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Iron Preparations - Complete Reference (Based on Katzung & Lippincott Pharmacology)

Note: KD Tripathi is not available in the library. The following is compiled from Katzung's Basic and Clinical Pharmacology (16th Ed) and Lippincott Illustrated Reviews: Pharmacology, which cover the same content as KDT.

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1. ORAL AND PARENTERAL IRON PREPARATIONS - Enumeration

Oral Iron Preparations

Ferrous salts are preferred because Fe2+ (ferrous) is more efficiently absorbed than Fe3+ (ferric).

Parenteral Iron Preparations

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2. ORAL IRON PREPARATIONS - Details

Enumerate

1. Ferrous sulfate
2. Ferrous gluconate
3. Ferrous fumarate
4. Ferrous succinate
5. Polysaccharide-iron complex
6. Carbonyl iron
7. Ferrous ascorbate (with vitamin C)
8. Ferric citrate (newer)

Adverse Effects of Oral Iron

• Nausea, epigastric discomfort, abdominal cramps
• Constipation (most common)
• Diarrhea
• Black/tarry stools (no clinical significance by itself, but may mask GI bleeding)
• Effects are dose-related - can be reduced by taking with meals or lowering the dose
• Different salts may suit different patients - switching preparations sometimes helps

Drug Treatment of Iron Deficiency Anaemia (IDA)

• Preferred agents: Ferrous sulfate, ferrous gluconate, or ferrous fumarate (all effective, inexpensive, high bioavailability)
• Target dose: 200-400 mg of elemental iron daily (based on 25% absorption of ferrous salts; 50-100 mg iron is incorporated into Hb daily)
• CDC recommends 60-120 mg/day elemental iron in divided doses, 2-3 times daily
• Duration: Continue 3-6 months after correction of cause to replenish iron stores
• Oral iron corrects anemia as rapidly as parenteral iron when GI absorption is normal

• Give on an empty stomach (best absorption), or between meals
• Vitamin C (ascorbic acid) enhances iron absorption
• Avoid dairy, antacids, calcium supplements, PPIs at same time

Precautions for Oral Iron

• Avoid in patients with hemochromatosis or iron overload states
• Use with caution in inflammatory bowel disease (may worsen symptoms)
• Iron inhibits absorption of: tetracyclines, fluoroquinolones, levodopa, methyldopa, thyroxine - separate dosing by at least 2 hours
• Accidental overdose risk in children - keep locked away
• Black stools must be differentiated from melena (GI bleeding)

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3. PARENTERAL IRON PREPARATIONS - Details

Enumerate

1. Iron dextran (IM/IV)
2. Sodium ferric gluconate complex (IV)
3. Iron sucrose (IV)
4. Ferric carboxymaltose (IV)
5. Ferumoxytol (IV)

Indications for Parenteral Iron

• Documented iron deficiency unable to tolerate or absorb oral iron
• Advanced chronic renal disease on hemodialysis (especially with erythropoietin therapy - high iron demand)
• Post-gastrectomy states and small bowel resection
• Inflammatory bowel disease involving proximal small bowel
• Malabsorption syndromes
• When rapid iron repletion is needed
• Extensive chronic anemia that cannot be maintained with oral iron alone

Adverse Effects of Parenteral Iron

• Headache, lightheadedness, fever, arthralgias
• Nausea and vomiting
• Back pain, flushing, urticaria
• Bronchospasm
• Anaphylaxis and death (rare but serious) - test dose always required
• Local pain and tissue staining with IM route
• Patients with prior allergic reactions to iron have higher hypersensitivity risk
• High-molecular-weight forms (DexFerrum) carry greater anaphylaxis risk than low-MW forms (INFEd)

• Lower risk of hypersensitivity than iron dextran
• Hypotension (especially rapid IV infusion)
• Nausea, dizziness, cramps

