Venofer (Iron Sucrose)
iron sucrose injection, USP
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Iron deficiency anemia in hemodialysis-dependent CKD | Adults; pediatric ≥2 years (maintenance only) | Iron replacement / maintenance | FDA Approved |
| Iron deficiency anemia in non-dialysis-dependent CKD | Adults; pediatric ≥2 years (maintenance only) | Iron replacement / maintenance | FDA Approved |
| Iron deficiency anemia in peritoneal dialysis-dependent CKD | Adults; pediatric ≥2 years (maintenance only) | Iron replacement / maintenance | FDA Approved |
Iron sucrose is an established intravenous iron preparation specifically indicated for the treatment of iron deficiency anemia in patients with chronic kidney disease, regardless of dialysis status. In CKD, iron deficiency is driven by ongoing blood losses during dialysis, impaired intestinal absorption, and blunted iron mobilisation from stores due to elevated hepcidin. The KDIGO 2012 guideline recommended considering IV iron when TSAT is ≤30% and ferritin is ≤500 ng/mL, and the updated KDIGO 2026 guideline continues to endorse IV iron as a cornerstone of CKD anemia management. Pediatric approval is limited to iron maintenance treatment in children aged 2 years and older who are receiving stable erythropoietin therapy; iron replacement dosing in pediatric CKD has not been established.
Iron deficiency anemia in pregnancy (2nd/3rd trimester) — Used when oral iron is not tolerated or insufficient. Multiple RCTs support efficacy and safety after the first trimester; generally not initiated before week 13–16 of gestation. Evidence quality: Moderate
Iron deficiency anemia in inflammatory bowel disease — Guidelines from ECCO and AGA support IV iron sucrose for IDA in IBD patients, particularly when oral iron exacerbates GI symptoms. Evidence quality: Moderate
Iron deficiency anemia refractory to oral therapy (non-CKD) — Used in patients with documented malabsorption, oral iron intolerance, or ongoing blood loss exceeding the capacity of oral replacement. Supported by observational data and clinical consensus. Evidence quality: Low–Moderate
Chemotherapy-associated anemia (iron-restricted erythropoiesis) — IV iron may improve response to erythropoiesis-stimulating agents in cancer-related anemia with functional iron deficiency. Evidence quality: Moderate
Dosing
Adult Iron Replacement — By Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| IDA in hemodialysis-dependent CKD — iron repletion | 100 mg per HD session | 100 mg per session x 10 sessions | 1000 mg cumulative course | Administer undiluted slow IV push over 2–5 min or diluted in max 100 mL NS over ≥15 min. Give early in HD session (within first hour). Repeat course if IDA recurs |
| IDA in non-dialysis-dependent CKD — standard protocol | 200 mg x 5 doses over 14 days | 200 mg on each of 5 occasions | 1000 mg cumulative course | Slow IV push over 2–5 min or infuse 200 mg in max 100 mL NS over 15 min. Repeat if iron deficiency recurs |
| IDA in non-dialysis-dependent CKD — extended infusion option | 500 mg on Day 1 | 500 mg on Day 14 | 1000 mg total (2 infusions) | Dilute 500 mg in max 250 mL NS; infuse over 3.5–4 hours. Limited experience with this regimen (FDA PI) |
| IDA in peritoneal dialysis-dependent CKD | 300 mg IV infusion (Day 1) | 300 mg (Day 15) then 400 mg (Day 29) | 1000 mg over 28 days (3 infusions) | 300 mg doses over 1.5 hr; 400 mg dose over 2.5 hr. Dilute in max 250 mL NS. All infusions ~14 days apart |
Pediatric Iron Maintenance — By CKD and Dialysis Status (Age ≥2 Years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Iron maintenance in HDD-CKD (on stable ESA therapy) | 0.5 mg/kg | 0.5 mg/kg every 2 weeks x 6 doses (12 wk) | 100 mg per dose | Undiluted slow IV push over 5 min, or diluted in NS (1–2 mg/mL) over 5–60 min. Iron replacement dosing not established in peds |
| Iron maintenance in NDD-CKD or PDD-CKD (on stable ESA therapy) | 0.5 mg/kg | 0.5 mg/kg every 4 weeks x 3 doses (12 wk) | 100 mg per dose | Same administration method as above. Do not dilute below 1 mg/mL. Not studied in patients <2 years |
For hemodialysis patients, administer iron sucrose early in the dialysis session (typically within the first hour) via the venous limb of the dialyser. The drug is not removed by dialysis. For all routes, avoid mixing with other medications or adding to parenteral nutrition solutions. When drawing up the dose, visually inspect for particulate matter and discoloration prior to use. Store undiluted product at 20–25°C; diluted solutions (in NS) are stable for 7 days at room temperature or under refrigeration.
