Iron supplementation: Practical tips for managing side effects

Sophia Auld

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Sophia Auld

Medical Writer

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Sophia Auld

Even inconsequential side effects of iron therapy sometimes land people in the ED undergoing needless tests, while the serious ones can be life-threatening.

Side effects of oral iron therapy are common

Approximately 40% of patients taking oral iron will experience either nausea, constipation, abdominal pain or a combination of these, says GP Clinical Associate Professor Pradeep Jayasuriya, founder of the WA Iron Centre, a Perth private clinic that treats people with iron deficiency issues.

These side effects may be mild to severe and can occur with any preparation, he says.

“Despite what the drug companies will tell you … the bottom line is that they are very similar in practice. It’s hard to predict which patients are going to get these side effects and which ones aren’t. The only way you know is by giving them the tablets and seeing what happens.”

It’s important to let patients know about these side effects—and to warn them their stools will turn black.

“That’s of no clinical consequence but it is obviously quite alarming when patients get that if they haven’t been forewarned. And every year there are attendances at ED departments with patients presenting with black stools.”

“And if doctors in the hospital don’t take a good medication history and don’t realise that they’re taking oral iron, they assume the black stools are from bleeding. And that leads to a whole cascade of unnecessary investigation and treatment.”

Clinical tip: Patients need to take approximately 100mg of elemental iron every second day, but iron tablets are not all the same. It’s essential to check the fine print for the elemental iron content. “My advice to GPs is become familiar with two or three iron preparations. And tell patients they need to ask their chemist for those particular preparations.”

Managing side effects of oral iron

Constipation is by far the most common side effect and some specialists routinely prescribe a stool softener with iron tablets, Associate Professor Jayasuriya says.

“My practice is I review them a few weeks after they’ve started iron therapy and if they’re getting constipation and it’s not too severe, I then suggest that they use a stool softener.”

Nausea and abdominal pain are a bit more difficult to manage, he says, although they often abate over time if minor. He recommends waiting a maximum of two weeks to see if they settle.

Reducing the frequency of the medication may help.

“The standard approach to oral supplementation is second daily medication. But if patients are getting nausea or abdominal pain, you might give it every third day, or two or three times a week, until their body adapts. And then you can increase the frequency back up to the alternate day.”

If side effects are severe, you can try a different oral preparation.

“My practice is to try two different agents and if they still get problems, I’d think of intravenous supplementation at that point.”

Intravenous iron side effects

Intravenous iron is safe, “but like anything that is injected, there is a risk of side effects,” Associate Professor Jayasuriya says.

Serious side effects

These are rare and include anaphylaxis, which occurs in about one in 250,000 cases, he says.

Putting this in context, “it is equivalent to the anaphylaxis reaction you get with intravenous contrasts to radiological investigations like CT scans.”

Certain conditions place people at a higher risk of anaphylaxis with IV iron therapy, including:

  • A previous reaction to IV iron or other medications
  • A fast iron infusion rate
  • Severe asthma or eczema
  • Systemic mastocytosis
  • Severe respiratory or cardiac disease
  • Old age
  • Use of beta-blockers or ACE inhibitors.

It’s important to screen carefully for these before an infusion, Associate Professor Jayasuriya says.

Patients at moderate risk may need pre-treatment with something—such as an antihistamine or steroids—before the infusion, he adds. This should be done in conjunction with an immunologist or other expert.

“And for those that are high risk, you may want to do them in a hospital setting.

Hypophosphatemia is common after IV iron therapy, but clinically significant hypophosphatemia is very rare, Associate Professor Jayasuriya says, so you don’t need to test phosphate before or after treatment unless patients have hypophosphatemia symptoms.

True hypophosphatemia often necessitates intravenous phosphate replacement.

Rashes are reported in approximately 1 in 10,000 cases and should be treated with an antihistamine.

Another relatively uncommon but potentially serious and irreversible consequence of IV iron is staining.

“This is not a side effect, but an error in administration,” Associate Professor Jayasuriya says, stressing that appropriate measures can help mitigate the risk.

“It’s really important that you find a decent sized vein in the forearm or elbow and that you’re absolutely sure the cannula is sitting in that vein, that you flush the line and make sure there is blood coming back. And if there’s any sign of pain or disturbance of flow, then the infusion needs to be stopped. A nurse or doctor needs to be with the patient all the time through the infusion so that they can be alert to this occurring.”

Infusion is the gold standard for administering IV iron, he adds, noting that an infusion pump will cut out if the cannula tissues. “That gives you an added layer of safety.”

“And if you’re not sure, either get someone else to do it, do it under ultrasound, or whatever. But if you’re in doubt, abandon.”

Minor side effects of IV iron

Approximately one in four people will experience headaches, nausea fever, muscle pain, diarrhoea, flu-like symptoms, a metallic taste in the mouth, or any combination of these for a few days after treatment. To prevent unnecessary worry, let patients know they might get these side effects.

The incidence of minor side effects may be reduced by ensuring the patient is well hydrated before and after the infusion and by using a lower infusion rate.

“We actually now start our infusions very slowly and then pick up the speed. That has reduced our minor adverse reactions by around 5-10%,” Associate Professor Jayasuriya says.

Importantly, another common minor reaction that can occur during the infusion—known as a Fishbane reaction—can mimic anaphylaxis.

“Patients are about five minutes into the infusion, they would complain of tightness in the chest, muscle pain, flushing. And the GP needs to ask themselves whether this represents anaphylaxis or not.”

The two can be distinguished, however.

“The hallmark of a Fishbane reaction is once you turn the infusion off, the symptoms will go away, and you can restart the infusion and they’re fine afterwards.”

Vital signs including blood pressure and oxygen saturation also remain stable during a Fishbane reaction.

When to refer for IV iron

Associate Professor Jayasuriya says this comes down to the level of risk of adverse reactions identified in screening and how comfortable you are managing side effects and adverse reactions. 

“Where do you draw the line in what risk you’re prepared to take in your practice and which ones you think need to go elsewhere? I think that’s a very individual decision.”

It may help to talk to an immunologist or someone experienced with anaphylaxis and allergic reactions before choosing whether to proceed, he adds.

The bottom line?

“If you’re not sure, don’t do it.”

Key messages:

Oral iron treatment

  • Gastrointestinal side effects occur in about 40% of patients.
  • Constipation is the most common and may be managed with a stool softener.
  • Minor nausea and abdominal pain often settle in the first week or two.
  • If side effects are significant or persistent you can trial another preparation. If they still have problems, consider IV iron.

IV iron treatment

  • Serious side effects include anaphylaxis and clinically significant hypophosphatemia, but these are rare.
  • It’s essential to conduct a thorough risk assessment before treatment and to explain risks to the patient.
  • A Fishbane reaction can mimic anaphylaxis, but symptoms stop when you cease the infusion, after which it can be restarted.
  • Rashes occur in about one in 10,000 cases and should be treated with an antihistamine.
  • Risk of staining can be mitigated by appropriate cannula positioning and a slow infusion rate.
  • A nurse or doctor should stay with the patient to quickly identify and deal with any adverse events.
  • If you’re not sure, refer.

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Sophia Auld

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Sophia Auld

Medical Writer

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