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Injectafer® (ferric carboxymaltose injection) videos
Injectafer® (ferric carboxymaltose injection) videos Click on the videos below to learn more about Injectafer.
Injectafer®
(ferric carboxymaltose injection) videos Click on the videos below to learn more about Injectafer.
Challenging Current Beliefs Around Iron Deficits
INDICATIONS
Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-dialysis dependent chronic kidney disease.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components.
WARNINGS AND PRECAUTIONS
Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases, hypophosphatemia resolved within three months.
Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.
In clinical studies, hypertension was reported in 3.8% (67/1775) of subjects. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.
In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.
ADVERSE REACTIONS
In two randomized clinical studies, a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a single maximum dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by ≥2% of Injectafer-treated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.0%).
The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event); nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria.
CLINICAL CONSIDERATIONS IN PREGNANCY
Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.
Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.
You are encouraged to report Adverse Drug Events to American Regent, Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
Injectafer® (ferric carboxymaltose injection) is an iron replacement product indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to or have had unsatisfactory response to oral iron or who have non-dialysis-dependent chronic kidney disease (NDD-CKD).
Injectafer or ferric carboxymaltose injection is a dextran-free iron formulation for intravenous use.
It has a shell made of a carbohydrate polymer called carboxymaltose, that is tightly bound around a colloidal iron (III) hydroxide core.
It has a neutral pH and physiologic osmolarity.
Its structure is similar to that of physiologic ferritin, the body's iron storage protein.
Together, the chemical characteristics of this molecular structure may enable Injectafer to deliver a large amount of iron in a controlled fashion.
After administration, enzymes in the blood partially degrade the Injectafer carbohydrate shell but no iron is released.
It is likely then taken up by macrophages of the reticuloendothelial system or RES.
Inside the macrophages, enzymes gradually break down the carbohydrate shell that is tightly bound to the iron core.
Iron is released slowly and may be stored mainly in the liver as ferritin, the storage protein.
Alternatively, it may be exported to the plasma. In the plasma, iron is bound by transferrin, the transport protein.
Transferrin delivers iron to cells in the liver and spleen or to the bone marrow, where it can be used for hemoglobin synthesis and red blood cell formation.
The chemical characteristic of the iron carbohydrate complex means that iron is released slowly.
As a result, the transferrin available for uptake does not become fully saturated with iron. This entire process results in a controlled release of iron into the bloodstream.
The number one IV iron in oncology clinics and fastest growing IV iron in the United States is Injectafer. A dextran-free iron carbohydrate complex with a controlled release of iron.
The Mechanism of Action of Injectafer
INDICATIONS
Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-dialysis dependent chronic kidney disease.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components.
WARNINGS AND PRECAUTIONS
Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases, hypophosphatemia resolved within three months.
Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.
In clinical studies, hypertension was reported in 3.8% (67/1775) of subjects. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.
In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.
ADVERSE REACTIONS
In two randomized clinical studies, a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a single maximum dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by ≥2% of Injectafer-treated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.0%).
The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event); nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria.
CLINICAL CONSIDERATIONS IN PREGNANCY
Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.
Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.
You are encouraged to report Adverse Drug Events to American Regent, Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
Injectafer® (ferric carboxymaltose injection) is an iron replacement product indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to or have had unsatisfactory response to oral iron or who have non-dialysis-dependent chronic kidney disease (NDD-CKD).
Injectafer or ferric carboxymaltose injection is a dextran-free iron formulation for intravenous use.
It has a shell made of a carbohydrate polymer called carboxymaltose, that is tightly bound around a colloidal iron (III) hydroxide core.
It has a neutral pH and physiologic osmolarity.
Its structure is similar to that of physiologic ferritin, the body's iron storage protein.
Together, the chemical characteristics of this molecular structure may enable Injectafer to deliver a large amount of iron in a controlled fashion.
After administration, enzymes in the blood partially degrade the Injectafer carbohydrate shell but no iron is released.
It is likely then taken up by macrophages of the reticuloendothelial system or RES.
