The U.S. Food and Drug Administration is strengthening an existing warning that serious, potentially fatal allergic reactions can occur with AMAG's anemia drug Feraheme (ferumoxytol). The drug was approved to treat iron deficiency anemia in chronic kidney disease patients in 2009.

The FDA has changed the prescribing instructions and approved a boxed warning, FDA’s strongest type of warning, regarding these serious risks. Also added is a new Contraindication, a strong recommendation against use of Feraheme in patients who have had an allergic reaction to any intravenous (IV) iron replacement product. Health care professionals should follow the new recommendations in the drug label, the FDA said. Patients should immediately alert their health care professional or seek emergency care if they develop breathing problems, low blood pressure, lightheadedness, dizziness, swelling, a rash, or itching during or after Feraheme administration.

All IV iron products carry a risk of potentially life-threatening allergic reactions, the FDA said. At the time of Feraheme’s approval in 2009, this risk was described in the Warnings and Precautions section of the drug label. Since then, serious reactions, including deaths, have occurred despite the proper use of therapies to treat these reactions and emergency resuscitation measures.

Anaphylactic reactions
The agency said a search of the FDA Adverse Event Reporting System database identified 79 cases of anaphylactic reactions associated with Feraheme administration, reported from the time of approval to June 30, 2014. Of the 79 cases, 18 were fatal, despite immediate medical intervention and emergency resuscitation attempts. The 79 patients ranged in age from 19 to 96 years. Nearly half of all cases reported that the anaphylactic reactions occurred with the first dose of Feraheme. Approximately 75 percent (60/79) of the cases reported that the reaction began during the infusion or within five minutes after administration completion. Frequently reported symptoms included cardiac arrest, hypotension, dyspnea, nausea, vomiting, and flushing. Of the 79 cases, 43% (34/79) of the patients had a medical history of drug allergy, and 24% had a history of multiple drug allergies.

The FDA said it has evaluated this risk further and have identified ways to reduce the risk of serious allergic reactions with Feraheme.

The boxed warning describes recommends that health care professionals take the following precautions:

  • Only administer IV iron products to patients who require IV iron therapy.
  • Do not administer Feraheme to patients with a history of allergic reaction to Feraheme or other IV iron products.
  • Only administer diluted Feraheme as an IV infusion over a minimum of 15 minutes. Feraheme should not be given as an undiluted IV injection.
  • Closely monitor patients for signs and symptoms of serious allergic reactions, including monitoring blood pressure and pulse during Feraheme administration and for at least 30 minutes following each infusion.
  • Carefully consider the potential risks and benefits of Feraheme administration in elderly patients with multiple or serious medical conditions, as these patients may experience more severe reactions.
  • Carefully consider the potential risks and benefits of Feraheme administration in patients with a history of multiple drug allergies. Patients with multiple drug allergies may also be at higher risk.

In January 2014, the FDA rejected AMAG's application for wider use of Feraheme in all adult, iron deficiency anemia patients who cannot tolerate an oral iron treatment because of safety concerns.