Parenteral Iron

Indications

Severe Iron Deficiency Anemia and iron malabsorption
Chronic bleeding not corrected by other means
Oral iron not tolerated
Severe Anemia and refusal of Blood Transfusion

Medications

Sodium Ferric Gluconate (Ferrlecit)
1. Dosing: 125 mg (10 ml) of 62.5 mg/5 ml solution diluted in 100 ml saline
2. May give weekly IV for 8 weeks (total: 1 gram)
3. Much safer than Iron Dextran
4. Test dose recommended with 2 ml diluted in 50 ml saline infused over 1 hour prior to first infusion
Iron sucrose (Venofer)
1. Much safer than Iron Dextran (no test dose needed)
2. Dosing: 100 mg (20 ml) IV of 20 mg/ml solution for 5 doses over 2 week period (1-3 times per week)
3. Risk of Hypophosphatemia
Ferumoxytol (Feraheme)
1. Single infusion given over 5 minutes supplies 510 mg elemental iron per 17 ml solution
2. May repeat in 3-8 days for second injection
3. U.S. FDA black box warning for serious Allergic Reactions (monitor for Hypersensitivity, Hypotension)
Ferric Carboxymaltose (Injectafer)
1. Available as 750 mg/15 ml solution
2. Monitor for Hypersensitivity
3. Variable Blood Pressure effects with Hypertension in 3.8% and Hypotension in 1% of patients
4. Risk of Hypophosphatemia (symptomatic in 25%, extreme in 2% with symptoms lasting weeks)
  1. Monitor Serum Phosphorus (esp. if iron infusion repeated)
  2. Less common when Creatinine Clearance <60 ml/min
  3. Dashwood (2021) J Clin Pharmacol 61(4):515-21 +PMID: 33051909 [PubMed]
5. Dosing
  1. Weight >50 kg (110 lb): Give 750 mg (15 ml) in 2 doses at 7 days apart
  2. Weight <50 kg (110 lb): Give 15 mg/kg in 2 doses at 7 days apart
Ferric Derisomaltose (Monoferric)
1. Dosing (single dose)
  1. Weight >50 kg (110 lb): 1000 mg for intravenous infusion over >=20 minutes
  2. Weight <50 kg (110 lb): 20 mg/kg intravenous infusion over >=20 minutes
Iron Dextran (Imferon, Dexferrum, Infed)
1. High rate of serious reaction (requires test dose of 0.5 ml one hour before infusion)
2. Replaced by newer agents (e.g. Ferrlecit, Feraheme, Venofer)
3. Intramuscular or Intravenous
4. Available as 50 mg/ml
5. Dose based on estimated iron deficits

Precautions

Intravenous Iron must be started very slowly
Avoid in patients with acute or chronic infections

Efficacy

Hemoglobin increased 2 g/dl (NNT 5)
Red Blood Cell Transfusion avoided (NNT 36)
Oral iron is as effective as Parenteral Iron in preventing Blood Transfusion and mortality
1. Oral iron is preferred in those without significant malabsorption or other barriers to oral ingestion
2. Mounsey (2022) Am Fam Physician 106(2): 191-2 [PubMed]

Adverse Effects

Skin staining at site of Intramuscular Injection
1. Consider Z-tract injection technique
Severe pain at injection site
Infection Risk (NNH: 62)
1. Avoid use in active Bacterial Infection, due to iron facilitating Bacterial growth
2. Beaudoin (2022) Am Fam Physician 106(3): 245A-C [PubMed]
3. Shah (2021) JAMA Netw Open 4(11): e2133935 [PubMed]
Delayed reaction (24-48 hours after administered)
1. Myalgias and Arthralgias
2. Headache
Anaphylaxis
1. Not an IgE mediated reaction
  1. Complement Activation related pseudoallergy
2. Agents newer than Iron Dextran have much lower infusion reactions
  1. Occurs in 0.61% of patients given Iron Dextran
  2. Occurs in 0.04% of patients given ferric gluconate
3. Risk Factors
  1. Prior reactions to IV iron
  2. Fast iron infusion rates
  3. Multiple drug allergies
Hyperphosphatemia
1. IV Iron increases fibroblast growth factor 23 (regulates Vitamin D and phosphate)
  1. Triggers phosphate increased renal loss
  2. Typically mild, but may be severe wth ferric carboxymaltose (Injectafer)

References