Asthma Management Handbook

Guide to systemic corticosteroids

Overview

Short courses of systemic corticosteroids are used to manage flare-ups and acute asthma. Oral prednisone/prednisolone is most commonly used. Parenteral corticosteroids are sometimes used to manage severe acute asthma in emergency departments.

Occasionally, longer-term use of oral corticosteroids is necessary to manage difficult-to-treat asthma under specialist supervision.

Table. Classification of asthma medicines Opens in a new window Please view and print this figure separately: http://www.asthmahandbook.org.au/table/show/79

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Oral corticosteroids for children: 0–5 years

Few clinical trials have assessed the effectiveness of oral corticosteroids for managing flare-ups of wheezing in preschool children,1 and there is very little evidence about their effects in children who are not being treated in hospitals or emergency departments.

Short courses of oral corticosteroids initiated by parents in response to the onset of wheezing symptoms do not appear to reduce the need for hospitalisation or treatment in the emergency department for preschool children.1 For children age 1–5 years with wheezing due to a respiratory tract virus such as the common cold, a short course of oral prednisolone does not reduce the severity of symptoms.23

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Oral corticosteroids for children: 6 years and over

A short course of oral corticosteroid may be helpful in gaining rapid asthma control, with a low risk of additional systemic adverse effects.4

Rarely, long-term systemic corticosteroids may be needed for children with severe persistent asthma that is poorly controlled despite high-dose inhaled corticosteroids and long-acting beta2 agonists.4 However, significant adverse effects may occur due to recurrent or long-term systemic corticosteroids.4

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Oral corticosteroids for severe chronic asthma in adults

In an Australian severe asthma registry study, 24% of patients with severe asthma who had been referred to a severe asthma specialist for assessment were being treated with oral corticosteroids in addition to inhaled corticosteroids and long-acting beta2 agonists.5

Efficacy

Maintenance treatment with oral corticosteroids for severe asthma has not been evaluated in randomised placebo-controlled trials.6

Small randomised trials of intramuscular depot triamcinolone in adults and children with severe asthma, in addition to maintenance or frequent oral corticosteroids, have reported reductions in hospitalisations and emergency department visits, improvement in lung function, and reduced eosinophilic inflammation.6 However, the use of triamcinolone is associated with more adverse effects than other systemic corticosteroids.

Maintenance treatment with oral corticosteroids should be avoided, if possible, because of the high risk of serious adverse effects.[REFERENCE2001], 8, 9

Monoclonal antibody therapy is one strategy to reduce oral corticosteroid use in adults with severe asthma.10, 11, 12

Other strategies for reducing oral corticosteroid use are being evaluated, such as internet-guided titration based on home monitoring of symptoms and fraction of exhaled nitric oxide (FeNO).13

Safety

Oral corticosteroid use in adults with asthma is associated with serious adverse events including severe infections, peptic ulcers, affective disorders, cataracts, cardiovascular events including acute myocardial infarction and hypertension, diabetes, fractures and osteoporosis.7, 14, 15

Dose–response relationships have been demonstrated for these adverse effects.7, 14, 15

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Oral corticosteroids for children: adverse effects

Oral corticosteroids may have adverse psychiatric effects in children, including aggression and hyperactivity.16 Effects in the general population include euphoria, hypomania, depression, disturbances of mood, cognition, sleep and behaviour.17

A short course of oral corticosteroid therapy (less than 2 weeks) is associated with little risk of long-term suppression of the hypothalamus–pituitary–adrenal axis.4 However, risk can accumulate if frequent courses (four or more per year) are given.4

Recurrent courses of oral corticosteroids may also affect bone mineral density, especially in boys.4,18

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Parent/carer-initiated oral corticosteroids for wheezing and asthma flare-ups
  • Oral corticosteroids are associated with adverse effects on behaviour and bone health. Frequent courses may affect the hypothalamus–pituitary–adrenal axis.

