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  • PHOSPHODIESTERASE 4 (PDE4) INHIBITORS
  • NOTE: This page is intended to be a quick reference for properties of phosphodiesterase 4 inhibitors. It is NOT a comprehensive review of these medications. Other drug interactions, side effects, precautions, and contraindications may exist for each drug.






Drug Dosage form Dosage Generic/Price Class/Mechanism of Action Indications
(FDA-approved)
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Roflumilast

(Daliresp®)
Tablet
  • 500 mcg
Severe COPD
  • Dosing: 500 mcg once daily

  • May take without regard to food

NO/$$$$
  • Phosphodiesterase 4 (PDE4) inhibitor - Roflumilast inhibition of PDE4 leads to accumulation of intracellular cyclic AMP. While the specific mechanism(s) by which roflumilast exerts its therapeutic action in COPD patients is not well defined, it is thought to be related to the effects of increased intracellular cyclic AMP in lung cells.
  • Severe COPD - severe COPD associated with chronic bronchitis and a history of exacerbations
NOTE: only side effects that occurred at an incidence of ≥ 2% and ≥ 1% more than placebo are presented

  • Diarrhea - 9.5%, P - 2.7%
  • Weight decrease - 7.5%, P - 2.1%
  • Nausea - 4.7%, P - 1.4%
  • Headache - 4.4%, P - 2.1%
  • Insomnia - 2.4%, P - 1%
  • Decreased appetite - 2.1%, P - 0.4%
  • Liver disease - moderate-to-severe liver disease (Child-Pugh B or C) - DO NOT USE; mild liver disease (Child-Pugh A) - use caution
  • Acute bronchospasm - roflumilast SHOULD NOT be used for the relief of acute bronchospasm
  • Psychiatric events - In trials, 6% of patients on roflumilast reported psychiatric events compared to 3.3% on placebo. Psychiatric events included insomnia, anxiety, and depression.
  • Weight decrease - in two trials, 20% of patients on roflumilast lost 5 - 10% of their body weight compared to 7% of patients on placebo. In addition, 7% of patients who received roflumilast compared to 2% of patients receiving placebo experienced severe (> 10% body weight) weight loss.
  • Kidney disease - no dose adjustment necessary



Study Criteria Intervention Primary outcome Results

Roflumilast
vs
Placebo
in patients with severe COPD

Lancet 2015

PubMed abstract

Main inclusion criteria:
  • Smoking history at least 20 pack-year
  • Diagnosis of COPD
  • FEV1/FVC ratio < 0.70; FEV1 ≤ 50% of predicted
  • History of ≥ 2 exacerbations in the previous year
  • Using inhaled corticosteroid + long-acting beta agonist for 12 months prior to enrollment

Baseline characteristics
  • Average age 65 years
  • 70% of patients were using a long-acting muscarinic antagonist
  • Average postbronchodilator FEV1/FVC was 40%
Group 1 (969 patients) - Roflumilast 500 mcg once daily

Group 2 (966 patients) - Placebo once daily
  • If a patient had an exacerbation that needed additional treatment during the study, the investigator could give them up to 40 mg prednisolone, administered systemically, per day for 7–14 days

  • The following treatments were not allowed: oral and parenteral glucocorticosteroids (except to treat acute exacerbations); long-acting beta agonist or inhaled corticosteroid monotherapy; short-acting muscarinic antagonists; any short-acting beta agonists (with the exception of salbutamol) or oral beta agonists
The primary endpoint was the rate of moderate-to-severe COPD exacerbations per patient per year. Moderate exacerbations were defined as those that needed treatment with oral or parenteral glucocorticosteroids (with or without antibiotics), and severe exacerbations were defined as those that needed hospital admission, led to death, or both. Patients were treated and followed-up for one year.
  • There was a borderline nonsignificant difference between the two groups for the primary outcome (Group 1 - 0.805 events/patient/year, Group 2 - 0.927 events/patient/year; RR 0.868, p=0.0529)

  • For the secondary outcome of change in FEV1 after 1 year, Group 1 was significantly better than Group 2 (Group 1 +52ml, Group 2 -4ml, p<0.0001)

  • Patients in Group 1 experienced significantly more diarrhea (10% vs 4%), weight loss (average 5.8 pound weight loss in Group 1), nausea (6% vs 2%), and headache (4% vs 2%) than Group 2



  • PRICING

    • $ = 0 - $50
    • $$ = $51 - $100
    • $$$ = $101 - $150
    • $$$$ = > $151

    • Pricing based on one month of therapy at standard dosing in an adult
    • Pricing based on survey of GoodRX.com®, HEB®, and Costco®, [accessed 3/2015]
    • Pricing may vary by region and availability



  • References:
  • 1 - Manufacturer's Package Insert