Pharmacology
Mechanism of Action
Iron sucrose is a sterile aqueous complex of polynuclear iron (III)-hydroxide in a sucrose shell, with a molecular weight of approximately 34,000–60,000 daltons. After intravenous administration, the complex is taken up by cells of the reticuloendothelial system (primarily in the liver, spleen, and bone marrow), where it dissociates into its iron and sucrose components. The released iron is either stored as ferritin or transported via transferrin to erythroid precursor cells in the bone marrow. There, iron is incorporated into the porphyrin ring of haem and ultimately into haemoglobin as red cells mature. This parenteral delivery mechanism bypasses the enterocyte absorption step entirely, making it useful in patients whose gastrointestinal absorption is impaired or whose iron losses exceed the absorptive capacity of the gut.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | 100% bioavailable (IV administration); no oral formulation | Bypasses GI tract entirely; useful when oral iron fails or is contraindicated |
| Distribution | Vd = 7.9 L; distributes to blood, liver, spleen, bone marrow | Bone marrow acts as an irreversible iron-trapping compartment for erythropoiesis |
| Metabolism | Dissociated by RES into Fe3+ and sucrose; no CYP involvement | No hepatic CYP-mediated drug interactions; iron enters normal physiological pool |
| Elimination | t½ = 6 h (adults), 8 h (adolescents); CL = 1.2 L/h; sucrose: 75.4% renally excreted by 24 h; ~5% of iron excreted in urine by 24 h | Not dialyzable; avoid serum iron measurements within 48 h of dosing (artificially elevated TSAT) |
Side Effects
Adverse reaction data below are derived from six pivotal clinical trials in the FDA prescribing information (N=231 HDD-CKD, N=139 NDD-CKD, N=75 PDD-CKD) and from post-marketing safety studies in 1,051 HDD-CKD patients. Rates vary significantly by CKD population and dialysis modality; the highest incidence rates (particularly for hypotension and muscle cramps) are seen in the HDD-CKD population and may be partly attributable to the dialysis procedure itself.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Hypotension | 39.4% | Most frequent in HDD-CKD (confounded by intradialytic hypotension); rate- and dose-related. Monitor BP during and after infusion. |
| Muscle cramps | 29.4% | Predominantly in HDD-CKD population; may overlap with dialysis-associated cramping. Much lower in NDD-CKD (0.7%). |
| Nausea | 14.7% | Dose-related; slowing the infusion rate may help. Also reported at 8.6% in NDD-CKD and 5.3% in PDD-CKD. |
| Headache | 12.6% | Generally self-limiting. Lower incidence in NDD-CKD (2.9%) and PDD-CKD (4.0%). |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Vomiting | 5.0–9.1% | Higher in HDD-CKD (9.1%) and PDD-CKD (8.0%); may be mitigated by slower administration |
| Diarrhea | 5.2–8.0% | Comparable across CKD populations; typically transient |
| Dysgeusia (metallic taste) | 7.9% | Most prominent in NDD-CKD; related to rapid increase in serum iron; self-resolving |
| Dizziness | 1.3–6.5% | Highest in HDD-CKD and NDD-CKD (6.5% each); PDD-CKD lower (1.3%). May be secondary to hypotension. |
| Hypertension | 6.5–8.0% | Observed across all CKD populations; monitor during and after infusion |
| Chest pain | 1.4–6.1% | Highest in HDD-CKD (6.1%); NDD-CKD lower (1.4%). Rule out hypersensitivity and cardiac causes. |
| Peripheral edema | 2.6–7.2% | Common in CKD regardless of therapy; higher in NDD-CKD (7.2%) |
