Main adverse events of Roflumilast are weight loss, loss of appetite, insomnia, headache,
diarrhea, vomiting, and nausea. Although the majority of these adverse reactions were mild or
moderate. They occurred mainly at the beginning of therapy and mostly resolved with continued
treatment around for two weeks according to experiences of clinicians. These adverse events
occur more often in Roflumilast 500 μg than 250 μg, having negative impact on compliance of
patients at the early stage of treatments.
Thus, investigators aim to compare the drop-out rates between the usual dosage (Roflumilast
500 μg once daily) and the dose escalation (Roflumilast 250 μg once daily for 4 weeks and
then escalating dose of 500 μg once daily).