Iron

Usage

• Iron supplements are primarily used to treat and prevent iron deficiency and iron deficiency anemia. Iron deficiency anemia arises when the body lacks sufficient iron to produce adequate amounts of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. This can lead to fatigue, weakness, shortness of breath, and other symptoms. Certain groups, including pregnant women, infants, and individuals with heavy menstrual bleeding, are at higher risk of iron deficiency. Iron supplements are also prescribed for conditions like restless legs syndrome and specific types of chronic kidney disease.

• Pharmacological classification: Iron supplements are classified as hematinics, specifically iron replacement therapy.

• Mechanism of action: Iron is an essential component of hemoglobin, the protein responsible for oxygen transport in red blood cells. Iron supplements replenish depleted iron stores, enabling the body to produce more hemoglobin and red blood cells, thus correcting or preventing anemia.

Alternate Names

• Elemental iron, ferrous sulfate, ferrous gluconate, ferrous fumarate, ferric carboxymaltose, iron sucrose, ferric derisomaltose.

• Brand names: Fer-In-Sol, Feosol, Slow Fe, Fergon, Feratab, and numerous others (brand names vary widely by region).

How It Works

• Pharmacodynamics: Iron exerts its primary effect by increasing hemoglobin synthesis, thereby improving oxygen delivery to tissues. This alleviates symptoms of anemia like fatigue and weakness. It also impacts cellular functions dependent on iron-containing enzymes.

• Pharmacokinetics:

  • Absorption: Iron is primarily absorbed in the duodenum and upper jejunum. Absorption is enhanced in an acidic environment and when iron stores are depleted. Factors like food (e.g., dairy products, tea, coffee) and certain medications can inhibit absorption. Vitamin C can improve absorption.
  • Metabolism: Absorbed iron is transported in the blood bound to transferrin. Excess iron is stored as ferritin and hemosiderin in the liver, spleen, and bone marrow.
  • Elimination: Iron is primarily lost through shedding of cells (e.g., skin, intestinal lining), and small amounts are excreted in bile and urine.

• Mode of action: Iron is incorporated into the protoporphyrin ring to form heme, the oxygen-binding component of hemoglobin. Increased iron availability enhances heme synthesis, leading to increased hemoglobin production.

• Receptor binding, enzyme inhibition, or neurotransmitter modulation: While iron’s primary action is not through receptor binding, its incorporation into various enzymes, such as those involved in the electron transport chain, is essential for their activity.

• Elimination pathways: The body has limited mechanisms for excreting iron. Most iron loss occurs through cell shedding, with small amounts excreted in bile and urine. There are no specific CYP enzymes directly involved in iron metabolism.

Dosage

Standard Dosage

Adults: The standard dosage for iron deficiency anemia is 100-200 mg of elemental iron daily, often divided into two or three doses. Lower doses (15-20 mg daily) may be as effective and better tolerated in some patients, especially the elderly.

Children: Pediatric dosing is based on body weight, typically 1 mg/kg/day for breastfed infants starting at 4 months of age until iron-rich foods are introduced. The dose for treating iron deficiency in children is 3-6 mg/kg/day.

Special Cases:

• Elderly Patients: Lower doses (15-30 mg elemental iron daily or every other day) are often recommended to minimize side effects.

• Patients with Renal Impairment: Dose adjustments may be necessary, particularly for those receiving intravenous iron. Consultation with a nephrologist is recommended.

• Patients with Hepatic Dysfunction: Caution is advised, but specific dose modifications are not routinely required for oral iron.

• Patients with Comorbid Conditions: Dose adjustments may be needed for patients with conditions like diabetes, cardiovascular disease, or inflammatory bowel disease.

Clinical Use Cases

• Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use: Intravenous iron may be administered in these settings to rapidly correct iron deficiency anemia if present and clinically indicated.

• Emergency Situations: Intravenous iron may be used in emergencies like severe hemorrhage, when rapid replenishment of iron is necessary.

Dosage Adjustments:

Dose modifications are based on individual patient factors, including renal/hepatic function, gastrointestinal tolerance, and response to therapy.

