Inhaled corticosteroids containing medicinal products indicated in the treatment of chronic obstructive pulmonary disease

• It has been known for some time that inhaled corticosteroid medicines increase the risk of pneumonia (infections of the lungs) in patients taking these medicines for the long-term lung disease COPD (chronic obstructive pulmonary disease).
• Corticosteroid inhalers reduce inflammation and swelling in the lungs and so help breathing in patients with COPD. In the EU, the available products include the active substances beclomethasone, budesonide, flunisolide, fluticasone furoate or fluticasone propionate.
• EMA has reviewed the risk of pneumonia in COPD patients using corticosteroid inhalers and has concluded that this risk applies to all medicines of this class. The evidence did not confirm any differences in risk between products.
• Patients need to alert their doctors if they start to get symptoms that suggest they are developing pneumonia, so that it can be identified and treated early. These symptoms can be like those of an exacerbation (an episode of worsening COPD) and include fever or chills, increased amounts of mucus (phlegm) or a change in its colour, or worsening of cough or breathing difficulties.
• Patients who have any concerns should discuss them with their doctor or other healthcare professional. They should not stop using their inhaler or change the way they use it without consulting their prescriber.

• Following a review of the available data, EMA has confirmed the risk of pneumonia with inhaled corticosteroids (ICS) in patients with COPD. There is no conclusive clinical evidence for intra-class differences in the magnitude of the risk among ICS products.
• There is some evidence of an increased risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all studies.
• The product information for all medicines of the class will be updated to reflect current knowledge about pneumonia risk.
• Healthcare professionals should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations.
• Patients should be advised to report any increased breathing difficulties or other symptoms suggestive of infection.
• The Agency's review included published data from randomised controlled clinical trials and a number of meta-analyses, as well as observational studies. No clinical trials directly examined the risk of pneumonia with ICS head to head, and only indirect comparison in meta-analyses/systematic reviews or from observational studies is available. Due to the variability in the clinical data and multiple uncertainties with study methodologies, this does not provide conclusive evidence for intra-class differences in the magnitude of risk.

Corticosteroids, also known as steroids, are anti-inflammatory medicines used for a wide range of conditions. They are similar to natural hormones normally produced by the adrenal glands (two small glands located above the kidneys). When taken by inhalation they attach to receptors in the airways and cause a reduction in lung inflammation, which makes breathing easier. They are usually taken using inhalers which either contain a corticosteroid alone or a corticosteroid in combination with another medicine (such as a long-acting beta₂ agonist that widens the airways). Beclomethasone, budesonide, flunisolide, fluticasone propionate and fluticasone furoate are corticosteroids authorised and marketed as inhalation formulations for use in COPD. Corticosteroid-containing medicines have been authorised in the EU through both central and national approval procedures.

The review was initiated at the request of the European Commission on 7 May 2015, under Article 31 of Directive 2001/83/EC.

The review has been carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations. The PRAC recommendations were sent to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which adopted the Agency's opinion. The CHMP opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States.

Commission Decision dates: 29/06/2016 (nationally authorised products), 24/06/2016 (Relvar Ellipta, Revinty Ellipta), 04/07/2016 (BiResp Spiromax, DuoResp Spiromax), 06/07/2016 (Budesonide/Formoterol Teva, Vylaer Spiromax).