Fatal and Serious Anaphylaxis Following Peginesatide Administration

In March 2012, the Food and Drug Administration (FDA) approved peginesatide as anemia therapy for chronic kidney disease patients. In December, the manufacturer warned that a large dialysis organization identified eight patients with peginesatide-associated anaphylaxis. In February 2013, the organization again reported five anaphylaxis events, including three deaths, and discontinued administering peginesatide. After a manufacturer’s review identified five peginesatide-associated anaphylaxis deaths, the manufacturer discontinued marketing the drug.

We reviewed peginesatide-associated anaphylaxis in FDA’s Adverse Event Reporting System (FAERS). Clinical findings and product lot numbers were analyzed. Inclusion criteria included peginesatide administration and toxicity within thirty minutes of administration.

Between July 2012 and February 2013, 38 CKD patients developed anaphylaxis within a median of five minutes following peginesatide administration (range, zero to 20 minutes). Findings included dyspnea (25 patients), chest pain (10), hypotension (18), diaphoresis (9), pruritis (11), rash (3), angioedema (5), and vomiting (9). Five deaths from cardio-respiratory arrests occurred. Exposure-adjusted incidence was 1.5 cases of anaphylaxis per 1,000 peginesatide-treated patients. Of five FAERS reports for anaphylaxis occurring in February 2013, three included the product lot number C18881 while two did not have lot numbers.  Of 33 FAERS anaphylaxis events reported prior to December 4, 2012; 18 included the lot number C18685, two reports included the lot number C18696, one included the lot number C18881, and lot numbers were not identified for the remaining 12 reports.

Anaphylaxis can occur within minutes of initiating peginesatide therapy. Production or supply chain management problems may be the underlying etiology.

Macdougall: Affymax and Takeda: Consultancy, Research Funding. Mikhail: Affymax and Takeda: Consultancy, Research Funding. Goldsmith: Affymax and Takeda: Consultancy, Research Funding.