Published: 5 December 2024

Publications

Reminder: risk of hypophosphataemia with iron infusions

Prescriber Update 45(4): 80–82
December 2024

Key messages

  • Hypophosphataemia is a known adverse reaction of iron infusions, especially ferric carboxymaltose.
  • Hypophosphataemia can be severe and prolonged. In some patients, it can cause complications such as osteomalacia and fractures.
  • Consider if a patient is at risk of hypophosphataemia when prescribing parenteral iron.


Parenteral iron is used to treat and/or prevent iron deficiency when oral iron preparations are unsuitable or have been unsuccessful.1 The following parenteral iron preparations are currently approved and funded for use in the community:2,3

  • ferric carboxymaltose (Ferinject)
  • iron polymaltose (Ferrosig).

Parenteral iron use, particularly ferric carboxymaltose, is increasing in New Zealand.4 This article is a reminder that hypophosphataemia can occur following iron infusions.

Risk of hypophosphataemia

Hypophosphataemia is a known adverse reaction associated with the use of ferric carboxymaltose and iron polymaltose,5,6 although the risk is highest with ferric carboxymaltose.7 In clinical trials with ferric carboxymaltose, hypophosphataemia was a common finding on laboratory testing.5

Mechanism

The proposed mechanism for treatment-related hypophosphataemia is an increase in fibroblast growth factor-23 (FGF23), which ultimately leads to excessive renal excretion of phosphate and low serum phosphate.7,8

Severity

Most cases of treatment-related hypophosphataemia are transient and asymptomatic.5 However, severe and prolonged hypophosphataemia and complications of hypophosphataemia (such as osteomalacia [softening of the bones] and fractures) can also occur, particularly in patients with risk factors.5,7,8

Risk factors

Table 1 lists risk factors for treatment-related hypophosphataemia. Patients requiring repeated iron infusions are most at risk of hypophosphataemia and its related complications.7

Table 1: Risk factors for the development of hypophosphataemia with iron infusions

Treatment with ferric carboxymaltose
Recurrent or ongoing blood loss (eg, abnormal uterine bleeding, hereditary haemorrhagic telangiectasia, gastrointestinal bleeding)
Malabsorptive disorders (eg, bariatric surgery, inflammatory bowel disease, coeliac disease)
Normal renal function
Severe iron deficiency
Low body weight
Low baseline serum phosphate
High serum parathyroid hormone (PTH)

Source: Table adapted from Van Doren L, Steinheiser M, Boykin K, et al. 2024. Expert consensus guidelines: Intravenous iron uses, formulations, administration, and management of reactions. American Journal of Hematology 99(7): 1338–48. DOI: 10.1002/ajh.27220 (accessed 16 October 2024).

New Zealand case reports

There were 45 case reports of hypophosphataemia following parenteral iron infusions reported during the period 1 January 2016 to 30 September 2024.

Of the 45 reports:

  • 39 were in females
  • 44 were associated with ferric carboxymaltose
  • 40 were serious.

There were no reports of osteomalacia or fracture with these medicines.

Prescribing considerations

When prescribing parenteral iron:5,7

  • consider the side effect profile of different iron preparations and patient risk factors for hypophosphataemia
  • inform patients about the risk of hypophosphataemia and symptoms to look out for (eg, bone pain, arthralgia, fatigue)
  • monitor phosphate levels in patients at increased risk of hypophosphataemia or related complications
  • re-evaluate treatment if hypophosphataemia occurs.

Further information

  • For more information about parental iron preparations, see the data sheet and consumer medicines information (CMI): Search for a data sheet or CMI.
  • Refer to local clinical guidelines for the management of hypophosphataemia or iron deficiency.

References

  1. New Zealand Formulary (NZF). 2024. NZF v148: Parenteral iron 1 October 2024. URL: nzf.org.nz/nzf_4931 (accessed 31 October 2024).
  2. Pharmac. 2024. Community Schedule 1 November 2024. URL: schedule.pharmac.govt.nz/ScheduleOnline.php (accessed 30 October 2024).
  3. Pharmac. 2024. Hospital Medicines List (HML) 1 November 2024. URL: schedule.pharmac.govt.nz/HMLOnline.php (accessed 30 October 2024).
  4. Health New Zealand. 2024. Pharmaceutical Data web tool version 12 September 2024 (data extracted from the Pharmaceutical Collection on 23 July 2024). URL: tewhatuora.shinyapps.io/pharmaceutical-data-web-tool/ (accessed 4 November 2024).
  5. Seqirus (NZ) Ltd. 2024. Ferinject New Zealand Data Sheet 18 July 2024. URL: medsafe.govt.nz/profs/datasheet/f/ferinjectinj.pdf (accessed 16 October 2024).
  6. Multichem NZ Ltd. 2024. Ferrosig New Zealand Data Sheet 19 January 2024. URL: medsafe.govt.nz/profs/datasheet/f/ferrosiginj.pdf (accessed 16 October 2024).
  7. Van Doren L, Steinheiser M, Boykin K, et al. 2024. Expert consensus guidelines: Intravenous iron uses, formulations, administration, and management of reactions. American Journal of Hematology 99(7): 1338–48. DOI: 10.1002/ajh.27220 (accessed 16 October 2024).
  8. Schaefer B, Tobiasch M, Wagner S, et al. 2022. Hypophosphatemia after intravenous iron therapy: Comprehensive review of clinical findings and recommendations for management. Bone 154: 116202. DOI: 10.1016/j.bone.2021.116202 (accessed 16 October 2024).
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