The safety and efficacy of ferumoxytol in the treatment of iron deficiency: a systematic review and meta‐analysis

Abstract

INTRODUCTION:Ferumoxytol is an intravenous (IV) iron formulation for treatment of iron deficiency (ID) that faced post-marketing reports of serious adverse events (SAEs). OBJECTIVES:To determine the safety and efficacy of ferumoxytol compared to other iron formulations and placebo. METHODS:We searched the Cochrane Library, Medline, and EMBASE from inception until February 2018 as well as trial registries and reference lists of relevant articles for randomized or quasi-randomized controlled trials. RESULTS:The review included nine studies with 5691 participants. Studies were at low risk of bias. When comparing ferumoxytol to other IV iron formulations, there is moderate quality evidence (QE) of little to no difference in treatment emergent adverse events (TEAEs) (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.80-0.97), treatment related adverse events (TRAEs) (RR 0.73, 95% CI 0.61-0.88), SAEs (RR 1.13, 95% CI 0.77-1.67), hypotension or hypersensitivity reactions (RR 0.58, 95% CI 0.31-1.09), or composite cardiovascular outcomes (RR 0.56, 95% CI 0.24-1.29), low QE of little to no difference in related SAEs (RR 0.55, 95% CI 0.05-6.16), and high QE of little to no difference in the number of patients with an increase in hemoglobin by at least 1 g/dL (RR 1.04, 95% CI 0.96-1.12). Ferumoxytol had less TEAEs compared to oral iron (RR 0.78, 95% CI 0.61-0.98), but more compared to placebo (RR 1.62, 95% CI 1.01-2.61). DISCUSSION: Ferumoxytol is as efficacious and safeas alternative IV iron formulations with no clear safety concerns.From the

Frequency and Associated Costs of Anaphylaxis- and Hypersensitivity-Related Adverse Events for Intravenous Iron Products in the USA: An Analysis Using the US Food and Drug Administration Adverse Event Reporting System

“…While real-world studies, both using spontaneous reporting databases and claims databases have shown results consistent with our analysis [4,8,15,16], other analyses have not [11]. In a meta-analysis of randomized controlled trials examining AEs across trials comparing ferumoxytol with other pooled IV iron preparations (iron sucrose and ferric carboxymaltose), oral iron, and placebo, an elevated rate of hypersensitivity reactions and hypotension was noted with ferumoxytol vs oral iron, but not vs the pooled IV iron group.…”

“…In a meta-analysis of randomized controlled trials examining AEs across trials comparing ferumoxytol with other pooled IV iron preparations (iron sucrose and ferric carboxymaltose), oral iron, and placebo, an elevated rate of hypersensitivity reactions and hypotension was noted with ferumoxytol vs oral iron, but not vs the pooled IV iron group. However, only three studies contributed to this latter comparison and all three studies specifically excluded patients with a prior history of allergies to drugs that did not include those under investigation [11]. In an earlier, but much larger, meta-analysis of 103 clinical trials, infusion reactions were increased with all IV iron preparations examined (iron sucrose, ferric gluconate, and ferric carboxymaltose) compared with placebo, oral iron, or no iron, and ferric carboxymaltose was associated with a reduced rate of cardiovascular AEs and AEs leading to discontinuation [13].…”

“…reactions and anaphylaxis [4] and black-box warnings for these events have been added to the prescribing information for some IV iron preparations [9,10], the risk is rare [7,8]. Given the rarity of these serious reactions, randomized controlled trial evidence and associated meta-analyses have been unable to demonstrate meaningful differences between IV iron preparations [11][12][13]. Large observational claims database retrospective analyses have suggested these reactions may be more frequent with iron dextran vs newer preparations [4] and with ferumoxytol vs iron sucrose (see Supplementary Table S5 in Wetmore et al [14]), and pharmacovigilance spontaneous reporting database analyses have suggested higher reporting rates with iron dextran, ferumoxytol, and iron isomaltoside than ferric gluconate or ferric carboxymaltose [8,[15][16][17][18].…”

Iron deficiency without anaemia: a diagnosis that matters

“…61 Ferumoxytol, which was withdrawn from European markets in 2015, continues to be available in the USA, and has been shown to be just as safe. 58,62 Excluding HMWID, the risk of severe reactions is very low (1:250,000 administrations). 57,63 Nevertheless, it is essential to administer IV iron in a setting where such adverse effects can be adequately managed.…”

Ներերակայի՞ն, Թե՞ Ներքին Ընդունում. Ո՞րն Ընտրել: Երկաթպակասորդային Սակավարյունության Բուժման Նորագույն Մոտեցումները

“…Ներերակային երկաթի դեպքում հնարավոր են ալերգիկ ռեակցիաներ, այդ թվում` կյանքին վտանգ սպառնացող: Սակայն ծանր կողմնակի ազդեցությունները հազվադեպ են և համեմատելի են առկա պրեպարատների միջև [1,2,8]: Ոչ ալերգիկ ինֆուզիոն ռեակցիաները` ինքնասահմանափակվող եղնջացան, սրտխփոց, գլխապտույտ, պարանոցի և մեջքի սպազմ, արձանագրվել են <1% դեպքերում և չեն հարաճում մինչև լուրջ ռեակցիաներ [27]: Ոչ ալերգիկ ռեակցիաներից է Ֆիշբեյնի ռեակցիան, որը դեմքի հիպերեմիա է, կրծքավանդակի և մեջքի միալգիա: Վերջինիս զարգացման մեխանիզմն անհայտ է, սակայն ենթադրվում է լաբիլ երկաթով կոմպլեմենտի ակտիվացմամբ պայմանավորված պսևդոալերգիա (CARPA), [5,9,25]:…”