Parenteral Iron Preparations

Parenteral iron preparations are iron-carbohydrate complexes given intravenously to replace deficit rapidly, bypassing intestinal absorption. They are used when oral iron fails or is not tolerated, when absorption is impaired, when losses are ongoing, or when speed matters. Modern preparations carry a low risk of serious hypersensitivity, but resuscitation facilities must be available.

Mechanism. The complex is taken up by macrophages of the reticuloendothelial system, which release iron to transferrin. Stronger complexes allow large single doses (up to 1000 mg); weaker complexes need smaller repeated doses.

Pharmacokinetics. Plasma half-life ranges from hours (iron sucrose) to 20 hours (ferric carboxymaltose, ferric derisomaltose). Haemoglobin rises within 1 to 2 weeks, faster than with oral iron.

Total iron deficit (Ganzoni). Weight in kg multiplied by the difference between target and actual haemoglobin in g/dL, multiplied by 2.4, plus 500 mg for stores (use 1000 mg stores for patients over 35 kg with heart failure or large deficits). Target haemoglobin is usually 15 g/dL.

• First-line. Intolerance of or failure to respond to oral iron; chronic kidney disease with iron deficiency; heart failure with iron deficiency (ferritin under 100 micrograms/L, or 100 to 299 micrograms/L with transferrin saturation under 20%); inflammatory bowel disease; malabsorption.
• Alternative. Second and third trimester of pregnancy with moderate or severe anaemia; before surgery when time is short; chemotherapy-related anaemia with iron deficiency.
• Specialist. Intravenous iron with erythropoiesis-stimulating agents in kidney disease; paediatric use.
• Emergency. Not used for acute resuscitation.

Selection. Large single-dose preparations reduce visits and cost of administration; use ferric derisomaltose or iron sucrose when repeated doses are expected to avoid hypophosphataemia; treat infection first.

Administration. Give in a setting with resuscitation equipment, adrenaline, oxygen and staff trained to recognise anaphylaxis. Observe for 30 minutes after infusion. A test dose is not needed for modern preparations. Do not give with oral iron.

Contraindications. Hypersensitivity; iron overload; anaemia not caused by iron deficiency; active infection or sepsis (relative); first trimester of pregnancy; decompensated liver disease (relative).

Serious adverse effects.

• Hypersensitivity, from infusion reactions (flushing, chest tightness, back pain; often not true allergy, settle with slowing or pausing) to anaphylaxis (rare, under 1 in 10 000).
• Hypophosphataemia with ferric carboxymaltose, which can cause osteomalacia with repeated doses.
• Hypotension, headache, nausea, skin staining from extravasation, fever and arthralgia.

Infusion reaction management. Stop the infusion, assess airway, breathing and circulation; if mild (flushing, back pain) restart at a slower rate after resolution; if anaphylaxis, give adrenaline 0.5 mg (0.5 mL of 1 in 1000) intramuscularly and start full anaphylaxis resuscitation.

Major interactions. Concurrent oral iron reduces absorption; ACE inhibitors may increase reaction severity (reported); iron may interfere with magnetic resonance imaging for several weeks.

Common prescribing errors.

• Dosing in mL rather than mg of elemental iron.
• Giving iron during sepsis.
• Giving more than the labelled single dose.
• Not monitoring phosphate after repeated ferric carboxymaltose.
• Repeating iron before ferritin has fallen back from the early post-infusion rise.

Special groups.

• Pregnancy: avoid in the first trimester; used in the second and third trimesters.
• Breastfeeding: compatible.
• Children: limited data; specialist use, weight-based dosing.
• Older adults: no change; check cardiac status.
• Kidney: routine in haemodialysis, with ferritin and transferrin saturation targets.
• Liver: avoid in iron overload.
• East Africa: treat malaria and bacterial infection before infusion; supply may be limited, and facilities without resuscitation capacity should not give it.

Monitoring. Blood pressure and observation for 30 minutes; haemoglobin at 2 to 4 weeks; ferritin and transferrin saturation no sooner than 4 weeks; phosphate after repeated ferric carboxymaltose.

Referral and escalation. Anaphylaxis; persistent hypophosphataemia with bone pain; no response after full repletion; suspected iron overload.

Comparison with alternative classes. Parenteral iron replaces iron faster and more reliably than oral iron and is better for chronic disease, but costs more and carries rare serious reactions. Transfusion remains the treatment for haemodynamic instability.