Roflumilast
Roflumilast Uses, Dosage, Side Effects, Food Interaction and all others data.
Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor which, due to its selective inhibition of the PDE4 isoenzyme, has potential antiinflammatory and antimodulatory effects in the pulmonary system. It is thought that the increased levels of intracellular cyclic AMP are responsible for the therapeutic actions of Roflumilast.
Roflumilast (and its active metabolite, roflumilast N-oxide) increases cyclic adenosine-3′, 5′-monophosphate (cAMP) in lung cells by inhibiting PDE4. Increased cAMP activates PKA, which inactivates transcription factors involved in inflammation. Romflumilast also decreases the amount of sputum neutrophils and eosinophils in COPD patients.
| Trade Name | Roflumilast |
| Availability | Prescription only |
| Generic | Roflumilast |
| Roflumilast Other Names | Roflumilast, Roflumilastum |
| Related Drugs | Trelegy Ellipta, ProAir Digihaler, prednisone, Symbicort, Breo Ellipta, Ventolin, Xopenex, Ventolin HFA, Spiriva, Anoro Ellipta |
| Weight | 250mcg, 500mcg |
| Type | Oral tablet |
| Formula | C17H14Cl2F2N2O3 |
| Weight | Average: 403.207 Monoisotopic: 402.034954148 |
| Protein binding | Roflumilast is 99% plasma protein bound. |
| Groups | Approved |
| Therapeutic Class | Antihistamines anti-allergies & hypo-sensitisation |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Roflumilast is used for:
- As add-on therapy to bronchodilator treatment.
- For the maintenance treatment of severe Chronic Obstructive Pulmonary Disease (COPD) associated with chronic bronchitis (i.e. patients with a history of chronic cough and sputum) in adult patients with a history of frequent exacerbations.
Roflumilast should not be used as a rescue medication.
Roflumilast is also used to associated treatment for these conditions: Chronic Obstructive Pulmonary Disease (COPD)
How Roflumilast works
Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor which, due to its selective inhibition of the PDE4 isoenzyme, has potential antiinflammatory and antimodulatory effects in the pulmonary system. It is thought that the increased levels of intracellular cyclic AMP are responsible for the therapeutic actions of Roflumilast.
Dosage
Roflumilast dosage
The recommended dosage for patients with COPD is one 500 mcg tablet daily, with or without food.
Side Effects
General disorders: Fatigue.
Metabolism and nutrition disorders: Decreased appetite, Weight decreased.
Musculoskeletal and connective tissue disorders: Back pain, muscle spasms.
Nervous system disorders: Dizziness, Headache, Tremor.
Psychiatric disorders: Anxiety, Depression, Insomnia.
Toxicity
Headache, weight loss, GI upset, insomnia, and loose stools.
Precaution
Not as emergency treatment for relief of acute brochospasm. Monitor body wt regularly. Severe immunological disease, severe acute infections, cancers (except basal cell carcinoma) or patients on immunosuppressants; CHF (NYHA grades III & IV). History of depression associated with suicidal ideation or behavior. Galactose intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption. Hepatic impairment. Pregnancy & lactation.
Interaction
A major step in Roflumilast metabolism is the N-oxidation of Roflumilast to Roflumilast N-oxide by CYP3A4 and CYP1A2. Therefore, the use of strong cytochrome P450 enzyme inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin) with Roflumilast is not recommended. The co-administration of Roflumilast 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 co-administration of Roflumilast with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased side effects.
Food Interaction
- Take with or without food. Administering roflumilast with a high-fat meal reduced and delayed the Cmax and Tmax, respectively, but did not impact the AUC of roflumilast or its active metabolite (roflumilast N‐oxide).
[Minor] Food intake does not affect the total exposure to roflumilast and its pharmacologically active N-oxide metabolite, but delays the time to maximum concentration (Tmax) of roflumilast by one hour and reduces its peak plasma concentration (Cmax) by approximately 40%.
The Tmax and Cmax of
roflumilast N-oxide are unaffected.
Roflumilast may be taken with or without food.
Roflumilast Drug Interaction
Moderate: budesonide / formoterolUnknown: fluticasone / salmeterol, fluticasone / vilanterol, rosuvastatin, duloxetine, apixaban, fluticasone nasal, furosemide, atorvastatin, guaifenesin, esomeprazole, albuterol, pantoprazole, tiotropium, tiotropium, fluticasone / umeclidinium / vilanterol, albuterol, cyanocobalamin, ascorbic acid, cholecalciferol
Roflumilast Disease Interaction
Volume of Distribution
Roflumilast has a Vd of 2.9L/kg with a dose of 500mcg. Permeability of roflumilast across the blood-brain barrier appears to be poor in rat studies.
Elimination Route
After a 500mcg dose, the bioavailability of roflumilast is about 80%. In the fasted state, maximum plasma concentrations are reached in 0.5 to 2 hours. While in the fed state, Cmax is reduced by 40%, Tmax is increased by one hour, and total absorption is unchanged.
