Xenofer

Approved Indications:

• Iron Deficiency Anemia (IDA):
• In adult and pediatric patients (≥2 years) with chronic kidney disease (CKD), when oral iron is ineffective or not tolerated.
• In patients undergoing hemodialysis or peritoneal dialysis receiving supplemental erythropoietin.
• In non-dialysis-dependent CKD (NDD-CKD) with iron deficiency not manageable by oral iron alone.
• Iron Deficiency in Pregnancy (Off-label in some regions):
• When oral iron is not tolerated or rapid correction is needed.

Clinically Accepted Off-Label Uses:

• Iron deficiency anemia in inflammatory bowel disease (IBD)
• Post-bariatric surgery iron deficiency
• Heart failure with iron deficiency (typically when ferritin <100 ng/mL or ferritin 100–299 ng/mL with TSAT <20%)

Administration Route: Intravenous (IV) only.

Adults:

• Hemodialysis-Dependent CKD:
  100 mg IV during each dialysis session; cumulative dose typically 1,000 mg over 10 sessions.
• Non-Dialysis-Dependent CKD:
  200 mg IV undiluted over 2 to 5 minutes, or diluted in 100 mL NS over 15 to 60 minutes, on 5 separate days within 14-day period (total of 1,000 mg).
• Peritoneal Dialysis-Dependent CKD:
  300 mg IV infused over 1.5 hours on days 1 and 15, followed by 400 mg on day 29 (total 1,000 mg).

Pregnancy (when indicated):

• Dose calculated based on iron deficit (e.g., Ganzoni formula), typically divided over multiple doses (100–200 mg per infusion).

Pediatrics (≥2 years, CKD-related IDA):

• 1.0 to 2.0 mg/kg IV up to 3 times/week (maximum single dose: 100 mg).

Special Groups:

• Hepatic Impairment: Use with caution; iron overload may exacerbate liver disease.
• Renal Impairment: Dose adjustments not needed; commonly used in CKD.

General Notes:

• Administer slowly to minimize risk of hypotension.
• Resuscitation equipment should be available during administration.

Iron sucrose is a complex of polynuclear iron (III) hydroxide in sucrose. After IV administration, the complex is taken up by the reticuloendothelial system, primarily in the liver, spleen, and bone marrow. Iron is gradually released from the complex and incorporated into ferritin, the primary iron storage protein. The released iron is utilized in the bone marrow for incorporation into hemoglobin, restoring oxygen-carrying capacity in anemic patients.

• Absorption: Not applicable (IV administration).
• Distribution: Rapidly taken up by macrophages; volume of distribution ~3–6 L.
• Metabolism: Not metabolized; iron is utilized or stored.
• Elimination:
• Very little free iron is renally excreted.
• Most iron is stored or incorporated into red blood cells.
• Bioavailability: 100% (IV).
• Half-life: 6 hours (distribution); terminal half-life ~20 hours.
• Time to Onset: Hemoglobin increases observed within 2–4 weeks of therapy initiation.

• Pregnancy:
• FDA Category B (older classification); animal studies show no harm, but human data are limited.
• May be used in pregnancy if benefits outweigh risks, especially when oral iron fails or rapid repletion is needed.
• Lactation:
• No known harmful effects; iron sucrose is not excreted in significant amounts into breast milk.
• Considered safe for breastfeeding mothers and infants.
• Caution: Monitor ferritin and hemoglobin to avoid iatrogenic iron overload during pregnancy.

• Primary Class: Hematinic / Iron Supplement
• Subclass: Parenteral Iron Replacement Therapy

• Known hypersensitivity to iron sucrose or its components
• Evidence of iron overload (e.g., high ferritin, hemochromatosis)
• Anemia not caused by iron deficiency (e.g., hemolytic anemia)
• First trimester of pregnancy (in some guidelines, due to limited safety data)
• Active systemic infection (iron may exacerbate infections)

• Hypersensitivity Reactions:
• May cause anaphylactoid or allergic reactions.
• Test doses not required, but monitor closely during initial administrations.
• Hypotension:
• Risk increases with rapid infusion; monitor BP during and after infusion.
• Iron Overload:
• Avoid use in patients with elevated ferritin or TSAT >50%.
• Infection Risk:
• Iron may support bacterial growth; avoid in active infections.
• Pediatric Use:
• Safety established in CKD patients ≥2 years; use caution in younger children.
• Monitoring Requirements:
• Regular monitoring of serum ferritin, hemoglobin, transferrin saturation (TSAT) is mandatory.

Common Side Effects (≥1%):

• General: Injection site reactions (pain, swelling)
• Gastrointestinal: Nausea, vomiting, diarrhea
• Neurological: Headache, dizziness
• Cardiovascular: Hypotension, flushing

Less Common / Serious Effects:

• Hypersensitivity (rash, pruritus, urticaria)
• Chest pain
• Back pain
• Dyspnea
• Tachycardia
• Arthralgia

Rare but Severe:

• Anaphylaxis
• Seizures (extremely rare)
• Iron overload (with prolonged or inappropriate use)

• Oral Iron Products:
• Should not be used concurrently with IV iron; may interfere with absorption or lead to overload.
• ACE Inhibitors:
• Increased risk of hypotension when used concurrently.
• Tetracyclines / Quinolones (with oral iron):
• Not directly relevant for iron sucrose (IV), but oral iron interferes with their absorption.
• No significant CYP450 interactions reported; iron sucrose is not metabolized via cytochrome P450 enzymes.

• KDIGO (Kidney Disease: Improving Global Outcomes) Guidelines:
• Emphasize iron repletion before or alongside erythropoiesis-stimulating agents in CKD.
• IV iron preferred in dialysis patients due to better bioavailability.
• Heart Failure Guidelines (ESC/AHA):
• Support IV iron therapy (including iron sucrose or ferric carboxymaltose) in patients with heart failure and iron deficiency to improve symptoms and reduce hospitalization.
• Updated Warnings:
• Reinforcement of careful monitoring to avoid iron overload.
• Highlighted importance of evaluating iron indices (ferritin, TSAT) before repeat dosing.

• Storage Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15–30°C.
• Protect from Light: Store in the original carton to protect from light.
• Do Not Freeze: Freezing may compromise stability.
• Dilution Stability: Once diluted in normal saline, the solution should be used immediately. If storage is necessary, it should be used within 12 hours at room temperature under aseptic conditions.
• Shake Gently if Sedimentation Appears: Do not use if precipitate forms.