INTRAVENOUS iron therapy has increased fivefold among Australian women of reproductive age, prompting a call for research into whether it is being used appropriately.

An analysis of the use of Pharmaceutical Benefits Scheme (PBS)-funded intravenous iron therapy for women aged 18–44 years, published in the MJA, found that dispensing claims increased from 17 920 in 2013 to 97 040 in 2017. The annual rate of intravenous iron increased from 0.4 per 100 women to 2.1 per 100 women during the same period, the researchers reported.

In 2017, intravenous iron was dispensed to one in 50 Australian women of reproductive age, five times the proportion dispensed in 2013, they wrote. Ferric carboxymaltose, which was available from mid-2014, was used for 90% of women.

This shift in practice had also come at a significant cost, the MJA authors noted. They reported that the annual cost of therapy had increased 35-fold, from $750 000 in 2013 to $29.9 million in 2017 (based on average PBS prices). They added that this was probably an underestimate because it did not include therapy administered to public hospital inpatients.

The authors said that although the reasons behind the increase remained unclear, it was likely driven by “increased awareness of patient blood management [PBM] guidelines, the ease of treatment, and the perception that its side effect profile [was] more favourable than for oral iron therapy”.

Dr Allison Mo, a haematologist at Monash Health and Austin Health, and Professor Erica Wood, a transfusion medicine specialist and haematologist at Monash Health, and Head of the Transfusion Research Unit at Monash University’s Department of Epidemiology and Preventive Medicine, agreed with the authors’ postulated reasons behind the increase in intravenous iron therapy. They said there had been a lot of effort invested in increasing the awareness of the PBM guidelines in the medical community.

“The Australian National Blood Authority PBM guidelines in obstetrics and maternity were published in 2015 and recommend the treatment of iron deficiency (with or without concurrent anaemia) in pregnant women. This ensures adequate iron stores are present for pregnancy and also at delivery (in case of postpartum bleeding). In particular, the guidelines recommend the use of [intravenous] iron in women who are not responding adequately to oral iron, or who have side effects or issues with gastrointestinal absorption,” they said in a joint email to InSight+.

“Iron replacement is also highlighted in other PBM guidelines (such as the medical module and the perioperative module) as a treatment for iron deficiency anaemia and to optimise patients’ iron stores pre operatively, and, again [intravenous] iron may be used in preference to oral iron for the same reasons.”

Dr Mo and Professor Wood said intravenous iron resulted in a quicker increase in iron stores than oral iron.

“[Intravenous iron] may be the preferred option in some patients, for example, for symptomatic iron deficiency anaemia where a transfusion may be avoided, or if surgery/delivery is imminently approaching.”

Dr Mo and Professor Wood said the ease of intravenous iron treatment had improved since the introduction of ferric carboxymaltose to PBS in 2013–2014 and this was reflected in the study findings.

“Prior to that, iron polymaltose was the main [intravenous] iron preparation and this required lengthy infusion times (approximately 5–6 hours), usually in a hospital setting,” they said.

“Ferric carboxymaltose, on the other hand, can be given over 15–30 minutes, and some recent studies have also shown safety and efficacy in more rapid administration rates. Anecdotally, there is increased uptake of ferric carboxymaltose being used in GP clinics, for instance.”

Professor Greg Anderson, Group Leader and Principal Research Fellow in Iron Metabolism at QIMR Berghofer Medical Research Institute, said iron therapy had proved very popular in Australia.

“It’s certainly true that there has been a large uptake in the use of [intravenous] iron in recent years, particularly in Australia, and this has become a global trend,” Professor Anderson said.

He said many women did not tolerate oral iron supplements well, and the gastrointestinal side effects often resulted in women stopping therapy.

“Iron is essential for normal metabolic function, but it’s also toxic, when present in excess. That’s why you can get organ damage in patients with iron overload disease,” Professor Anderson.

Professor Anderson said that the average dietary iron intake was around 15–20 mg, of which about 2 mg or 10% would be absorbed by the body.

“Oral iron supplements, depending on the preparation, commonly contain 50–60 mg of iron, and sometimes up to 200 mg. So, you are looking up to ten times the amount of iron you would normally have in your diet each day, being given in as a very concentrated dose,” he said.

Professor Anderson said intravenous iron therapy was a more efficient method for replenishing iron stores.

“[Intravenous iron therapy] can deliver a lot of iron very quickly. You don’t have the adverse gastrointestinal effects and you can deliver a lot of iron very quickly,” he said. “Of course, the procedure is not without its limitations. It is more invasive than oral iron supplementation and needs to be delivered by a health care professional, so it is less convenient. Severe reactions to the iron infusions can occur, but they are rare, and some intravenous iron preparations have also led to low body phosphate levels (hypophosphatemia). But, by and large, it has proved a very effective way to deliver a lot of iron quickly and safely.”

