[usPropHeader] Error loading user control: The file '/CMSWebParts/WK.HLRP/LNC/LNCProductHeader.ascx' does not exist.

Article Content

AUTHOR RESPONSE AND CORRECTIONS

I appreciate the careful review of the article "Reducing Disease Burden and Improve Lung Function-Roflumilast" by Dr Laurenzi of the Forest Research Institute. The Forest Research Institute, a scientific subsidiary of Forest Laboratories, provides medical and scientific support for marketed products (http://www.frx.com/research/). In addition, full prescribing information for roflumilast is available at http://www.frx.com/products/.

 

Before addressing Dr Laurenzi's review, it is important to establish that articles appearing in the journal's Pharmacology Consult Column are for informational purposes and are not intended to substitute for prescribing information. The reader is always provided multiple resources in the references section for further information. Information from the review and references provide supplemental information to prescribing literature.

 

About the Column:

 

1. The subtitle "Approved for Moderate to Severe COPD" is inaccurate with regard to indications for prescribing, as roflumilast is prescribed for severe COPD. However, the subtitle was intended to describe classes of patients (moderate and severe) of COPD that demonstrated positive benefits receiving roflumilast in clinical trials (see references 2, 4, and 5).

 

2. The approved dose range for prescribing is 500 [mu]g once daily is correct. The dose range of 250 [mu]g to 1000 [mu]g describes the dose range reported from clinical trials since 2004. [Additional reference: Huennemeyer A, Hauns B, David M et al. Pharmacokinetics and safety of roflumilast, a once-daily, oral, selective PDE4 inhibitor, and its active metabolite Roflumilast N-oxide in healthy subjects. J Allergy Clin Immun. 2004; 113(2): Supplement. p. S222. ISSN: 0091-6749, DOI: 10.1016/j.jaci.2004.01.250].

 

3. With regard to reports of common adverse events, the described adverse neuropsychiatric events is accurate. The text is also supported by the findings described in the Summary Review of Regulatory Action-Dated February 25, 2011 for Roflumilast Approval. From page 11 of the document-"Psychiatric adverse events were more common in the roflumilast group compared to the placebo in the COPD clinical program. Common adverse events in this category were insomnia (3.0% roflumilast 500 mcg vs 1.1% placebo), anxiety (1.4% roflumilast 500 mcg vs 0.8% placebo), and depression (1.4% roflumilast 500 vs 0.8% placebo). Psychiatric adverse events were also more common in the roflumilast group compared to the placebo group in other roflumilast programs." Available at http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022522Orig1s000SumR.pdf. Accessed August 31, 2011.

 

4. With regard to dose adjustment in renal impairment, prescribing information based on study results of 12 persons indicates that dose modification is not necessary for persons with renal impairment. Roflumilast has not been studied in patients with end-stage renal disease requiring hemodialysis (see reference 7).

 

5. With regard to cancer risk, some clarification of this section of column may be helpful. As reported in reference 7 (page 109), 218 tumor events were reported in 208 patients during the drug development program. One hundred and thirty-one (60%) of the tumors occurred in the roflumilast group, and 86 (40%) occurred in the placebo group. This was consistent with findings observed in patients with COPD where 105 of 185 (57%) in the roflumilast group and 80 of 185 (43%) of the placebo-treated groups developed tumors. More lung and prostate cancers were reported for patients treated with roflumilast (33 and 14) compared with those who received placebo (17 and 7). Reference: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs. Accessed August 31, 2011.

 

Again taking from page 13 of the Summary Review of Regulatory Action-Dated February 25, 2011 for Roflumilast Approval-"Roflumilast was found to cause nasal tumors in rodents. Thus, cancer frequency in humans is a topic of special interest. The overall number of tumors reported as adverse events in the roflumilast group was comparable to that of the placebo group (105 tumors in 6563 roflumilast treated patients vs 80 from 5491 placebo treated patients), but more patients in the roflumilast group compared to the placebo group had lung cancer (29 in 5752 roflumilast treated patients vs 17 in 5505 placebo treated patients), prostate cancer (13 in 5752 roflumilast treated patients vs 5 in 5505 placebo treated patients), and colorectal cancer (9 in 5752 roflumilast treated patients vs 2 in 5505 placebo treated patients). Many of these cancers were identified early during treatment suggesting uncovering of existing cancers rather than development of new cancers. Appearance of common cancers more frequently in roflumilast treated patients is difficult to explain. A definite link between roflumilast and human cancers cannot be proven or excluded. The animal findings provide a biological plausibility, but occurrence of cancers early in treatment with short duration of exposure argues against it. The product label will describe the cancer findings and acknowledge this possible risk."

 

Available at http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022522Orig1s000SumR.pdf. Accessed August 31, 2011.

 

For your review of this article, as well as the concise recommendations to correct any misunderstandings, thank you, Dr Laurenzi.

 

Patricia Anne O'Malley, PhD, RN, CNS

 

Miami Valley Hospital

 

Dayton, Ohio

 

pomalley@mvh.org