Children aged 1–5 years

Short courses of oral corticosteroids initiated by parents/carers in response to children’s wheezing, or at the first sign of a cold, are not effective in managing symptoms in preschool children.19, 23

There is inconsistent evidence for the benefits of systemic corticosteroids in preschool children with acute viral-induced wheezing presenting to acute care services.32021 Current evidence does not strongly support their use in this age group.22

The Thoracic Society of Australia and New Zealand position statement on the use of corticosteroids in children4 recommends that oral corticosteroid treatment in preschool children, particularly those with intermittent viral-induced wheezing, should be limited to children with wheeze severe enough to need admission to hospital.

Children aged 6 years and over

A Cochrane systematic review found that there was insufficient evidence supporting the use of parent-initiated courses of oral corticosteroids in school-aged children,23 although some clinical trials have reported benefits.

In a clinical trial in children aged 6–14 years with a history of recurrent episodes of acute asthma, short courses of oral prednisolone (1 mg/kg a day), initiated by parents in response to an asthma flare-ups, reduced asthma symptoms and the number of missed school days.24 Another quasi-experimental study found that home initiation of corticosteroids reduced the rate of emergency department visits among school-aged children with moderate-to-severe persistent asthma, compared with rates pre-intervention.25

The Thoracic Society of Australia and New Zealand position statement on the use of corticosteroids in children4 recommends a short course of systemic corticosteroid therapy for children with moderate-to-severe acute asthma or when there is an incomplete response to beta-agonists, and does not recommend against parent/carer-initiated courses.

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Managing flare-ups in adults: oral corticosteroids

The use of oral corticosteroids is accepted as part of the management of severe asthma flare-ups, including in most asthma clinical trials.

Most clinical trials that have specifically evaluated the use of oral corticosteroids to manage flare-ups have been conducted in patients attending emergency departments. Oral corticosteroids courses of 5–10 days are effective in regaining control of asthma after an acute flare-up.2627282930 A 5-day course of prednisolone 40 mg per day may be as effective as a 10-day course in adults.28

Abruptly ceasing oral prednisolone after a short course appears to be equally effective as tapering over a longer period. Tapering the dose does not reduce the risk of suppression of adrenal function.2629 The dose should be tapered if oral corticosteroids have been taken for more than 2 weeks.

Action plans for worsening asthma that include instructions for the use of oral corticosteroids as well as instructions to increase the dose of inhaled corticosteroid, are effective in improving lung function and reducing hospital admissions.31

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Systemic corticosteroids in acute asthma

Systemic corticosteroids in acute asthma

In adults and school-aged children with acute asthma, systemic corticosteroids given within 1 hour of presentation to an emergency department reduce the need for hospital admission.32 In children admitted to hospital with acute asthma, systemic corticosteroid treatment may achieve earlier discharge and fewer relapses.33

In preschool children with acute viral-induced wheezing, there is inconsistent evidence for the benefits of systemic corticosteroids.20, 3, 21 Oral corticosteroids may be beneficial in children younger than 6 years with frequent acute wheezing or asthma, but current evidence does not strongly support their use in this age group.22 The Thoracic Society of Australia and New Zealand position statement on the use of corticosteroids in children4 recommends that the use of systemic corticosteroids in preschool children, particularly those with intermittent viral induced wheezing, should be limited to those with wheeze severe enough to need admission to hospital.

After an acute asthma episode, treatment with systemic corticosteroids (intramuscular corticosteroids, oral prednisone/prednisolone, or oral dexamethasone) at discharge from the emergency department reduces the risk of relapse in adults34 and children.35, 36

Formulation and route of administration

In adults and children with acute asthma, oral prednisone/prednisolone is as effective as intravenous or intramuscular corticosteroids.32, 37

Oral dexamethasone is as effective as prednisone/prednisolone in adults and children38, 39, 40, 41, 42, 43, 44, 30, 45

Dose

In adults, 40 mg per day prednisolone/prednisone,46  up to 80 mg/day methylprednisolone, or up to 400 mg/day hydrocortisone47 are adequate.

