Iron products

Pharmacological Class: Iron Products
Category: Hematinics / Antianemic Agents
Therapeutic Use: Treatment and prevention of iron deficiency anemia

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Definition
Iron products are pharmaceutical preparations that replenish iron stores in the body and facilitate the synthesis of hemoglobin, myoglobin, and various enzymes involved in oxygen transport and cellular metabolism. They are essential for patients with iron deficiency anemia, which may result from inadequate dietary intake, malabsorption, blood loss, chronic diseases, or increased physiological needs (e.g., pregnancy). Iron products are available in various oral and parenteral forms, each with distinct pharmacokinetic profiles and indications.

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1. Physiological Role of Iron

• Hemoglobin synthesis: 65–70% of total body iron is incorporated in hemoglobin.

• Myoglobin and enzymes: Iron serves as a cofactor for enzymes like catalase, cytochromes.

• Cellular respiration: Supports mitochondrial electron transport and energy production.

• Immune function: Supports proliferation and maturation of lymphocytes.

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2. Indications

• Iron-deficiency anemia (microcytic, hypochromic)

• Latent iron deficiency (depleted iron stores without anemia)

• Iron supplementation during:

  • Pregnancy/lactation

  • Adolescence

  • Heavy menstrual bleeding

  • Chronic kidney disease (CKD)

  • Post-surgical or post-hemorrhagic states

• Malabsorption syndromes (e.g., celiac disease, bariatric surgery)

• Support in erythropoiesis-stimulating agent (ESA) therapy

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3. Classification of Iron Products

A. Oral Iron Preparations

Most common first-line therapy

Type	Examples	Elemental Iron Content
Ferrous sulfate	Feosol, Ferrograd, FeroSul	~20%
Ferrous gluconate	Fergon, Simron	~12%
Ferrous fumarate	Ferro-Sequels, Ferretts	~33%
Polysaccharide-iron complex	Niferex, Ferrex-150	~100% (complexed form)
Carbonyl iron	Icar, Feosol Natural	~100%
Heme iron polypeptide	Proferrin	~11%
Ferric maltol	Accrufer (US), Feraccru (UK)	30 mg per capsule (non-ionic)

B. Parenteral Iron Preparations

Used when oral iron is ineffective, not tolerated, or rapid repletion is necessary

Type	Examples	Features
Iron sucrose	Venofer	Requires multiple small doses
Ferric gluconate	Ferrlecit	Moderate molecular weight
Iron dextran	INFeD, Dexferrum	Risk of anaphylaxis (esp. high MW)
Ferric carboxymaltose	Injectafer (US), Ferinject (EU)	High-dose, single-infusion
Ferumoxytol	Feraheme	Rapid administration, CKD use
Iron isomaltoside	Monofer (EU), Rizomacro (UK)	High-dose, low hypersensitivity
Ferric derisomaltose	Monoferric	Newer, high-dose IV iron

4. Mechanism of Action

• Oral Iron: Absorbed primarily in the duodenum and proximal jejunum, ferrous (Fe²⁺) form is absorbed more efficiently than ferric (Fe³⁺).

• In blood: Iron binds to transferrin and is delivered to bone marrow for hemoglobin synthesis or stored as ferritin and hemosiderin.

• Parenteral Iron: Bypasses GI tract, iron is bound to transferrin or stored in reticuloendothelial system for gradual release.

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5. Dosage and Administration

A. Oral Iron

• Adult dose: 100–200 mg elemental iron/day in divided doses

• Administration:

  • Take on empty stomach for optimal absorption (if tolerated)

  • May be taken with vitamin C (ascorbic acid) to enhance absorption

  • Avoid co-administration with calcium, antacids, tea, coffee, dairy

B. Parenteral Iron

• Dose calculated using Ganzoni formula or standardized weight-based regimens.

• Administer via IV infusion or slow injection depending on product.

• Pre-treatment test dose required for iron dextran due to anaphylaxis risk.