Half Life
Plasma half-life of roflumilast is 17 hours and its metabolite is 30 hours (oral dose).
Clearance
~9.6 L/hour.
Elimination Route
Roflumilast is excreted 70% in the urine as roflumilast N-oxide.
Pregnancy & Breastfeeding use
Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Roflumilast should not be used during pregnancy & lactation.
Contraindication
Hypersensitivity to Roflumilast or to any of the excipients. Moderate to severe liver impairment.
Special Warning
Geriatrics ( 65 years of age): There were no overall differences in safety and effectiveness of Roflumilast in the elderly compared to younger patients with COPD. Therefore, no dose adjustment is necessary.
Pediatrics (<18 years of age): Safety and effectiveness of Roflumilast in children and adolescents below 18 years of age have not been established.
Hepatic Impairment: Roflumilast is not recommended for use in patients with moderate or severe liver impairment.
Renal impairment: No dosage adjustment is necessary for patients with renal impairment
Acute Overdose
No case of overdose has been reported in clinical studies with Roflumilast. However, during the Phase I studies of Roflumilast, at an increased rate after a single oral dose of 2500 mcg and a single dose of 5000 mcg,
The following symptoms were observed: headache, gastrointestinal disorders, dizziness, palpitations, lightheadedness, clamminess and arterial hypotension.
Missed Dose: Patients should be advised that if they forget to take a tablet at the usual time, they should take the tablet as soon as they remember or continue on the next day with the next tablet at the usual time. Patients should not take a double dose to make up for a forgotten dose.
Storage Condition
Store below 30° C, keep away from light, moisture. Keep out of the reach of children.
Innovators Monograph
You find simplified version here Roflumilast
Roflumilast contains Roflumilast see full prescribing information from innovator Roflumilast Monograph, Roflumilast MSDS, Roflumilast FDA label
FAQ
What is Roflumilast used for?
Roflumilast is used in people with severe chronic obstructive pulmonary disease to reduce the number of episodes or worsening of COPD symptoms.
How safe is Roflumilast?
As for the safety of Roflumilast treatment, the overall cumulative incidence of adverse drug reaction was 54.2% in the Roflumilast group and 48.2% in the placebo group.
How does Roflumilast work?
Roflumilast works by decreasing swelling in the lungs.
What are the common side effects of Roflumilast?
Common side effects of Roflumilast are include:
- diarrhea.
- nausea.
- dizziness.
- headache.
- back pain.
- muscle spasm.
- decrease in appetite.
- uncontrollable shaking of a part of your body.
Is Roflumilast safe during pregnancy?
The manufacturer makes no recommendation regarding use during pregnancy.Roflumilast disrupted the labor and delivery process in animal studies. Do not use this drug during labor and delivery.
Is Roflumilast safe during breastfeeding?
Excretion into human milk is probable.Animals given 1 mg/kg of this drug orally had breastmilk concentrations of active drug or its metabolites of 0.32 mcg/gram after 8 hours.
When should best taken of Roflumilast?
It is usually taken with or without food once a day. Take Roflumilast at around the same time every day.
How quickly does Roflumilast work?
Your breathing difficulty and other symptoms of chronic obstructive pulmonary disease may improve within several weeks of taking Daliresp.
Does Roflumilast cause depression?
Depression, anxiety, and insomnia occur about twice as often in patients taking Roflumilast as in those taking placebo.
Who should not take Roflumilast?
You should not use Roflumilast if you are allergic to it, or if you have moderate or severe liver disease. Tell your doctor if you have ever had: liver disease,depression, mental illness, or suicidal thoughts or actions.
Can I take Roflumilast for a long time?
You should take it once daily for the first 4 weeks only. After the first 4 weeks, you will increase to the 500-mcg dose. The 250-mcg dose is a starting dose only.Roflumilast is not the effective dose and should not be taken for more than the first 4 weeks.
What happens if I miss a dose of Roflumilast?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
Does Roflumilast cause weight loss?
Roflumilast can cause weight loss. You should check your weight on a regular basis. You will also need to see your doctor regularly to have your weight checked. If you notice that you are losing weight, call your doctor.
What is Roflumilast indication?
Roflumilast is 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.Roflumilast is not a bronchodilator, and it is not indicated for the treatment of acute bronchospasm.
Can Roflumilast be crushed?
Nothing in the prescribing information accompanying the drug would indicate that the tablets cannot be crushed.
What happens if I overdose of Roflumilast?
Seek emergency medical attention.
Can I stop Roflumilast suddenly?
You should keep taking Roflumilast until your doctor discontinues the treatment. Do not stop taking Roflumilast without talking to your doctor, even if you are feeling better and are no longer having symptoms of chronic obstructive pulmonary disease.
