Differences between the original iron sucrose complex Venofer® and the iron sucrose similar Generis®,and potential implications

TOBLLI, J. E.; CAO, G.; OLIVERI, L.; ANGEROSA, M

Port J Nephrol Hypert

Publicações Ciência e Vida

Año: 2009 p. 53 - 63

0872-0169

The original iron sucrose complex (Venofer®) is used to treat iron deficiency anaemia, however ‘generic’ compounds known as iron sucrose similar are now available that have subtle structural differences. This study explores possible haemodynamic and functional differences between Venofer® and a Portuguese iron sucrose similar (Generis®). Thirty rats were divided into three groups and assigned to receive Generis®, Venofer® (ORIGINATOR) or isotonic saline solution (control). Five single intravenous doses of iron (40 mg iron/kg) or saline (equivalent volume) were administered every 7 days for 4 weeks. Blood and urine samples were collected for biological assessment prior to sacrifice (day 28) after which kidney, liver, and heart homogenates were collected for determination of antioxidant enzyme levels. Immmunohistochemistry techniques were used to identify tissue ferritin and pro-inflammatory markers. Systolic blood pressure was significantly reduced in the Generis® group relative to the ORIGINATOR and control groups (p<0.01). Creatinine clearance was also reduced (p<0.01) and proteinuria marked (p<0.01) in the Generis® group relative to the ORIGINATOR and control groups throughout the study. Liver enzymes were increased in the Generis® group after 28 days. A significant increase in catalase, thiobarbituric reactive species, CuZn-superoxide dismutase and glutathione peroxidase activity, and a decrease in the reduced to oxidized glutathione ratio (p<0.01) were observed at 4 weeks in the Generis® group (liver, heart and kidney). Serum iron and percentage transferrin saturation were elevated in all groups (except control) (p<0.01) and no differences in haemoglobin concentration were observed. TNF-á and IL6 were significantly elevated in the Generis® group (liver, heart and kidney) compared with the ORIGINATOR and control on day 28 (p<0.01). These findings suggest significant safety and efficacy differences between the ORIGINATOR and Generis®, which may be attributed to the different stability of Generis®. Further studies are needed to investigate the safety profile of iron sucrose similar compounds.