| Pain in extremity | 2.7–5.6% | May include infusion-related discomfort; generally self-limiting |
| Dyspnea | 1.3–5.8% | Higher in NDD-CKD (5.8%); distinguish from anaphylactoid bronchospasm |
| Pruritus | 2.2–3.9% | May herald hypersensitivity; observe closely and stop infusion if progressive |
| Arthralgia | 1.4–4.0% | Transient; no dose adjustment typically required |
| Back pain | 1.3–2.2% | May occur during or shortly after infusion; monitor for Fishbane reaction |
| Injection site reactions | 2.2–5.8% | Includes pain, burning, and extravasation discoloration; ensure stable IV access |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Anaphylactic-type reactions | Rare | Within 30 min of infusion | Stop infusion immediately. Administer epinephrine, IV fluids, corticosteroids, and antihistamines. Permanent discontinuation. |
| Severe hypotension / cardiovascular collapse | Rare (post-marketing) | During or within 30 min of infusion | Stop infusion; IV fluids; Trendelenburg positioning. Slow rate on re-challenge if deemed necessary. |
| Acute myocardial ischaemia (in context of hypersensitivity) | Very rare (post-marketing) | During or shortly after infusion | Standard acute coronary syndrome management. Permanent discontinuation of IV iron. |
| Seizures / loss of consciousness | Very rare (post-marketing) | During infusion | Stop infusion; supportive care; neurological assessment. Do not re-challenge. |
| Bronchospasm | Rare (post-marketing) | During or within 30 min of infusion | Stop infusion; administer bronchodilators and supplemental oxygen. Consider epinephrine if severe. |
| Iron overload / hemosiderosis | Dose-dependent | Cumulative (weeks to months) | Monitor ferritin and TSAT regularly. Withhold iron if ferritin >700 ng/mL or TSAT ≥40% (KDIGO 2026). Consider chelation if symptomatic overload. |
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Hypersensitivity reaction | Rare (individual cases) | No life-threatening hypersensitivity in pivotal trials; reported in post-marketing |
| Severe hypotension | Rare (individual cases) | Rate-related; may be mitigated by slower infusion; often not a reason for permanent cessation |
| Iron overload (ferritin-driven hold) | Protocol-dependent | Therapy withheld when iron indices exceed targets; not a true discontinuation but a planned hold |
Hypotension is the most clinically significant routine adverse effect of iron sucrose, particularly in hemodialysis patients. It is related to both the rate and total dose of administration. If hypotension occurs during infusion, slow the rate or stop the infusion temporarily. Administer IV normal saline. Symptoms often resolve with rate reduction and fluid support. For patients with recurrent intradialytic hypotension, consider administering iron sucrose in the first hour of dialysis before ultrafiltration targets are approached, and ensure the patient’s dry weight assessment is up to date.
Drug Interactions
Iron sucrose has a relatively limited interaction profile because it does not undergo hepatic cytochrome P450 metabolism. The primary concern is its potential to reduce absorption of concomitantly administered oral medications through cation binding in the GI tract. Although iron sucrose is given intravenously, residual free iron in the gut (or concurrent oral iron use) can chelate with certain drugs. The following interactions are clinically relevant.
