From the Guidelines
Intravenous iron transfusions can cause side effects, including infusion reactions, with the most common being complement activated related pseudo-allergy (CARPA), and true anaphylaxis is exceedingly rare, occurring with <1:200,000 administrations 1. The side effects of intravenous iron transfusion can be categorized into common and rare reactions. Common side effects include:
- Temporary discoloration of the skin at the injection site
- Headache
- Nausea
- Vomiting
- Joint or muscle pain
- Low blood pressure during administration Some patients may experience an allergic reaction characterized by itching, rash, swelling, or difficulty breathing, which requires immediate medical attention. More serious but rare side effects include:
- Anaphylaxis (a severe, potentially life-threatening allergic reaction)
- Iron overload (when too much iron accumulates in the body)
- Hypophosphatemia (low phosphate levels) According to the expert consensus guidelines, the risk of side effects varies depending on the specific iron preparation used, with newer formulations generally having fewer adverse effects than older ones 1. Additionally, the American Gastroenterological Association clinical practice update suggests that all intravenous iron formulations have similar risks, and true anaphylaxis is very rare, with the vast majority of reactions being complement activation–related pseudo-allergy (infusion reactions) 1. Healthcare providers should monitor patients closely during and after the infusion to detect any adverse reactions early, and patients with a history of allergies, asthma, or inflammatory conditions should inform their healthcare provider before treatment 1.
From the FDA Drug Label
The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1)] Hypotension [see Warnings and Precautions ( 5.2)] Iron Overload [see Warnings and Precautions ( 5.3)] Adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for Venofer exceeds the rate for comparator are listed by indication in Table 1. The most common adverse reactions (>2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%). The following adverse reactions have been identified during post-approval use of Venofer. Immune system disorders: anaphylactic-type reactions, angioedema Psychiatric disorders: confusion Nervous system disorders: convulsions, collapse, light-headedness, loss-of-consciousness Cardiac disorders: bradycardia Vascular disorders: shock Respiratory, thoracic and mediastinal disorders: bronchospasm, dyspnea Musculoskeletal and connective tissue disorders: back pain, swelling of the joints Renal and urinary disorders: chromaturia General disorders and administration site conditions: hyperhidrosis Symptoms associated with Venofer total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse Adult patients: The most common adverse reactions (≥2%) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. Pediatric patients: The most common adverse reactions (≥2%) are headache, respiratory tract viral infection, peritonitis, vomiting, pyrexia, dizziness, cough, nausea, arteriovenous fistula thrombosis, hypotension, and hypertension.
The side effects of intravenous iron transfusion include:
- Hypersensitivity reactions
- Hypotension
- Iron overload
- Headache
- Respiratory tract viral infection
- Peritonitis
- Vomiting
- Pyrexia
- Dizziness
- Cough
- Nausea
- Arteriovenous fistula thrombosis
- Hypertension
- Anaphylactic-type reactions
- Angioedema
- Confusion
- Convulsions
- Collapse
- Light-headedness
- Loss-of-consciousness
- Bradycardia
- Shock
- Bronchospasm
- Dyspnea
- Back pain
- Swelling of the joints
- Chromaturia
- Hyperhidrosis
- Diarrhea
- Pruritus
- Pain in extremity
- Arthralgia
- Muscle cramp
- Injection site reactions
- Chest pain
- Peripheral edema 2, 2, 2
From the Research
Side Effects of Intravenous Iron Transfusion
The side effects of intravenous iron transfusion can be categorized into minor and major reactions.
- Minor infusion reactions are not common and are self-limited, due to labile iron and not hypersensitivity 3.
- Acute hypersensitivity reactions to current intravenous iron formulation are believed to be caused by complement activation-related pseudo-allergy, though exceedingly rare (<1:250,000 administrations) 3, 4.
- Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases 4, 5.
- Other potential side effects include hypotension, which could be considered to be due to hypersensitivity or vascular reaction to labile iron 3.
- Anaphylaxis is a rare but life-threatening side effect of intravenous iron transfusion 6, 5.
Management of Side Effects
- Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff 4, 5.
- In the event of a reaction, the very first intervention should be the immediate cessation of the infusion, followed by evaluation of severity and treatment 3.
- Premedication with antihistamines or corticosteroids is not recommended for all patients, but should be considered in high-risk patients 6.
- Staff should inform all patients about infusion reactions and identify those patients with increased risk of hypersensitivity or contraindications for intravenous iron prior to the infusion 3.