Esteve Pharmaceuticals, S.A.: celecoxib

Please refer to your new drug application (NDA) dated and received May 15, 2019, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for celecoxib and tramadol hydrochloride tablets.

We acknowledge receipt of your major amendment dated March 2, 2020, which extended the goal date by three months.

Satisfactory inspection is required before this application may be approved.

We refer to the draft labeling and medication guide received via email on June 12, 2020, and March 12, 2020, respectively, which incorporated our requested revisions, also enclosed with the letter.

We reserve additional comments on the proposed labeling and medication guide until the application is otherwise adequate.

Resubmit the revised draft labeling and medication guide with your complete response submission.

Section 505-1 of the Federal Food, Drug, and Cosmetic Act (FDCA) authorizes FDA to require the submission of a risk evaluation and mitigation strategy (REMS) if FDA determines that such a strategy is necessary to ensure that the benefits of the drug outweigh the risks [section 505-1 (a)].

May 15, 2019, which contains a Medication Guide, elements to assure safe use, an implementation system and a timetable for submission of assessments of the REMS.

In accordance with section 505-1 of the FDCA, we agree that a REMS will be necessary for celecoxib and tramadol hydrochloride tablets, if it is approved, to ensure that the benefits of the drug outweigh the risks of addiction, unintentional overdose, and death resulting from inappropriate prescribing, abuse, and misuse.

REMS and other REMS-related materials in Microsoft Word format.

We have the following comments that are not approvability issues, however, they should be addressed in your complete response to this action:

Winnall WR, Muir JA, Liew S, et al. Effects of chronic celecoxib on testicular function in normal and lipopolysaccharide-treated rats.

Selmanoglu G, Kockaya EA, Akay MT, et al. Subacute toxicity of celecoxib on thyroid and testis of rats: Hormonal and histopathological changes.