Roflumilast
Tablet · Oral
Uses
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 are 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 are 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 )
Dosage and administration
The maintenance dose of roflumilast tablet is one 500 micrograms (mcg) tablet per day, with or without food. Starting treatment with a dose of Roflumilast tablets 250 mcg once daily for 4 weeks and increasing to Roflumilast tablets 500 mcg once daily thereafter may reduce the rate of treatment discontinuation in some patients [see Clinical Studies (14.1) ]. However, 250 mcg per day is not the effective (therapeutic) dose. The maintenance dose for patients with COPD is one 500 mcg tablet per day, with or without food. Starting treatment with a dose of roflumilast tablets 250 mcg once daily for 4 weeks and increasing to roflumilast tablets 500 mcg once daily thereafter may reduce the rate of treatment discontinuation in some patients. ( 2 )
Dosage forms and strengths
Roflumilast 250 mcg tablets supplied as yellowish, round, beveled-edge tablets, debossed with "A" over "116" on one side and plain on other side. Roflumilast 500 mcg tablets are supplied as white to off-white, round, beveled-edge tablets, debossed with "A" over "117" on one side and plain on other side. Tablets: 250 mcg, 500 mcg ( 3 )
Contraindications
The use of Roflumilast tablets are contraindicated in the following condition: Moderate to severe liver impairment (Child-Pugh B or C) [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.6) ] . Moderate to severe liver impairment (Child-Pugh B or C) ( 4 )
Warnings and precautions
Acute Bronchospasm: Do not use for the relief of acute bronchospasm. ( 5.1 ) Psychiatric Events including Suicidality: Advise patients, their caregivers, and families to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes, and if such changes occur to contact their healthcare provider. Carefully weigh the risks and benefits of treatment with roflumilast in patients with a history of depression and/or suicidal thoughts or behavior. ( 5.2 ) Weight Decrease: Monitor weight regularly. If unexplained or clinically significant weight loss occurs, evaluate weight loss and consider discontinuation of roflumilast. ( 5.3 ) Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended. ( 5.4 ) 5.1 Treatment of Acute Bronchospasm Roflumilast is not a bronchodilator and should not be used for the relief of acute bronchospasm. 5.2 Psychiatric Events including Suicidality Treatment with roflumilast tablets is associated with an increase in psychiatric adverse reactions. In 8 controlled clinical trials 5.9% (263) of patients treated with roflumilast 500 mcg daily reported psychiatric adverse reactions compared to 3.3% (137) treated with placebo. The most commonly reported psychiatric adverse reactions were insomnia, anxiety, and depression which were reported at higher rates in those treated with roflumilast tabelts 500 mcg daily (2.4%, 1.4%, and 1.2% for roflumilast versus 1.0%, 0.9%, and 0.9% for placebo, respectively) [see Adverse Reactions (6.1) ] . Instances of suicidal ideation and behavior, including completed suicide, have been observed in clinical trials. Three patients experienced suicide-related adverse reactions (one completed suicide and two suicide attempts) while receiving roflumilast compared to one patient (suicidal ideation) who received placebo. One patient completed suicide while receiving roflumilast in Trial 9 [see Clinical Studies (14.1) ] , which assessed the effect of adding roflumilast to a fixed-dose combination (FDC) of ICS/LABA on rates of exacerbations in COPD patients over 1 year of treatment. Cases of suicidal ideation and behavior, including completed suicide, have been observed in the post-marketing setting in patients with or without a history of depression. Before using roflumilast tabelts in patients with a history of depression and/or suicidal thoughts or behavior, prescribers should carefully weigh the risks and benefits of treatment with roflumilast tablets in such patients. Patients, their caregivers, and families should be advised of the need to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes, and if such changes occur to contact their healthcare provider. Prescribers should carefully evaluate the risks and benefits of continuing treatment with roflumilast tablets if such events occur. 5.3 Weight Decrease Weight loss was a common adverse reaction in roflumilast tablets clinical trials and was reported in 7.5% (331) of patients treated with roflumilast tablets 500 mcg once daily compared to 2.1% (89) treated with placebo [see Adverse Reactions (6.1) ] . In addition to being reported as adverse reactions, weight was prospectively assessed in two placebo-controlled clinical trials of one year duration. In these studies, 20% of patients receiving roflumilast experienced moderate weight loss (defined as between 5 to 10% of body weight) compared to 7% of patients who received placebo. In addition, 7% of patients who received roflumilast compared to 2% of patients receiving placebo experienced severe (>10% body weight) weight loss. During follow-up after treatment discontinuation, the majority of patients with weight loss regained some of the weight they had lost while receiving roflumilast tablets. Patients treated with roflumilast tablets should have their weight monitored regularly. If unexplained or clinically significant weight loss occurs, weight loss should be evaluated, and discontinuation of roflumilast tablets should be considered. 5.4 Drug Interactions A major step in roflumilast metabolism is the N-oxidation of roflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2. The administration of the cytochrome P450 enzyme inducer rifampicin resulted in a reduction in exposure, which may result in a decrease in the therapeutic effectiveness of roflumilast tablets. Therefore, the use of strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) with roflumilast tablets is not recommended [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] .
