Iron - a medication update

ANF iFOLIO CLINICAL UPDATE: Iron: a medication update Iron: a medication update

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Brand names: Ferrous fumarate - Ferro-tab1 Iron polymaltose - Maltofer, Ferrosig, Ferrum1 Ferrous sulfate - Ferro-grad, Ferrovance, FerroLiquid1 Iron sucrose - Venofer1 Ferric carboxymaltose - Ferinject1 Ferric derisomaltose - Monofer1

Drug class: endocrine and metabolic1

MECHANISM OF ACTION

Iron plays a crucial role in oxygen transport, oxidative metabolism, cellular proliferation, and many catalytic reactions.2 Iron supplements replace the body’s iron stores and encourage erythropoiesis (the development of mature red blood cells) and oxygen transportation throughout the body.3

ADMINISTRATION

Iron supplements are generally administered orally.1,3 However, iron supplements may be administered by intravenous injection or infusion when oral supplements are ineffective, inappropriate, or not tolerated.1,3,4

Intramuscular administration is no longer recommended due to severe injection site pain, skin staining, and inconsistent absorption.3,5

INDICATIONS

The only indication for iron supplements is the prevention and treatment of iron deficiency anaemia.1

CONTRAINDICATIONS

Iron is contraindicated in patients with:4,6

• Hypersensitivity to iron • Anaemia not caused by iron deficiency • Evidence of iron overload, such as haemochromatosis and haemosiderosis • Evidence of disturbance in the utilisation of iron. INTERACTIONS

Iron has a number of clinically meaningful drug interactions.

Antacids, calcium, proton pump inhibitors, H2receptors antagonists, and tetracyclines may decrease the absorption of oral iron supplements.5,7 Administration times should be separated by as long as possible to minimise interactions.7

Iron supplements affect the absorption of levodopa, carbidopa, quinolones, eltrombopag, bictegravir, oral bisphosphonates, thyroid hormones, penicillamine, tetracyclines, and dolutegravir.7 Administration times should be separated by as long as possible to minimise interactions: 7

• Doses of iron and quinolone, bictegravir, oral bisphosphonates, penicillamine, or tetracyclines should be separated by at least two hours • Doses of iron and eltrombopag should be separated by four hours • Doses of iron and thyroid hormones should be separated by four to five hours • Iron should be administered at least six hours before or two hours after dolutegravir. Intravenous iron supplements may decrease the absorption of oral iron supplements.4 Oral iron supplements should not be administered for at least five days after the last dose of intravenous iron therapy.4

DOSAGE

The dosage and duration of iron supplementation should be individualised to the patient based upon the extent of iron deficiency.1

Iron dosage is express in terms of elemental iron (1mg elemental iron is approximately equivalent to 3mg ferrous fumarate, 3.7mg iron polymaltose, 3mg dried ferrous sulfate, 5mg liquid ferrous sulfate).1

Treatment of iron deficiency anaemia1

Adult oral 100-200mg elemental iron daily or IV dose in accordance with local protocols

Child

oral 3-6mg/kg (maximum 100200mg) elemental iron daily or IV dose in accordance with local protocols

Prevention of iron deficiency anaemia1

Pregnant adult oral 60-120mg elemental iron daily

Child 4-12 months

Child >12 months oral 1mg/kg elemental iron daily

oral 1-2mg/kg (maximum 15-30mg) elemental iron daily

Gastrointestinal tolerability of oral iron supplements may be increased by starting at a low dose and gradually increasing after two to four weeks, by divided doses, by alternate day dosing, or by taking supplements with food.1,5 To prevent teeth discolouration liquid oral supplements may be diluted with water, consumed through a straw, and followed with a drink of plain water.1

Patients receiving intravenous iron should be closely monitored for adverse effects for at least 30 minutes after administration.1

PRECAUTIONS

Hepatic impairment

Ferric carboxymaltose should be used with caution in patients with hepatic impairment.4 Ferric carboxymaltose should only be used if the expected benefit is considered to outweigh the potential risk, and the patient’s liver function is closely monitored.4

