What are the common side effects of iron infusion?

Common Side Effects of Iron Infusion

The most common side effects of iron infusion include nausea (7.2%), hypertension (4%), flushing (4%), injection site reactions (3%), and hypophosphatemia (2.1%), with most reactions being mild and self-limiting. 1

Acute Infusion-Related Side Effects

Most Frequent Reactions (During or Immediately After Infusion)

• Nausea occurs in approximately 7% of patients and is the most common side effect 1
• Hypertension and transient blood pressure elevations affect 4% of patients, sometimes accompanied by facial flushing, dizziness, or nausea, typically resolving within 30 minutes 1
• Flushing (hot flush sensation) occurs in 4% of patients 1
• Injection site reactions (pain, discoloration, irritation, bruising, swelling) affect 3% of patients 1
• Dizziness (including vertigo and balance disorders) occurs in 2.1% of patients 1
• Vomiting affects 2% of patients 1
• Headache (including migraine) occurs in 1.3% of patients 1
• Altered taste (dysgeusia) affects 1.2% of patients 1
• Hypotension occurs in 1% of patients and can be managed with IV hydration 2, 1

Less Common Acute Reactions

• Rash and urticaria occur in approximately 1% of patients 1
• Elevated liver enzymes (ALT/AST) in 1.2% of patients 1
• Abdominal pain, diarrhea, paresthesia, and sneezing occur in ≥0.5% of patients 1

Delayed Side Effects (Hours to Days After Infusion)

Flu-Like Symptoms

• Delayed infusion reactions can occur several hours to days after the infusion 2
• Common symptoms include flu-like symptoms, arthralgias (joint pain), myalgias (muscle pain), and fever 2
• These symptoms typically last up to 24 hours and are easily managed with NSAIDs 2
• Symptoms lasting more than a few days require provider evaluation and may indicate other pathologies such as hypophosphatemia 2

Hypophosphatemia: A Critical Formulation-Specific Side Effect

Incidence and Severity

• Treatment-emergent hypophosphatemia is now widely recognized, particularly with ferric carboxymaltose (FCM), occurring within the first 2 weeks after administration 2
• FCM has the highest incidence (47-75%) compared to other formulations (<10% with low-molecular-weight iron dextran, ferumoxytol, and iron dextran) 2
• Transient decreases in blood phosphorus levels (<2 mg/dL) occur in 27% of patients across all formulations in clinical trials 1
• The PHOSPHARE-IBD trial reported 51% incidence of hypophosphatemia with FCM from baseline to Day 35 2

Clinical Manifestations

• Moderate hypophosphatemia symptoms include fatigue, proximal muscle weakness, and bone pain—symptoms that can mimic iron deficiency anemia itself 2
• Severe cases can present with asthenia, myopathy, and respiratory failure 2
• FCM has been associated with severe and prolonged hypophosphatemia lasting up to 6 months, though the true duration remains unknown 2
• Symptomatic hypophosphatemia with serious outcomes including osteomalacia and fractures requiring clinical intervention has been reported in post-marketing surveillance 1

Risk Factors for Hypophosphatemia

• History of gastrointestinal disorders with malabsorption of fat-soluble vitamins or phosphate 1
• Inflammatory bowel disease 1
• Medications affecting proximal renal tubular function 1
• Hyperparathyroidism, vitamin D deficiency, malnutrition 1
• Hereditary hemorrhagic telangiectasia (HHT or Osler-Weber-Rendu syndrome) 1

Severe Reactions (Extremely Rare)

Anaphylaxis and Life-Threatening Reactions

• Severe life-threatening reactions are extremely rare but can occur with any iron formulation 2
• The risk of serious hypersensitivity reactions with newer IV iron preparations is very low (38 incidents per million administrations) 3
• Anaphylactic/anaphylactoid reactions are more common with high-molecular-weight iron dextran (Dexferrum) than newer formulations 3
• True anaphylaxis from IV iron should be managed as a medical emergency, the same as anaphylaxis from any cause 2

Important Clinical Caveats

Management Principles

• Most minor infusion reactions are self-limiting and resolve spontaneously within 15 minutes after stopping the infusion 2
• Avoid first-generation antihistamines (diphenhydramine) and vasopressors for minor reactions, as these can convert minor reactions into hemodynamically significant serious adverse events, including exacerbation of hypotension, tachycardia, diaphoresis, sedation, and shock 2
• There is no physiological basis to observe patients for 30 minutes after infusion completion, as IV iron is not associated with severe delayed reactions 2

Formulation Differences

• Newer iron compounds (iron sucrose, iron gluconate, iron carboxymaltose) generally have fewer adverse effects than iron dextran 3
• Low-molecular-weight iron dextran (INFed) is preferred if iron dextran must be used 3
• Test doses are required for iron dextran but only recommended for ferric gluconate and iron sucrose in patients with previous sensitivities or multiple drug allergies 3

Monitoring Recommendations

• Correct pre-existing hypophosphatemia prior to initiating therapy 1
• Monitor serum phosphate levels in patients at risk for chronic low serum phosphate 1
• Check serum phosphate levels prior to repeat courses of treatment in at-risk patients and in any patient receiving a second course within three months 1
• Monitor for signs and symptoms of hypertension following each administration 1