Monitoring
-
Haemoglobin / Haematocrit
Baseline, then every 1–4 weeks during treatment
Routine Target Hb increase of ≥1 g/dL within 2–4 weeks of completing a treatment course. If no response, reassess iron status, bleeding, inflammation, and ESA adequacy. Avoid over-correction. -
Serum Ferritin
Baseline, then every 1–3 months during ESA therapy
Routine Withhold iron if ferritin exceeds 700 ng/mL (KDIGO 2026) or 500 ng/mL (KDIGO 2012 threshold). Ferritin is an acute-phase reactant; interpret in context of CRP and clinical state. -
Transferrin Saturation (TSAT)
Baseline, then every 1–3 months
Routine Do NOT measure serum iron for at least 48 hours after IV iron sucrose dosing — TSAT will be artefactually elevated. Consider withholding iron if TSAT ≥40% (KDIGO 2026). -
Blood Pressure
During and for ≥30 min after every infusion
Routine Iron sucrose can cause significant hypotension, particularly in HDD-CKD patients. Rate-related and dose-related. Stop or slow infusion if symptomatic drop occurs. -
Signs of Hypersensitivity
During and for ≥30 min after every infusion
Routine Observe for rash, urticaria, pruritus, dyspnoea, wheezing, angioedema, and haemodynamic instability. Ensure resuscitation equipment and trained personnel are immediately available. -
Reticulocyte Count
Optional; 5–10 days post-treatment
Trigger-based Peak reticulocytosis occurs 5–10 days after IV iron; useful to confirm erythropoietic response, especially when Hb response is delayed. -
Infection Status
Before each IV iron course
Trigger-based KDIGO recommends avoiding IV iron during active systemic infections, as iron may promote bacterial growth. Reassess when infection is controlled.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to iron sucrose or any component of the formulation
- Anemia not caused by iron deficiency (e.g., haemolytic anaemia, megaloblastic anaemia) — iron supplementation will not correct the underlying cause and risks iron overload
- Evidence of iron overload (elevated ferritin and TSAT beyond treatment thresholds) — risk of iatrogenic haemosiderosis
Relative Contraindications (Specialist Input Recommended)
- Active systemic infection — KDIGO advises withholding IV iron until the infection is controlled, as iron may promote microbial growth. Requires infectious disease or nephrology input regarding timing.
- First trimester of pregnancy — Insufficient safety data in the first trimester; IV iron is generally deferred until after week 13–16. Requires obstetric–haematology shared decision-making.
- Prior severe reaction to another IV iron product — Cross-reactivity between parenteral iron preparations is not well established but cannot be excluded. Test dose may be considered under specialist supervision.
Use with Caution
- Elderly patients — Greater frequency of decreased hepatic, renal, or cardiac function; start cautiously (FDA PI)
- Patients prone to hypotension — Those on antihypertensives, dialysis patients with low dry weight, or those with autonomic dysfunction; consider slower infusion rate
- Hepatic impairment — No specific dose adjustment, but the liver is a major iron storage organ; monitor ferritin more closely
- History of atopy or asthma — Potentially increased risk of hypersensitivity reactions with parenteral iron; ensure resuscitation readiness
Serious hypersensitivity reactions, including anaphylactic-type reactions — some of which have been life-threatening and fatal — have been reported in patients receiving parenteral iron products, including iron sucrose. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Most reactions occur within 30 minutes of completing the infusion. Only administer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Monitor all patients for at least 30 minutes after each infusion and until clinically stable.
Patient Counselling
Purpose of Therapy
Iron sucrose provides iron directly into the bloodstream to build up depleted iron stores and support red blood cell production. It is used when the body cannot absorb enough iron from pills or when iron stores are severely low. This treatment helps improve energy levels, reduce breathlessness, and decrease the need for blood transfusions. The iron infusion does not work instantly — it typically takes 2 to 4 weeks to see an improvement in haemoglobin, and the full benefit may take longer.
How to Receive Treatment
Iron sucrose is given as a slow intravenous injection or infusion at a hospital, clinic, or dialysis centre. The number of sessions depends on the patient’s condition: hemodialysis patients typically receive 10 doses of 100 mg each (one per dialysis session), while other patients may receive fewer but larger infusions spread over 2 to 4 weeks. Each infusion usually takes between 15 minutes and 2.5 hours, depending on the dose. Patients must remain for at least 30 minutes after each infusion for observation.