Pregnancy and breastfeeding

Oral and intravenous iron supplements have been shown to be safe and effective in the treatment of iron deficiency anaemia in pregnancy.8,9,10,11 However, oral supplementation is preferred during the first trimester due to limited evidence in the use of intravenous supplements.8,9,10,11 Oral and intravenous iron supplements are safe to use while breastfeeding.8,9,10,11

ADVERSE EFFECTS

The most common adverse effects associated with oral iron supplementation are gastrointestinal, such as nausea, vomiting, bloating, constipation, abdominal pain, diarrhoea, and black discolouration of the faeces.1 Liquid oral supplements are also associated with black discolouration of teeth.1

Intravenous iron is generally well tolerated.5 Adverse effects associated with intravenous iron are nausea, vomiting, taste disturbance, injection site reactions, headache, fever, arthralgia, myalgia, blood pressure changes, chest pain, tachycardia, bronchospasm, rash, and hypophosphataemia.1 Rarely, intravenous iron is associated with anaphylactic reactions.1,3 REFERENCES

1.

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4.

5. Iron. 2021 [cited 2021 Aug 10]. In: Australian Medicines Handbook [Internet]. Adelaide (Australia): Australian Medicines Handbook. Available from: https://amhonlineamh-net-au/chapters/blood-electrolytes/drugs-anaemias/other-drugs-anaemias/iron

Yiannikourides A, Latunde-Dada GO. A Short Review of Iron Megabolism and Pathophysiology of Iron Disorders. Medicines [Internet]. 2019 [cited 2021 Aug 30];6(85). doi: 10.3390/medicines6030085

Nguyen M, Tadi P. Iron Supplementation. 2021 [cited 2021 Aug 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing LLC. Available from: https:// www.ncbi.nlm.nih.gov/books/NBK557376

Ferinject. 2021 [cited 2021 Aug 31]. In: MIMS Online database [Internet]. North Sydney (Australia): MIMS Australia. Available from: https://www.mimsonline. com.au/Search/FullPI.aspx?ModuleName=Product %20Info&searchKeyword=Ferric+carboxymaltose&PreviousPage=~/Search/QuickSearch.aspx&SearchType=&ID=91220001_2#Top

Iron deficiency. 2021 [cited 2021 Aug 31]. In: eTG Complete [Internet]. Melbourne (Australia): Therapeutic Guidelines Limited. Available from: https://tgldcdptg-org-au/ viewTopic?topicfile=iron-deficency#toc_ d1e234

6.

7.

8. Maltofer. 2021 [cited 2021 Aug 31]. In: MIMS Online database [Internet]. North Sydney (Australia): MIMS Australia. Available from: https://www.mimsonline.com. au/Search/FullPI.aspx?ModuleName=Product %20Info&searchKeyword=maltofer&PreviousPage=~/Search/ QuickSearch.aspx&SearchType=&ID=6800001_2

Drug interactions: Iron. 2021 [cited 2021 Aug 30]. In: Australian Medicines Handbook [Internet]. Adelaide (Australia): Australian Medicines Handbook. Available from: https://amhonline.amh.net.au/interactions/iron

Ferric carboxymaltose. 2020 [cited 2021 Aug 31]. In: Pregnancy and Breastfeeding Medicines Guide [Internet]. Melbourne (Australia): The Royal Women’s Hospital. Available from: https://thewomenspbmg.org.au/ medicines/ferric-carboxymaltose

9. Ferrous fumarate/sulfate. 2020 [cited 2021 Aug 31].

In: Pregnancy and Breastfeeding Medicines Guide [Internet]. Melbourne (Australia): The Royal Women’s Hospital. Available from: https://thewomenspbmg.org.au/ medicines/ ferrous-fumarate-sulphate 10. Iron polymaltose. 2020 [cited 2021 Aug 31]. In: Pregnancy and Breastfeeding Medicines Guide [Internet].

Melbourne (Australia): The Royal Women’s Hospital.

Available from: https://thewomenspbmg.org.au/ medicines/iron-polymaltose 11. Iron sucrose. 2019 [cited 2021 Aug 31]. In: Pregnancy and Breastfeeding Medicines Guide [Internet]. Melbourne (Australia): The Royal Women’s Hospital. Available from: https://thewomenspbmg.org.au/ medicines/ iron-sucrose