Roflumilast 250mcg Tablets
It is used to treat COPD (chronic obstructive pulmonary disease).Do not use this drug to treat intense flare-ups of shortness of breath. Use a rescue inhaler. If you have questions, talk with the doctor.
Drug Class
Selective Phosphodiesterase-4 (PDE4) Inhibitor
Pharmacologic Class
PDE4 Inhibitor
Pregnancy Category
Category C
FDA Approved
Mar 2011
DEA Schedule
Not Controlled
Overview
What is this medicine?
Roflumilast is a medication used to help reduce flare-ups (exacerbations) in people with severe chronic obstructive pulmonary disease (COPD) that is associated with chronic bronchitis and a history of exacerbations. It works by reducing inflammation in the lungs.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food, and continue taking it even if you feel well. It's essential to adhere to your doctor's or healthcare provider's advice to ensure the best results.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep all medications in a safe location, out of reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult your pharmacist for guidance on the proper disposal method. You may also want to explore drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food, and continue taking it even if you feel well. It's essential to adhere to your doctor's or healthcare provider's advice to ensure the best results.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep all medications in a safe location, out of reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult your pharmacist for guidance on the proper disposal method. You may also want to explore drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Continue to avoid smoking, as it can worsen COPD.
- Follow your doctor's instructions for all other COPD medications, including bronchodilators and inhaled corticosteroids.
- Maintain a healthy diet and regular exercise as tolerated to support overall lung health.
- Report any significant or unexplained weight loss to your doctor.
- Be aware of and report any changes in mood, behavior, or thoughts, especially feelings of depression or thoughts of self-harm.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
250 mcg orally once daily for 4 weeks, then increase to 500 mcg orally once daily.
Dose Range:
250 - 500 mg
Condition-Specific Dosing:
COPD Maintenance Therapy:
Initial dose of 250 mcg once daily for 4 weeks to reduce gastrointestinal side effects, then increase to 500 mcg once daily. The 250 mcg tablet is primarily for initiation.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No adjustment needed
Moderate:
No adjustment needed
Severe:
No adjustment needed
Dialysis:
No adjustment needed; not significantly removed by dialysis.
Hepatic Impairment:
Mild:
No adjustment needed (Child-Pugh A)
Moderate:
Contraindicated (Child-Pugh B)
Severe:
Contraindicated (Child-Pugh C)
Pharmacology
Mechanism of Action
Roflumilast and its active metabolite, roflumilast N-oxide, are selective inhibitors of phosphodiesterase 4 (PDE4). PDE4 is the predominant PDE in inflammatory and immune cells. Inhibition of PDE4 leads to an increase in intracellular cyclic AMP (cAMP), which in turn reduces inflammation by suppressing the activity of various inflammatory cells and mediators involved in the pathogenesis of COPD.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80% (oral)
Tmax:
Roflumilast: Approximately 1 hour; Roflumilast N-oxide: Approximately 8 hours
FoodEffect:
Food delays Tmax but does not significantly affect AUC or Cmax of roflumilast or its active metabolite.
Distribution:
Vd:
Approximately 2.9 L/kg
ProteinBinding:
Roflumilast: Approximately 99%; Roflumilast N-oxide: Approximately 97%
CnssPenetration:
Limited
Elimination:
HalfLife:
Roflumilast: Approximately 17 hours; Roflumilast N-oxide: Approximately 30 hours
Clearance:
Not available (primarily metabolic clearance)
ExcretionRoute:
Approximately 70% renal, 20% fecal
Unchanged:
Less than 1% (renal)
Pharmacodynamics
OnsetOfAction:
Not acutely acting for bronchodilation; clinical benefits (reduction in exacerbations) are observed over time with chronic use.
PeakEffect:
Steady-state plasma concentrations are achieved within approximately 4 days for roflumilast and 6 days for roflumilast N-oxide.
DurationOfAction:
Sustained effect with once-daily dosing due to long half-life of active metabolite.
Safety & Warnings
Side Effects
Important Side Effects to Report to Your Doctor Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Additionally, patients taking this medication may be at a higher risk of experiencing suicidal thoughts or behaviors, especially if they have a history of such thoughts or actions. If you or your loved ones notice any new or worsening symptoms, such as:
Depression
Nervousness
Restlessness
Irritability
Panic attacks
Changes in mood or behavior
Suicidal thoughts or actions
call your doctor immediately.
Other Possible Side Effects
Like all medications, this drug can cause side effects, although not everyone will experience them. If you encounter any of the following side effects, or if they bother you or persist, contact your doctor:
Dizziness or headache
Upset stomach
Diarrhea
Weight loss
Back pain
Flu-like symptoms
Trouble sleeping
Decreased appetite
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Additionally, patients taking this medication may be at a higher risk of experiencing suicidal thoughts or behaviors, especially if they have a history of such thoughts or actions. If you or your loved ones notice any new or worsening symptoms, such as:
Depression
Nervousness
Restlessness
Irritability
Panic attacks
Changes in mood or behavior
Suicidal thoughts or actions
call your doctor immediately.
Other Possible Side Effects
Like all medications, this drug can cause side effects, although not everyone will experience them. If you encounter any of the following side effects, or if they bother you or persist, contact your doctor:
Dizziness or headache
Upset stomach
Diarrhea
Weight loss
Back pain
Flu-like symptoms
Trouble sleeping
Decreased appetite
This is not an exhaustive list of potential side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Significant or unexplained weight loss
- New or worsening feelings of depression or sadness
- Thoughts of harming yourself or others
- Severe anxiety or agitation
- Difficulty sleeping (insomnia)
- Unusual changes in behavior or mood
- Severe or persistent diarrhea, nausea, or stomach pain
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have liver disease, as this may affect how your body processes the medication.
