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

Side Effects of Venofer (Iron Sucrose) Therapy

Venofer is generally well-tolerated with a favorable safety profile compared to other intravenous iron preparations, particularly iron dextran, with serious hypersensitivity reactions being rare but potentially life-threatening. 1

Common Side Effects (≥1% to <10%)

The most frequently reported adverse effects during clinical trials and post-marketing surveillance include: 2

• Dizziness
• Headache
• Hypertension
• Hypophosphataemia
• Injection-site reactions
• Nausea

Additional common reactions documented across multiple studies include hypotension, vomiting, diarrhea, pain, dyspnea, pruritus, and fever. 2

Serious Adverse Reactions

Hypersensitivity and Anaphylaxis

Serious hypersensitivity reactions, including anaphylactic-type reactions that can be life-threatening and fatal, have been reported with Venofer. 1 However, the incidence is markedly lower than with iron dextran:

• Hypersensitivity reaction frequency: ≥0.1% to <1% during clinical trials and post-marketing surveillance 2
• No test dose is required for iron sucrose, unlike iron dextran, though test doses are strongly recommended for patients with prior sensitivities to other IV iron preparations or multiple drug allergies 3
• Most reactions occur within 30 minutes of infusion completion 1

Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. 1 Resuscitation facilities must be immediately available, and patients should be monitored for at least 30 minutes after administration until clinically stable. 1

Hypotension

Venofer may cause clinically significant hypotension that is related to the rate of administration and/or total dose. 1 This can occur as:

• An acute reaction during or immediately after infusion 1
• Part of a hypersensitivity reaction 1
• A dose-related phenomenon, particularly with rapid administration 4

Iron Overload and Toxicity

Excessive therapy with parenteral iron can lead to iatrogenic hemosiderosis. 1 Key considerations include:

• Do not administer to patients with evidence of iron overload 1
• Transferrin saturation values increase rapidly after IV administration; serum iron measurements should not be performed for at least 48 hours after dosing 1
• In a pediatric case report, systemic iron toxicity with hepatocellular damage occurred after administration of 16 mg/kg of iron sucrose (exceeding recommended dosing) 2

Pediatric Safety Data

Iron sucrose is the most extensively studied IV iron preparation in children, with rare serious adverse events. 2 In six studies totaling 232 children who received 1,624 doses:

• No anaphylactic reactions occurred in a randomized study of 145 children, adolescents, and young adults 2
• Only one adverse event (skin rash) was considered drug-related 2
• In one series of 38 children receiving 510 doses, only 6 adverse reactions occurred, with the only significant reaction in a patient receiving a dose exceeding the recommended maximum of 300 mg 2

Comparative Safety Profile

Iron sucrose and iron gluconate are considered to have significantly fewer adverse effects than iron dextran. 2 Key distinctions:

• Iron dextran carries a "black-box" warning and requires a mandatory test dose due to risk of anaphylactic reactions from preformed dextran antibodies 2, 4
• Iron sucrose carries no black-box warning and no test dose requirement 4
• Life-threatening anaphylactoid reactions are markedly lower with iron sucrose compared to iron dextran 4
• Over 20,000 infusions of iron sucrose showed no anaphylactic reactions in one large clinical experience 5

Oxidative Stress and Acute Injury Concerns

Emerging research has identified potential acute effects that warrant consideration:

• Iron sucrose infusion produces oxidative stress, demonstrated by increased plasma malondialdehyde levels 6
• Endothelial dysfunction has been documented following iron sucrose infusion 6
• Acute renal injury markers including increased urinary albumin, N-acetyl-beta-glucosaminidase, and monocyte chemoattractant protein-1 have been observed 6

While long-term clinical significance remains unproven, these findings suggest caution with repeated high-dose administration. 6

Delayed Reactions

Delayed reactions characterized by arthralgias and myalgias are dose-related and rarely occur with doses of 100 mg or less. 2 These reactions:

• Are more common with total dose infusions (up to 59% incidence) 2
• Should prompt dose reduction if they occur 2
• Are distinct from the acute arthralgias/myalgias reported with iron gluconate 2

Critical Safety Monitoring

All patients receiving Venofer require periodic monitoring of hematologic and iron parameters including hemoglobin, hematocrit, serum ferritin, and transferrin saturation. 1

Administration Precautions

• Stop Venofer immediately if hypersensitivity reactions or signs of intolerance occur 1
• Monitor for signs and symptoms of hypotension following each administration 1
• Maximum individual dose should not exceed 300 mg 3
• Administer only when personnel and therapies for treating serious hypersensitivity reactions are immediately available 1

Contraindications

Do not administer iron sucrose to patients with:

• Evidence of iron overload 1
• Active infection (per NCCN guidelines, due to concerns about promoting inflammation and bacterial growth) 2