Inside the macrophages, enzymes gradually break down the carbohydrate shell that is tightly bound to the iron core.
Iron is released slowly and may be stored mainly in the liver as ferritin, the storage protein.
Alternatively, it may be exported to the plasma. In the plasma, iron is bound by transferrin, the transport protein.
Transferrin delivers iron to cells in the liver and spleen or to the bone marrow, where it can be used for hemoglobin synthesis and red blood cell formation.
The chemical characteristic of the iron carbohydrate complex means that iron is released slowly.
As a result, the transferrin available for uptake does not become fully saturated with iron. This entire process results in a controlled release of iron into the bloodstream.
The number one IV iron in oncology clinics and fastest growing IV iron in the United States is Injectafer. A dextran-free iron carbohydrate complex with a controlled release of iron.
Gastroenterology Educational Video
INDICATIONS
Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-dialysis dependent chronic kidney disease.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components.
WARNINGS AND PRECAUTIONS
Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases, hypophosphatemia resolved within three months.
Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.
In clinical studies, hypertension was reported in 3.8% (67/1775) of subjects. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.
In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.
ADVERSE REACTIONS
In two randomized clinical studies, a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a single maximum dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by ≥2% of Injectafer-treated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.0%).
The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event); nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria.
CLINICAL CONSIDERATIONS IN PREGNANCY
Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.
Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.
You are encouraged to report Adverse Drug Events to American Regent, Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
Introduction
Hi there. I’m Dr. Rahul Dixit, a practicing gastroenterologist based out of Santa Monica, California. At my single-specialty practice, I see a lot of young, adult patients with a wide variety of pathology. During my experience, I’ve come across many patients who have developed iron deficiency anemia as a result of their gastrointestinal (GI) conditions.
[Beaker slide]
Identification and diagnosis
Disease state education
Today, we are going to talk about iron deficiency anemia, or IDA. IDA occurs when the balance of iron intake, existing iron stores, and iron depletion cannot fully support the production of erythrocytes.
There are three main causes of IDA: blood loss, insufficient absorption of iron, and insufficient intake of iron. A few examples include: peptic ulcers, colon cancer, Crohn’s disease, celiac disease, and decreased absorption after intestinal surgeries, such as bariatric surgery.
Because anemia can often be found in patients with a variety of GI conditions, your patients may be at higher risk of developing IDA. For instance, IDA is particularly prevalent in patients with gastrointestinal bleeding, celiac disease, inflammatory bowel disease (IBD), and patients who have had bariatric surgery.
For instance, bariatric gastric bypass surgery disrupts the physiological absorption of iron in the duodenum by decreasing the area available to absorb iron.
Another factor that plays a role in iron absorption is the hormone, hepcidin. Hepcidin is a protein that serves as a regulator of the entry of iron into the circulatory system. When hepcidin decreases, the stored iron in the body is released. In patients with iron deficiency anemia, hepcidin suppression can be an early sign of iron deficiency.
IDA may be difficult to spot in your practice because the symptoms aren’t ones patients normally report to a gastroenterologist. Some patients with mild to moderate IDA may exhibit non-specific symptoms, or may even be completely asymptomatic. In more severe cases, you may see patients who experience signs and symptoms that include: weakness, fatigue, pica, shortness of breath, arrhythmia, pale skin, pale conjunctiva, sore tongue, tinnitus, brittle nails, hair loss, headache, chest pain, coldness in the hands and feet, and dizziness.
IDA is frequently under-reported, so to prevent misdiagnosis, I tend to ask my patients about specific symptoms that can be caused by IDA. If your patients have any of the previously mentioned conditions that contribute to IDA risk, it is important to routinely test their iron levels, even when your patients aren’t exhibiting symptoms.
Diagnosing IDA
There are three key indices for evaluating IDA: hemoglobin, transferrin saturation or TSAT, and ferritin.
Normal hemoglobin values are 13.5-17.5 g/dL for men and 12.0-15.5 g/dL for women. Ferritin levels range from 12-300 ng/mL for men and 12-150 ng/mL for women. Normal levels for TSAT are from 20%-50%.
