[Generic drugs: quality, efficacy, safety and interchangeability]. / Generika: Qualität, Wirksamkeit, Sicherheit und Austauschbarkeit.

Since the introduction of generic drugs to the pharmaceutical market a sometimes emotional debate exists whether they are well-investigated and of high quality. There is some uncertainty about whether evidence of bioequivalence is enough to guarantee efficacy and safety of generic drugs. Some physicians ask the question if competent authorities are able to ascertain that the pharmaceutical quality of generics is acceptable. Doctors and patients sometimes are ill at ease about the interchangeability of innovator and generic products. This article describes how the European Union legislation ensures that a generic drug is only approved if its risk-benefit relationship is favourable and that it is essentially similar to the innovator product. In this context pharmacokinetic parameters are accepted as surrogates for clinical results because bioequivalence means therapeutic equivalence as well. For most drugs, current bioequivalence testing generally enables clinicians to routinely substitute generic for innovator products. Published findings, however, suggest that particular drugs may not be ideally suited for generic substitution when a patient is already on that drug. These are the so called critical dose medicinal products (drugs with a narrow therapeutic range). When starting a new therapy with any generic drug, however, its similarity to the innovator drug in terms of efficacy, safety and quality is guaranteed.

High-dose parenteral iron sucrose depresses neutrophil intracellular killing capacity.

BACKGROUND: Iron is essential for the formation of hemoglobin. During long-term treatment with human recombinant erythropoietin (rhEPO), the majority of end-stage renal disease (ESRD) patients will not respond adequately to rhEPO unless substituted with intravenous iron. However, concern exists about possible detrimental effects of parenteral iron on cellular host defense and iron-mediated increments of oxidative stress. METHODS: We analyzed phagocytic functions of polymorphonuclear leukocytes (PMN) isolated from 20 ESRD patients on peritoneal dialysis in response to 300 mg of iron sucrose or placebo administered intravenously over two hours in a randomized, double-blind manner. We evaluated Fc gamma R-dependent phagocytosis and killing (primary outcome variable) of opsonized Escherichia coli, Fc gamma R-dependent oxidative burst capacity, and complement receptor 3 (CR3, Mac1, CD11b/CD18)/tumor necrosis factor alpha (TNFalpha)-mediated release of bactericidal lactoferrin before, during, one hour, and two days after administration. RESULTS: The absolute count and the percentage of E. coli killed by PMN of iron sucrose-treated peritoneal dialysis patients decreased significantly over time in comparison to placebo-treated patients (F = 3.48, df = 4, P = 0.008; F = 3.99, df = 4, P = 0.006, respectively). All secondary outcome variables were not different between both groups over time. CONCLUSIONS: Killing capacity of PMN isolated from ESRD patients decreases in response to high-dose parenteral iron sucrose, possibly in part explaining reported higher hospitalization rates and lower survival rates of dialysis patients receiving frequent and high-dose parenteral iron.