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This management algorithm has been commissioned and funded by Norgine Pharmaceuticals Ltd and developed in partnership with Guidelines. Norgine Pharmaceuticals Ltd reviewed and approved the scope and pre-meeting documents, suggested a Chair and the experts for the group, and carried out full medical approval on all materials to ensure compliance with regulations. The sponsorship fee included honoraria for the participants. The views and opinions of the participants are not necessarily those of Norgine Pharmaceuticals Ltd, Guidelines, its publisher, advisers, or advertisers.

Index image - IDA management algorithm_new PI

Primary care management of iron deficiency anaemia

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Group members

  • Dr Kevin Barrett (Chair, GPwSI in Gastroenterology)
  • Dr Sonica Goel (GP)
  • Dr Christian Selinger (Consultant Gastroenterologist)
  • Anja St Clair-Jones (Consultant Pharmacist Gastroenterology)

Background

  • Iron deficiency anaemia (IDA) occurs when production of red blood cells is diminished due to a long-term negative balance of stored iron,2 or due to chronic gastrointestinal bleeding, and is a common cause of referral to gastroenterologists2
  • The underlying cause of IDA should be determined and treated, but it is important to intervene in primary care to restore haemoglobin and red blood cells to normal levels, and to replenish iron stores while the underlying cause is investigated2
  • Published guidelines suggest starting treatment of IDA with oral ferrous salts (OFS); if these are not tolerated or the patient does not respond, parenteral iron is the suggested next step3,4
  • An option not considered in existing UK guidelines before escalating to parenteral iron is ferric maltol. In a phase III randomised double-blind clinical trial in patients with inflammatory bowel disease who previously failed to respond to, or were intolerant to OFS, ferric maltol showed clinically meaningful improvements in haemoglobin concentrations, and gastrointestinal side effects reported were similar to those seen with placebo; the most common adverse reactions were gastrointestinal in nature, and of mild or moderate severity5
  • A working party group was brought together to develop an algorithm that includes the option of ferric maltol for the treatment of IDA based on existing clinical guidance, local UK pathways and protocols, and expert consensus. This algorithm excludes:
    • pregnant women, who should be managed as per local guidance and according to the recommendations of the Royal College of Obstetricians & Gynaecologists6
    • patients with chronic kidney disease, who should be managed according to NICE Guideline 87
    • patients with compromised cardiovascular systems, who require hospital admission

Management of patients with IDA

Primary care management of iron-deficiency anaemia

Primary care management of iron-deficiency anaemia

BNF=British National Formulary; FBC=full blood count; OTC=over the counter; SmPC=summary of product characteristics.*Refer to SmPc, BNF or local formulary for dosing and interactions; Table 1 lists key drug interactions.†If no improvement within 3 months, check compliance, consider switching to another oral iron and further investigations. If anaemia worsens or patient becomes moderately or severely symptomatic, refer to secondary care for further investigations, if not already investigated, and for consideration of parenteral iron rather than trying alternative oral iron.

Initial assessment

  • In patients confirmed to have IDA: 
    • identify and investigate red flags according to NICE Guideline 121
    • treat underlying cause of IDA (Box 1) or refer to specialist

Box 1: Possible causes of iron-deficiency anaemia

  • Dietary deficiency
  • Menorrhagia
  • Gastroenterological causes (e.g. coeliac disease, inflammatory bowel disease)
  • Renal causes (e.g. chronic kidney disease, bladder cancer)
  • Medications (e.g. non-steroidal anti-inflammatory drugs)
  • Blood donation
  • Acute blood loss

Management of IDA

  • Start iron treatment while investigations for the underlying cause are underway or while specialist referral is awaited
    • Box 2 provides examples of the ferrous products available, with the amount of elemental iron per dose8

Box 2: Examples of available iron preparations (with amount of elemental iron per dose)8

  • Ferrous fumarate (preferably prescribed as non-proprietary formulation)
    • 210mg tablets (contains 65-70mg elemental iron per tablet)
    • 322 mg tablet (contains 100 mg elemental iron per tablet)
    • 140mg/ml syrup (contains 45mg elemental iron per 5ml)
  • Ferrous gluconate (preferably prescribed as non-proprietary formulation)
    • 300 mg tablet (contains 35 mg elemental iron per tablet)
  • Ferrous sulphate (preferably prescribed as non-proprietary formulation)
    • 200 mg tablet (contains 65 mg elemental iron per tablet)
  • Sodium feredetate (sodium iron edetate) (preferably prescribed as non-proprietary formulation)
    • 190mg/5ml oral solution (contains 27.5mg of elemental iron/5ml)
    • 27.5mg/5ml oral solution (contains 27.5 mg of iron)
  • Ferric maltol
    • 30 mg capsule contains 30 mg elemental iron

