Iron, intravenous

The first parenteral iron was marketed in Europe in 1947 as iron saccharide. High-molecular-weight iron dextran was introduced in 1954, and low-molecular-weight iron dextran in 1959.

Iron (III) carboxymaltose came on the market in Europe in 2007 (Biggar 2019).

Iron plays a critical role in cellular respiration, oxygen transport, and oxygen storage (Gafter- Gvili 2019).

In iron deficiency, therapeutic use of iron can be oral or parenteral (Herold 2022).

Indication:

The guideline recommends that iron be substituted parenterally only in cases of severe and untreatable absorption disorders (Behnisch 2021).

This may be the case in patients who

- cannot tolerate oral iron

- whose need is quite acute

- suffer from gastrointestinal diseases

- in severe renal insufficiency with large iron depots, but which cannot be mobilized (Wick 2013)

- In certain palliative situations, such as severe heart failure, (Lundgren 2018).

Here, parenteral iron administration for iron deficiency (even without anemia) can relieve symptoms (Lundgren 2018).

- In patients who require iron continuously (Kasper 2015) such as hemodialysis patients (Kuhlmann 2015).

- Hemodialysis patients:

In a meta-analysis of 28 studies, hemodialysis patients were shown to have higher ferritin levels and better transferrin saturation after parenteral substitution of iron than after oral substitution. For this reason, parenteral administration of iron has now become the standard form of administration for these patients. The iron requirement here is between 1,000 - 3,000 mg per year (Kuhlmann 2015).

In peritoneal dialysis patients or predialytic patients, oral iron substitution should primarily be attempted, as their iron requirements are lower (Kuhlmann 2015).

Dosage recommendation:

Trivalent iron is found in the blood bound to the transport protein transferrin (Herold 2022). Trivalent iron is also used in intravenous administration, in contrast to oral therapy where bivalent iron is administered.

Iron from dextran-free high molecular weight stable complexes should be used for parenteral administration. Mixed injections should be avoided at all costs (Herold 2022).

- Iron- (III)- carboxymaltose such as Ferinject should be injected as an infusion up to 1,000 mg 1 x / week -.

- For iron (III) derisomaltose such as MonoFer, the maximum single dose is 20 mg / kg .

- For iron (III) sodium gluconate complex such as Ferrlecit, the maximum single dose is 62.5 mg.

- For iron (III) hydroxide sucrose complex such as Venofer, the maximum single dose is 200-500 mg that can be injected (Herold 2022).

The respective manufacturer's instructions should always be followed.

The injection should be administered slowly (follow the manufacturer's exact time instructions). A short infusion in 100 ml NaCl has proven to be best (Herold 2022).

Side effects:

Parenteral substitution carries a risk of severe allergic reactions. Although the risk of anaphylaxis is lower with modern iron preparations, in addition, high-molecular-weight dextran preparations are now no longer commercially available in Germany (Kuhlmann 2015).

Side effects include:

• Severe allergic reactions
  • occur in 33 cases per 10 million applications with iron dextran
  • occur with iron gluconate in 9 cases per 10 million applications
  • occur with iron sucrose in 6 cases per 10 million applications (Kuhlmann 2015)
• extra-venous injection with
  • severe pain at the injection site (Hitchings 2022)
  • Phlebitis
  • persistent brown discoloration of the skin (Hitchings 2022)
• Headache
• Nausea
• Vomiting
• metallic taste
• cardiac pain
• danger of overdose
• thrombophlebitis (Herold 2022)

Patients with an atopic disposition should not receive parenteral iron because they are at significantly increased risk of serious complications (Hitchings 2022)

In October 2013, because of severe anaphylactic reactions, the German Medical Association and the European Supervisory Authority issued a warning for intravenous iron administration, stating:

- The indication for intravenous therapy is only given after unsuccessful oral treatment

- Possible risk groups are to be identified before starting therapy

- A detailed explanation is necessary before the first treatment and should be repeated at regular intervals.

- The first injection must be given under the direct supervision of a physician.

- Personnel experienced in resuscitation must be in the immediate vicinity

- The recommended infusion duration of 15 - 30 min must be strictly observed

- After the infusion, follow-up monitoring is required. This is 60 min for the first administration and ≥ 30 min for subsequent infusions (Kuhlmann 2015)

However, side effects are found relatively rarely in hemodialysis patients (Kuhlmann 2015).

Duration of use:

The total requirement is based on the product information. The normalization of hemoglobin is the surest indicator of sufficient substitution.

Serum ferritin should reach about 100 µg / l and transferrin saturation (TSAT) should be between 20 - 45% (Herold 2022). In any case, an increase in transferrin saturation to > 50 % should be avoided, as iron is toxic to cells. If this transferrin saturation persists for a long time, it is an indication of tissue iron overload (Kasper 2015).

Preparations:

- Ferric (III) carboxymaltose such as Ferinject.

- Iron (III) derisomaltose, e.g. MonoFer

- Iron (III) sodium gluconate complex such as Ferrlecit

- Iron (III) hydroxide-sucrose complex, e.g. Venofer (Herold 2022)

Iron preparations based on high-molecular-weight dextran are no longer commercially available in Germany because of the high risk of anaphylaxis (Biggar 2019).

In recent years, parenteral administration has increased significantly (Kasper 2015).

Laboratory controls:

An increase in Hb- levels is already found after 2 - 3 weeks (Kuhlmann 2015).

However, the earliest laboratory control should be 8 - 12 weeks after the last iron administration, as false positive values may be indicated before that (Herold 2022).

1. Behnisch W, Muckenthaler M, Kulozik A (2021) AWMF guideline: Iron deficiency anemia. Registration number 025 - 021
2. Biggar P, Langguth P, Krayenbühl P A, Brandenburg V (2019) Intravenous iron substitution in chronic disease - in whom, when and how? Dtsch Med Wochenschr(144) 969 - 977.
3. Gafter- Gvili A, Schechter A, Rozen- Zvi B (2019) Iron deficiency anemia in chronic kidney disease. Acta Haematol. 142 (1) 44 - 50
4. Herold G et al (2022) Internal Medicine. Herold Publishers 33 - 38
5. Hitchings A, Lonsdale D, Burrage D, Baker E, Waldner M, Jefremow A, Bott A (2022) The top 100 drugs: practical pharmacology for everyday clinical practice. Elsevier Urban and Fischer Publishers Munich
6. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education, 625 - 629
7. Kuhlmann U, Böhler J, Luft F C, Alscher M D, Kunzendorf U (2015) Nephrology: pathophysiology - clinic - renal replacement procedures. Georg Thieme Verlag Stuttgart / New York 412 - 413.
8. Lundgren C et al (2018) Drug therapy in the elderly. Elsevier Urban and Fischer Publishers 104 - 105.
9. Wick M, Pinggera W, Lehmann P (2013) Clinic and laboratory - iron metabolism and anemia: new concepts in renal and tumor anemias. Springer Verlag Vienna 80