NPC Archive Item: Oral roflumilast▼ launched as add-on treatment for COPD

NOTE – This is an archive post from the NPC and has not been updated since first publication. Therefore, some hyperlinks may no longer be working.
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13 October 2010

Roflumilast has been marketed as a once daily add-on treatment to bronchodilator therapy in patients with severe chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. Weight loss was observed in trials hence the SmPC advice that the body weight of underweight patients taking roflumilast is checked at each visit.

The recently updated NICE guideline on COPD provides advice on drug therapy, but did not include roflumilast. While a NICE technology appraisal is planned, a publication date is not yet available. The NICE guidance should be borne in mind as commissioners and prescribers engage to identify those patients for whom roflumilast may be appropriate and agree a local policy for its use.

Roflumilast (Daxas® 500 microgram tablets) is a once-daily oral phosphodiesterase 4 enzyme inhibitor. It is licensed for maintenance treatment of severe COPD (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add-on to bronchodilator treatment. It is available at a cost of £37.71 for 30 x 500microgram tablets or £113.14 for a 90 tablet pack.

We recently reviewed the four key studies that formed the basis of the European licence application and have provided further information in our On the Horizon bulletin. Patients participating in the trials were described as having “bronchitic symptoms” defined by chronic cough and sputum production. Therefore, only these specific patients should be considered for treatment.

The studies did not provide information about whether roflumilast (in addition to inhaled bronchodilator treatment) provides any significant benefit when used instead of, or in addition to, an inhaled corticosteroid (ICS). Many patients in the trials were already receiving an ICS prior to enrolment, which was discontinued; therefore it is not possible to extrapolate the results of these trials to patients in the real world.

Weight loss was observed in patients receiving the drug in the clinical trials and the Summary of Product Characteristics (SmPC) advises prescribers that the body weight of underweight patients should be checked at each visit. Patients should be advised to check their weight on a regular basis.  Educational packs incorporating the above advice, and other warnings/precautions for use, must be provided to healthcare professionals before they prescribe the drug.

Adverse effects frequently observed in trials include diarrhoea and nausea.  The drug is associated with an increased risk of psychiatric disorders such as insomnia, anxiety, nervousness and depression. The SmPC provides further information.

An updated NICE guideline on COPD was published in June 2010 and did not include roflumilast. The guidance recommends that in people with stable COPD who remain breathless or have exacerbations, despite use of short-acting bronchodilators as required, the following be considered as maintenance therapy:

–        if FEV1 50% predicted use either LABA or long-acting muscarinic antagonist (LAMA)

–        if FEV1 < 50% predicted use either LABA with an ICS in a combination inhaler, or LAMA. If ICS cannot be tolerated then a LABA plus LAMA combination is an alternative.

In patients with persistent exacerbations or breathlessness various combinations are advised including a LAMA in addition to LABA+ ICS. A short-acting beta agonist as required may continue at all stages.

Roflumilast has been referred for a single technology appraisal. Currently no timelines are available for publication of this guidance. The Scottish Medicines Consortium recently rejected the drug on the basis that a sufficiently robust economic analysis for its use in Scotland had not been made by the manufacturer.

Information on the management of COPD is available on the COPD section of NPC.

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