Oral ferrous salts

  • Initiate OFS (unless the patient is being referred through the cancer pathway)
    • refer to summary of product characteristics (SmPCs), British National Formulary (BNF), or local formulary for dosing and drug interactions
      • Table 1 provides a summary of common drug–drug interactions8
      • Box 3 provides information on optimising tolerability
    • check tolerability 
      • if tolerated, continue treatment
      • if not tolerated, try a different oral ferrous salt (see Box 1)
    • check full blood count (FBC) in 1 month
      • if FBC is significantly improved on first-line OFS, continue for another 3 months
      • if no improvement within 3 months: 
        • check compliance 
        • consider switching to another oral ferrous salt and further investigations
      • if anaemia worsens or patient is moderately or severely symptomatic, refer to secondary care for: 
        • further investigations, if not already investigated 
        • consideration of parenteral iron rather than trying an alternative oral iron
  • Try an alternative OFS if the patient has poor tolerability or poor response to the first-line OFS:
    • refer to SmPCs, BNF, or local formulary for dosing and drug interactions, as described above (see Table 1; Box 3)
    • check tolerability, as described above
      • if tolerated, continue treatment
      • if not tolerated, try ferric maltol (see Box 1)
    • check FBC in 1 month
      • if FBC is significantly improved on second-line OFS, continue for another 3 months
      • if no improvement within 3 months:
        • check compliance 
        • consider switching to ferric maltol and further investigations
      • if anaemia worsens or patient is moderately or severely symptomatic, refer to secondary care for: 
        • further investigations, if not already investigated 
        • consideration of parenteral iron rather than trying alternative oral iron

For further information on interactions, please refer to the individual SmPCs available at medicines.org.uk

Table 1: Drug-drug interactions8
Medication affected by iron supplement absorptionInteraction/advice

Biphosphonates

  • Complex formation with iron and decrease in bioavailability of biphosphonates
  • Avoid iron supplements 6 hours before or 1–2 hours after biphosphonates 

Levodopa/beneldopa/carbidopa

  • Decrease in bioavailability of carbidopa and/or levodopa
  • Separate times between iron and these drugs by as long as possible

Levothyroxine

  • Decrease in bioavailability of thyroxine (thyroxine and iron form a poorly soluble complex in vitro)
  • Separate absorption by at least 4-5 hours

Bictecravir

  • Iron interferes with gastrointestinal absorption of bictegravir
  • Bictecravir should be administered at least 2 hours before iron supplements or taken together with food

Dolutegravir

  • Chelation of dolutegravir by divalent cations 
  • Administer dolutegravir 2 hours before or 6 hours after iron
  • Alternatively, dolutegravir can be taken simultaneously with iron supplements or with food

Methyldopa

  • Decrease in bioavailability of methyldopa
  • Take methyldopa 2 hours before taking iron supplements

Penicillamine

  • Oral absorption of penicillamine may be reduced by concomitant administration of iron
  • Separate administration by 2 hours

Quinolones

  • Reduced absorption of quinolones
  • Quinolones should be administered 1–2 hours before or at least 4 hours after iron supplements

Tetracyclines

  • Absorption of tetracycline from gastrointestinal tract is impaired by concomitant administration of divalent and trivalent cations such as iron 
  • Take 2–3 hours after iron supplement

Antacids

  • Reduced absorption of iron
  • Take iron 1 hour before or 2 hours after antacids

Calcium supplements

  • Reduced absorption of iron
  • Allow a minimum period of 4 hours before taking calcium

Chloramphenicol

  • Unlikely to occur with ophthalmic preparations

Citric or ascorbic acid and acidic fruit juices (orange juice)

  • Increase absorption of iron
  • Ascorbic acid seems to have an important role in metal ion metabolism, including gastrointestinal absorption of iron and its transport between plasma and storage organs

Other interactions

Entacapone

  • Entacapone may chelate with iron in gastrointestinal tract leading to reduction in absorption of both medications 
  • Entacapone and iron preparations should be taken at least 2–3 hours apart

Trientine

  • Trientine may chelate with iron in gastrointestinal tract leading to reduction in absorption of both medications 
  • Trientene and iron preparations should be taken at least 2–3 hours apart

Zinc

  • Zinc and iron supplements decrease absorption of each other

For further information on interactions, please refer to the individual SmPCs available at medicines.org.uk

Ferric maltol

  • If the patient fails to respond to two different OFS, consider ferric maltol
    • refer to SmPC, BNF, or local formulary for dosing and drug interactions, as described above (Table 1; Box 3)
    • check tolerability, as described above
      • if tolerated, continue treatment
      • if not tolerated, consider parenteral iron
    • check FBC in 1 month
      • if FBC is significantly improved on ferric maltol, continue for another 3 months
      • if no improvement within 3 months:
        • check compliance 
        • consider parenteral iron and further investigations
      • if anaemia worsens or patient is moderately or severely symptomatic, refer to secondary care for: 
        • further investigations, if not already investigated 
        • consideration of parenteral iron rather than trying another alternative oral iron