The MJA authors noted that possible adverse reactions to intravenous iron therapy included permanent skin staining and the risk, albeit rare, of potentially fatal anaphylaxis.

Dr Mo and Professor Wood said other risks associated with intravenous iron included milder allergic reactions (such as urticaria), other minor side effects (nausea, headache) and complications relating to intravenous cannulation (eg, thrombophlebitis and pain).

“Hypophosphatemia is also another risk associated with [intravenous] iron preparations and phosphate levels should be monitored particularly in patients requiring recurrent or high doses of [intravenous] iron,” they said.

“Despite its relative ease of use and advantages, there are potential complications of [intravenous] iron and patients should certainly be counselled about these risks beforehand.”

Dr Mo and Professor Wood agreed that the cost-effectiveness of the treatment was also very important. They said the PBS price for a standard dose of ferric carboxymaltose (1 g) was $292. “Compared to giving a red cell transfusion (which is around $400 for the manufacturing cost price of one unit, without including hospital/blood bank costs), [intravenous] iron is a cost-effective treatment of iron deficiency anaemia. However, it is more expensive than taking one tablet of oral iron for 4–6 weeks (Ferro-grad C [Mylan Health] costs about $20 for 30 tablets),” they said.

“So, yes, from an overall societal health economy perspective, it is important that [intravenous] iron is used appropriately. We probably need a more detailed formal health economics analysis though, as these are just basic costs, and don’t take into consideration indirect costs such as time off work to have [intravenous] iron versus the benefits of more rapid improvement in symptoms for [intravenous] versus oral iron.”

The MJA authors concluded that the rapid growth in intravenous iron therapy required further scrutiny.

“The rapid growth raises concerns about whether it is being employed appropriately and cost-effectively, given the potential harms and the lack of a strong evidence base for its value for improving quality of life and reproductive health outcomes.”


Poll

Intravenous iron therapy is being overused
  • Strongly agree (24%, 54 Votes)
  • Disagree (24%, 53 Votes)
  • Agree (22%, 48 Votes)
  • Strongly disagree (18%, 41 Votes)
  • Neutral (12%, 27 Votes)

Total Voters: 223

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16 thoughts on “Intravenous iron therapy: are we using it appropriately?

  1. Bridget Caird says:

    I’m a single full time working parent in SA with two daughters recently diagnosed (through GP referred blood tests) with low iron levels. The 12 year old is at level 13 and 15 year old at 23. I am upset because I think we have a good diet with lots of vegetables and red meat. But rapid growth and menstruation seems to have taken it’s toll. My 12 year old has gone from being a very physically active and athletic girl to constantly tired and just wants to lie on her bed and read all day. The treatment is maltofer iron tablets every 2nd day with another blood test in 3 months (I’m also pumping them full of iron rich foods). But I’ve been told it will take 9-12 months to build up their stores! I understand it’s not the protocol or guideline to provide iron infusion for them unless they don’t tolerate the oral iron. The girls exhaustion affects not only them but the whole family. 9-12 months will be a long haul for all of us.

    My question is what is the protocol /guideline on iron infusion versus oral supplementation in this instance? And how long will it take for them to start to feel less tired without an infusion? Should I try to pursue an infusion through the GP anyway?

    Kind regards,
    Bridget

  2. Peter Bradley says:

    All I can say is after 45 years in GP, I personally never had a patient that had true iron deficient anaemia that could not be treated with oral for up to 3 months on alternate days, bar one. She was a patient that was intriguing. Only got iron deficient when pregnant, that is true anaemia – the often common mild anaemia seen in pregnant women is not, being just due to the haemo-dilution one sees in pregnant women from increased plasma volume – something that catches many out, I suspect. This lass did justify parenteral, as she could not absorb it orally when pregnant. Strangely when not pregnant she could. Mystifying…anyway, she elected to have deep IMI injections, after due warning re ‘the stain’ – which she never got because I was careful to retract the subcutaneous tissue and skin aside. Not difficult.

    Then I did have the odd one who was actually early leukaemia, and in one or two cases the ca bowel the surgeon mentioned. And of course a smattering of those with various degrees of thalassaemia.

    This may be a bit harsh or cynical, but knowing how tight the profits are now in GP, (I’m nw retired, but I know how it is, and that was before Covid), I suspect because iron infusion has a separate item in addition to the basic consult, and quite a generous one too, whereas just diagnosing anaemia and putting someone on iron is just a routine consult, may well have had an impact on numbers performed.

