Information on New Drug Approvals and Medication Safety

Drug Safety

Pegloticase (Krystexxa), the Food and Drug Administration (FDA)–approved intravenous (IV) treatment for refractory chronic gout has a Risk Evaluation and Mitigation Strategy (REMS) to ensure benefits of drug use outweigh its risks related to anaphylaxis, infusion reactions, and contraindications in patients with glucose-6-phosphate dehydrogenase deficiency.¹ The agent should be administered in healthcare settings and by providers prepared to manage both anaphylaxis and infusion reactions. The “Dear Healthcare Provider” letter, which was part of the initial REMS approval, was issued on October 31, 2011, and summarizes the REMS information. It states that anaphylaxis was reported in 6.5% of patients treated with pegloticase in clinical trials, and that all of these patients received pretreatment medication. Additionally, infusion reactions occurred in 26% of patients who received 8 mg every two weeks and in 41% who received 8 mg every four weeks (versus 5% of placebo-treated patients). Management recommendations include monitoring the serum uric acid (sUA) levels prior to infusions and discontinuing treatment when the sUA is greater than 6 mg/dL. To prevent infusion reactions, all patients should be premedicated with antihistamines and corticosteroids and observed for an appropriate time following drug administration. A medication guide accompanies the full prescribing information for the agent and should be given to patients every time pegloticase is administered. The FDA and the manufacturer encourage healthcare professionals to report adverse events associated with this agent by either calling 1-888-578-7839, 1-800-FDA-1088, or visiting https://www.accessdata.fda.gov/scripts/medwatch.

The FDA has approved changes to the warning sections of the package inserts for IV methotrexate (MTX) sodium products related to concomitant administration of proton pump inhibitors.² Specifically, the new text includes the information related to case reports and published population pharmacokinetic studies suggesting that combined use of some proton pump inhibitors (e.g., omeprazole, esomeprazole, pantoprazole) along with MTX (mostly high dose) causing decreased MTX (and/or hydroxymethotrexate, its metabolite) elimination and the potential for serious toxicity resulting from elevated serum drug levels.

REMS Resource Center and Database: The American Society of Health-System Pharmacists (ASHP) has created a REMS Resource Center that links with the FDA REMS Center.³ The FDA information is accessible to all; however, certain information in the ASHP database is available to members only. The site can be accessed at: www.ashp.org/menu/PracticePolicy/ResourceCenters/REMS.aspx.

Pipeline

BCX4208 is a next-generation, once-daily, oral, purine nucleoside phosphorylase inhibitor being developed for the chronic treatment of gout.⁴ It is being studied as an add-on therapy working synergistically with xanthine oxidase to lower sUA production. Results of a 24-week blinded phase IIb study showed that BCX4208, in combination with allopurinol 300 mg daily, was superior to allopurinol monotherapy in patients who had failed to reach an sUA goal of less than 6 mg/dL, in 279 randomized gout patients. There were five study arms (BCX4208 at doses of 5 mg, 10 mg, 20 mg, and 40 mg, and placebo). The primary endpoint was the proportion of patients, at Day 85, who had an sUA less than 6 mg/dL. The BCX4208 response rates ranged from 33% to 49%, with approximately double the proportion of patients reaching goal versus allopurinol monotherapy (18%). Adverse events were similar between treatment groups. It was well tolerated at all of the studied doses.