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 ?
1]] The study showed that roflumilast significantly reduced the rate of severe exacerbations by 24.
Management of exacerbation-prone patients with COPD includes vaccinations, addition of a phosphodiesterase-4 inhibitor, roflumilast and daily azithromycin and NAC.
A new class of tablets (called phosphodiesterase inhibitors), such as the new Roflumilast, hold great promise.
Roflumilast is a drug for the treatment of asthma and respiratory diseases.
Roflumilast was approved by the FDA this month to decrease the frequency of exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations.
Phosphodiesterase inhibitors, such as Roflumilast, have been shown to be effective in phase iii clinical trials but are not yet registered for use in South Africa.
2) Specific phosphodiesterase E4 inhibitors such as cilomilast and roflumilast are currently undergoing clinical trials.
SAN DIEGO -- Roflumilast improved lung function and prevented exacerbations in patients with COPD with chronic bronchitis and severe airflow obstruction in a large 12-month randomized trial.
8 sgb v acetate into finished medicinal products called gefitinib, leuprorelin, roflumilast and urapidil.
2]] The new expert Report draws on a post-hoc analysis presented at ERS 2012, which suggests that roflumilast significantly reduces exacerbations when added to tiotropium in symptomatic COPD patients with moderate to severe lung function impairment and a baseline mMRC grade ≥2 (GOLD category B and D) by 45 percent.
New data analysis presented at ERS 2011 supports the ability of roflumilast to shift COPD patients from the frequent to the more stable infrequent exacerbator state[sup.
and Nycomed A/S have received US FDA approval for Roflumilast to treat symptoms associated with severe chronic obstructive pulmonary disease (COPD).