Ferric Citrate

Usage

Ferric citrate is prescribed for two main purposes:

1. Control of Serum Phosphorus Levels: In patients with chronic kidney disease (CKD) on dialysis, ferric citrate acts as a phosphate binder, helping to reduce the absorption of phosphate from the diet. This helps manage hyperphosphatemia, a condition where phosphorus levels in the blood become excessively high.

2. Treatment of Iron Deficiency Anemia: In adults with CKD not on dialysis, ferric citrate is used to treat iron deficiency anemia. Iron deficiency anemia occurs when the body doesn’t have enough iron to produce adequate amounts of hemoglobin, the protein in red blood cells that carries oxygen.

Pharmacological Classification: Ferric citrate can be classified as both a phosphate binder and an iron replacement product.

Alternate Names

• Chemical Name: 2-Hydroxy-1,2,3-propanetricarboxylic acid, iron(3+) salt, hydrate
• Brand Name: Auryxia

How It Works

Pharmacodynamics: Ferric citrate binds to dietary phosphate in the gastrointestinal tract, forming an insoluble complex that is excreted in the feces. This reduces the amount of phosphate absorbed into the bloodstream, thereby lowering serum phosphorus levels. Additionally, the iron component of ferric citrate is absorbed and utilized by the body to synthesize hemoglobin, thus addressing iron deficiency anemia.

Pharmacokinetics:

• Absorption: Iron is absorbed primarily in the duodenum and upper jejunum. Absorption is enhanced in an acidic environment and when iron stores are low.
• Distribution: After absorption, ferric iron binds to transferrin, a protein that transports iron in the blood.
• Metabolism: Iron is not metabolized in the traditional sense but is incorporated into hemoglobin, myoglobin, and various enzymes.
• Elimination: Iron is primarily lost through shedding of cells lining the gastrointestinal tract, skin, and urinary tract. Very little iron is actively excreted by the kidneys. Unabsorbed phosphate bound to ferric citrate is eliminated in the feces.

Dosage

Standard Dosage

Adults:

• Hyperphosphatemia (CKD on dialysis): Starting dose: 420 mg (two tablets) three times daily with meals. The dose can be adjusted at intervals of one week or longer, in increments or decrements of 1-2 tablets per day, to achieve the target serum phosphorus level. The maximum dose is 12 tablets per day. The average dose required in clinical trials was 8-9 tablets per day.

• Iron Deficiency Anemia (CKD not on dialysis): Starting dose: 210 mg (one tablet) three times daily with meals. The dose can be titrated as needed to achieve and maintain the target hemoglobin level, up to a maximum of 12 tablets per day. In a clinical trial, the average dose was 5 tablets per day.

Children:

The safety and efficacy of ferric citrate have not been established in pediatric patients.

Special Cases:

• Elderly Patients: No specific dose adjustment is recommended for elderly patients. Clinical studies have not shown significant differences in response between elderly and younger patients. However, it’s crucial to monitor for potential side effects and adjust the dose as needed based on individual patient response and renal function.

• Patients with Renal Impairment: Ferric citrate is used in patients with chronic kidney disease, including those on dialysis. Dose adjustments are based on serum phosphorus levels rather than the degree of renal impairment. For patients not on dialysis, dose adjustments are made to achieve target hemoglobin levels.

• Patients with Hepatic Dysfunction: No specific dose adjustment is recommended for patients with hepatic dysfunction. However, close monitoring is advised, and dose modifications may be necessary based on individual patient response.

• Patients with Comorbid Conditions: Patients with iron overload syndromes (e.g., hemochromatosis) should not take ferric citrate. Caution is advised in patients with inflammatory bowel disease or stomach/bowel problems.

Clinical Use Cases

Dosing for clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not specifically different from the standard dosing guidelines. Dose adjustments should be based on individual patient needs and the specific medical context.

Side Effects

Common Side Effects:

• Diarrhea
• Nausea
• Constipation
• Vomiting
• Dark stools (due to iron content)
• Cough

Rare but Serious Side Effects:

• Iron overload (indicated by increased ferritin and transferrin saturation)
• Hyperkalemia

Long-Term Effects:

Long-term effects primarily relate to potential iron overload. Regular monitoring of iron parameters is essential.

