DALIRESP SIDE EFFECTS

SIDE EFFECTS

The following adverse reactions are described in greater detail in other sections:

• Psychiatric Events Including Suicidality.
• Weight Decrease.

Adverse Reactions In Clinical Studies

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described below reflect exposure of 4438 patients to DALIRESP 500 mcg once daily in four 1- year placebo-controlled trials, two 6-month placebo-controlled trials, and two 6-month drug add-on trials. In these trials, 3136 and 1232 COPD patients were exposed to DALIRESP 500 mcg once daily for 6 months and 1 year, respectively.

The population had a median age of 64 years (range 40-91), 73% were male, 92.9% were Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV₁) of 8.9 to 89.1% predicted. In these trials, 68.5% of the patients treated with DALIRESP reported an adverse reaction compared with 65.3% treated with placebo.

The proportion of patients who discontinued treatment due to adverse reaction was 14.8% for DALIRESPtreated patients and 9.9% for placebo-treated patients. The most common adverse reactions that led to discontinuation of DALIRESP were diarrhea (2.4%) and nausea (1.6%).

Serious adverse reactions, whether considered drug-related or not by the investigators, which occurred more frequently in DALIRESP-treated patients include diarrhea, atrial fibrillation, lung cancer, prostate cancer, acute pancreatitis, and acute renal failure.

Table 1 summarizes the adverse reactions reported by ≥2% of patients in the DALIRESP group in 8 controlled COPD clinical trials.

Table 1: Adverse Reactions Reported by ≥2% of Patients Treated with DALIRESP 500 mcg daily and Greater Than Placebo

Adverse reactions that occurred in the DALIRESP group at a frequency of 1 to 2% where rates exceeded that in the placebo group include:

Gastrointestinal disorders – abdominal pain, dyspepsia, gastritis, vomiting

Infections and infestations – rhinitis, sinusitis, urinary tract infection

Musculoskeletal and connective tissue disorders – muscle spasms

Nervous system disorders – tremor

Psychiatric disorders – anxiety, depression

The safety profile of roflumilast reported during Trial 9 was consistent with the key pivotal studies.

Postmarketing Experience

The following adverse reactions have been identified from spontaneous reports of DALIRESP received worldwide and have not been listed elsewhere. These adverse reactions have been chosen for inclusion due to a combination of seriousness, frequency of reporting or potential causal connection to DALIRESP. Because these adverse reactions were reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency or establish a causal relationship to DALIRESP exposure: hypersensitivity reactions (including angioedema, urticaria, and rash), gynecomastia.