If you are currently taking any of the following medications: carbamazepine, phenobarbital, phenytoin, or rifampin, as these may interact with this drug.
If you are breastfeeding, as you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor to ensure your safety.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have liver disease, as this may affect how your body processes the medication.
If you are currently taking any of the following medications: carbamazepine, phenobarbital, phenytoin, or rifampin, as these may interact with this drug.
If you are breastfeeding, as you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor to ensure your safety.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
This medication may cause weight loss, so regular weight checks will be necessary while you are taking it. Be sure to discuss any concerns or questions you have about weight loss with your doctor.
If you are pregnant or planning to become pregnant, it is crucial to consult with your doctor. You and your doctor will need to carefully weigh the benefits and risks of using this medication during pregnancy to make an informed decision.
This medication may cause weight loss, so regular weight checks will be necessary while you are taking it. Be sure to discuss any concerns or questions you have about weight loss with your doctor.
If you are pregnant or planning to become pregnant, it is crucial to consult with your doctor. You and your doctor will need to carefully weigh the benefits and risks of using this medication during pregnancy to make an informed decision.
Overdose Information
Overdose Symptoms:
- Severe headache
- Nausea
- Diarrhea
- Dizziness
- Palpitations
- Lightheadedness
- Low blood pressure
What to Do:
In case of suspected overdose, seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment is supportive and symptomatic.
Drug Interactions
Major Interactions
- Strong CYP3A4/CYP1A2 inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin): May significantly decrease roflumilast exposure, reducing efficacy.
- Strong CYP3A4/CYP1A2 inhibitors (e.g., fluvoxamine, cimetidine, erythromycin, ketoconazole): May significantly increase roflumilast exposure, increasing risk of adverse effects.
Moderate Interactions
- Oral contraceptives containing ethinyl estradiol and gestodene: May increase roflumilast exposure (clinical significance uncertain).
- Theophylline: Co-administration may increase adverse effects due to additive PDE inhibition, though no significant pharmacokinetic interaction.
Monitoring
Baseline Monitoring
Liver Function Tests (LFTs)
Rationale: Roflumilast is contraindicated in moderate to severe hepatic impairment. Baseline assessment helps identify patients at risk.
Timing: Prior to initiation, especially if hepatic impairment is suspected.
Psychiatric history assessment
Rationale: Roflumilast is associated with psychiatric adverse reactions, including suicidal ideation. Baseline assessment helps identify patients at higher risk.
Timing: Prior to initiation.
Routine Monitoring
Weight
Frequency: Periodically, especially during the first few months of treatment.
Target: Maintain stable weight
Action Threshold: Significant, unexplained weight loss (e.g., >5-10% of body weight) should prompt investigation and consideration of discontinuation.
Psychiatric symptoms (e.g., insomnia, anxiety, depression, mood changes, suicidal ideation)
Frequency: Regularly, especially during the initial weeks/months of treatment and with dose changes.
Target: Absence of new or worsening psychiatric symptoms
Action Threshold: Development or worsening of psychiatric symptoms, particularly depression or suicidal ideation, requires immediate evaluation and consideration of discontinuation.
Gastrointestinal symptoms (e.g., diarrhea, nausea, abdominal pain)
Frequency: Regularly, especially during the initial weeks of treatment.
Target: Tolerable symptoms
Action Threshold: Severe or persistent GI symptoms may necessitate dose reduction or discontinuation.
Symptom Monitoring
- Unexplained weight loss
- New or worsening insomnia
- Anxiety
- Depressed mood
- Suicidal thoughts or behavior
- Changes in behavior
- Diarrhea
- Nausea
- Abdominal pain
- Headache
Special Patient Groups
Pregnancy
Roflumilast is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Animal studies showed developmental toxicity (e.g., reduced fetal weight, skeletal variations) at exposures higher than clinical doses.
Second Trimester:
Similar risks as first trimester, based on animal data.
Third Trimester:
Similar risks as first trimester, based on animal data.
Lactation
It is not known whether roflumilast or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Not available; potential for serious adverse reactions.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Roflumilast is not indicated for use in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly (âĨ65 years) and younger adult patients. No specific dose adjustment is required based on age.
Clinical Information
Clinical Pearls
- Roflumilast is a maintenance therapy for severe COPD with chronic bronchitis and history of exacerbations; it is not a bronchodilator and should not be used for acute bronchospasm.
- Initiate with the 250 mcg dose for 4 weeks to mitigate gastrointestinal side effects before increasing to the 500 mcg maintenance dose.
- Counsel patients on potential psychiatric side effects (insomnia, anxiety, depression, suicidal ideation) and weight loss, and instruct them to report these immediately.
- Contraindicated in moderate to severe hepatic impairment (Child-Pugh B or C).
- Monitor for drug interactions, especially with strong CYP3A4/1A2 inhibitors or inducers, which can significantly alter roflumilast exposure.
Alternative Therapies
- Inhaled corticosteroids (ICS)
- Long-acting beta-agonists (LABA)
- Long-acting muscarinic antagonists (LAMA)
- Combination ICS/LABA
- Combination LABA/LAMA
- Triple therapy (ICS/LABA/LAMA)
- Azithromycin (for some patients with frequent exacerbations)
Cost & Coverage
Average Cost:
Varies widely, typically high per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 3 or 4 (Specialty/Non-preferred Brand)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure your safety and the effectiveness of your treatment, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. It is crucial to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, seek immediate medical attention or contact your local poison control center. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred. This information will help healthcare professionals provide you with the most appropriate care and treatment.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. It is crucial to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, seek immediate medical attention or contact your local poison control center. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred. This information will help healthcare professionals provide you with the most appropriate care and treatment.