Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Vifor France, 100-101 Terrasse Boieldieu, Tour Franklin La Défense 8, 92042, Paris La Défense Cedex, France Tel. +33 (0)1 41 06 58 90 Fax +33 (0)1 41 06 58 99
Pharmacotherapeutic group: Anti-anaemic preparation, iron, parenteral preparation
ATC code: B03AC
Iron sucrose, the active ingredient of Venofer, is composed of a polynuclear iron(III)-hydroxide core surrounded by a large number of non-covalently bound sucrose molecules. The complex has a weight average molecular weight (Mw) of approximately 43 kDa. The polynuclear iron core has a structure similar to that of the core of the physiological iron storage protein ferritin. The complex is designed to provide, in a controlled manner, utilisable iron for the iron transport and storage proteins in the body (i.e., transferrin and ferritin, respectively).
Following intravenous administration, the polynuclear iron core from the complex is taken up predominantly by the reticuloendothelial system in the liver, spleen, and bone marrow. In a second step, the iron is used for the synthesis of Hb, myoglobin and other iron-containing enzymes, or stored primarily in the liver in the form of ferritin.
Study LU98001 was a single arm study to investigate the efficacy and safety of 100 mg iron as Venofer for up to 10 sessions over 3-4 weeks in haemodialysis patients with iron deficiency anaemia (Hb >8 and <11.0 g/dl, TSAT <20%, and serum ferritin ≤300 μg/l) who were receiving rHuEPO therapy. A Hb ≥11 g/dl was attained in 60/77 patients. The mean increase in serum ferritin and TSAT was significant from baseline to the end of treatment (Day 24) as well as to the 2 and 5 weeks follow-up visit.
Study 1VEN03027 was a randomised study comparing Venofer (1000 mg in divided doses over 14 days) and oral ferrous sulphate (325 mg 3 times daily for 56 days) in non-dialysis dependent chronic kidney disease patients (Hb ≤11.0 g/dl, serum ferritin ≤300 μg/l, and TSAT ≤25%) with or without rHuEPO. A clinical response (defined as Hb increase ≥1.0 g/dl and serum ferritin increase ≥160 μg/l) was more frequently observed in patients treated with Venofer (31/79; 39.2%) compared to oral iron (1/82; 1.2%); p<0.0001.
A randomised, controlled study compared Venofer (single IV dose of 200 mg iron once per week or every second week until the cumulative dose was reached) with oral iron (200 mg twice daily for 20 weeks) in patients with inflammatory bowel disease and anaemia (Hb <11.5 g/dl). At the end of treatment, 66% of patients in the Venofer group had an increase in Hb ≥2.0 g/dl compared to 47% in the oral iron group (p=0.07).
A randomised, controlled trial in women with postpartum iron deficiency anaemia (Hb <9 g/dl and serum ferritin <15 μg/l at 24–48 hours post-delivery) compared 2 × 200 mg iron given as Venofer on Days 2 and 4 (n=22) and 200 mg of oral iron given as ferrous sulphate twice daily for 6 weeks (n=21). The mean increase in Hb from baseline to Day 5 was 2.5 g/dl in the Venofer group and 0.7 g/dl in the oral iron group (p<0.01).
In a randomised, controlled study, women in their third trimester of pregnancy with iron deficiency anaemia (Hb 8 to 10.5 g/dl and serum ferritin <13 µg/l) were randomised to Venofer (individually calculated total dose of iron administered over 5 days) or oral iron polymaltose complex (100 mg 3× daily until delivery). The increase in Hb from baseline was significantly greater in the Venofer group compared to the oral iron group at Day 28 and at delivery (p<0.01).
The ferrokinetics of iron sucrose labelled with 52Fe and 59Fe were assessed in 6 patients with anaemia and chronic renal failure. In the first 6–8 hours, 52Fe was taken up by the liver, spleen and bone marrow. The radioactive uptake by the macrophage-rich spleen is considered to be representative of the reticuloendothelial iron uptake.
Following intravenous injection of a single 100 mg iron dose of iron sucrose in healthy volunteers, maximum total serum iron concentrations were attained 10 minutes after injection and had an average concentration of 538 µmol/l. The volume of distribution of the central compartment corresponded well to the volume of plasma (approximately 3 litres).
Upon injection, sucrose largely dissociates and the polynuclear iron core is mainly taken up by the reticuloendothelial system of the liver, spleen, and bone marrow. At 4 weeks after administration, red cell iron utilization ranged from 59 to 97%.
The iron sucrose complex has a weight average molecular weight (Mw) of approximately 43 kDa, which is sufficiently large to prevent renal elimination. Renal elimination of iron, occurring in the first 4 hours after injection of a Venofer dose of 100 mg iron, corresponded to less than 5% of the dose. After 24 hours, the total serum iron concentration was reduced to the pre-dose level. Renal elimination of sucrose was about 75% of the administered dose.
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity and toxicity to reproduction and development.
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