Clinical case reports raise doubts about the therapeutic equivalence of an iron sucrose similar preparation compared with iron sucrose originator

Abstract

Intravenous iron sucrose has been used to treat iron deficiency and iron deficiency anaemia associated with different chronic diseases for several decades. Despite the complex structure of iron sucrose, copies called iron sucrose similars (ISSs) have been approved according to the generic approach and therefore, therapeutic equivalence is taken for granted. In February 2011, three patients who previously tolerated well the prescribed iron sucrose originator experienced urticaria, oedema and headache within 1 hour after infusion of an ISS that had been substituted for the originator at the pharmacy level. One patient collapsed due to severe hypovolaemic dysregulation and required hospitalisation. Due to emerging evidence that ISSs differ from the iron sucrose originator in safety and efficacy profiles, it seems prudent for physicians as well as patients who require intravenous (i.v.) iron to have available data on therapeutic equivalence of new ISS preparations versus the originator. This may be especially important in patients who are chronically ill and need iron supplementation on a regular, long-term basis.

The Complete Study of the Switch from Iron-Sucrose Originator to Iron- Sucrose Similar and Vice Versa in Hemodialysis Patients

“…Evidence from published clinical studies suggests that ISS preparations may not be equivalent to IS in either effectiveness or safety [20][21][22][23][24]. Our observations also support these findings as the effectiveness of the ISS was inferior to the original IS.…”

“…Side effects in patient populations have also been observed with other ISS in gastroenterology [21], gynecology [23], and recently partly in nephrology with the changes induced after switching from a generic formulation to an original formulation [42]. Our recommendation is that the selection of a specific iron should not be based solely on financial considerations, between original molecules and their similar, assuming comparable efficacy and safety, because original and similar formulations might not be interchangeable.…”

“…iron therapy. A recent safety analysis showed the reporting rate of adverse events with ISSs to be nil, which is virtually impossible given the widespread, multinational use of ISS preparations [19], as well as the fact that several studies have demonstrated evidence for increased adverse events with the substitution of an ISS in clinical practice [20][21][22][23].…”

Nanoparticle iron medicinal products – Requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies

“…Published papers (Toblli et al, 2009;Toblli et al, 2012;Rottembourg et al, 2011;Stein et al, 2012) involving existing iron sucrose copies report on differences between the intended copy and the originator preparation related to physicochemical, biological (non-clinical) and clinical effects. Subtle differences in the multistep manufacturing processes of originator products and intended copies, such as starting materials, reaction time, pH or temperature may affect the physicochemical properties of ISS preparations.…”

“…However, growing evidence has raised doubts about the interchangeability and/or substitutability of intended copies and originator (Martin-Malo et al, 2011;Rottembourg et al, 2011;Stein et al, 2012;Toblli et al, 2009Toblli et al, , 2011. The recent data from a clinical study in haemodialysis patients, where substitution of the iron sucrose originator preparation by an intended copy of this product (a so-called iron sucrose similar, ISS) resulted in a significant reduction of hemoglobin (Hb) levels (Rottembourg et al, 2011).…”