Do inhaled corticosteroids (ICS) pose a similar risk of adrenal suppression as oral corticosteroids (oral steroids)?

From the Guidelines

Inhaled corticosteroids are significantly less likely to cause adrenal suppression compared to oral steroids, but high doses and prolonged use can still pose a risk. At standard prescribed doses, inhaled corticosteroids like fluticasone, budesonide, and beclomethasone have minimal systemic effects compared to oral corticosteroids such as prednisone or dexamethasone, as shown in a study by 1. However, higher doses of inhaled corticosteroids, particularly above 1000 mcg/day of fluticasone or equivalent, can lead to measurable adrenal suppression in some patients.

Key Considerations

• The risk of adrenal suppression increases with longer duration of use, higher doses, and more potent inhaled corticosteroid formulations.
• Children may be more susceptible to these effects than adults.
• The reduced risk with inhaled corticosteroids occurs because they are delivered directly to the lungs with minimal systemic absorption, and undergo significant first-pass metabolism in the liver when swallowed, as noted in 1.
• Patients on high-dose inhaled corticosteroids should be monitored for symptoms of adrenal insufficiency such as fatigue, weakness, nausea, and hypotension, especially during times of stress when additional steroid coverage might be needed.
• Using spacer devices with metered-dose inhalers and rinsing the mouth after use can further reduce systemic absorption and associated risks, as recommended in 1.

Recommendations for Use

• Advise patients to use spacers or valved holding chambers with nonbreath-activated metered-dose inhalers to reduce local side effects.
• Advise patients to rinse the mouth after inhalation.
• Use the lowest dose of inhaled corticosteroids that maintains asthma control.
• Consider adding a long-acting beta agonist or alternative adjunctive therapy to a low or medium dose of inhaled corticosteroids rather than using a higher dose of inhaled corticosteroids to maintain asthma control, as suggested in 1.

From the FDA Drug Label

Adrenal insufficiency is a condition where the adrenal glands do not make enough steroid hormones. This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and start taking a medicine containing an inhaled steroid (such as Wixela Inhub®) During this transition period when your body is under stress such as from fever, trauma (such as a car accident), infection, surgery, or worse COPD symptoms, adrenal insufficiency can get worse and may cause death Symptoms of adrenal insufficiency include: o feeling tired o lack of energy o weakness o nausea and vomiting o low blood pressure (hypotension)

Inhaled corticosteroids, such as fluticasone propionate, may cause adrenal insufficiency, especially when transitioning from oral corticosteroids. However, the risk is generally considered lower compared to oral steroids. Key points to consider:

• Adrenal insufficiency can occur when switching from oral corticosteroids to inhaled corticosteroids.
• Symptoms of adrenal insufficiency include fatigue, weakness, nausea, and low blood pressure.
• Risk of adrenal insufficiency may be increased during periods of stress, such as infection or surgery. 2

From the Research

Adrenal Suppression Comparison

• Inhaled corticosteroids (ICS) can cause adrenal insufficiency, but the risk is generally lower compared to oral steroids 3, 4.
• High doses of ICS appear to be a significant independent risk factor for adrenal insufficiency, with an increased risk estimated for the highest tertile of ICS dose 3.
• The risk of adrenal insufficiency with ICS varies depending on the dose and duration of treatment, with higher doses and longer treatment durations associated with a higher risk 4.

Risk Factors for Adrenal Insufficiency

• The route of administration, disease, treatment dose, and duration all play a role in determining the risk of adrenal insufficiency 4.
• Stratified by administration form, percentages of patients with adrenal insufficiency ranged from 4.2% for nasal administration to 52.2% for intra-articular administration 4.
• In asthma patients, the risk of adrenal insufficiency varied according to dose, from 2.4% (low dose) to 21.5% (high dose), and according to treatment duration, from 1.4% (<28 days) to 27.4% (>1 year) 4.

Comparison with Oral Steroids

• Oral corticosteroids (OCS) are associated with a higher risk of adrenal insufficiency compared to ICS 5, 4.
• The use of biologic agents may help reduce the need for OCS and minimize the risk of adrenal insufficiency in patients with severe asthma 5.
• However, the optimal strategy for identifying and treating adrenal insufficiency, as well as safely withdrawing OCS, remains to be defined 5.

Clinical Implications

• Physicians prescribing ICS at high doses should be aware of the signs and symptoms of adrenal insufficiency in their patients 3.
• The threshold to test corticosteroid users for adrenal insufficiency should be low in clinical practice, especially for those patients with nonspecific symptoms after cessation 4.
• Further research is needed to determine the comparative safety and efficacy of different ICS and to identify the most effective strategies for minimizing the risk of adrenal insufficiency 6.