Which inhaled corticosteroid?
- The various inhaled corticosteroids (ICS) do not seem to differ in efficacy (assuming a potency ratio of beclometasone and fluticasone of 2:1).
- Adverse effects are class effects and do not differ significantly between the different inhaled corticosteroids (ICS) at either low or high doses. Increased doses of ICS are associated with an increased risk of local and systemic adverse effects. There is evidence that provided the recommended dose is used, ICS are effective and safe in children aged under 5 years [SIGN and BTS, 2011].
- Prodigy recommends beclometasone, budesonide, or fluticasone because they are available in a range of formulations at different doses and for a range of ages.
- Ciclesonide (available as a pressurized metered-dose inhaler) and mometasone (available as a dry-powder inhaler) are once-daily alternatives. Neither drug is licensed for children younger than 12 years. Mometasone has black triangle status and further post-marketing data are needed to confirm its safety.
- Use the lowest dose of inhaled corticosteroid (ICS) that maintains effective control of asthma.
- Start ICS at a dose appropriate to the severity of symptoms [SIGN and BTS, 2011]:
- Suitable starting doses for beclometasone-CFC free as Clenil Modulite® are:
- Age > 12 years: 200 micrograms twice daily.
- Age 5–12 years: 100 micrograms twice daily.
- Age < 5 years: 100 micrograms twice daily; higher doses may be required to ensure adequate drug delivery.
- If beclometasone CFC-free is started as Qvar® use half the dose listed above (licensed only for age > 12 years).
- Table 1 and Table 2 show comparable total daily doses of ICS.
- Suitable starting doses for beclometasone-CFC free as Clenil Modulite® are:
- Higher doses of ICS may be needed in people who smoke. At low doses, smokers with mild persistent asthma are less sensitive than non-smokers to the therapeutic effects of ICS treatment. This disparity is reduced at high doses of ICS [Tomlinson et al, 2005].
- Treatment with ICS should initially be twice a day (except ciclesonide, which is licensed for once-a-day use) [SIGN and BTS, 2011]:
- Most ICS are slightly more effective when used twice rather than once a day, but people with milder disease may use them once a day. There is little evidence of benefit for administration more frequently than twice a day.
- Once-daily inhalation of ICS at the same total daily dose, within the product license, may be considered if good control is established.
- Prescribe CFC-free beclometasone inhalers by brand name (Clenil Modulite® or Qvar®) [MHRA, 2006a]. They are not equivalent and must not be interchanged.
- When changing from a CFC pMDI to a CFC-free pMDI [BNF 53, 2007; SIGN and BTS, 2011]:
- Clenil Modulite® may be substituted for beclometasone CFC pMDI at 1:1 dosing.
- Qvar® may be substituted for beclometasone CFC pMDI at 1:2 dosing if asthma is well controlled, but consider 1:1 dosing if asthma is poorly controlled. Monitor the person closely to ensure that adequate control is maintained.
Clarification / Additional information
- Comparable doses of inhaled corticosteroids are shown in Table 1 (adults and children > 12 years of age) and Table 2 (children).
- Beclometasone inhalers that contain chlorofluorocarbons (CFC) have been phased out and are no longer available.
Table 1. Recommended daily doses of inhaled corticosteroid delivered by pressurized metered-dose inhaler (pMDI) for adults and children aged 12 years of age or older. Dosage adjustment may be necessary for alternative devices.
|pMDI||Age (Years)||Dose of inhaled corticosteroid|
|Low dose||Usual start dose (step 2)||High dose (step 3)||Maximum dose|
|Clenil Modulite® (beclometasone CFC-free)||>12||100 micrograms twice daily||200 micrograms twice daily||400 micrograms twice daily||1000 micrograms twice daily|
|Qvar® (beclometasone CFC-free)*||>12||50 micrograms twice daily||100 micrograms twice daily||200 micrograms twice daily||400 micrograms twice daily|
|Fluticasone‡||>12||50 micrograms twice daily||100 micrograms twice daily||250 micrograms twice daily||500 micrograms twice daily|
|*When converting from CFC beclometasone to Qvar®, double the dose in the table if control of asthma is poor. Note that this does not apply to Clenil Modulite®, which is equipotent.
‡The maximum licensed daily dose of fluticasone for adults is 2000 micrograms. The Committee on Safety of Medicines (CSM) has advised that doses of fluticasone above 1000 micrograms a day should only be prescribed for adults with severe asthma, and should only be initiated by a physician with a special interest in asthma [CSM, 2001]
Table 2. Recommended daily doses of inhaled corticosteroid delivered by pressurized metered-dose inhaler (pMDI) for children < 12 years of age. Dosage adjustment may be necessary for alternative devices.
|pMDI||Age (years)||Dose of inhaled corticosteroid|
|Low dose||Ususal start dose (step 2)||High dose (step 3)||Maximum dose|
|Clenil Modulite®(Beclometasone CFC-free)||5–11||50 micrograms twice daily||100 micrograms twice daily||200 micrograms twice daily||400 micrograms twice daily (unlicensed)|
|< 5||50 micrograms twice daily||100 micrograms twice daily||—||200 micrograms twice daily†|
|Qvar®(Beclometasone CFC-free)*||< 12||Unlicensed for children under the age of 12|
|Budesonide||5–11||50 micrograms twice daily||100 micrograms twice daily||200 micrograms twice daily||400 micrograms twice daily|
|< 5||50 micrograms twice daily||100 micrograms twice daily||—||200 micrograms twice daily|
|Budesonide CFC-free||5–11||100 micrograms once daily||100 micrograms twice daily||200 micrograms twice daily||400 micrograms twice daily|
|2–5||100 micrograms once daily||100 micrograms twice daily||—||200 micrograms twice daily|
|< 2||Unlicensed for children < 2 years|
|Fluticasone‡||5–11||25 micrograms twice daily||50 micrograms twice daily||100 micrograms twice daily||200 micrograms twice daily|
|4||25 micrograms twice daily||50 micrograms twice daily||—||100 micrograms twice daily|
|< 4||Unlicensed for children < 4 years|
|* When converting from CFC beclometasone to Qvar®, double the dose in the table if control of asthma is poor. Note that this does not apply to Clenil Modulite®, which is equipotent.