Side effects
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, Call or contact Amici Pharma, Inc. at 1-866-760-2646 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 tablets 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 tablets 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 (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 tablets 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 tablets group in 8 controlled COPD clinical trials. Table 1: Adverse Reactions Reported by ≥2% of Patients Treated with Roflumilast Tablets 500 mcg daily and Greater Than Placebo Treatment Adverse Reactions (Preferred Term) Roflumilast tablets 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 tablets 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 tablets 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 tablets. 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.
Drug interactions
7 DRUG INTERACTIONS A major step in roflumilast metabolism is the N-oxidation of roflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2 [see Clinical Pharmacology (12.3) ] . Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) will increase roflumilast systemic exposure and may result in increased adverse reactions. The risk of such concurrent use should be weighed carefully against benefit. ( 7.2 ) 7.1 Drugs that Induce Cytochrome P450 (CYP) Enzymes Strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness of roflumilast tablets. Therefore the use of strong cytochrome P450 inducers (e.g., rifampicin, phenobarbital, carbamazepine, and phenytoin) with roflumilast tablets is not recommended [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.3) ]. 7.2 Drugs that Inhibit Cytochrome P450 (CYP) Enzymes The co-administration of roflumilast tablets (500 mcg) with CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) may increase roflumilast systemic exposure and may result in increased adverse reactions. The risk of such concurrent use should be weighed carefully against benefit [see Clinical Pharmacology (12.3) ]. 7.3 Oral Contraceptives Containing Gestodene and Ethinyl Estradiol The co-administration of roflumilast tablets (500 mcg) with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased side effects. The risk of such concurrent use should be weighed carefully against benefit [see Clinical Pharmacology (12.3) ].
Use in specific populations
Nursing Mothers: Roflumilast should not be used by women who are nursing as excretion of roflumilast and/or its metabolites into human milk is probable and there are no human studies that have investigated effects of roflumilast on breast-fed infants. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no randomized clinical studies of roflumilast tablets in pregnant women. In animal reproductive toxicity studies, roflumilast tablets administered to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities. The highest roflumilast tablets dose in these studies was approximately 30 and 26 times, respectively, the maximum recommended human dose (MRHD). Roflumilast tablets induced post-implantation loss in rats at doses greater than or equal to approximately 10 times the MRHD. Roflumilast tablets induced stillbirth and decreased pup viability in mice at doses corresponding to approximately 16 and 49 times, respectively, the MRHD. Roflumilast tablets has been shown to adversely affect pup post-natal development when dams were treated with the drug during pregnancy and lactation periods in mice at doses corresponding to 49 times the MRHD ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Labor and delivery Roflumilast tablets should not be used during labor and delivery. There are no human studies that have investigated effects of roflumilast tablets on preterm labor or labor at term; however, animal studies showed that roflumilast tablets disrupted the labor and