In children the majority of studies in children have used 1–2 mg/kg of oral prednisolone (maximum 60 mg) given initially then 1 mg/kg per day. Current evidence does not support the use of higher doses.37

Studies evaluating oral dexamethasone in adults have used a single dose of 12 mg38 or 16 mg on 2 consecutive days.45 Most studies evaluating oral dexamethasone in children have used 0.6 mg/kg per dose on one or two consecutive days.41

Duration

In adults, an oral or intramuscular corticosteroid course of at least 7 days appears more effective than a shorter course in preventing relapse within 10 days of discharge after acute asthma,34 although one clinical trial evaluating prednisone reported that 5 days was as effective as 10 days.28 Courses less than 5 days are not recommended.

In children, a 3-day course of prednisone/prednisolone is generally as effective as a 5-day course,48 but 5 days may be needed for children with severe or life-threatening acute asthma.4

It is not necessary to taper the dose after a short course of oral prednisone/prednisolone.34, 26, 29

Dexamethasone has a longer half-life than prednisone/prednisolone. Longer courses may more pronounced mineralocorticoid adverse effects. Oral dexamethasone treatment in adults or children should not exceed 2 days.

Adverse effects

Short-term use of oral corticosteroids to treat acute asthma is often well tolerated in children and adults,32, 33, 3, 30 but many patients report significant adverse effects, particularly mood changes, gastrointestinal disturbances,50 nocturia, and difficulty sleeping. While short courses of high-dose systemic treatment cause fewer adverse effects than prolonged courses of lower doses,17 more recent analyses have shown a significant association between short courses of oral corticosteroids and sepsis, thromboembolism and fracture.7, 8

Oral dexamethasone appears to be well tolerated in adults.38 In children it may be associated with less vomiting than prednisone/prednisolone.39, 40, 41, 42, 42, 43, 44 The risk of unwanted mineralocorticoid effects are increased if dexamethasone is taken for more than 2 days.

In people with diabetes or impaired glucose tolerance, corticosteroids increase blood glucose levels. Impaired glucose tolerance is common among people aged over 65 years. In patients with diabetes or impaired glucose tolerance, blood glucose monitoring (e.g. morning and evening samples) may be indicated during treatment with oral corticosteroids.

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Systemic corticosteroids in acute asthma: adverse effects

Short-term use of oral corticosteroids is unlikely to cause harm – the majority of adverse effects are due to long-term high-dose use.51  Adverse effects associated with prednisone or prednisolone use include headache, nausea, vomiting, increased appetite, diarrhoea or constipation, vertigo, restlessness, insomnia and increased activity, salt and water retention, and increased blood pressure. High doses can be associated with behavioural changes, facial plethora, bruising and increased sweating.51

In people with diabetes or impaired glucose tolerance, corticosteroids increase blood glucose levels. Impaired glucose tolerance is common among people aged over 65 years. In patients with diabetes or impaired glucose tolerance, blood glucose monitoring (e.g. morning and evening samples) may be indicated during treatment with oral corticosteroids.

Long-term use of oral corticosteroids increases the risk of cataracts and osteoporosis in older patients,52 and may increase body weight.

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Systemic corticosteroids: psychiatric effects

Systemic corticosteroids can have a range of psychological effects. Large doses of prednisone or prednisolone can cause mood and behavioural changes, including nervousness, euphoria or mood swings, psychotic episodes including manic or depressive states, paranoid states and acute toxic psychoses.51 These adverse effects can occur in people without a previous history of psychiatric illness.51

Systemic corticosteroid treatment has been associated with elevated mood and reduction in depression among patients with asthma.5354 With long-term prednisone or prednisolone therapy, initial mood changes appear to stabilise over time.55

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Systemic corticosteroids and breast milk

Peak plasma level of systemic corticosteroid occurs at approximately 2 hours post dose, so peak milk level will also occur around this time. Therefore, the infant’s exposure to corticosteroids in breast milk can be further reduced by breastfeeding the infant just before each daily dose and avoiding feeding again until at least 4 hours after the dose.56, 57

If high-dose corticosteroids need to be used for longer than 10 days, the infant should be monitored for growth and development.5657

The US National Library of Medicine’s Drugs and Lactation Database (LactMed) states that: limited information indicates that maternal doses of prednisolone up to 50 mg produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants. With high maternal doses, avoiding breastfeeding for 4 hours after a dose should markedly decrease the dose received by the infant. However, this [manoeuvre] is probably not necessary in most cases.

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References

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