roflumilast


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Related to roflumilast: indacaterol, PDE4 inhibitor

roflumilast

(row-floo-mi-last) ,

Daliresp

(trade name),

Daxas

(trade name)

Classification

Therapeutic: copd agents
Pharmacologic: phosphodiesterase inhibitors
Pregnancy Category: C

Indications

To ↓ the risk of exacerbations in severe COPD patients that have a history of chronic bronchitis with exacerbations.

Action

Roflumilast and one active metabolite (roflumilast N-oxide) act as selective inhibitors of phosphodiesterase 4 (PDE4), responsible for breaking down 3', 5'-adenosine monophosphate (cAMP). Resulting intracellular accumulation of cAMP in lung tissue.
Reduces cells (neutrophils, eosinophils and total cells) in sputum.

Therapeutic effects

↓ exacerbations in COPD patients.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Parent drug and metabolites probably enter breast milk.
Protein Binding: Roflumilast—99%; roflumilast N-oxide—97%.
Metabolism and Excretion: Mostly metabolized (87.5%), primarily by CYP3A4 and CYP1A2 enzyme systems One metabolite, roflumilast N-oxide in pharmacologically active. Inactive metabolites excreted in urine.
Half-life: Roflumilast—17 hr; roflumilast N-oxide—30 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
PO unknown1 (4–13†)24 hr
†For roflumilast N-oxide.

Contraindications/Precautions

Contraindicated in: Acute bronchospasm;Moderate to severe hepatic impairment;Concurrent use of strong inducers of CYP3A4 and CYP1A2 enzymes; Lactation: Avoid breast-feeding.
Use Cautiously in: History of depression/suicidal thoughts; Obstetric: Use only if potential maternal benefit justifies potential risk to the fetus; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • suicidal thoughts (life-threatening)
  • anxiety
  • depression
  • dizziness
  • headache
  • insomnia

Dermatologic

  • rash

Gastrointestinal

  • diarrhea (most frequent)
  • abdominal pain
  • ↓ appetite
  • dyspepsia
  • gastritis
  • nausea
  • vomiting

Metabolic

  • weight loss

Musculoskeletal

  • muscle spasms

Neurologic

  • tremor

Miscellaneous

  • hypersensitivity reactions including angioedema (life-threatening)

Interactions

Drug-Drug interaction

Strong inducers of the CYP3A4 and CYP1A2 enzyme systems, including rifampicin, phenobarbital, carbamazepine, and phenytoin ↓ blood levels and effectiveness; concurrent use should be avoided.Blood levels and risk of adverse reactions ↑ by concurrent use of inhibitors of the CYP3A4 enzyme system and dual inhibitors of the CP3A4 and CYP1A2 enzyme systems including erythomycin, ketoconazole, fluvoxamine, and cimetidine.Gestodene and ethinyl estradiol may also ↑ levels and risk of adverse reactions; risk should be considered.

Route/Dosage

Oral (Adults) 500 mcg once daily.

Availability

Tablets: 500 mcg

Nursing implications

Nursing assessment

  • Assess respiratory status periodically during therapy.
  • Monitor weight regularly. If unexplained or clinically significant weight loss occurs, evaluate weight loss and consider discontinuation of roflumilast.
  • Assess mental status (orientation, mood, behavior) before and periodically during therapy. Assess for suicidal tendencies.
  • Monitor for signs and symptoms of hypersensitivity reactions (angioedema, urticaria, rash). Discontinue therapy and treat symptomatically if symptoms occur.

Potential Nursing Diagnoses

Ineffective airway clearance

Implementation

  • Oral: Administer without regard to food.

Patient/Family Teaching

  • Instruct patient to take roflumilast as directed. Advise patient to read Medication Guide before starting therapy and with each Rx refill; new information may be available.
  • Inform patient that roflumilast is not a bronchodilator and should not be used for treating sudden breathing problems.
  • Advise patient to monitor weight regularly. If weight loss occurs, notify health care professional; may require discontinuation of therapy.
  • Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide, trouble sleeping, new or worse depression, new or worse anxiety, acting on dangerous impulses, or other unusual changes in behavior or mood or signs and symptoms of hypersensitivity reactions occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products without consulting health care professional.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • ↓ in the number of flare-ups or the worsening of COPD symptoms (exacerbations).

roflumilast

A selective inhibitor the phosphodiesterase type 4 (PDE4), which is used as maintenance therapy of severe chronic obstructive pulmonary disease with a forced expiratory volume at one second < 50% of predicted in a background of chronic bronchitis.
References in periodicals archive ?
The positive control group was treated with roflumilast (5 mg/kg body wt) via oral gavage 1 h before CS exposure.
AstraZeneca, which has marketed roflumilast in the United States under the name Daliresp since the first quarter of 2015, said that it would pay $575 million to Takeda.
Roflumilast inhibits the release of chemokines and TNF-a from human lung macrophages stimulated with lipopolysaccharide.
Como opcion al manejo con roflumilast, la evidencia mostro que la adicion de macrolidos a la terapia con BALA+EI+ACLA en los pacientes con antecedente de exacerbaciones mostraba tambien impacto benefico en la frecuencia de estas (RR 0.
Management of exacerbation-prone patients with COPD includes vaccinations, addition of a phosphodiesterase-4 inhibitor, roflumilast and daily azithromycin and NAC.
One of the most promising new treatments for COPD is Roflumilast, a first-in-class phosphodiesterase (PDE4) inhibitor that is the only licensed oral therapy that targets COPD-specific inflammation," said Dr Osama Al-Nawasany, medical affairs director, Takeda Pharmaceuticals.
Takeda said the acquisition includes the roflumilast franchise, a market-leading treatment for chronic lung disease, which is expected to be a major source of revenue growth for the Japanese firm.
The pill, Roflumilast, tested by patients at University Hospital Aintree, treats one of the world's biggest killers - chronic obstructive pulmonary disease (COPD), a term for chronic bronchitis and emphysema.
Announcing the Cork project as part of its 2003 investment programme, Altana said the Roflumilast tablet-producing factory in Cork was to be its biggest investment for the year.
The recommendation for roflumilast in patients with GOLD Class 2 to 4 symptoms remains unchanged since the introduction of this agent as a treatment option for COPD.
Make pointed out that a history of chronic bronchitis and at least one COPD exacerbation requiring systemic corticosteroids and/or hospitalization were among the inclusion criteria for two pivotal trials that led to the 2011 approval by the FDA of the phosphodiesterase-4 inhibitor roflumilast (Daliresp).
The acquisition includes the roflumilast franchise (Daliresp in the United States and the Daxas trade name in Europe), a first-in-class treatment for chronic obstructive pulmonary disease that is expected to be a major source of revenue growth for Takeda.