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6. Adverse Effects

Oral Iron

• Gastrointestinal:

  • Nausea, epigastric pain, constipation or diarrhea

  • Dark-colored stools (harmless)

• Metallic taste

• Poor adherence due to side effects

Parenteral Iron

• Infusion reactions:

  • Hypotension, flushing, dizziness

  • Anaphylaxis (especially with high-molecular-weight iron dextran)

• Arthralgia, back pain, myalgia (transient)

• Iron overload (rare, with repeated doses)

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7. Contraindications

• Hemochromatosis, hemosiderosis

• Anemia not due to iron deficiency (e.g., hemolytic anemia)

• Hypersensitivity to iron products

• Active infection (parenteral iron may worsen outcomes)

• Iron overload states or repeated transfusions

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8. Precautions

• Monitor serum ferritin and transferrin saturation (TSAT) during therapy

• Oral iron should be stopped 48 hours before fecal occult blood test

• Avoid long-term iron without medical supervision due to iron toxicity risk

• Use caution in patients with inflammatory bowel disease (oral iron may exacerbate symptoms)

• Do not mix IV iron products interchangeably without physician guidance

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9. Iron Absorption and Influencing Factors

Enhancers	Inhibitors
Vitamin C (ascorbic acid)	Calcium-containing products
Empty stomach	Phytates (in grains, legumes)
Heme iron (from meat)	Polyphenols (tea, coffee, wine)
Gastric acid	Proton pump inhibitors (PPIs)

10. Drug Interactions

Interacting Drug/Class	Effect
Antacids, calcium supplements	↓ Iron absorption
Tetracyclines, fluoroquinolones	↓ Absorption of both iron and antibiotic
Levothyroxine	↓ Absorption of levothyroxine
Methyldopa, levodopa	↓ Effectiveness due to chelation
PPIs, H2 blockers	↓ Iron absorption by reducing acidity

Spacing iron 2–4 hours apart from these medications can minimize interaction.

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11. Monitoring Parameters

• Hemoglobin (Hb) and hematocrit (Hct) – weekly to monthly

• Ferritin (goal: >100 ng/mL in CKD, >30 ng/mL in general anemia)

• Transferrin saturation (TSAT) – maintain >20–30%

• Reticulocyte count – rise expected within 7–10 days

• CRP (if chronic disease suspected)

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12. Iron Overdose and Toxicity

• Acute toxicity (mainly in children):

  • Nausea, vomiting, GI bleeding, lethargy, metabolic acidosis

  • Potentially fatal >60 mg/kg elemental iron

  • Treatment: IV deferoxamine (iron-chelating agent)

• Chronic toxicity:

  • Liver fibrosis, diabetes (in hemochromatosis)

  • Monitor iron indices regularly in long-term users

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13. Use in Special Populations

• Pregnancy: Iron supplementation often recommended (e.g., ferrous sulfate 30–60 mg elemental iron daily)

• Pediatrics: Dose based on weight; liquid formulations preferred

• Chronic kidney disease (CKD): IV iron preferred, especially in patients on dialysis

• Inflammatory bowel disease: Parenteral iron better tolerated than oral

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14. Comparison of Oral Iron Preparations

Formulation	Elemental Iron	GI Tolerability	Absorption	Notes
Ferrous sulfate	20%	Moderate	High	Widely available, inexpensive
Ferrous fumarate	33%	Lower	High	Higher iron load per dose
Ferrous gluconate	12%	Better tolerated	Lower	Requires more frequent dosing
Polysaccharide iron	100%	High	Slow	Lower GI side effects
Ferric maltol	30 mg	Very well tolerated	Controlled	Expensive, for IBD/CKD patients

15. Clinical Practice Guidelines

• WHO: Recommends routine iron-folic acid supplementation in pregnancy

• KDIGO (Kidney Disease): IV iron preferred over oral for patients on dialysis or with ESA therapy

• British Society of Gastroenterology (BSG): Recommends IV iron in IBD with moderate-severe anemia

• American College of Obstetricians and Gynecologists (ACOG): 27 mg elemental iron daily in pregnancy

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16. Selected Brand Names

Generic	US Brands	UK Brands	Global/Other
Ferrous sulfate	Feosol, FeroSul	Ironorm, Ferrograd	Feroplex
Ferrous fumarate	Ferretts, Ferro-Sequels	Galfer	Feramax
Ferrous gluconate	Fergon	Glucofer	Simron
Iron sucrose	Venofer	Venofer	Venofer
Ferric carboxymaltose	Injectafer	Ferinject	Rasi Injectafer
Ferric maltol	Accrufer	Feraccru	Feraccru (EU, ME)