I believe that IDA screening is an important part of care for my patients. However, current screening and management practices may be suboptimal. One study showed that 1/3 of patients with ulcerative colitis went unscreened for IDA. This study also showed that of those patients who were diagnosed, nearly 25% did not receive oral iron supplementation. Furthermore, none of the patients treated for IDA received IV iron. Oral iron therapy was the only iron therapy used at initial diagnosis.
Let’s examine a hypothetical case for a patient with IDA. Sara is 26 years old and has been struggling with ulcerative colitis. She is currently being treated with a corticosteroid and she was shown to be intolerant to oral iron in the past. In addition to having 4-5 episodes of bloody diarrhea per day, Sara also reported generalized malaise and mild dyspnea on exertion. Lab testing shows that her hemoglobin level is 10.5 g/dL, which falls below the lower threshold of normal.
Let’s explore potential treatment options for patients like Sara whom you might see in your practice.
[Breaker slide]
Treatment goals and options
Treatment goals
The optimal outcome of treatment for IDA is iron repletion above the lower threshold of normal. This means that the patient’s TSAT, ferritin, and hemoglobin must be within normal ranges. Let’s review what the normal levels are.
Treatment options
There are two treatment options for stable patients diagnosed with IDA: oral iron and intravenous (IV) iron. Both forms of treatment have pros and cons to consider for your patients’ individual needs.
I usually start with oral iron for all of my patients with IDA as first-line therapy. It is obtainable without a prescription, can be readily found at a pharmacy, and has a dosage of 1-3 times a day.
However, oral iron absorption can be inhibited due to a variety of conditions, which can interfere with digestive processes and compromise its efficacy. Even in healthy patients, less than 10% of oral iron is absorbed due to the fact that the duodenum can maximally absorb only 10-20 mg daily. That means nearly 90% of oral iron may be going to waste.
Additionally, reports indicate that adherence rates range from 40%-60% for oral iron therapy. This may be due to the side effects of oral iron, which include epigastric discomfort, nausea, vomiting, diarrhea, and constipation.
If patients in my practice are 4-8 weeks into treatment and their iron levels are still not within normal limits, oral iron may be the wrong option for them. In fact, some patients may show indications of failing oral iron within as little as 14 days.
IV iron may be an option for your patients if oral iron fails. 100% of IV iron is delivered into the bloodstream, so your patients can restore their iron in less time.
As IV iron may only be administered in an infusing center by a healthcare professional, it may be less convenient for some patients. Although every infusion experience is different, some of your patients may be more familiar with infusions due to other conditions for which they already receive similar treatment.
Whether you infuse in your office or not, it is important to monitor your patients’ labs throughout their treatment journey to see if their therapy is working.
Some side effects for IV iron include nausea, hypertension, injection site reactions, hypotension, and headache. Serious hypersensitivity reactions may also occur. If you are unfamiliar with IV iron treatment options, it is important to note that dextran-free IV iron options are now available.
Let’s revisit Sara, the hypothetical patient with ulcerative colitis who showed low hemoglobin levels. In order to assess whether Sara has developed IDA, Sara’s doctor ordered tests for her ferritin and TSAT levels. These results showed that Sara is low across all three indices, confirming that she does, in fact, have IDA.
Given what we already know about Sara’s previously reported intolerance to oral iron, how would you proceed with her care? Next, we will explore an IV iron treatment option that may be appropriate for a patient like Sara.
[Breaker slide]
Choosing Injectafer
Injectafer benefits
I is an iron replacement product indicated for the treatment of IDA in adult patients who have intolerance or have had unsatisfactory response to oral iron, or who have non–dialysis dependent chronic kidney disease.
Injectafer is a dextran-free IV iron. Injectafer can be used after oral iron failure in adult patients with IDA of various etiologies that may contribute to iron deficits of approximately 1500 mg. These include cancer, a wide range of GI pathologies, abnormal uterine bleeding, post-partum bleeding, post-gastric bypass, and heart failure, as well as non–dialysis dependent chronic kidney disease.
