Possible side effects
Daxas® is generally well-tolerated and can be given concomitantly with inhaled maintenance treatments for COPD.1-3 For more information on side effects, please read the EU SmPC.4
In Daxas® clinical COPD studies involving 12,000 patients, approximately 16% of patients taking Daxas® experienced adverse reactions, compared with 5% of patients taking placebo.4 Side effects were typically mild to moderate, occurred mainly within the first weeks of treatment, and mostly resolved with continued Daxas® therapy. The most commonly reported adverse reactions were diarrhoea, weight decrease, nausea, abdominal pain and headache, which were experienced by a small percentage of patients (Table 1).1,2,4
It is important to inform patients about the possible side effects associated with Daxas®. Highlighting their transient nature may encourage compliance.
* % of study populationTable 1. Most commonly reported adverse reactions in Daxas® clinical COPD studies.3
Daxas® is contraindicated in patients with hypersensitivity to roflumilast or to any of the excipients, or with moderate or severe hepatic impairment (Child-Pugh B or C).
Special warnings and precautions for use
Some patients lost body weight while being treated with Daxas® in clinical studies.1,2 Weight decrease was transient (occurring mostly within the first 6 months of Daxas® treatment). After discontinuation of Daxas®, the majority of patients had regained body weight after 3 months.1,2,5 Furthermore, bio-impedance studies indicated that the weight decrease resulted primarily from loss of fat mass.6
At present, there is no clear explanation of the mechanisms behind the weight decrease associated with Daxas®, but this will be addressed in further clinical studies.
Therefore, it is recommended that patients who are underweight, or are at risk of becoming underweight, should be monitored closely for changes in their body weight throughout the Daxas® treatment period. In the event of an unexplained and clinically concerning weight decrease, prescription of Daxas® should be discontinued and body weight should be monitored.
Daxas® is associated with an increased risk of psychiatric disorders such as insomnia, anxiety, nervousness and depression. Rare instances of suicidal ideation and behaviour, including completed suicide, have been observed in clinical trials. Therefore, the risks and benefits of starting or continuing treatment with Daxas® should be carefully assessed if patients report previous or existing psychiatric symptoms or if concomitant treatment with other medicinal products likely to cause psychiatric events is intended. Patients should be instructed to notify their prescriber of any changes in behaviour or mood and of any suicidal ideation. Moreover, Daxas® is not recommended in patients with a history of depression associated with suicidal ideation or behaviour.
Adverse events such as diarrhoea, nausea, abdominal pain and headache may occur in a small percentage of patients, mainly within the first weeks of Daxas® therapy. Most adverse events are transient and resolve with continued treatment. However Daxas® treatment should be reassessed in cases of persistent intolerability. This might be the case in special populations that may have higher exposure, such as in black, non-smoking females, or in patients concomitantly treated with the CYP1A2 inhibitor fluvoxamine or the dual CYP3A4/1A2 inhibitors enoxacin and cimetidine.
There are no clinical data to support the concomitant treatment of Daxas® with theophylline for COPD maintenance therapy. Therefore, concomitant treatment with theophylline is not recommended.
Daxas® tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
- Calverley PMA, Rabe KF, Goehring U-M, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374:685-694.
- Fabbri LM, Calverley PMA, Izquierdo-Alonso JL, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet 2009;374:695-703.
- Calverley PM, Sanchez-Toril F, McIvor A, et al. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;176:154-161.
- Daxas® European Summary of Product Characteristics, 2011.
- Martinez FI, Rabe KF, Wouters EFM, et al. Time course and reversibility of weight decrease with roflumilast, a phosphodiesterase inhibitor. Am J Respir Crit Care Med 2010;181:A4441.
- Wouters EFM, Teichmann P, Brose M, et al. Effects of roflumilast, a phosphodiesterase inhibitor, on body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;181:A4473.
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