  3. Dr Daniel Byrne says:

    The flip side is how many iron infusions are now done in general practice instead of hospital. For example we infuse a patient with coeliac disease every three months or so saving her almost a full day compared to her previous hospital infusions. Our local public hospital refers patients to our general practice for iron infusions – saving public hospital time for more serious conditions.

  4. An Aesthetic says:

    As an anaesthetist who does a lot of perioperative medicine clinics I find IV iron (our hospital only has carboxy) absolutely essential, for 3 reasons:
    -The rate of IDA is very high in surgical patients.
    -The time we have available to treat IDA is short.
    -Many patients have inflammation related to their surgical pathology (due to cancers and arthritis mostly) and cannot absorb oral iron effectively.
    We start a lot of oral iron as well, if we have time, especially for those who are not anemic but have low iron stores: a drop of 20-30 in Hb after a big operation is part of the stress response, in the absence of surgical bleeding, and low iron stores delays functional recovery. I am waiting on the results of a trial to decide how to manage the non-anemic but iron deficient patients. In my hands they mostly get oral iron unless very, very iron deficient. It is very common to see LSCS patients with ferritins of 6- ie absolutely no iron stores; they usually get iron on discharge but should have had it weeks pre-op…….
    We refer a lot of patients for investigation of the cause of their IDA/iron deficiency. When we can we delay anemic patients, even for cancer surgery. But it is tricky in all situations to delay a patient who has already been given a date.

    Preoperative anemia is the main risk factor for perioperative transfusion. Transfusion brings MI, AKI, surgical site infections and, probably/maybe, cancer recurrence. Gulp. Of course the patient has been referred to a surgeon by a doctor who hasn’t done anything about the IDA and seen by a surgeon who hasn’t done anything about the IDA either so perhaps on a systems level me having to use IV iron at the last minute could be seen as a missed opportunity to dodge surgical complications earlier in the process, at less cost. Bearing in mind that not everyone can tolerate or absorb oral iron.

  5. Anonymous says:

    I am EP for 23 years and even in recent times I have been on shifts where people have been referred to the ED for iron transfusions including a toddler who would only drink cows milk, a woman with a Mediterranean background anaemia and a low MCV way out of proportion of the anaemia and a family history of thalassaemia, a woman with 4 children under 10 and a part time job with excessive tiredness Hb in the middle of normal range and a iron just outside the normal range with normal ferritin . Unfortunately these patients wait for hours to be seen among the sick and infectious because somehow it is more urgent on a Friday evening.

    Unfortunately we live in a “if this then that society” where “if low iron then iron transfusion”. What did we do with these patients before the easy iron transfusion and is the general population or even individuals’ health better off because of this? An if so how much better off? I am pleased to see however that it is not only the ED that I work in that gets these referrals.

    There is of course the occasional success story also, the most recent that comes to mind is a 17 yo girl with menorrhagia (being investigated and treated) and symptomatic anaemia with a Hb of 65, who was sent to ED by her gynaecologist for a blood transfusion but advised against it in preference for an iron transfusion. Repeat Hb 10 days later was 95.

    The reason for this boom in therapy in a society that enjoy better health than ever before can only be attributed to ‘social normative behaviour’ and diagnosis creep (overdiagnosis) rather than increase disease prevalence.

  6. Randal Williams says:

    As a general surgeon I have seen many patients over the years treated for iron deficiency anaemia (IDA) for prolonged time periods without checking for a cause. While IDA is common in pregnant women and those with menorrhagia, an explanation otherwise needs to be sought. Every patient presenting with IDA outside these groups got an endoscopy and colonoscopy in my practice. When these were normal the anaemia could be confidently treated with iron therapy. When I was a trainee surgeon it was drummed into me that iron deficiency anaemia is due to colon cancer until proven otherwise, especially in males who have no natural reason to be losing blood. I have seen many cases where this sage advice was ignored, and colon cancer ( usually on the right side) diagnosed too late. These days we also need to check for coeliac disease .

  7. Anonymous says:

    We have a very “now” mentality in Australia at the moment and people want a quick fix rather than 3 months of oral iron. I am always sceptical of “can’t tolerate iron” so needs IV iron infusion. Good to avoid blood transfusions but again as an emergency physician we have patients now presenting every day for iron infusion without a trial of oral iron. Noting the 10 fold expense of IV over oral iron, with the time and money of a prolonged infusion – usually in hospital – we need to be using tablets more. There is always something else to spend medical dollars on. $30 million per year equates to the cost of my ED seeing 210 patients per day – 75000 per year.