Injectafer has a carbohydrate shell that is tightly bound around a colloidal iron (III) hydroxide core. This molecular structure was designed for the controlled release of iron to deliver 1500 mg in 2 administrations of 750 mg separated by at least 7 days.
Efficacy data
Let’s examine the efficacy and safety data for Injectafer in adult patients with IDA when compared to oral iron and iron sucrose.
This study was designed as a randomized, open label, active-controlled, multicenter trial with 1011 adult subjects randomized at 84 US centers. Inclusion criteria for the study were that patients had to have hemoglobin levels of ≤11.0 g/dL, ferritin levels ≤100 ng/mL or ≤300 ng/mL when TSAT ≤30%, and IDA of any etiology, including heavy uterine bleeding; GI disorders; postpartum, nutritional, or dietary deficiency; and others. Patients with a history of iron intolerance and a history of drug allergy were also included.
After a 14-day run-in period of oral ferrous sulfate dosed at 325 mg, 3 times daily, eligible patients with hemoglobin <12 g/dL who had an inadequate response to oral iron were randomized to receive ferric carboxymaltose or to continue oral iron therapy. These patients formed Cohort 1. Those who were unable to tolerate oral iron during the run-in period were randomized to receive ferric carboxymaltose or standard of care IV iron treatment, thus forming Cohort 2.
The primary endpoint of the study was mean change to highest observed hemoglobin from baseline to Day 35 or time of intervention for subjects in Cohort 1. The same measurement was a secondary endpoint in Cohort 2.
In Cohort 1, results showed that Injectafer provided significantly greater increases in hemoglobin levels vs oral iron to Day 35 and improvements in hemoglobin were greater with Injectafer vs oral iron by Day 14 (1.6 vs 0.8 respectively). Also, the mean change in iron indices was greater with Injectafer vs oral iron from baseline to Day 35 or time of intervention.
One other point of note is that by the end of the study, patients supplemented with oral iron demonstrated diminished iron stores compared to their baseline levels, suggesting that iron losses outpaced oral iron supplementation.
In Cohort 2, the mean change in hemoglobin from baseline to highest value between baseline and Day 35 or time of intervention was greater with Injectafer vs iron sucrose, and improvement in hemoglobin levels were greater with Injectafer vs IV iron standard of care by Day 7. Furthermore, the mean change in ferritin and TSAT was greater with Injectafer vs iron sucrose during that time period.
Safety data
The composite safety endpoint for Cohorts 1 and 2 included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure, arrhythmias, and protocol-defined hypotension or hypertension.
Seven participants (2.9%) in Group A (Injectafer), 4 (1.6%) in Group B (oral iron), 10 (4%) in Group C (Injectafer), and 12 (4.9%) in Group D (iron sucrose) met the primary composite safety endpoint.
The most commonly observed components of the composite safety endpoint for both cohorts were protocol-defined hypertension and death due to any cause.
Worldwide experience
Injectafer has real-world experience that supports its use for patients with IDA. Injectafer is approved in 75 countries, with a total global exposure of approximately 7.5 million patient years. Injectafer is also the #1 selling IV iron in the US with more than 680,000 patients treated to date.
Let’s wrap up our conversation with Sara, the hypothetical patient we have previously spoken about. Sara’s labs showed that her hemoglobin, ferritin, and TSAT levels were all below normal. Because Sara is also oral-iron intolerant, she was prescribed Injectafer. As early as 4 weeks after her infusion, her doctor ordered another round of labs which showed that Sara’s hemoglobin had risen from 10.5 mg/dL to a normal level of 12.1 mg/dL. Her TSAT and ferritin levels had also risen to within normal ranges.
If you see patients like Sara in your practice, you might want to consider Injectafer. To learn more about Injectafer, including the full Prescribing Information, patient savings offerings, and more, visit injectaferhcp.com
OB/GYN Patient Exam Room Video
INDICATIONS
Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-dialysis dependent chronic kidney disease.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components.
