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Company Clears Up Exparel-Related FDA Warning Letter

Agency had criticized promotional claims

Pacira Pharmaceuticals has announced the resolution of matters pertaining to certain promotional aspects of Exparel (bupivacaine liposome injectable suspension) detailed in a recent Warning Letter from the FDA’s Office of Prescription Drug Promotion (OPDP). Pacira announced receipt of the Warning Letter on September 25, 2014 and has since been in discussions with the OPDP.

In its 2014 letter, the OPDP stated that it had reviewed educational technique flashcards and a journal ad for Exparel submitted by Pacira. The journal ad was also submitted as a complaint to the OPDP Bad Ad Program. According to the OPDP, the administration guides provided evidence that Exparel was intended for new uses for which it lacked FDA approval, and for which the labeling did not provide adequate directions for use, which rendered Exparel “misbranded” within the meaning of the Federal Food, Drug, and Cosmetic Act. In addition, the journal ad was false or misleading because it overstated the efficacy of Exparel. Thus, the journal ad also misbranded the drug.

In its agreement with the OPDP, Pacira now states the following:

  • Exparel is broadly indicated for administration into the surgical site to produce postsurgical analgesia. Approval of the drug was based on pivotal trials conducted in excisional hemorrhoidectomy and bunionectomy surgical models, and thus, the basis for assessment of safety and efficacy was limited to those two procedures.
  • Regarding the duration of efficacy, in both pivotal trials Exparel demonstrated a significant reduction in pain-intensity scores compared with placebo for up to 24 hours. In the hemorrhoidectomy trial, which had a primary endpoint of cumulative pain scores during the first 72 hours, there was minimal to no difference in pain- intensity scores between Exparel and placebo from 24 to 72 hours; however, there was a cumulative decrease in opioid consumption through 72 hours. The clinical benefit of that reduction was not demonstrated.

As per the FDA approval documents, the mean pain-intensity score for the patients receiving placebo decreased to levels similar to that of the patients given Exparel in both clinical trials. All of the patients had access to rescue opioid medication to control pain, as needed, after surgery; in the hemorrhoidectomy trial, 88% of the patients in the placebo group had received rescue opioids by 24 hours.

Exparel is indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia. The product combines bupivacaine with DepoFoam, a product-delivery technology that delivers medication over a desired period. According to Pacira, Exparel is the only multivesicular liposome local anesthetic that can be used in the peri- or postsurgical setting in the same fashion as current local anesthetics. By using the DepoFoam platform, a single dose of Exparel delivers bupivacaine over time, providing reductions in cumulative pain scores with a 45% decrease in opioid consumption; the clinical benefit of the opioid reduction was not demonstrated.

Exparel is contraindicated in obstetrical paracervical-block anesthesia. The drug has not been studied for use in patients younger than 18 years of age.

Sources: Pacira Pharmaceuticals; February 11, 2015; Pacira Pharmaceuticals; September 25, 2014; and FDA Warning Letter; September 22, 2014.

 

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