Roflumilast (Daliresp) is a selective inhibitor of phosphodiesterase 4 inhibitor in the lungs. It acts as an anti-inflammatory drug by inhibiting the neutrophilic infiltration of cells into the lungs.

Roflumilast (Daliresp) Indications:

• COPD:

  • In patients with chronic bronchitis and severe COPD, it is advised to lower the risk of recurring exacerbations.
  • It is not advised to treat acute bronchospasm or acute COPD exacerbations.

Roflumilast (Daliresp) Dose in Adults

Roflumilast (Daliresp) Dose in the treatment of COPD:

• For four weeks, take 250 mcg once day; after that, take 500 mcg once daily.

Note: 

To evaluate and enhance tolerance, an initial dose of 250 mg is administered once day. It is not deemed therapeutic to use this lower dose.

Roflumilast (Daliresp) use in Children:

The drug's effectiveness and safety in children have not been shown.

Roflumilast Pregnancy Risk Category: C

• Studies on animal reproduction have shown that fetal outcomes can be adverse.

Use during breastfeeding:

• Although the amount of drug excreted into breastmilk cannot be determined, it is possible.
• It is best to avoid it while breastfeeding, according to the manufacturer.

Dose in Renal Disease:

Adjustment in the dose is not necessary.

Roflumilast Dose in liver disease:

• Mild impairment (Child-Pugh class A):

  • It should be taken with caution in these patients even if it hasn't been researched in these patients.
  • No dose modifications have been offered by the manufacturer.

• Moderate to severe impairment (Child-Pugh class B or C):

  • Avoid using the drug in severe liver disease.

Side Effects of Roflumilast (Daliresp):

• Central Nervous System:

  • Headache
  • Dizziness
  • Insomnia

• Endocrine & Metabolic:

  • Weight Loss

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Decreased Appetite

• Infection:

  • Influenza

• Neuromuscular & Skeletal:

  • Back Pain

Contraindications to Roflumilast (Daliresp):

• Patients suffering from moderate to severe liver disease
• You may have severe allergic reactions to any ingredient of the drug.

Warnings and precautions

• Neuropsychiatric:

  • Regular assessments should be done on patients for signs of anxiety, depression, or sleep disorders.
  • Neuropsychiatric symptoms such as suicidal behavior or suicidal thoughts can be associated with long-term drug use.
  • Patients who have had psychiatric symptoms in the past should be cautious about taking this drug.
  • Patients and caregivers should be instructed not to ignore any psychiatric symptoms.

• Weight loss:

  • Long-term use may lead to weight loss.
  • At regular intervals, the patient's weight should be checked.
  • The drug should be stopped if significant weight loss occurs.

Monitor:

• Liver function tests;
• Monitor weight
• In particular, keep an eye out for neuropsychiatric symptoms including new or worsening sleeplessness, anxiety or sadness, suicidal thoughts, or other mood changes.

How to administer Roflumilast (Daliresp)?

It is administered orally without regard to meals.

Mechanism of action of Roflumilast (Daliresp):

• Roflumilast reduces the infiltration of neutrophilic (other Leukocytes), inflammatory cytokines, and other leukocytes in the lungs.
• Roflumilast is also believed to reduce pulmonary remodeling and mucociliary dysfunction.
• It is believed that the anti-inflammatory properties of the drug and N-oxide's active metabolite N are mediated through selective inhibition of phosphodiesterase-4, which results in the accumulation cyclic AMP within the structural and inflammatory tissues.

Protein binding is 99%; N-oxide metabolite: 97%

Metabolism: It is converted by the liver to an active N-oxide metabolite via CYP3A4 and CYP1A2. As well, it goes through conjugation.

Bioavailability of the drug is about 80%

Half-life elimination of the drug is 17 hours and that of the active metabolite N-oxide metabolite is about 30 hours

The time to peak serum concentration is about 1 hour (delayed by food) and that of the N-oxide metabolite is about 8 hours

Excretion: It is excreted mainly in Urine (~70% as metabolites)

International Brands of Roflumilast:

• Daliresp
• Daxas
• Adair
• Borgilast
• Daxxas
• Libertek
• Lumast
• Roflast
• Roxair

Roflumilast brand names in Pakistan:

• Raxus (Searle)
• Romilast (Scilife)