Iron infusion surge triggers phosphate safety warning

Iron infusions have become part of the routine for a lot of Australian women managing fatigue, hair loss, and the slow drain of iron deficiency. The appeal makes sense: oral iron is unpredictable, the tablets are difficult to tolerate, and an infusion promises to solve it in an hour rather than a month of stomach upset. So the numbers have grown — a recent analysis in the Internal Medicine Journal documents a sharp rise in intravenous iron use across Australia over the past decade.

Last month, the US Food and Drug Administration added its highest-level safety warning — a boxed warning — to ferric carboxymaltose (Ferinject in Australia), flagging the risk of hypophosphataemia: dangerously low blood phosphate. The TGA has noted the US action and is evaluating whether Australia will follow. No new Australian guidance has been issued yet.

This is worth knowing about. Not because iron infusions are about to be cancelled, but because a real risk is being under-communicated, and the patients most affected are women — the same women who are coming in more often to get them.

What phosphate has to do with iron

Ferric carboxymaltose is a newer formulation that allows high-dose iron to be given in a single session. It works. It also, in a subset of patients, drives significant phosphate loss through the kidneys. The mechanism — described by Bond University GP Dr Kieran Le Plastrier — involves the drug interfering with FGF23, a hormone that regulates kidney phosphate excretion. When FGF23 activity is disrupted, the kidneys excrete more phosphate than the body can replace.

Phosphate is not optional. It underpins energy production, muscle contraction, bone mineralisation, and respiratory drive. When it drops far enough, patients feel weak and generally unwell. Palpitations appear. In severe cases — like Kate Russell, the 46-year-old teacher from Toowoomba whose story is at the centre of the ABC reporting — the outcome included induced coma, ICU admission, and months of specialist care. She was told to watch for iron staining at the needle site. Nobody mentioned phosphate.

The TGA reported 46 Australian cases of ferric carboxymaltose-associated hypophosphataemia in 2025, up from 17 cases in 2020 — nearly a tripling in five years, during a period when infusion use has been rising. These are reported cases; the real number is likely higher, because mild cases are often not recognised and not reported.

Both-and: a useful treatment with an unequally communicated risk

The both-and framing: intravenous iron is genuinely useful. For women with iron-deficiency anaemia who cannot tolerate oral iron, who have ongoing blood loss that exceeds what oral repletion can manage, or who are pre-operatively anaemic, IV iron is not an elective luxury — it is effective, evidence-based treatment. The RACGP’s co-deputy chair Dr Aadhil Aziz says as much: a boxed warning would not stop the treatment, only prompt closer monitoring.

The problem is the gap between clinical indication and the settings where infusions are now being delivered. The growth in infusion use has not been matched by growth in informed consent practice, pre-infusion phosphate assessment, or post-infusion safety netting. When a patient leaves after an infusion without being told to return if she develops muscle weakness or palpitations, and then develops hypophosphataemia three days later, the gap between what we knew and what we told her becomes a clinical near-miss — or worse.

The system did not fail Kate Russell at the level of evidence. The evidence on hypophosphataemia with ferric carboxymaltose has been accumulating for years. It failed her at the level of what gets communicated at the bedside when someone receives an infusion in a day procedure unit and goes home the same afternoon.

2 cents

Three things that can change in the consulting room this week, without waiting for the TGA to match the FDA:

Discuss oral iron first. Dr Aziz’s advice is direct: before an infusion is organised, have a conversation about whether oral iron — with meal timing adjustments, vitamin C co-administration, and a formulation the patient can actually tolerate — is feasible. Ferrous bisglycinate causes significantly less gastrointestinal upset than ferrous sulfate in many patients. It is worth the conversation before going straight to IV.

Safety-net the phosphate question. For any patient who has recently had a ferric carboxymaltose infusion and returns with fatigue, generalised weakness, palpitations, or malaise — serum phosphate belongs on the request. Dr Le Plastrier has described finding it low in patients who had no other clear explanation. It is a simple, inexpensive test, and in this context it is clinically warranted.

Consider pre-infusion phosphate in higher-risk patients. For patients with malabsorption, vitamin D deficiency, or prior phosphate issues, a baseline phosphate level before infusion may identify who needs closer monitoring afterwards. This is not yet formal guidance in Australia, but it is the kind of clinical reasoning Dr Aziz describes as appropriate given the current evidence.

The TGA is watching the US move. The guidance may change. In the meantime, the patients who are already getting infusions, and the patients who are about to, deserve a fully informed conversation about what to watch for.

Verdict: yes — a real complication in a rising-use treatment, a regulatory gap between Australia and the US, and a straightforward clinical response that does not require waiting for new guidelines.

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Sources cited

1. Surge in iron infusions prompts warning over serious side effect — ABC News
2. Rising intravenous iron use in Australia — Internal Medicine Journal (Wiley)
3. FDA adds boxed warning for ferric carboxymaltose (Injectafer)