Iron Deficiency Anemia: Drug Therapy

Therapeutic target

  • Normalization of the iron balance

Therapy recommendations

  • Iron supplementation (iron substitution; underlying disease must be treated independently) should be given whenever there is manifest iron deficiency anemia:
    • Hemoglobin (Hb) ≥ 8 g/dl, oral iron supplementation; intake on an empty stomach results in 20% higher absorption/uptake (parenteral substitution (here: into the vein) only in exceptional cases, i.e., only if the Hb value does not increase under oral iron supplementation).
    • Hemoglobin (Hb) < 7-8 g/dl, think about red cell concentrate (EC) (How is the patient? Clinical anemia (anemia) symptoms such as headache, floppiness, palpitations? Is there a concurrent infection? Is the Hb on the descending or ascending branch).
    • Hemoglobin (Hb) < 6 g/dl, usually erythrocyte concentrate (EC).
    • Hemoglobin (Hb) < 4.5-5.0 g/dl (< 2.8-3.1 mmol/l): absolute transfusion indication.
  • See also under “Further therapy“.

Further notes

  • Even if the Hb level does not fall below 7 g/dL after gastrointestinal (GI) surgery, but the hemoglobin level has dropped by half or more, postoperative complications must be expected, according to one study. In patients after heart surgery, increased postoperative complications (increased risk of mortality (death rate), apoplexy (stroke), myocardial infarction (heart attack) and renal failure) could also be observed in such cases already in the past.
  • Oral iron supplementation in patients with iron deficiency anemia can be assessed quite reliably after only two weeks. An Hb increase ≥ 1 g/dL by day 14 was considered successful: this was achieved by 73% of patients (= responders). The increase predicted longer-term success with a sensitivity of 90.1% and a specificity of 70.3%; the response was independent of the cause of anemia (anemia).
  • Non-anemic iron-deficient patients (IDNA, iron-deficient non-anaemic) show an improvement in subjectively perceived fatigue after iron therapy, but it has no effect on objectively measurable performance.
  • Patients with anemia due to chronic inflammation (“anemia of chronic inflammation”, ACI) should receive i.v. iron supplementation because of the blockade of enteral iron absorption triggered by hepcidin. As an alternative or adjuvant to iron supplementation, oral lactoferrin can be used in such cases. This reduces the release of proinflammatory cytokines, such as IL-6 and thus the hepcidin release. Note: Hepcidin decreases the function of the iron transport protein ferroportin, resulting in decreased enteric iron absorption (iron uptake by the intestine) and at the same time decreased release of iron from macrophages (phagocytes) and hepatocytes (liver cells).

Active ingredients (main indication)

Iron

  • Iron substitution should be oral with bivalent iron → better absorption than trivalent iron (this is used in parenteral substitution; indicated only in exceptional cases) and fewer side effects
  • Forms of action
    • Oral therapy: ferrous II sulfate, ferrous II gluconate, ferrous II succinate, ferrous II glycine sulfate complex; recommended daily dose for:
      • Adults: 100-200 mg elemental iron
      • Children: 3 – 6 mg/kg body weight (divided into two doses).
    • Parenteral therapy* : Iron III hydroxide dextran complex, iron III sodium gluconate complex, iron III chloride, iron sucrose; only if the Hb level does not increase under oral iron substitution, i.e. iron is poorly absorbed orally due to malabsorption syndrome (diseases caused by impaired absorption of substrates from the intestine).
    • Note: Dextran preparations are reported to have an increased risk of anaphylactic reaction:
      • 2.6-fold increased risk of anaphylaxis compared with use of preparations not containing dextran (odds ratio [OR: 2.6; 95% confidence interval between 2.0 and 3.3; p ˂ 0.001).
      • The lowest risk is reported for the use of iron sucrose.
  • Dosage information: Daily dose of 100-200 mg in two single doses; improve oral iron absorption by simultaneous administration of vitamin C-rich fruit juices.
  • Caveat.Iron intoxication in children already by 5 times the therapeutic dose of an adult! Typical symptoms are nausea, vomiting, diarrhea, toxic hepatitis (liver necrosis), heart failure and metabolic acidosis.
  • Iron overload (especially with parenteral iron supplementation): administration of deferoxamine or deferasirox.
  • Side effects: mainly gastrointestinal symptoms; blackening of the stool.
  • Side effects associated with parenteral administration of iron preparations (iron sucrose, iron carboxymaltose, iron isomaltoside, iron dextran, iron sodium gluconate): Kounis syndrome (acute allergic coronary artery spasm that may lead to myocardial infarction; incidence not known).
  • Duration of therapy: 3-6 months
  • Therapy monitoring based on ferritin levels; successful iron substitution results in an increase in reticulocytes within 1 week of starting therapy. Target parameters (determine after >7 d after iron supplementation):