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Ferric carboxymaltose and low blood phosphorous

Medicines Safety Update

27 February 2020

Health professionals are reminded that symptomatic hypophosphataemia is a known risk associated with use of ferric carboxymaltose and it is recommended that you routinely evaluate patient risk factors before commencing this medicine and follow up at-risk patients.

Ferric carboxymaltose is marketed in Australia under the brand name Ferinject. It is administered intravenously for treatment of iron deficiency when oral iron preparations are ineffective or cannot be used. The diagnosis must be based on laboratory tests.

Ferric carboxymaltose is known to cause mild asymptomatic transient hypophosphataemia. Ferric carboxymaltose is also associated with a rare risk of severe, symptomatic hypophosphataemia. In clinical trials, the minimum serum phosphate values were obtained after approximately 2 weeks, and in most cases returned to baseline values by 12 weeks following ferric carboxymaltose treatment. The Ferinject Product Information was updated in 2019 to include additional details about this precaution.

Mild hypophosphataemia is usually asymptomatic, but may present with pain, nausea, and asthenia. Severe hypophosphataemia may be associated with symptomatic physiological dysfunction. Acute manifestations include:

  • muscular symptoms (weakness, asthenia, leading to progressive myopathy including cardiorespiratory compromise and death)
  • neurological symptoms (tingling, altered mental status, seizures, paralysis)
  • haematological changes.

The development of clinically significant hypophosphataemia following parenteral iron is more likely in patients on long-term iron replacement, and in those with lower baseline ferritin, gastrointestinal disorders, malnutrition or other causes of phosphate deficiency (low whole body phosphate).

Hypophosphataemia can be the cause of asthenia, fatigue, muscular weakness, breathlessness, tachycardia and headaches, which might otherwise be misdiagnosed as failure to respond to treatment of iron deficiency anaemia, therefore consider hypophosphataemia as a potential reason for a patients' symptoms continuing after use of ferric carboxymaltose.

In pregnancy the maximum cumulative dose is restricted to 1000 mg for patients with Hb ≥90 g/L, or 1500 mg in patients with Hb <90 g/L. No more than 1000 mg iron should be administered in one week.

The TGA adverse event database has 15 reports of hypophosphataemia with ferric carboxymaltose (including 14 where it was the sole suspected medicine). There were six reports of hypophosphataemia relating to iron polymaltose, and no reports involving other parenteral iron products.

For ferric carboxymaltose, serum phosphate was reported in six cases, with severe hypophosphataemia (<0.3mmol/L) reported in four cases. Five cases reported systemic symptoms of hypophosphataemia (fatigue, malaise, lethargy) and skeletal manifestations of hypophosphataemia were reported in three cases. Most patients recovered with oral phosphate, calcitriol or with IV phosphate supplementation, but the outcome was reported as 'not recovered' in two cases.

Time to onset, where reported, was generally from a few days up to two weeks after starting ferric carboxymaltose.


What to report? You don't need to be certain, just suspicious!

The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.

We particularly request reports of:

  • all suspected reactions to new medicines(look for the Black Triangle ▼ in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
  • all suspected medicines interactions
  • suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.

Reports may be submitted:

For more information about reporting, visit www.tga.gov.au or contact the TGA's Pharmacovigilance and Special Access Branch ADR.Reports@tga.gov.au.

Disclaimer

Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.

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Medicines Safety Update is written by staff from the Pharmacovigilance and Special Access Branch.

Editor: Dr Grant Pegg

Deputy Editor: Mr Michael Pittman

Contributor: Dr Neillan Nandapalan