FDA Update: Priority Review for Non-Opioid Treatment & New Warning for Fluoroquinolones

The U.S. Food and Drug Administration (FDA) has granted priority review to a non-opioid, postoperative pain treatment, HTX-011. Additionally, the agency has issued a warning about the risks of aortic aneurysm or aortic dissection for patients taking fluoroquinolones.

FDA Grants Priority Review to HTX-011
In late December 2018, the FDA has granted priority review to HTX-011, which is designed to manage inflammation and postoperative pain in a single, surgical site administration. The treatment is a long-acting, extended-release formulation of the local anesthetic bupivacaine in a fixed-dose combination with meloxicam.¹

The new drug application for HTX-011 was submitted in late October 2018. It includes data from five Phase 2 and two Phase 3 clinical trials, with data from more than 1,000 patients who underwent five different surgical procedures. The study results showed significant reductions in pain intensity and the need for opioid treatment through 72 hours after surgery compared with placebo and standard care (bupivacaine solution). The safety of this combination treatment was shown to be no different than bupivacaine alone.

Currently, the priority review has a Prescription Drug User Fee Act date of April 30, 2019. However, due to the U.S. government shutdown, this date may not be fixed.

FDA Updates Fluoroquinolones Warning
In late December 2018, the FDA updated its warning on fluoroquinolones related to tendon/muscle rupture. This new warning includes the occurrence of rare aortic aneurysm or aortic dissection with this class of agents.²

The FDA reviewed cases of aortic aneurysm and/or dissection reported through the FDA Adverse Event Reporting System and four observational studies published between 2015 and 2018. The studies showed an increased risk of aortic aneurysm or aortic dissection associated with fluoroquinolones. They estimated the background risk of aortic aneurysm to be nine aortic aneurysm events per 100,000 people per year in the general population to 300 aortic aneurysm events per 100,000 people per year in individuals at highest risk (i.e. people 85 years and older). Multiple studies showed the rate of aortic aneurysm rupture and aortic dissection to be approximately two times higher for patients taking fluoroquinolones, warranting the FDA’s warning.

The FDA recommends healthcare professionals not prescribe fluoroquinolones to patients at risk of an aortic aneurysm or who have an aortic aneurysm. High-risk patients include those with peripheral atherosclerotic vascular diseases, hypertension, Marfan syndrome, Ehlers-Danlos syndrome and elderly patients. Fluoroquinolones should be prescribed to these patients only if no other treatment options are available. Before starting a patient on a fluoroquinolone, healthcare professionals should ask the patient if they have a potential risk factor for aortic dissection or aneurysm, or any of the increased risks noted above.

Patients should be informed of the symptoms of an aortic aneurysm and dissection, including sudden, severe and constant pain in the stomach and chest or back. Symptoms usually don’t arise until after an aneurysm bursts, which is a medical emergency. If these symptoms occur, patients should seek immediate medical attention by going to an emergency department or calling 9-1-1.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Heron Therapeutics Inc. News release: FDA grants priority review designation for Heron Therapeutics’ NDA for HTX-011, a non-opioid for postoperative pain management. 2018 Dec 31.
2. U.S. Food and Drug Administration. Drug safety and availability: FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. 2018 Dec 20.