  8. Dr Roger Browning says:

    Iron deficiency is a real disease associated with real patient morbidity, which happens to be extremely prevalent in the community and in women of reproductive age. It is not surprising or wrong that we are now actually treating these patients with a treatment that actually works. However like all things in life there needs to be a balance and the decision should be considered and evidence based. There should be evidence that they have an iron deficit, either iron studies or as in my hospital based practice a history of recent major blood loss.
    The pharmacoeconomic evaluation also needs to include an assessment of the overall savings /costs in the health system. Inappropriate use of red cell transfusions for iron deficiency in the community, avoidable perioperative and peripartum transfusions which occur because women and patients turn up for surgery or delivery anaemic. The overall national expenditure on provision of red cells for example have markedly improved over this same time period and I suspect overall national health expenditure on this issue is either neutral or possibly lower.

  9. Michael says:

    I think veganism is part of it. I see lots of women who don’t eat meat and would like an iron infusion as another way of getting iron. I remain unsure of the ethics of this.

  10. Rural GP says:

    Being able to provide Iron Infusions from the surgery has been huge boon for patients and General Practice alike
    I do not think the service is being overused. Patients health and well being has greatly benefited by having this service away from the hospital
    There is abundant evidence that iron deficiency alone causes symptoms and requires treatment. If patient’s attend emergency its because we can find no other access point for them to receive this service.
    Agreed it is never an emergency.
    Our problem is that the traditional spoke and wheel model of hospital care with the specialist / community nurse, makes it is very difficult for us provide this service. Like venesections, if New South Wales Health was to supply us with appropriate materials, we would be more than happy to take on more of his work. We have the skills.
    But where is the funding? If General Practice were funded, we could even provide hospital in the home services, but we cant compete with a free service. But I also suspect a long held hospital culture, with lack of respect and understanding of models for primary care and their funding. The trouble for the Emergency department is that they are at pointy end of a very hospital centered service. Could A+E Managers and NSW Health take a bigger look and consider how they could facilitate General Practice or the MBS to fund this service.
    GP’s have shown they are already taking up the challenge.

  11. Anonymous says:

    agree with Bob Scott.
    It is totally inappropriate that these patients are being sent to Emergency departments, particularly on weekends and after 5PM, with a request for an iron infusion. regardless of someone’s delusion as to its benefits, it is NOT an emergency.
    I would remind Chris Lemoh that the purpose of iron in the body is in making Haemoglobin.
    if a person has low iron but Haemoglobin within normal range, how can it possibly improve mental and physical wellbeing other than as a placebo ?
    furthermore it ishould not be an emergency department issue.

  12. Dr Shamim Siddiqui says:

    Iron infusions are very beneficial especially in pregnant females who have morning sickness and cannot rely on dietary or oral supplements.
    It is good to know that the awareness of iron deficiency has increased and corrected.

  13. James Hurley (general physician) says:

    From the perspective of a general medicine clinic which sees +++ referrals for iron infusion without justification.
    An iron infusion is a great therapy for iron deficiency and nothing else (e.g. ‘chronic fatigue and low mood’ etc, etc).
    The criteria which demonstrate iron deficiency are
    – iron studies (numerous issues in interpretation)
    – microcytic hypochromic anaemia (simple interpretation).
    Without these – iron infusion , no matter how many times it is given, is futile, wasteful and potentially harmful.
    A referral need to have an FBE AND irons studies attached.

  14. Adrian Jameson says:

    Also used postnatally after a PPH where Hb is less than 90 and mother is relatively asymptomatic. It is replacing blood transfusion in these circumstances.
    Hospital based iron infusions are still using the longer slower Iron polymaltose infusion, despite longer stay, staff costs, higher infusion disposable costs, Increased side effects to the patient, unless the patient brings Their own Iron Carboxymaltose supply with them, ie still PBS funded.

  15. Chris Lemoh says:

    I think IV iron has great potential for improving physical and mental health – I see a lot of women with chronic fatigue and low mood, who appear to have symptomatic improvement with IV iron, because their adherence to, and tolerance of of, oral iron supplements is not good.
    I do wonder whether the overall risk-benefit ratio favours IV iron: specifically, are the infusion-related adverse events adequately factored in; and are the risks of iron overload (particularly long-term risks) being accounted for.
    This needs more study in the primary care setting, including long-term quality of life and health measures for women from a diverse range of backgrounds, particularly women from culturally and linguistically diverse backgrounds and those experiencing marginalisation and social disadvantage.

  16. Dr Bob Scott says:

    I agree that that intravenous iron is being overused. I would like to see clear evidence to suggest benefit vs placebo and also conventional oral iron and haematinic supplements.

    As an Emergency physician I’m fed up being sent patients both from general practice and other specialists for an ’emergency iron infusion’. Please stop doing it and I’ll stop refusing to do it and sending these patients back to you.

    Yes, honestly, it’s now become an Emergency thing.

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