A retrospective survey on the safety of Replenate®, a high-purity factor VIII concentrate

Purpose To assess the safety of a highly purified, plasma‐derived factor VIII concentrate (Replenate®) in routine clinical use. Methods Following guidelines entitled safety assessment of marketed medicines (SAMM), safety data were collected in the UK on 194 patients who received an estimated 47.6 million IU of Replenate®. This population included 47 patients undergoing 53 surgical operations or dental extractions. Results The study detected four cases of new factor VIII inhibitor development and twelve other adverse events, five that were unrelated to the product, five whose causality was unknown, one that was possibly product‐related and one case due to possible lack of efficacy. Only one of these cases had been notified to the manufacturer through conventional spontaneous reporting procedures. Three patients were switched from Replenate® as a result of an adverse event (one case of infusion site irritation and two cases of a rise in titre of an existing inhibitor), but no unexpected adverse reactions were noted and there were no reports of virus transmission. The median factor VIII recovery value was 2.17 IU/dl per IU/kg, but recovery was shown to be dependent on several variables, namely inhibitor status, treatment centre and the patient's body weight. The median factor VIII recovery in inhibitor‐free patients was 2.28 IU/dl per IU/kg (range: 1.20–6.62). Conclusions The study confirms that Replenate® is well tolerated by the majority of patients in routine clinical practice. © Crown copyright 2004. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.