delivery process in mice. Data Animal data In an embryo-fetal development study, pregnant rats were dosed orally during the period of organogenesis with up to 1.8 mg/kg/day roflumilast tablets (approximately 30 times the MRHD on an AUC basis). No evidence of structural abnormalities or effects on survival rates were observed. Roflumilast tablets did not affect embryo-fetal development at approximately 3 times the MRHD (on a mg/m 2 basis at a maternal oral dose of 0.2 mg/kg/day). In a fertility and embryo-fetal development study, male rats were dosed orally with up to 1.8 mg/kg/day roflumilast tablets for 10 weeks and females for two weeks prior to pairing and throughout the organogenesis period. Roflumilast tablets induced pre- and post-implantation loss at doses greater than or equal to approximately 10 times the MRHD (on a mg/m 2 basis at maternal oral doses greater than or equal to 0.6 mg/kg/day). Roflumilast tablets did not cause fetal structural abnormalities at exposures up to approximately 29 times the MRHD (on an AUC basis at maternal oral doses up to 1.8 mg/kg/day). In an embryo-fetal development study in rabbits, pregnant does were dosed orally with 0.8 mg/kg/day roflumilast tablets during the period of organogenesis. Roflumilast tabletsdid not cause fetal structural abnormalities at exposures approximately 26 times the MRHD (on a mg/m 2 basis at maternal oral doses of 0.8 mg/kg/day). In pre- and post-natal developmental studies in mice, dams were dosed orally with up to 12 mg/kg/day roflumilast tablets during the period of organogenesis and lactation. Roflumilast tablets induced stillbirth and decreased pup viability at doses corresponding to approximately 16 and 49 times, respectively, the MRHD (on a mg/m 2 basis at maternal doses >2 mg/kg/day and 6 mg/kg/day, respectively). Roflumilast tablets induced delivery retardation in pregnant mice at doses greater or equal to approximately 16 times the MRHD (on a mg/m 2 basis at maternal doses >2 mg/kg/day). Roflumilast tablets decreased pup rearing frequencies at approximately 49 times the MRHD (on a mg/m 2 basis at a maternal dose of 6 mg/kg/day) during pregnancy and lactation. Roflumilast also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at approximately 97 times the MRHD (on a mg/m 2 basis at a maternal dose of 12 mg/kg/day). 8.2 Lactation Risk Summary There is no information regarding the presence of roflumilast in human milk, the effects on the breastfed infant, or the effects on milk production. Roflumilast and/or its metabolites are excreted into the milk of lactating rats. Excretion of roflumilast and/or its metabolites into human milk is probable. Roflumilast tablets should not be used by women who are nursing. Data Animal data Roflumilast and/or its metabolite concentrations measured 8 hours after an oral dose of 1 mg/kg given to lactating rats were 0.32 and 0.02 mcg/g in the milk and pup liver, respectively. 8.4 Pediatric Use COPD does not normally occur in children. The safety and effectiveness of roflumilast tablets in pediatric patients have not been established. 8.5 Geriatric Use Of the 4438 COPD subjects exposed to roflumilast tablets for up to 12 months in 8 controlled clinical trials, 2022 were >65 years of age and 471 were >75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on available data for roflumilast, no adjustment of dosage in geriatric patients is warranted [see Clinical Pharmacology (12.3) ]. 8.6 Hepatic Impairment Roflumilast 250 mcg once daily for 14 days was studied in subjects with mild-to-moderate hepatic impairment classified as Child-Pugh A and B (8 subjects in each group). The AUCs of roflumilast and roflumilast N-oxide were increased by 51% and 24%, respectively, in Child-Pugh A subjects and by 92% and 41%, respectively, in Child-Pugh B subjects, as compared to age-, weight-, and gender-matched healthy subjects.
