200 μg/day
Mometasone furoate standard particle >400 μg/day

These doses are expressed as total daily doses and should be seen as a guide only. Doses are based on information from manufactures’ summaries of product characteristics, Global Initiative for Asthma (2023), and the British National Formulary.

^cStrong inhibitors include boceprevir, ceritinib, clarithromycin, cobicistat, darunavir, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, mifepristone, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, and voriconazole.

^dSuggested strategies include consideration of reduced doses, frequencies, and alternative treatments, but sufficient control of the underlying glucocorticoid dependent disease remains paramount

Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus.

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