Intravenous Immunoglobulins: In-Depth Review of Excipients and Acute Kidney Injury Risk

Abstract

Background: Used in a variety of approved and off-label indications, there are several intravenous immunoglobulin (IVIG) preparations available which differ in the excipients (e.g. sucrose, glucose, maltose, <smlcap>D</smlcap>-sorbitol, glycine or <smlcap>L</smlcap>-proline) used to stabilize the protein in the solution. A very rare, but severe adverse drug reaction (ADR) reported with sucrose-stabilized IVIGs, acute renal failure, is well established, but the relative risks with sucrose-free IVIGs are unknown. Methods: Medline and Embase were searched for published data on ADRs involving the kidney, and DrugCite, a public database of >4,000,000 ADRs from the USA, was also searched. Renal impairment-associated ADRs and categories were summarized. Results: Compared with sucrose-containing IVIGs, reports of ADRs involving the kidney were relatively rare with sucrose-free IVIGs: 12 cases were published prior to February 28, 2012; incidences reported in DrugCite were also relatively low and similar among sucrose-free preparations. The incidence of hemolysis-related ADRs, a potential cause of secondary acute renal impairment, was higher with glycine- and <smlcap>L</smlcap>-proline-stabilized IVIGs. Reported incidences of renal impairment with sucrose-free IVIGs are similar between products and much lower than with sucrose-stabilized IVIGs. Conclusions: It is recommended that the choice of IVIG should be guided by the patient's medical history, present comorbidities and concomitant medications. Prospective studies with inclusion of creatinine values, as well as rigorous reporting of cases in the literature and/or via pharmacovigilance systems, are imperative to better define patient profiles.

Tolerability and safety of the intravenous immunoglobulin octagam®10% in patients with immune thrombocytopenia: a post-authorisation safety analysis of two non-interventional phase IV trials

“…All manufacturers of IVIG products are now required to identify steps in their manufacturing process that effectively remove procoagulant contaminants [17,25]. Acute renal failure and haemolytic anaemia are other serious but rare ADRs associated with IVIG that can be influenced by the physicochemical composition of the preparation: hyperosmolar IVIG formulations containing sucrose as a stabiliser appear to be disproportionately associated with renal dysfunction and acute renal failure [26], and IVIGrelated haemolysis has been linked to anti-A and anti-B haemagglutinins in the preparation [27]. There were no cases of TEE, acute renal failure or haemolytic anaemia associated with octagam® 10% in our patients with ITP.…”

Actual issues of production and use of immunological drugs from human blood plasma in modern medicine (based on the materials of the First Intercontinental Academy on Immunology and Congenital Angioedema)

“…Уместно также иметь в виду, что существуют особые требования для педиатрии и в особенности детской ге-матологии-онкологии: высокая концентрация раствора (10 %), наибольшее содержание IgG c физиологическим соотношением подклассов IgG, минимальное содер-жание IgA, низкое содержание натрия, осмоляльность, близкая к физиологической, оптимальный стабилиза-тор и уровень рН, а также высокий уровень вирусной безопасности [3]. Особо хотелось бы отметить, что вы-сокая концентрация раствора не только снижает нагруз-ку объемом на организм пациента, что крайне важно для определенных групп больных, но и способствует эконо-мии времени медицинского персонала за счет более бы-строго введения препарата при относительно невысоком риске развития нежелательных явлений [4].…”

Intravenous immunoglobulin: pharmacological properties and use in polyneuropathies

“…Side effects are mostly transient and mild, estimated to occur between 1 to 15% of infusions, and many of them can be reversed even by temporarily stopping or slowing the infusion [60]. The most frequently encountered adverse effects include headache, chills and fever, nausea, mild hypotension or hypertension, and mild arthralgias.…”