Pregnancy
8.1 Pregnancy Risk Summary There are no randomized clinical studies of roflumilast tablets in pregnant women. In animal reproductive toxicity studies, roflumilast tablets administered to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities. The highest roflumilast tablets dose in these studies was approximately 30 and 26 times, respectively, the maximum recommended human dose (MRHD). Roflumilast tablets induced post-implantation loss in rats at doses greater than or equal to approximately 10 times the MRHD. Roflumilast tablets induced stillbirth and decreased pup viability in mice at doses corresponding to approximately 16 and 49 times, respectively, the MRHD. Roflumilast tablets has been shown to adversely affect pup post-natal development when dams were treated with the drug during pregnancy and lactation periods in mice at doses corresponding to 49 times the MRHD ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Labor and delivery Roflumilast tablets should not be used during labor and delivery. There are no human studies that have investigated effects of roflumilast tablets on preterm labor or labor at term; however, animal studies showed that roflumilast tablets disrupted the labor and delivery process in mice. Data Animal data In an embryo-fetal development study, pregnant rats were dosed orally during the period of organogenesis with up to 1.8 mg/kg/day roflumilast tablets (approximately 30 times the MRHD on an AUC basis). No evidence of structural abnormalities or effects on survival rates were observed. Roflumilast tablets did not affect embryo-fetal development at approximately 3 times the MRHD (on a mg/m 2 basis at a maternal oral dose of 0.2 mg/kg/day). In a fertility and embryo-fetal development study, male rats were dosed orally with up to 1.8 mg/kg/day roflumilast tablets for 10 weeks and females for two weeks prior to pairing and throughout the organogenesis period. Roflumilast tablets induced pre- and post-implantation loss at doses greater than or equal to approximately 10 times the MRHD (on a mg/m 2 basis at maternal oral doses greater than or equal to 0.6 mg/kg/day). Roflumilast tablets did not cause fetal structural abnormalities at exposures up to approximately 29 times the MRHD (on an AUC basis at maternal oral doses up to 1.8 mg/kg/day). In an embryo-fetal development study in rabbits, pregnant does were dosed orally with 0.8 mg/kg/day roflumilast tablets during the period of organogenesis. Roflumilast tabletsdid not cause fetal structural abnormalities at exposures approximately 26 times the MRHD (on a mg/m 2 basis at maternal oral doses of 0.8 mg/kg/day). In pre- and post-natal developmental studies in mice, dams were dosed orally with up to 12 mg/kg/day roflumilast tablets during the period of organogenesis and lactation. Roflumilast tablets induced stillbirth and decreased pup viability at doses corresponding to approximately 16 and 49 times, respectively, the MRHD (on a mg/m 2 basis at maternal doses >2 mg/kg/day and 6 mg/kg/day, respectively). Roflumilast tablets induced delivery retardation in pregnant mice at doses greater or equal to approximately 16 times the MRHD (on a mg/m 2 basis at maternal doses >2 mg/kg/day). Roflumilast tablets decreased pup rearing frequencies at approximately 49 times the MRHD (on a mg/m 2 basis at a maternal dose of 6 mg/kg/day) during pregnancy and lactation. Roflumilast also decreased survival and forelimb grip reflex and delayed pinna detachment in mouse pups at approximately 97 times the MRHD (on a mg/m 2 basis at a maternal dose of 12 mg/kg/day).
Pediatric use
8.4 Pediatric Use COPD does not normally occur in children. The safety and effectiveness of roflumilast tablets in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Of the 4438 COPD subjects exposed to roflumilast tablets for up to 12 months in 8 controlled clinical trials, 2022 were >65 years of age and 471 were >75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on available data for roflumilast, no adjustment of dosage in geriatric patients is warranted [see Clinical Pharmacology (12.3) ].
Overdosage
10.1 Human Experience No case of overdose has been reported in clinical studies with roflumilast tablets. During the Phase I studies of roflumilast tablets, the following symptoms were observed at an increased rate after a single oral dose of 2500 mcg and a single dose of 5000 mcg: headache, gastrointestinal disorders, dizziness, palpitations, lightheadedness, clamminess, and arterial hypotension. 10.2 Management of Overdose In case of overdose;, patients should seek immediate medical help. Appropriate supportive medical care should be provided. Since roflumilast is highly protein bound, hemodialysis is not likely to be an efficient method of drug removal. It is not known whether roflumilast is dialyzable by peritoneal dialysis.