WARNINGS AND PRECAUTIONS
Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases, hypophosphatemia resolved within three months.
Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.
In clinical studies, hypertension was reported in 3.8% (67/1775) of subjects. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.
In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.
ADVERSE REACTIONS
In two randomized clinical studies, a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a single maximum dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by ≥2% of Injectafer-treated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.0%).
The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event); nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria.
CLINICAL CONSIDERATIONS IN PREGNANCY
Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.
Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.
You are encouraged to report Adverse Drug Events to American Regent, Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
Introduction
Hi there. I’m Dr. Rahul Dixit, a practicing gastroenterologist based out of Santa Monica, California. At my single-specialty practice, I see a lot of young, adult patients with a wide variety of pathology. During my experience, I’ve come across many patients who have developed iron deficiency anemia as a result of their gastrointestinal (GI) conditions.
[Beaker slide]
Identification and diagnosis
Disease state education
Today, we are going to talk about iron deficiency anemia, or IDA. IDA occurs when the balance of iron intake, existing iron stores, and iron depletion cannot fully support the production of erythrocytes.
There are three main causes of IDA: blood loss, insufficient absorption of iron, and insufficient intake of iron. A few examples include: peptic ulcers, colon cancer, Crohn’s disease, celiac disease, and decreased absorption after intestinal surgeries, such as bariatric surgery.
Because anemia can often be found in patients with a variety of GI conditions, your patients may be at higher risk of developing IDA. For instance, IDA is particularly prevalent in patients with gastrointestinal bleeding, celiac disease, inflammatory bowel disease (IBD), and patients who have had bariatric surgery.
For instance, bariatric gastric bypass surgery disrupts the physiological absorption of iron in the duodenum by decreasing the area available to absorb iron.
Another factor that plays a role in iron absorption is the hormone, hepcidin. Hepcidin is a protein that serves as a regulator of the entry of iron into the circulatory system. When hepcidin decreases, the stored iron in the body is released. In patients with iron deficiency anemia, hepcidin suppression can be an early sign of iron deficiency.
IDA may be difficult to spot in your practice because the symptoms aren’t ones patients normally report to a gastroenterologist. Some patients with mild to moderate IDA may exhibit non-specific symptoms, or may even be completely asymptomatic. In more severe cases, you may see patients who experience signs and symptoms that include: weakness, fatigue, pica, shortness of breath, arrhythmia, pale skin, pale conjunctiva, sore tongue, tinnitus, brittle nails, hair loss, headache, chest pain, coldness in the hands and feet, and dizziness.
IDA is frequently under-reported, so to prevent misdiagnosis, I tend to ask my patients about specific symptoms that can be caused by IDA. If your patients have any of the previously mentioned conditions that contribute to IDA risk, it is important to routinely test their iron levels, even when your patients aren’t exhibiting symptoms.
Diagnosing IDA
There are three key indices for evaluating IDA: hemoglobin, transferrin saturation or TSAT, and ferritin.
Normal hemoglobin values are 13.5-17.5 g/dL for men and 12.0-15.5 g/dL for women. Ferritin levels range from 12-300 ng/mL for men and 12-150 ng/mL for women. Normal levels for TSAT are from 20%-50%.
I believe that IDA screening is an important part of care for my patients. However, current screening and management practices may be suboptimal. One study showed that 1/3 of patients with ulcerative colitis went unscreened for IDA. This study also showed that of those patients who were diagnosed, nearly 25% did not receive oral iron supplementation. Furthermore, none of the patients treated for IDA received IV iron. Oral iron therapy was the only iron therapy used at initial diagnosis.
Let’s examine a hypothetical case for a patient with IDA. Sara is 26 years old and has been struggling with ulcerative colitis. She is currently being treated with a corticosteroid and she was shown to be intolerant to oral iron in the past. In addition to having 4-5 episodes of bloody diarrhea per day, Sara also reported generalized malaise and mild dyspnea on exertion. Lab testing shows that her hemoglobin level is 10.5 g/dL, which falls below the lower threshold of normal.