Contraindications

• Iron overload syndromes (e.g., hemochromatosis)

Drug Interactions

Ferric citrate can chelate with other drugs in the gastrointestinal tract, reducing their absorption. Clinically significant interactions include those with:

• Bisphosphonates (e.g., alendronate): Take these at least 2 hours before or after ferric citrate.
• Certain quinolone antibiotics (e.g., ciprofloxacin, levofloxacin): Take these several hours before or after ferric citrate.
• Tetracycline antibiotics (e.g., doxycycline): Take these at least 1 hour before or after ferric citrate.
• Thyroid medications (e.g., levothyroxine): Take these several hours before or after ferric citrate.

Other potential interactions exist, so a comprehensive medication review is essential before initiating ferric citrate therapy.

Pregnancy and Breastfeeding

• Pregnancy: There are no adequate and well-controlled studies in pregnant women. Iron requirements increase during pregnancy, but iron overdose can be harmful. Consult with a healthcare professional to assess the risks and benefits.
• Breastfeeding: Ferric citrate can pass into breast milk. Consult with a healthcare professional before taking ferric citrate while breastfeeding.

Drug Profile Summary

• Mechanism of Action: Phosphate binder and iron replacement product. Binds to dietary phosphate and prevents its absorption. Provides iron for hemoglobin synthesis.
• Side Effects: Diarrhea, nausea, constipation, vomiting, dark stools, cough. Rarely, iron overload and hyperkalemia.
• Contraindications: Iron overload syndromes.
• Drug Interactions: Numerous, including bisphosphonates, quinolones, tetracyclines, and thyroid medications.
• Pregnancy & Breastfeeding: Consult a healthcare professional.
• Dosage: Hyperphosphatemia: 420 mg TID with meals, adjustable. Iron deficiency anemia: 210 mg TID with meals, adjustable. Maximum 12 tablets/day.
• Monitoring Parameters: Serum phosphorus, hemoglobin, ferritin, transferrin saturation (TSAT), and potassium levels.

Popular Combinations

Ferric citrate is often used in combination with other medications commonly prescribed to dialysis patients, such as vitamin D analogues and calcimimetics, to manage secondary hyperparathyroidism and mineral bone disease.

Precautions

• General Precautions: Assess iron parameters before initiating therapy and monitor regularly. Monitor for gastrointestinal side effects. Keep out of reach of children.
• Specific Populations (See “Pregnancy and Breastfeeding” and “Dosage - Special Cases”)

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ferric Citrate?

A: For hyperphosphatemia in CKD patients on dialysis, the starting dose is 420 mg (two tablets) three times daily with meals. For iron deficiency anemia in CKD patients not on dialysis, the starting dose is 210 mg (one tablet) three times daily with meals. Dosages are adjustable based on patient response and lab values, up to a maximum of 12 tablets per day.

Q2: What are the common side effects of Ferric Citrate?

A: The most common side effects are gastrointestinal, including diarrhea, nausea, constipation, vomiting, and dark stools.

Q3: How does Ferric Citrate work in the body?

A: It works by binding to dietary phosphate in the gut and preventing its absorption, lowering serum phosphorus. It also provides absorbable iron for hemoglobin production.

Q4: Who should not take Ferric Citrate?

A: Patients with iron overload syndromes, such as hemochromatosis, should not take Ferric Citrate.

Q5: Can Ferric Citrate be taken during pregnancy or while breastfeeding?

A: Consult a healthcare professional before using ferric citrate during pregnancy or while breastfeeding.

Q6: What are the important drug interactions with Ferric Citrate?

A: Ferric citrate can interact with many medications, including bisphosphonates, quinolone and tetracycline antibiotics, and thyroid medications. These interactions can decrease the effectiveness of these drugs. It is therefore important to separate the administration of ferric citrate from interacting medication.

Q7: Are there any special considerations for elderly patients taking Ferric Citrate?

A: Close monitoring of renal function and potential side effects is essential in elderly patients.

Q8: What should be monitored in patients taking Ferric Citrate?

A: Serum phosphorus, hemoglobin, ferritin, transferrin saturation, and potassium levels should be monitored regularly.

Q9: Is Ferric Citrate safe for children?

A: The safety and efficacy of Ferric Citrate in children have not been established.

Please note that this information is current as of February 16, 2025, and is intended for qualified Indian doctors. Always consult the latest prescribing information and individual patient factors before making treatment decisions.