Sources
- Venofer (iron sucrose injection, USP) — Full Prescribing Information. American Regent, Inc. Revised 06/2022. NDA 021135. FDA Label (2024 update) Primary source for all dosing, adverse reactions, pharmacokinetics, and contraindication data in this monograph.
- American Regent, Inc. Venofer Dosing and Administration Guide. venofer.com/dosing Manufacturer resource summarising dosing by CKD population with administration instructions.
- Charytan C, Levin N, Al-Saloum M, et al. Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial. Am J Kidney Dis. 2001;37(2):300–307. doi:10.1053/ajkd.2001.21293 Pivotal Study A (HDD-CKD) referenced in FDA PI demonstrating Hb increase of ~1.0–1.3 g/dL with 1000 mg iron sucrose.
- Van Wyck DB, Roppolo M, Martinez CO, et al. A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD. Kidney Int. 2005;68(6):2846–2856. doi:10.1111/j.1523-1755.2005.00758.x Study D in the FDA PI; showed 44.3% of iron sucrose patients achieved ≥1 g/dL Hb increase vs 28% with oral iron (p=0.03).
- Agarwal R, Rizkala AR, Bastani B, et al. A randomized controlled trial of oral versus intravenous iron in chronic kidney disease. Am J Nephrol. 2006;26(5):445–454. doi:10.1159/000096174 Supports superiority of IV iron sucrose over oral iron for raising ferritin and TSAT in NDD-CKD.
- Warady BA, Kausz AT, Lerner G, et al. Iron therapy in the pediatric hemodialysis population. Pediatr Nephrol. 2004;19(6):655–661. doi:10.1007/s00467-004-1457-5 Early pediatric data informing iron sucrose dosing in children with HDD-CKD.
- KDIGO Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int Suppl. 2012;2(4):279–335. kdigo.org Prior international guideline establishing TSAT ≤30% and ferritin ≤500 ng/mL thresholds for IV iron initiation in CKD.
- Babitt JL, Tonelli M, et al. KDIGO 2026 Clinical Practice Guideline for the Management of Anemia in Chronic Kidney Disease. Kidney Int. 2026;109(1 Suppl):S1–S99. doi:10.1016/j.kint.2025.06.006 Updated international guideline with revised iron thresholds; suggests withholding iron if ferritin >700 ng/mL or TSAT ≥40%.
- Dignass AU, Gasche C, Bettenworth D, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis. 2015;9(3):211–222. doi:10.1093/ecco-jcc/jju009 ECCO guideline supporting IV iron (including iron sucrose) for IDA in IBD when oral iron is ineffective or not tolerated.
- Danielson BG. Structure, chemistry, and pharmacokinetics of intravenous iron agents. J Am Soc Nephrol. 2004;15(Suppl 2):S93–S98. doi:10.1097/01.ASN.0000143814.49713.C5 Comprehensive review comparing physicochemical properties and safety profiles of different IV iron preparations.
- Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011;3(1):12–33. doi:10.3390/pharmaceutics3010012 Detailed comparison of PK parameters across IV iron formulations; supports the favourable labile iron release profile of iron sucrose.
- Chandler G, Harchowal J, Macdougall IC. Intravenous iron sucrose: establishing a safe dose. Am J Kidney Dis. 2001;38(5):988–991. doi:10.1053/ajkd.2001.28587 Early dose-finding study establishing the safety of 200–300 mg single-dose iron sucrose in CKD patients.
- Breymann C, Honegger C, Hösli I, Surbek D. Diagnosis and treatment of iron-deficiency anaemia in pregnancy and postpartum. Arch Gynecol Obstet. 2017;296(6):1229–1234. doi:10.1007/s00404-017-4526-2 Reviews evidence for IV iron (including iron sucrose) in pregnancy-associated IDA; supports use from the second trimester onward.