In response to the saline shortage, companies that make IV iron are reminding GPs that it can be injected in its undiluted form – but could changing the method of delivery put GPs and patients at risk?

Two pharmaceutical companies that market IV iron have begun promoting direct undiluted injections as a solution to the ongoing saline shortage.

Last week our clinic, which specialises in IV iron infusions, received a direct e-mail from one of these companies to “reassure” us that their product could be administered by IV injection using undiluted solution.

Meanwhile a Frequently Asked Questions (FAQ) document circulated by another one of these companies suggests that if time or resources are limited, practitioners can opt for a quicker bolus injection of iron.

This advice is questionable, as iron deficiency is typically a chronic condition, and treatment delays are rarely life-threatening. Urgent intravenous iron is only necessary in specific situations, such as third-trimester pregnancy, acute bleeding to avoid transfusion, and preoperative cases.

What is the evidence behind the two approaches for intravenous iron delivery

To understand the potential safety and legal implications of changing the method of administration, it helps to know a bit more about the protocols and evidence-base for the widely-used diluted infusion method of administration and the less common direct undiluted injection.

Infusion method:

This involves diluting iron in varying amounts of saline and delivering it at different rates. The optimal dilution and speed for infusion are not yet fully supported by robust evidence.

However, the most common approach, favoured by hospitals, involves a 15-20 minute infusion in 100 ml of saline.

This method gained popularity because it was the approach used in many large-scale clinical trials that established the efficacy and safety of intravenous iron. Consequently, it can be regarded as the “standard” from a legal perspective.

While faster infusions with smaller dilutions are possible, these variations have not been rigorously evaluated for safety.

Direct intravenous injection:

This method, administered over a short span of 2-3 minutes, is rarely used, and its safety compared to standard infusion remains uncertain. A review of existing literature reveals a lack of high-quality research, with no well-designed independent studies conducted on representative populations. Interestingly, the Product Information (PI) for the two most commonly used iron products in Australia lists both methods.

However, supportive evidence for direct injection is scant.

One company provided a single small-scale study which showed no statistical difference, but a greater number of patients with adverse events in the group that had the direct injection method. The other company has yet to provide any substantial evidence, despite me requesting it several days ago, raising questions about why regulatory bodies like the Therapeutic Goods Administration (TGA) allowed this method to be included in the first place.

The FAQ being circulated cites secondary outcomes from two small clinical trials (here and here) that showed comparable incidence of adverse events between different therapeutic arms.

Disregarding the tenuous evidence supporting direct injections, the argument that it is acceptable practice because it is in the PI is questionable. After all, intramuscular injection remains in the PI for iron polymalotse, whilst it is not recommended as a mode of administration.

Safety concerns and legal implications

The safety of intravenous iron is well-established, but it must be administered according to accepted protocols to minimise adverse reactions. One of the most concerning complications is skin staining, which occurs when iron leaks outside the vein during administration. This issue is particularly significant for younger women, who constitute the majority of recipients.

The incidence of staining ranges from 0.68% to 1.3%, which is still considered unacceptable by some. To mitigate this risk, best practices include using an infusion pump, adhering to endorsed protocols, having a nurse present during the procedure, and ensuring proper patient education and consent.

Direct injection theoretically increases the risk of staining due to the higher mobility of the cannula and the larger amount of iron that could leak in the event of extravasation. However, no conclusive studies have confirmed this risk, leaving practitioners in a difficult position. Given this uncertainty, the safer option remains the diluted infusion method, which allows for greater control.

Safety vs commercial interests

Prescriptions for intravenous iron have grown enormously over the last five years, with most prescribed in primary care.

The sudden promotion of direct injection is puzzling, especially considering that these companies have previously invested heavily in supporting the infusion method, including funding clinical trials that use infusion.

While we can’t know for sure what is driving the shift in approach, one does wonder if commercial realities could be at play. The suggestion that a potentially less safe method should be adopted due to time constraints is illogical.

The Bottom Line

The current saline shortage highlights how commercial realities in the pharmaceutical industry can shape medical practices.

As the saline shortage continues to affect the administration of iron in general practice, it is essential that decisions are based on sound evidence rather than industry pressure.

Unlike the COVID-19 pandemic, this situation does not warrant urgent changes to established practices. Practitioners and health service managers must prioritise patient safety and consider the medico-legal risks when deciding on alternative methods.

Moving away from ‘standard’ practice without clear evidence benefits only the pharmaceutical industry, while the responsibility for any adverse outcomes ultimately falls on the practitioners.

In conclusion, while the saline shortage presents challenges, it should not push healthcare providers into adopting practices that may compromise patient safety.

The infusion method remains the safer choice until more reliable evidence supports the alternatives.