What are the side effects of intravenous iron sucrose (Venofer)?

Side Effects of Intravenous Iron Sucrose

Iron sucrose is generally well-tolerated with common side effects including hypotension, nausea, vomiting, diarrhea, headache, and dizziness, occurring in approximately 0.5% of patients as hypersensitivity-type reactions—significantly lower than iron dextran formulations. 1, 2

Common Adverse Effects

The most frequently reported side effects with iron sucrose include:

• Cardiovascular: Hypotension and hypertension 3, 4
• Gastrointestinal: Nausea, vomiting, diarrhea, and dysgeusia 3, 4
• Musculoskeletal: Arthralgias, myalgias, back pain, and joint swelling 3, 4
• Neurological: Headache, dizziness, and light-headedness 3, 4
• Dermatological: Pruritus and flushing 3, 4
• Respiratory: Dyspnea and cough 4
• General: Pain at infusion site, fatigue, and pyrexia 4, 5

Most of these reactions are mild, self-limited, and occur within 30 minutes of infusion completion. 4

Serious Hypersensitivity Reactions

Life-threatening anaphylactic-type reactions can occur but are rare with iron sucrose compared to iron dextran formulations. 4, 6

• Serious reactions may present with shock, clinically significant hypotension, loss of consciousness, collapse, bronchospasm, angioedema, or cardiac arrest 4, 6
• The incidence of serious hypersensitivity reactions with newer IV iron preparations is very low at 38 incidents per million administrations 2
• Most reactions occur within 30 minutes of completing the infusion, requiring monitoring during this period 4
• Resuscitation facilities and trained personnel must be immediately available during administration 4

Complement Activation-Related Pseudo-Allergy (CARPA)

Iron sucrose can cause CARPA, a non-IgE-mediated reaction to labile free iron:

• Characterized by flushing, myalgias, arthralgias, back pain, and chest pressure without true anaphylaxis symptoms 3
• Usually self-limited and resolves without treatment 3
• Occurs due to iron sucrose's smaller core size releasing larger amounts of labile free iron after injection 3
• Does not require prior sensitization and can occur at any time, most frequently at infusion start 3

Dose-Related Adverse Effects

The maximum safe single dose is 200 mg, with doses of 400-500 mg associated with unacceptably high rates of adverse reactions. 1, 7

• A study of 335 infusions found that 500 mg doses caused reactions in 36% of patients (8/22), while 400 mg doses caused reactions in 6% (2/35) 7
• Both 200 mg and 300 mg doses over 2 hours were safe with no adverse events 7
• Symptoms related to excessive dosage or rapid infusion include hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse 4

Metabolic Complications

• Hypophosphatemia occurs in only 1% of iron sucrose patients, compared to 58% with ferric carboxymaltose 1, 2
• Iron overload can occur with excessive therapy, requiring periodic monitoring of hemoglobin, hematocrit, serum ferritin, and transferrin saturation 4
• Systemic iron toxicity with hepatocellular damage has been reported when doses exceed recommended maximums 1

Oxidative Stress and Organ Injury

Research suggests potential acute effects:

• Iron sucrose infusion produces oxidative stress with increased lipid peroxidation products (malondialdehyde) 8
• Acute renal injury and inflammation demonstrated by increased urinary albumin, enzymes, and cytokines 8
• Endothelial dysfunction may occur acutely following infusion 8

Special Populations and Risk Factors

Patients at higher risk for reactions include those with:

• Active infection or bacteremia (absolute contraindication) 3, 1, 2
• History of severe asthma, eczema, or mastocytosis 3
• Multiple drug allergies or prior reactions to IV iron 3
• Collagen vascular diseases (increased incidence of adverse effects) 2

In pediatric patients (ages 2 years and older), the safety profile is similar with headache (6%), respiratory tract viral infection (4%), and peritonitis (4%) being most common. 4

Critical Management Considerations

Key pitfalls to avoid:

• Do not exceed 200 mg single dose to minimize anaphylactoid reactions 1, 7
• Never administer during active bacteremia, though chronic infection alone is not an absolute contraindication if risk/benefit favors treatment 1, 2
• Avoid rapid infusion rates—slower rates are associated with lower reaction incidence 3
• Do not perform serum iron measurements for at least 48 hours after dosing due to spuriously elevated transferrin saturation 4
• Monitor serum phosphate in patients receiving long-term or multiple high-dose infusions 1

Comparison to Other IV Iron Preparations

Iron sucrose has a superior safety profile compared to iron dextran:

• Test doses are NOT required for iron sucrose (unlike iron dextran which requires a 25 mg test dose) 3, 1, 2
• Most adverse events associated with iron dextran occur with high-molecular-weight formulations (Dexferrum) 3, 2
• Iron sucrose has fewer adverse effects than iron dextran formulations, particularly high molecular weight iron dextran 1, 2
• However, test doses are recommended for patients with history of IV iron sensitivities or multiple drug allergies 3, 1