EU reviews injectable iron treatments after severe bone complications emerge

The European Medicines Agency has begun reviewing the safety of every injectable iron medicine available in the European Union after severe cases of hypophosphatemia were reported. Some cases were associated with osteomalacia, a condition in which bones fail to mineralize properly, and with fractures.

The EMA will assess whether current safety measures are adequate or whether the medicines’ authorizations need to be changed. The review covers ferric carboxymaltose, ferric derisomaltose, ferric gluconate, iron hydroxide polymaltose complex, iron dextran and iron sucrose. Depending on the product, the medicines can be administered by injection or intravenous infusion, intramuscularly, or through dialysis equipment.

Injectable iron is used when oral treatment cannot be given, does not work, or when the body needs to replenish its iron stores quickly. Patients receiving dialysis for kidney failure may use it, as may people before or after certain operations, people with heart failure, and women with severe iron deficiency during or after pregnancy. It is also prescribed for some diseases that impair nutrient absorption in the intestine.

Oral iron treatments are not part of the review. The EMA says they provide much smaller amounts of iron over a given period and therefore have a lower likelihood of causing hypophosphatemia. Phosphate supports essential processes, including the formation and maintenance of bone structure. If levels fall too far, people can experience fatigue and muscle or bone pain. Severe or prolonged deficiency can impair bone mineralization and lead to osteomalacia, which can cause bone pain and, in some cases, fractures.

Hypophosphatemia and related osteomalacia are already listed as adverse reactions for injectable ferric carboxymaltose. The EMA classifies hypophosphatemia as a common adverse reaction, meaning it may affect up to one in 10 treated people. Available data do not establish how often osteomalacia associated with hypophosphatemia occurs.