† In children under 5 years of age, doses higher than 200 micrograms twice a day of beclometasone (or equivalent ICS) should only be used under specialist supervision.
What are the adverse effects of inhaled corticosteroids and how can they be managed?
- Take into account the use of other systemic or topical corticosteroids when assessing risk.
- Elderly people and children may be particularly susceptible to adverse effects.
Local adverse effects:
- Oral candidiasis, sore mouth, dysphonia, and hoarseness are commonly recognized problems with inhaled corticosteroid (ICS) use, especially in high doses:
- For people using a pressurized metered-dose inhaler, these effects may be reduced by using a large-volume spacer device (which reduces oropharyngeal deposition by filtering out larger particles) [DTB, 2000; RPSGB, 2006].
- Oral candidiasis can be minimized by rinsing the mouth with water after ICS inhalation.
- Oropharyngeal deposition is high with dry-powder inhalers and autohalers.
Systemic adverse effects — adults:
- Osteoporosis: there are concerns that inhaled corticosteroids may affect bone mineral density, particularly when given in high doses for long periods, but the evidence regarding this is conflicting [SIGN and BTS, 2011]:
- In people who require high doses of ICS for prolonged periods of time, general measures to counteract osteoporosis (such as regular exercise, smoking cessation, and adequate dietary calcium) are prudent.
- Adrenal suppression: evidence indicates that high doses of ICS (equivalent to 1.5 mg/day CFC-containing beclometasone) result in significant adrenal suppression [EBM, 1999]. The risk of adrenal insufficiency is dose related and is largely due to use of oral corticosteroids, although inhaled corticosteroids may have an effect when they are taken at higher doses [Mortimer et al, 2006]:
- Titrate the dose of inhaled steroid to the lowest dose at which effective control of asthma is maintained [SIGN and BTS, 2011].
Systemic adverse effects — children:
- The Committee on Safety of Medicines has ‘strongly advised that the paediatric licensed doses of all inhaled corticosteroids should not be exceeded’ [CSM, 2002]. Use the lowest dose of ICS that will maintain disease control. If adequate control is not achieved, consider using add-on agents rather than increasing the dose of ICS [SIGN and BTS, 2011].
- Childhood growth: some initial slowing of growth may occur in children who have used ICS, but final adult height does not appear to be affected [Childhood Asthma Management Program Research Group, 2000; MeReC, 2002]:
- All children receiving prolonged treatment with ICS should have their height regularly and accurately monitored using a growth chart [CSM, 1998]. Any slowing of growth should prompt a reduction in dose if possible, or referral to a specialist, or both.
- Bone mineral density: one long-term study in children with chronic asthma treated with ICS suggests no adverse effect of ICS on bone mineral density in children [Agertoft and Pedersen, 2000]. Further long-term studies are needed to confirm this. However, experts suggest that with careful ICS dose adjustment, this risk is likely to be outweighed by the ability of ICS to reduce the need for multiple courses of oral corticosteroids [Kelly et al, 2008].
- Very rarely psychiatric disorders including psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, and behavioural changes (predominantly in children), have been reported [ABPI Medicines Compendium, 2011a].
- Acute adrenal crisis: in a small number of children, doses of inhaled ICS at or above 400 micrograms per day of beclometasone have been associated with growth failure and adrenal suppression. The exact dose and duration of ICS treatment to put a child at risk of adrenal insufficiency is unknown, but it is likely to be 1000 micrograms or more of beclometasone or equivalent daily [SIGN and BTS, 2011]:
- Specific written advice about steroid replacement in the event of a severe intercurrent illness should be part of the management plan for children treated with 800 micrograms or more of beclometasone or equivalent daily.
- Any child receiving this dose should be under the care of a specialist paediatrician for the duration of the treatment.
- Consider use of a steroid treatment card.
- Consider the possibility of adrenal insufficiency in any child maintained on inhaled steroids presenting with shock or decreased consciousness:
- Check serum biochemistry and blood glucose levels urgently.
- Consider whether intramuscular hydrocortisone is required.
Advice for patients
- Advise people that smoking can reduce the effectiveness of inhaled corticosteroids (ICS) [SIGN and BTS, 2011].
- Advise people to rinse their mouth with water (or clean children’s teeth) after inhalation of a dose of ICS to reduce the risk of oral candidiasis [BNF 53, 2007].
- Advise on general measures to counteract osteoporosis (such as regular exercise, smoking cessation, and adequate calcium intake) in people using high doses of ICS for prolonged periods.
- Advise parents to immediately report non-specific symptoms, such as anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, decreased consciousness, hypoglycaemia, and seizures, in children using high doses of ICS (400 micrograms or more per day of beclometasone).
- Consider use of a steroid treatment card:
- People using prolonged high doses (off-label high doses, or maximum doses in conjunction with oral corticosteroids) of ICS should be given a steroid treatment card which gives guidance on minimizing risk and provides details of prescriber, drug, dosage, and duration of treatment [CHM, 2006].