ROFLUMILAST
Generic: ROFLUMILAST
Basic Information
Manufacturer
Aurobindo Pharma Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
7cb11d48-6bb9-437b-bc7f-382050a2d3e6
Indications & Usage
1 INDICATIONS AND USAGE Roflumilast tablets are indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.
Limitations of Use Roflumilast tablets are not a bronchodilator and is not indicated for the relief of acute bronchospasm.
Roflumilast tablets 250 mcg is a starting dose, for the first 4 weeks of treatment only and is not the effective (therapeutic) dose.
Roflumilast is a selective phosphodiesterase 4 inhibitor indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.
( 1 , 14 ) Limitations of Use: Roflumilast tablets are not a bronchodilator and is not indicated for the relief of acute bronchospasm.
( 1 , 14 ) Roflumilast tablets 250 mcg is a starting dose, for the first 4 weeks of treatment only and is not the effective (therapeutic) dose.
( 2 , 14 )
Limitations of Use Roflumilast tablets are not a bronchodilator and is not indicated for the relief of acute bronchospasm.
Roflumilast tablets 250 mcg is a starting dose, for the first 4 weeks of treatment only and is not the effective (therapeutic) dose.
Roflumilast is a selective phosphodiesterase 4 inhibitor indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.
( 1 , 14 ) Limitations of Use: Roflumilast tablets are not a bronchodilator and is not indicated for the relief of acute bronchospasm.
( 1 , 14 ) Roflumilast tablets 250 mcg is a starting dose, for the first 4 weeks of treatment only and is not the effective (therapeutic) dose.
( 2 , 14 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Psychiatric Events Including Suicidality [see Warnings and Precautions (5.2) ] Weight Decrease [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥2%) are diarrhea, weight decrease, nausea, headache, back pain, influenza, insomnia, dizziness and decreased appetite.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc.
at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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 roflumilast 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 [see Clinical Studies (14.1) ].
In these trials, 3136 and 1232 COPD patients were exposed to roflumilast 500 mcg once daily for 6 months and 1 year, respectively.
The population had a median age of 64 years (range 40 to 91), 73% were male, 92.9% were Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV 1 ) of 8.9 to 89.1% predicted.
In these trials, 68.5% of the patients treated with roflumilast 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 roflumilast-treated patients and 9.9% for placebo-treated patients.
The most common adverse reactions that led to discontinuation of roflumilast 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 roflumilast-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 roflumilast group in 8 controlled COPD clinical trials.
Table 1: Adverse Reactions Reported by ≥2% of Patients Treated with Roflumilast 500 mcg daily and Greater Than Placebo Treatment Adverse Reactions (Preferred Term) Roflumilast Placebo (N=4438) (N=4192) n (%) n (%) Diarrhea 420 (9.5) 113 (2.7) Weight decreased 331 (7.5) 89 (2.1) Nausea 209 (4.7) 60 (1.4) Headache 195 (4.4) 87 (2.1) Back pain 142 (3.2) 92 (2.2) Influenza 124 (2.8) 112 (2.7) Insomnia 105 (2.4) 41 (1.0) Dizziness 92 (2.1) 45 (1.1) Decreased appetite 91 (2.1) 15 (0.4) Adverse reactions that occurred in the roflumilast 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.
6.2 Postmarketing Experience The following adverse reactions have been identified from spontaneous reports of roflumilast 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 roflumilast.
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 roflumilast exposure: hypersensitivity reactions (including angioedema, urticaria, and rash), gynecomastia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc.
at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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 roflumilast 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 [see Clinical Studies (14.1) ].
In these trials, 3136 and 1232 COPD patients were exposed to roflumilast 500 mcg once daily for 6 months and 1 year, respectively.
The population had a median age of 64 years (range 40 to 91), 73% were male, 92.9% were Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV 1 ) of 8.9 to 89.1% predicted.
In these trials, 68.5% of the patients treated with roflumilast 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 roflumilast-treated patients and 9.9% for placebo-treated patients.
The most common adverse reactions that led to discontinuation of roflumilast 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 roflumilast-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 roflumilast group in 8 controlled COPD clinical trials.
Table 1: Adverse Reactions Reported by ≥2% of Patients Treated with Roflumilast 500 mcg daily and Greater Than Placebo Treatment Adverse Reactions (Preferred Term) Roflumilast Placebo (N=4438) (N=4192) n (%) n (%) Diarrhea 420 (9.5) 113 (2.7) Weight decreased 331 (7.5) 89 (2.1) Nausea 209 (4.7) 60 (1.4) Headache 195 (4.4) 87 (2.1) Back pain 142 (3.2) 92 (2.2) Influenza 124 (2.8) 112 (2.7) Insomnia 105 (2.4) 41 (1.0) Dizziness 92 (2.1) 45 (1.1) Decreased appetite 91 (2.1) 15 (0.4) Adverse reactions that occurred in the roflumilast 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.
6.2 Postmarketing Experience The following adverse reactions have been identified from spontaneous reports of roflumilast 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 roflumilast.
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 roflumilast exposure: hypersensitivity reactions (including angioedema, urticaria, and rash), gynecomastia.