If you’re one of millions of Americans who are prescribed Injectafer, you may need to heed the warnings of a potentially deadly side effect from taking it. The injectable iron supplement has been linked to causing hypophosphatemia (HPP), a condition that causes abnormally low blood levels of phosphate.
What is Injectafer?
Injectafer is used to treat iron deficiency anemia (IDA) in adults who are unable to take iron supplements, or those diagnosed with chronic kidney disease who are not on dialysis. It is an injectable iron complex manufactured by American Regent, Inc., a subsidiary of Luitpold Pharmaceuticals, Inc.
Injectafer has been around since 2013, when it was approved and released onto the US consumer market. Injectafer contains an injectable form of certain types of iron complexes. The injection slowly releases iron directly into the bloodstream to help reduce the side effects and symptoms of iron deficiency anemia. Patients who have to take Injectafer are typically given two administrations within a matter of at least seven days.
Injectafer has quickly gained popularity on the market, but comes with an increased risk of HPP as opposed to other iron supplements.
What does iron do anyway?
Iron helps in the production of hemoglobin, the part of red blood cells that is responsible for transporting oxygen through the body to organs and cells. If there is not enough hemoglobin produced in the body, this means organs and cells are not getting enough oxygen. This can then cause the body to experience a plethora of potentially severe and ultimately deadly conditions if left untreated.
Iron deficiency anemia symptoms include pale skin, muscle weakness, cold hands and feet, chest pain, shortness of breath, lightheadedness, brittle nails, and excessive fatigue. Some side effects also include unusual cravings.
Many individuals experience IDA for a variety of reasons such as blood loss, a general lack of iron in the diet, pregnancy, or an inability to absorb iron. Those at risk of IDA include infants, children, women, those on a vegetarian or vegan diet, frequent blood donors, or those with digestive disorders such as celiac or Chrohn’s disease.
How is iron deficiency addressed?
Many doctors begin to address IDA by prescribing oral iron supplements, as blood-iron levels are expected to stabilize after a few months. However, some people are unable to tolerate iron supplements which is when an intravenous solution, such as Injectafer, is needed.
Overview of Hypophosphatemia
Let’s begin by addressing phosphate and why low levels are dangerous to our bodies.
We naturally absorb phosphate in foods such as milk, eggs, meat, or beans. When phosphorous combines with oxygen, the body produces phosphate. This is then used to help support important structures such as bones, teeth, muscles, and nerves.
When the phosphate levels start to drop from conditions such as hypophosphatemia, the body cannot function normally. This means the bones, teeth, muscles, and nerves phosphate was keeping healthy are no longer receiving support. The longer the body is deprived of normal levels of iron, the more severe HPP becomes.
What is Hypophosphatemia?
Hypophosphatemia is a condition in which naturally occurring phosphate levels of the body drop to an unhealthy number. This can cause a myriad of problems that, if left untreated and continue to decline, can lead to death. Hypophosphatemia can occur in anyone from infants to adults. It’s important to understand the signs and symptoms of hypophosphatemia in order to keep you and your body healthy.
There are two types of diagnosis for hypophosphatemia; acute and chronic. Acute hypophosphatemia develops quickly, whereas chronic hypophosphatemia develops over time. There is a rare possibility for someone to experience familial hypophosphatemia, which is passed down genetically.
The name hypophosphatemia is derived from the Latin words ‘hypo-’ which means beneath or lower; ‘phosphate-’ refers to phosphate levels; ‘-emia’ refers to blood or a substance in the blood. Therefore, hypophosphatemia is roughly translated to low phosphate in the blood.
It’s important to understand the relationship between phosphate and our bodies. Anytime we have abnormal levels of chemicals or minerals in our bodies, we risk these levels impacting multiple systems that depend upon one another.
Healthy phosphorus levels in adults are anywhere from 2.5 to 4.5 mg/dL. When these levels drop, it is considered hypophosphatemia. On the contrary,phosphatemia is an overabundance of phosphate levels. For the purpose of this article, we will only be discussing hypophosphatemia.
Phosphate is a type of mineral that helps to build new cells, improves our bone structure, and creates energy in our bodies. The recommended daily intake of phosphorus in adults is around 700mg, but some people may require more, such as teens or pregnant women.
Signs and Symptoms of Hypophosphatemia
As with any medical or health concerns, you should always consult your doctor or health care practitioner. Many people who have mild hypophosphatemia may not notice symptoms unless they drop to very low levels. When that happens, the following symptoms may occur:
- Bone pain
- Bone fractures
- Appetite loss
- Muscle weakness
- Slowed grown or shorter than normal height in children
- Tooth decay or late baby teeth (this occurs in familial hypophosphatemia)
Complications From Hypophosphatemia
Complications from hypophosphatemia if left untreated can cause serious trouble in our bodies.
Severe hypophosphatemia symptoms include:
- Rhabdomyolysis (muscle wasting)
- Muscle pain
- Respiratory failure
- Heart failure
- Acute hemolytic anemia (a condition in which red blood cells are destroyed too quickly)
- Fatal arrhythmias (heart rhythm abnormalities)
- Bone pain and fractures
American Regent has failed to investigate, nor provide adequate warnings about the risk of hypophosphatemia from Injectafer.
This puts many patients at risk of developing side effects that they were not expecting. Currently, the only side effects American Regent lists from taking Injectafer are considered mild such as nausea, headaches, and low levels of phosphorus in the blood.
Diagnosis of Hypophosphatemia
Your doctor will run a blood test to measure how much phosphate is in the blood. A concentration of less than 0.81 mmol/L (2.5 mg/dL) of phosphate in the blood is considered a diagnosis of hypophosphatemia. Sometimes it may take a specialist such as an endocrinologist, a rheumatologist, or nephrologist to get to the underlying causes of hypophosphatemia.
Research concludes Injectafer increases risk of hypophosphatemia
In 2015, a study of 52 patients who received iron sucrose injections indicated only 22% of those with sucrose suffered HPP. However, 51% of 78 patients who were injected with FCM developed HPP, including 13% who reported severe HPP. The researchers concluded, “Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue.”
In 2016, researchers in Austria found patients injected with a particular type of iron used in Injectafer were more likely to experience hypophosphatemia.
Injectafer is equipped with ferric carboxymaltose (FCM). Studies found patients injected with FCM were 45.5% more likely to experience HPP, with a prevalence of 32% experiencing severe HPP. Compared to an alternative iron supplement, iron isomaltoside (IIM), only a significantly lower 4% of patients experienced HPP with no severe cases reported.
The average time in which it took for the body to achieve full-blown HPP from taking FCM was around 41 days. The researchers concludes that IIM has a significantly lower risk of HPP in comparison to the FCM in Injectafer.
In a letter to the editor of Ailmentary Phamacology and Therapeutics in 2017, four medical professionals wrote about the occurrence of HPP in patients being injected with FCM. In it, they cited many studies on the effects of FCM versus oral or alternative iron supplements.
They indicated, “..hypophosphatemia occurs more frequently as an adverse event than it is reported as adverse drug reaction and has indeed been described to occur in up to 70% of patients treated with ferric carboxymaltose.”