Let’s explore potential treatment options for patients like Sara whom you might see in your practice.
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Treatment goals and options
Treatment goals
The optimal outcome of treatment for IDA is iron repletion above the lower threshold of normal. This means that the patient’s TSAT, ferritin, and hemoglobin must be within normal ranges. Let’s review what the normal levels are.
Treatment options
There are two treatment options for stable patients diagnosed with IDA: oral iron and intravenous (IV) iron. Both forms of treatment have pros and cons to consider for your patients’ individual needs.
I usually start with oral iron for all of my patients with IDA as first-line therapy. It is obtainable without a prescription, can be readily found at a pharmacy, and has a dosage of 1-3 times a day.
However, oral iron absorption can be inhibited due to a variety of conditions, which can interfere with digestive processes and compromise its efficacy. Even in healthy patients, less than 10% of oral iron is absorbed due to the fact that the duodenum can maximally absorb only 10-20 mg daily. That means nearly 90% of oral iron may be going to waste.
Additionally, reports indicate that adherence rates range from 40%-60% for oral iron therapy. This may be due to the side effects of oral iron, which include epigastric discomfort, nausea, vomiting, diarrhea, and constipation.
If patients in my practice are 4-8 weeks into treatment and their iron levels are still not within normal limits, oral iron may be the wrong option for them. In fact, some patients may show indications of failing oral iron within as little as 14 days.
IV iron may be an option for your patients if oral iron fails. 100% of IV iron is delivered into the bloodstream, so your patients can restore their iron in less time.
As IV iron may only be administered in an infusing center by a healthcare professional, it may be less convenient for some patients. Although every infusion experience is different, some of your patients may be more familiar with infusions due to other conditions for which they already receive similar treatment.
Whether you infuse in your office or not, it is important to monitor your patients’ labs throughout their treatment journey to see if their therapy is working.
Some side effects for IV iron include nausea, hypertension, injection site reactions, hypotension, and headache. Serious hypersensitivity reactions may also occur. If you are unfamiliar with IV iron treatment options, it is important to note that dextran-free IV iron options are now available.
Let’s revisit Sara, the hypothetical patient with ulcerative colitis who showed low hemoglobin levels. In order to assess whether Sara has developed IDA, Sara’s doctor ordered tests for her ferritin and TSAT levels. These results showed that Sara is low across all three indices, confirming that she does, in fact, have IDA.
Given what we already know about Sara’s previously reported intolerance to oral iron, how would you proceed with her care? Next, we will explore an IV iron treatment option that may be appropriate for a patient like Sara.
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Choosing Injectafer
Injectafer benefits
I is an iron replacement product indicated for the treatment of IDA in adult patients who have intolerance or have had unsatisfactory response to oral iron, or who have non–dialysis dependent chronic kidney disease.
Injectafer is a dextran-free IV iron. Injectafer can be used after oral iron failure in adult patients with IDA of various etiologies that may contribute to iron deficits of approximately 1500 mg. These include cancer, a wide range of GI pathologies, abnormal uterine bleeding, post-partum bleeding, post-gastric bypass, and heart failure, as well as non–dialysis dependent chronic kidney disease.
Injectafer has a carbohydrate shell that is tightly bound around a colloidal iron (III) hydroxide core. This molecular structure was designed for the controlled release of iron to deliver 1500 mg in 2 administrations of 750 mg separated by at least 7 days.
Efficacy data
Let’s examine the efficacy and safety data for Injectafer in adult patients with IDA when compared to oral iron and iron sucrose.
This study was designed as a randomized, open label, active-controlled, multicenter trial with 1011 adult subjects randomized at 84 US centers. Inclusion criteria for the study were that patients had to have hemoglobin levels of ≤11.0 g/dL, ferritin levels ≤100 ng/mL or ≤300 ng/mL when TSAT ≤30%, and IDA of any etiology, including heavy uterine bleeding; GI disorders; postpartum, nutritional, or dietary deficiency; and others. Patients with a history of iron intolerance and a history of drug allergy were also included.
