Patients on long-term iron replacement with parenteral ferric carboxymaltose (Ferinject) may be at risk of hypophosphataemia, the TGA has advised.

There have been 15 reports of hypophosphataemia with ferric carboxymaltose,  with severe hypophosphataemia (<0.3mmol/L) in four of six cases where serum phosphate was reported, the regulator says in the latest Medicines Safety Bulletin.

The TGA says the product information for the product has been updated to include additional details about the known risk of hypophosphataemia associated with use of the intravenous product “and it is recommended that you routinely evaluate patient risk factors before commencing this medicine and follow up at-risk patients.”

“Hypophosphataemia can be the cause of asthenia, fatigue, muscular weakness, breathlessness, tachycardia and headaches, which might otherwise be misdiagnosed as failure to respond to treatment of iron deficiency anaemia, therefore consider  hypophosphataemia as a potential reason for a patients’ symptoms continuing after use of ferric carboxymaltose,” it advises.

In rare cases, severe hypophosphataemia may be associated with symptomatic physiological dysfunction with acute manifestations including muscular symptoms (weakness, asthenia, leading to progressive myopathy including cardiorespiratory compromise and death) neurological symptoms (tingling, altered mental status, seizures, paralysis) and haematological changes.

In five of the cases reported to the TGA there were systemic symptoms of hypophosphataemia (fatigue, malaise, lethargy) and skeletal manifestations of hypophosphataemia were reported in three cases.

“Most patients recovered with oral phosphate, calcitriol or with IV phosphate supplementation, but the outcome was reported as ‘not recovered’ in two cases.”

The TGA advises that clinically significant hypophosphataemia following parenteral iron is more likely in patients on long-term iron replacement, and in those with lower baseline ferritin, gastrointestinal disorders, malnutrition or other causes of phosphate deficiency (low whole body phosphate).

Time to onset, where reported, was generally from a few days up to two weeks after starting ferric carboxymaltose.