Side Effects

Common Side Effects

• Constipation
• Nausea
• Dark stools
• Abdominal discomfort

Rare but Serious Side Effects

• Allergic reactions (rash, itching, swelling, difficulty breathing)
• Iron overload (in patients with hemochromatosis or other iron overload disorders)

Long-Term Effects

• Iron overload (with chronic excessive intake)

Adverse Drug Reactions (ADR)

• Anaphylaxis (rare but life-threatening allergic reaction)

Contraindications

• Hemochromatosis
• Hemosiderosis
• Other iron overload disorders
• Known hypersensitivity to any iron preparation

Drug Interactions

• Antacids
• Tetracyclines
• Fluoroquinolones
• Levothyroxine
• Levodopa
• Proton pump inhibitors
• Calcium supplements
• Food (especially dairy, tea, coffee)

Pregnancy and Breastfeeding

• Iron supplements are generally considered safe during pregnancy and breastfeeding. They are often prescribed to prevent and treat iron deficiency, particularly during pregnancy. The recommended daily allowance for pregnant women is 27 mg.

• Breast milk contains iron, but the amount may not be sufficient for infants after the first few months. Hence, iron supplementation may be needed for exclusively breastfed infants starting at 4 months.

Drug Profile Summary

• Mechanism of Action: Replenishes iron stores, allowing for increased hemoglobin and red blood cell production.

• Side Effects: Constipation, nausea, dark stools, abdominal discomfort. Rarely: allergic reactions, iron overload.

• Contraindications: Iron overload disorders, hypersensitivity.

• Drug Interactions: Numerous, including antacids, antibiotics, levothyroxine.

• Pregnancy & Breastfeeding: Generally safe and often recommended.

• Dosage: Adults: 100-200 mg elemental iron daily; Children: Varies by age and indication.

• Monitoring Parameters: Hemoglobin, hematocrit, ferritin, transferrin saturation.

Popular Combinations

Iron is often combined with folic acid, especially in prenatal vitamins.

Precautions

• General Precautions: Screen for iron overload disorders before initiating therapy. Assess gastrointestinal function.

• Specific Populations:

  • Pregnant Women: Monitor for iron deficiency and supplement as needed.
  • Breastfeeding Mothers: May need iron supplementation.
  • Children & Elderly: Use age-appropriate dosing.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Iron?

A: For adults with iron deficiency anemia, 100-200 mg of elemental iron daily is typically recommended, often divided into two or three doses. Lower doses may be sufficient for some patients. For children, the dose is weight-based.

Q2: How should I counsel patients on taking iron supplements?

A: Advise patients to take iron on an empty stomach, ideally one hour before or two hours after meals, for optimal absorption. Inform them that iron can cause dark stools and constipation. Encourage intake of fiber-rich foods and fluids. Recommend taking iron with vitamin C to enhance absorption. Avoid co-administration with antacids, dairy products, tea, or coffee.

Q3: When should intravenous iron be considered?

A: Intravenous iron is indicated when oral iron is ineffective, not tolerated, or contraindicated. It can be used in patients with malabsorption, inflammatory bowel disease, or those requiring rapid iron replenishment.

Q4: What are the signs and symptoms of iron overload?

A: Symptoms can include fatigue, joint pain, abdominal pain, and skin discoloration. Long-term complications can affect the liver, heart, and pancreas. Serum ferritin and transferrin saturation levels should be monitored.

Q5: What is the difference between ferrous and ferric iron?

A: Ferrous iron (Fe2+) is the form of iron better absorbed by the body and is typically the preferred form in oral supplements. Ferric iron (Fe3+) is less readily absorbed.

Q6: How long does it take to see a response to iron therapy?

A: Hemoglobin levels typically begin to rise within a few weeks of starting iron supplementation. It may take several months to fully replenish iron stores.

Q7: Are there any specific dietary recommendations for patients taking iron?

A: Patients should be encouraged to consume iron-rich foods, such as red meat, leafy green vegetables, and legumes. Consuming vitamin C-rich foods with iron can improve absorption, while avoiding foods like dairy products, tea, and coffee, which can inhibit absorption, is advised.

Q8: How should iron deficiency be diagnosed?

A: A complete blood count (CBC) to assess hemoglobin and hematocrit levels, along with serum ferritin and transferrin saturation tests, are essential for diagnosing iron deficiency. Additional testing may be necessary to identify the underlying cause of iron deficiency.

Q9: What are the monitoring parameters during iron therapy?

A: Hemoglobin, hematocrit, ferritin levels, and transferrin saturation should be monitored regularly to assess response to iron therapy.