Description
The active ingredient in roflumilast tablets is roflumilast, USP. Roflumilast and its active metabolite (roflumilast N-oxide) are selective phosphodiesterase 4 (PDE4) inhibitors. The chemical name of roflumilast is N-(3,5-dichloropyridin-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxy-benzamide. Its empirical formula is C 17 H 14 Cl 2 F 2 N 2 O 3 and the molecular weight is 403.22. The chemical structure is: The drug substance is a white to off-white non-hygroscopic powder with a melting point of 160°C. It is practically insoluble in water and hexane, sparingly soluble in ethanol and freely soluble in acetone. Roflumilast tablets are supplied as yellowish or white to off-white, round, beveled-edge tablets, debossed with "A" over "116" or "A" over "117" on one side and plain on other side. Each tablet contains 250 mcg or 500 mcg of roflumilast. Each tablet of roflumilast for oral administration contains the following inactive ingredients: lactose monohydrate, magnesium stearate, and pregelatinized starch. Yellow iron oxide is present in the 250 mcg tablet. structure
Mechanism of action
12.1 Mechanism of Action Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors of phosphodiesterase 4 (PDE4). Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic-3′,5′-adenosine monophosphate (cyclic AMP)-metabolizing enzyme in lung tissue) activity leads to accumulation of intracellular cyclic AMP. While the specific mechanism(s) by which roflumilast exerts its therapeutic action in COPD patients is not well defined, it is thought to be related to the effects of increased intracellular cyclic AMP in lung cells.
How supplied
16.1 How Supplied Roflumilast tablets 250 mcg are supplied as yellowish, round, beveled-edge tablets, debossed with "A" over "116" on one side and plain on oher side. Each tablet contains 250 mcg of roflumilast. Roflumilast tablets 250 mcg are available: Blister pack 20: NDC 69292-630-20 Blister pack 28: NDC 69292-630-28 Roflumilast tablets 500 mcg are supplied as white to off-white, round, beveled-edge, debossed with "A" over "117" on one side and plain on other side. Each tablet contains 500 mcg of roflumilast. Roflumilast tablets 500 mcg are available: Bottles of 30: NDC 69292-631-30 Bottles of 90: NDC 69292-631-90 16.2 Storage and Handling Store roflumilast tablets at 20º - 25ºC (68º - 77ºF); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide) . Bronchospasm Roflumilast is not a bronchodilator and should not be used for immediate relief of breathing problems (i.e., as a rescue medication). Psychiatric Events including Suicidality Treatment with roflumilast tablets is associated with an increase in psychiatric adverse reactions. Cases of suicidal ideation and behavior, including completed suicide, have been observed in the post-marketing setting in patients with or without a history of depression. The risks and benefits of treatment with roflumilast tablets in patients with a history of depression and/or suicidal thoughts or behavior should be carefully considered. Advise patients, caregivers, and families to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes, and if such changes occur to contact their healthcare provider so that the risks and benefits of continuing treatment with roflumilast tablets may be considered [see Warnings and Precautions (5.2) ]. Weight Decrease Weight loss was a common adverse reaction in roflumilast tablets clinical trials. During follow-up after treatment discontinuation, the majority of patients with weight loss regained some of the weight they had lost while receiving roflumilast tablets. Advise patients treated with roflumilast tablets to have their weight monitored regularly. If unexplained weight loss occurs, patients should inform their healthcare provider so that the weight loss can be evaluated, as discontinuation of roflumilast tablets may need to be considered [see Warnings and Precautions (5.3) ] . Drug Interactions The use of cytochrome P450 enzyme inducers resulted in a reduction in exposure which may result in decreased therapeutic effectiveness of roflumilast tablets. The use of strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) with roflumilast tablets is not recommended [see Drugs that Induce Cytochrome P450 (CYP) Enzymes (7.1) and Clinical Pharmacology (12.3) ] . Distributed by: Amici Pharma, Inc. Melville, NY 11747 Code. L7183/00 Rev # 11/2025
Label text from the FDA structured product label by Amici Pharma Inc. (revised Sep 1, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Roflumilast in 27 products
Roflumilast NDC products (27)
Frequently asked questions
What is Roflumilast used for?
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 are not indicated for the relief of acute bronchospasm. Roflumilast tablets 250 mcg is a starting dose, for the first 4 weeks of treatment only…
What are the side effects of Roflumilast?
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… See the full label for the complete list.
Who makes Roflumilast?
Roflumilast is listed by 16 labelers in the FDA NDC directory, including American Health Packaging, Amici Pharma Inc., Ascend Laboratories, LLC, Aurobindo Pharma Limited.