Parenteral iron

  • If the patient fails to respond to or tolerate OFS or ferric maltol, refer for parenteral iron
  • If anaemia worsens or the patient is moderately or severely symptomatic, refer to secondary care for further investigations, if not already investigated

Follow up

  • Re-check FBC every 3 months for 1 year and then annually going forward (or sooner if the patient becomes symptomatic)
  • Discuss self-management—for example, with over-the-counter iron products and improved nutrition (see Box 4)
  • Consider iron for maintenance, if needed

Box 3: Tips for improving tolerability and absorption9

  • Iron preparations are best absorbed on an empty stomach, to reduce gastrointestinal side-effects:
    • taking with a small amount of food (without high fibre, bran or caffeine, particularly tea, milk or antacid) improves tolerability 
    • taking with orange or vitamin C improves absorption 
  • Iron supplements are prescribed for about 6 months and maintenance on a single daily dose, but alternate-day dosing can be effective for patients with poor tolerability10
  • Switching to a preparation with a lower elemental content may increase tolerability
    (see Box 1)
  • Ferrous sulphate works best when taken on an empty stomach; however, if it upsets the stomach it can be taken with or after food
  • Recommend taking ferrous sulphate with orange juice or a vitamin C supplement—vitamin C is believed to increase the amount of iron absorbed by the body
  • The tablet or capsule should be swallowed whole with a glass of water; they should not be sucked, chewed, or kept in the mouth 
  • Supplements should not be taken with tea, coffee, eggs, dairy products, and soybean products, as they can reduce the amount of iron that gets into the system; when taking ferrous sulphate (or when eating foods that are high in iron), a 2-hour gap should be left before having these foods or drinks

Box 4: Good sources of iron11

  • Liver (should be avoided during pregnancy)
  • Meat 
  • Pulses (beans, peas and lentils)
  • Nuts 
  • Dried fruit (e.g. dried apricots)
  • Wholegrains (e.g. brown rice) 
  • Fortified cereals and breads (with extra iron)
  • Soybean flour 
  • Most dark-green leafy vegetables (e.g. watercress and curly kale)

References

  1. NICE. Suspected cancer: recognition and referral. NICE Guideline 12, 2017. Available at: www.nice.org.uk/ng12  
  2. NICE. Anaemia—iron deficiency. Clinical Knowledge Summary, 2018. Available at: cks.nice.org.uk/anaemia-iron-deficiency  
  3. Goddard A, James M, McIntyre A et al. Guidelines for the management of iron deficiency anaemia. Gut 2011;60: 1309–1316.
  4. Royal College of Nursing. Iron deficiency anaemia in adults—guidance for nursing practice. London, 2019. Available at: www.rcn.org.uk/professional-development/publications/pub-007460#detailTab  
  5. Gasche C, Ahmad T, Tulassay Z et al. Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program. Inflamm Bowel Dis 2015; 21: 579–588.
  6. Royal College of Obstetricians & Gynaecologists. Anaemia. elearning.rcog.org.uk//principles-antenatal-care/screening-maternal-disease/screening-clinical-1 
  7. NICE. Chronic kidney disease: managing anaemia. NICE Guideline 8, 2015. Available at: www.nice.org.uk/ng8  
  8. Electronic Medicines Compendium. www.medicines.org.uk/emc
  9. Auerbach M. Treatment of iron deficiency anemia in adults. Available at: www.uptodate.com/contents/treatment-of-iron-deficiency-anemia-in-adults
  10. Stoffel N, Cercamondi C, Brittenham G et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol 2017; 4 (11): e524–e533.
  11. NHS. Iron. Available at: www.nhs.uk/conditions/vitamins-and-minerals/iron/ 

Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk. Adverse events should also be reported to Norgine Pharmaceuticals Ltd on:
Tel. +44 (0)1895 826 606
E-mail medinfo@norgine.com

This management algorithm has been commissioned and funded by Norgine Pharmaceuticals Ltd and developed in partnership with Guidelines. Norgine Pharmaceuticals Ltd reviewed and approved the scope and pre-meeting documents, suggested a Chair and the experts for the group, and carried out full medical approval on all materials to ensure compliance with regulations. The sponsorship fee included honoraria for the participants. The views and opinions of the participants are not necessarily those of Norgine Pharmaceuticals Ltd, Guidelines, its publisher, advisers, or advertisers.

UK-HAE-FER-2100104

Date of preparation: July 2021