FDA strengthens warnings and changes prescribing instructions to
`decrease the risk of serious allergic reactions with anemia drug
`Feraheme (ferumoxytol)
`
`Safety Announcement
`
`[3-30-2015] The U.S. Food and Drug Administration (FDA) is strengthening an existing
`warning that serious, potentially fatal allergic reactions can occur with the anemia drug
`Feraheme (ferumoxytol). We have 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. 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.
`
`Feraheme is in a class of medicines called IV iron replacement products. It is used to
`treat iron-deficiency anemia―a condition in which there is a lower than normal number
`of oxygen-carrying red blood cells because of too little iron. People with anemia may feel
`tired or weak, and if left untreated, anemia can damage the heart, brain, and other organs.
`Feraheme is specifically approved for use only in adults with iron deficiency anemia in
`patients with chronic kidney disease. It is given as an IV infusion by health care
`professionals in a hospital, outpatient clinic, or medical office. Like other IV iron
`products, Feraheme may only be given where emergency personnel and equipment are
`immediately available to treat the potentially life-threatening allergic reactions that can
`occur with treatment.
`
`All IV iron products carry a risk of potentially life-threatening allergic reactions. 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 (see Data Summary). We have evaluated this risk further and
`have identified ways to reduce the risk of serious allergic reactions with Feraheme.
`
`Based on our evaluation, the prescribing instructions and other label information were
`updated, adding a Boxed Warning that describes these serious risks and recommending
`that health care professionals:
`• Only administer IV iron products to patients who require IV iron therapy.
`
`Pharmacosmos, Exh. 1036, p. 1
`
`

`
`• 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.
`We are continuing to monitor and evaluate the risk of serious allergic reactions with all
`IV iron products, and we will update the public as new information becomes available.
`We urge health care professionals and patients to report side effects involving Feraheme
`or other IV iron products to the FDA MedWatch program, using the information in the
`“Contact FDA” box at the bottom of the page.
`
`Facts about Feraheme (ferumoxytol)
`
`• Feraheme is a prescription medicine used to treat iron-deficiency anemia in adults
`with chronic kidney disease. Iron-deficiency anemia is a condition in which there
`is a lower than normal number of red blood cells because of too little iron.
`• Feraheme is in a class of medicines called iron replacement products. It works by
`replenishing iron so that the body can make more red blood cells that carry
`oxygen throughout the body.
`• Feraheme is given as an intravenous infusion by a health care professional in a
`hospital, outpatient clinic, or medical office.
`
`Additional Information for Patients and Caregivers
`
`•
`
`•
`
`• Serious allergic reactions, some of which resulted in death, have occurred in
`patients receiving Feraheme (ferumoxytol).
`Inform your health care professional if you have any drug allergies or a prior
`history of reactions to intravenous iron products before receiving Feraheme for
`the first time and before each dose of Feraheme.
`Immediately notify your health care professional or seek emergency care if you
`develop any of the following signs and symptoms during and after Feraheme
`administration:
`• Breathing problems
`• Low blood pressure
`• Dizziness or lightheadedness, which are symptoms of low blood pressure
`• Swelling
`
`Pharmacosmos, Exh. 1036, p. 2
`
`

`
`• Rash or itching
`• Talk to your health care professional if you have any questions or concerns about
`Feraheme.
`• Report side effects from Feraheme to the FDA MedWatch program, using the
`information in the "Contact FDA" box at the bottom of this page.
`
`Additional Information for Health Care Professionals
`
`• Fatal and serious hypersensitivity reactions including anaphylaxis have occurred
`in patients receiving Feraheme (ferumoxytol). Initial symptoms may include
`hypotension, syncope, unresponsiveness, and cardiac/cardiorespiratory arrest with
`or without signs of rash.
`• All intravenous (IV) iron products carry a risk of anaphylaxis; therefore, these
`products should be administered only in patients who require IV iron therapy.
`Feraheme is only approved for use in adults with iron-deficiency anemia in the
`setting of chronic kidney disease.
`• Feraheme is contraindicated in patients with a history of hypersensitivity to
`Feraheme or any other IV iron product.
`• Only administer Feraheme and other IV iron products when personnel and
`therapies are immediately available for the treatment of anaphylaxis and other
`hypersensitivity reactions.
`• Patients with a history of multiple drug allergies may have a greater risk of
`anaphylaxis with parenteral iron products. Carefully consider the potential risks
`and benefits before administering Feraheme to these patients.
`• Feraheme should only be administered as an IV infusion in 50-200 mL of 0.9%
`sodium chloride or 5% dextrose over a minimum period of 15 minutes following
`dilution. Do not administer Feraheme by undiluted IV injection.
`• Closely monitor patients for signs and symptoms of hypersensitivity reactions,
`including monitoring blood pressure and pulse during administration and for at
`least 30 minutes following each infusion of Feraheme.
`• Elderly patients 65 years of age and older with multiple or serious comorbidities
`who experience hypersensitivity reactions or hypotension or both following
`administration of Feraheme may have more severe outcomes.
`• Advise patients to immediately report any signs and symptoms of hypersensitivity
`that may develop during and following Feraheme administration, such as
`respiratory distress, hypotension, dizziness or lightheadedness, edema, rash, or
`itching. Advise patients to seek immediate medical attention if these signs and
`symptoms occur.
`• Allow at least 30 minutes between administration of Feraheme and administration
`of other medications that could potentially cause serious hypersensitivity
`reactions or hypotension or both, such as chemotherapeutic agents or monoclonal
`antibodies.
`• Report adverse events involving Feraheme to the FDA MedWatch program, using
`the information in the "Contact FDA" box at the bottom of this page.
`
`Data Summary
`
`Pharmacosmos, Exh. 1036, p. 3
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`

`
`In the initial clinical trials of Feraheme (ferumoxytol), conducted predominantly in
`patients with chronic kidney disease, serious hypersensitivity reactions were reported in
`0.2 percent (3/1,726) of patients receiving Feraheme. Other adverse reactions potentially
`associated with hypersensitivity (e.g., pruritus, rash, urticaria or wheezing) were reported
`in 3.7 percent (63/1,726) of these patients. In other trials that did not include patients
`with chronic kidney disease, moderate to severe hypersensitivity reactions, including
`anaphylaxis, were reported in 2.6 percent (26/1,014) of patients treated with Feraheme.
`
`Since the approval of Feraheme on June 30, 2009, cases of serious hypersensitivity
`reactions, including death, have occurred. 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
`5 minutes after administration completion. Frequently reported symptoms included
`cardiac arrest, hypotension, dyspnea, nausea, vomiting, and flushing. Of the 79 cases, 43
`percent (34/79) of the patients had a medical history of drug allergy, and 24 percent had a
`history of multiple drug allergies.
`
`
`Pharmacosmos, Exh. 1036, p. 4