After a 14-day run-in period of oral ferrous sulfate dosed at 325 mg, 3 times daily, eligible patients with hemoglobin <12 g/dL who had an inadequate response to oral iron were randomized to receive ferric carboxymaltose or to continue oral iron therapy. These patients formed Cohort 1. Those who were unable to tolerate oral iron during the run-in period were randomized to receive ferric carboxymaltose or standard of care IV iron treatment, thus forming Cohort 2.
The primary endpoint of the study was mean change to highest observed hemoglobin from baseline to Day 35 or time of intervention for subjects in Cohort 1. The same measurement was a secondary endpoint in Cohort 2.
In Cohort 1, results showed that Injectafer provided significantly greater increases in hemoglobin levels vs oral iron to Day 35 and improvements in hemoglobin were greater with Injectafer vs oral iron by Day 14 (1.6 vs 0.8 respectively). Also, the mean change in iron indices was greater with Injectafer vs oral iron from baseline to Day 35 or time of intervention.
One other point of note is that by the end of the study, patients supplemented with oral iron demonstrated diminished iron stores compared to their baseline levels, suggesting that iron losses outpaced oral iron supplementation.
In Cohort 2, the mean change in hemoglobin from baseline to highest value between baseline and Day 35 or time of intervention was greater with Injectafer vs iron sucrose, and improvement in hemoglobin levels were greater with Injectafer vs IV iron standard of care by Day 7. Furthermore, the mean change in ferritin and TSAT was greater with Injectafer vs iron sucrose during that time period.
Safety data
The composite safety endpoint for Cohorts 1 and 2 included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure, arrhythmias, and protocol-defined hypotension or hypertension.
Seven participants (2.9%) in Group A (Injectafer), 4 (1.6%) in Group B (oral iron), 10 (4%) in Group C (Injectafer), and 12 (4.9%) in Group D (iron sucrose) met the primary composite safety endpoint.
The most commonly observed components of the composite safety endpoint for both cohorts were protocol-defined hypertension and death due to any cause.
Worldwide experience
Injectafer has real-world experience that supports its use for patients with IDA. Injectafer is approved in 75 countries, with a total global exposure of approximately 7.5 million patient years. Injectafer is also the #1 selling IV iron in the US with more than 680,000 patients treated to date.
Let’s wrap up our conversation with Sara, the hypothetical patient we have previously spoken about. Sara’s labs showed that her hemoglobin, ferritin, and TSAT levels were all below normal. Because Sara is also oral-iron intolerant, she was prescribed Injectafer. As early as 4 weeks after her infusion, her doctor ordered another round of labs which showed that Sara’s hemoglobin had risen from 10.5 mg/dL to a normal level of 12.1 mg/dL. Her TSAT and ferritin levels had also risen to within normal ranges.
If you see patients like Sara in your practice, you might want to consider Injectafer. To learn more about Injectafer, including the full Prescribing Information, patient savings offerings, and more, visit injectaferhcp.com
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Choosing Injectafer:FAQ
Choosing Injectafer: FREQUENTLY ASKED QUESTIONS
Important Safety Information
INDICATIONS
Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-dialysis dependent chronic kidney disease.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components.
WARNINGS AND PRECAUTIONS
Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases, hypophosphatemia resolved within three months.
Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects
In clinical studies, hypertension was reported in 4% (67/1775) of subjects in clinical trials 1 and 2. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects in these two clinical trials. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.
In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.
ADVERSE REACTIONS
In two randomized clinical studies [Studies 1 and 2], a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a maximum single dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by ≥2% of Injectafer-treated patients were nausea (7.2%); hypertension (4%); flushing (4%); injection site reactions (3%); erythema (3%); hypophosphatemia (2.1%); dizziness (2.1%); and vomiting (2%).
The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event); nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria; pregnancy: fetal bradycardia.
CLINICAL CONSIDERATIONS IN PREGNANCY
Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.
Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.
You are encouraged to report Adverse Drug Events to American Regent, Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