• Hypotension, flushing, dizziness
• Ferumoxytol: boxed warning - serious hypersensitivity reactions including anaphylaxis

Precautions for Parenteral Iron

• Test dose mandatory before full iron dextran infusion
• Have resuscitation equipment and personnel available during IV infusion
• Avoid in active infection (iron may worsen bacterial infections - iron is a growth factor for many pathogens)
• Monitor for signs of iron overload (hemosiderosis) with repeated doses
• Rapid IV administration can cause cardiovascular collapse - infuse slowly per protocol
• Monitor serum ferritin and transferrin saturation to avoid overload

Therapeutic Uses of Parenteral Iron

• Iron deficiency anemia in CKD/hemodialysis patients on erythropoietin
• Pre-operative anemia optimization (rapid repletion)
• Inflammatory bowel disease with iron deficiency
• Malabsorption states
• Chemotherapy-associated anemia with concurrent erythropoietin use
• Post-bariatric surgery iron deficiency

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4. IRON POISONING - Antidote and Detailed Treatment

Antidote

• Mechanism: chelates free ferric iron (Fe3+), forming ferrioxamine complex which is water-soluble and renally excreted, turning urine vin rose (pink-orange) color
• Route: preferred IM or SC; IV used in severe poisoning (slow infusion to avoid hypotension)

Clinical Stages of Iron Poisoning

Detailed Treatment Protocol (from Tintinalli's Emergency Medicine & Katzung)

• Clinical diagnosis: treat based on signs/symptoms, not serum iron alone
• Serum iron: levels >500 mcg/dL (>90 mmol/L) indicate severe toxicity
• When serum iron > total iron-binding capacity (TIBC, normal ~250-370 mcg/dL) - deferoxamine indicated
• CBC, electrolytes, renal/liver function, coagulation, glucose, ABG, serum lactate
• Abdominal X-ray: ferrous sulfate tablets are radiopaque - visible and guides GI decontamination
• Stabilize: airway, breathing, circulation (ABC)
• IV access, fluid resuscitation for hypotension and metabolic acidosis
• Antiemetics (metoclopramide, ondansetron) for persistent vomiting

• Activated charcoal does NOT bind iron - not useful
• Gastric lavage: may be considered if large ingestion and presentation within 1-2 hours
• Whole bowel irrigation (WBI) with polyethylene glycol (PEG): recommended when tablets visible on X-ray; continue until no radiopaque material on repeat X-ray or rectal effluent clear
• Endoscopic removal: considered if massive bezoar of tablets in stomach

• Indications for deferoxamine:
  • Serum iron > TIBC, or serum iron > 500 mcg/dL
  • Symptomatic patients: metabolic acidosis, persistent vomiting, lethargy, shock, coma
  • Positive deferoxamine challenge (urine turns vin rose color)
• Route: IV infusion (preferred in severe cases); IM in mild cases
• Dose: 15 mg/kg/hour IV (max 6 g/day); continue until clinical improvement and urine clears
• Duration: Generally 24 hours; do not exceed 24 hours if possible (risk of pulmonary toxicity with prolonged infusion - ARDS)
• Endpoint: Resolution of symptoms AND urine color returns to normal (ferrioxamine clears)
• Caution: Rapid IV infusion causes hypotension, tachycardia, flushing - infuse slowly

• Hemodialysis: does NOT remove iron directly, but may be needed to remove ferrioxamine-iron complex in renal failure patients
• Exchange transfusion: considered in extremely severe poisoning
• Supportive care: Correct metabolic acidosis (sodium bicarbonate if severe), treat coagulopathy, manage hepatic failure
• With early treatment, mortality reduced from ~45% to <1%

• Asymptomatic patients with no toxic dose ingested: observe, no specific treatment
• Patients with GI symptoms that resolve AND remain hemodynamically stable: low risk of systemic toxicity
• Early treatment dramatically reduces mortality

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Summary Table: Oral vs Parenteral Iron