Post-authorization safety study (PASS) on roflumilast


Roflumilast (DAXAS®) is a Phosphodiesterase-4-inhibitor with an anti-inflammatory and bronchodilatatic effect that was approved as add-on therapy to bronchodilatators for the long-term treatment of patients with severe chronic obstructive pulmonary disease (COPD) in Germany in September 2010.

In the approval studies, several adverse drug reactions were observed such as diarrhea, nausea, unexplained weight loss, headache, disorders of the nervous system, psychiatric disorders and cardiovascular disease and - in patients in depressive state - suicides or suicide attempts. Furthermore, in animal studies, an increased risk for cancers was observed. So far, data on the safety of roflumilast from studies with duration of more than 12 months were not available. In a risk management plan, the European Medicines Agency (EMA) requested safety studies after market approval (Post-Authorization Studies, PASS) from the Marketing Authorization Holder AstraZeneca that should be conducted in different countries in which roflumilast is available.

Based on data from the German Pharmacoepidemiological Research Database (GePaRD), several endpoints (all-cause mortality, cardiovascular diseases, newly diagnosed cancer, depression, tuberculosis, hepatitis and hospitalizations due to respiratory disease, diarrhea, weight loss or suicidal ideation or action) will be assessed in a cohort study and compared between roflumilast-treated COPD patients and COPD patients who were not treated with roflumilast in the study period from 2010 to 2018.

For this study, about 9,000 roflumilast-treated COPD-patients and 41,000 COPD-patients who were not treated with roflumilast were identified. The maximum follow-up time ranges between 5 years and 8 years, 5 months, depending on the time of initiation of roflumilast treatment.

Currently, the final analysis is conducted.

Similar studies that are also part of the PASS program are conducted in Sweden and the US.

Funding period

Begin:   December 2013
End:   December 2022


  • Pharmaceutical industry


 Wiebke Schäfer