Safety of rapid injection of undiluted ferric carboxymaltose to patients with iron-deficiency anaemia: a Phase II single-arm study.
administration and dosage
anaemia
iron deficiency
Journal
Internal medicine journal
ISSN: 1445-5994
Titre abrégé: Intern Med J
Pays: Australia
ID NLM: 101092952
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
revised:
13
07
2020
received:
18
10
2019
accepted:
30
12
2020
pubmed:
20
1
2021
medline:
21
9
2021
entrez:
19
1
2021
Statut:
ppublish
Résumé
Ferric carboxymaltose is increasingly utilised to treat iron deficiency and is usually diluted in saline and administered as an intravenous infusion over 15 min. Although this is highly convenient compared with older formulations, we hypothesised the drug could be administered, safely given as a rapid bolus injection. To define the risk of serious adverse events following administration of an undiluted, rapid, high-dose ferric carboxymaltose injection. Secondary aims included all other adverse events, as well as longitudinal effects on haemoglobin, iron stores, phosphate and hepcidin. In a single-arm, Phase II study in 121 patients with iron-deficiency anaemia, we administered up to 1000 mg of ferric carboxymaltose as a rapid undiluted bolus injection, and recorded adverse events and collected blood samples over the first hour, and again at 2 and 4 weeks post-treatment. No patient experienced a serious adverse event. Flushing during the injection was common, as was a transient headache in the subsequent weeks. One patient experienced Grade 3 chest tightness, necessitating emergency department assessment but not admission or treatment. Treatment produced an average 12.3 g/L improvement in haemoglobin within 2 weeks, but commonly caused reductions in serum phosphate (although none of these was clinically symptomatic). Parenteral iron caused elevations in hepcidin sustained to 4 weeks post-injection. Patients stated they would be prepared to receive the treatment again. Rapid injection of undiluted ferric carboxymaltose is well tolerated and could provide an approach to treat patients in the ambulatory setting.
Sections du résumé
BACKGROUND
BACKGROUND
Ferric carboxymaltose is increasingly utilised to treat iron deficiency and is usually diluted in saline and administered as an intravenous infusion over 15 min. Although this is highly convenient compared with older formulations, we hypothesised the drug could be administered, safely given as a rapid bolus injection.
AIMS
OBJECTIVE
To define the risk of serious adverse events following administration of an undiluted, rapid, high-dose ferric carboxymaltose injection. Secondary aims included all other adverse events, as well as longitudinal effects on haemoglobin, iron stores, phosphate and hepcidin.
METHODS
METHODS
In a single-arm, Phase II study in 121 patients with iron-deficiency anaemia, we administered up to 1000 mg of ferric carboxymaltose as a rapid undiluted bolus injection, and recorded adverse events and collected blood samples over the first hour, and again at 2 and 4 weeks post-treatment.
RESULTS
RESULTS
No patient experienced a serious adverse event. Flushing during the injection was common, as was a transient headache in the subsequent weeks. One patient experienced Grade 3 chest tightness, necessitating emergency department assessment but not admission or treatment. Treatment produced an average 12.3 g/L improvement in haemoglobin within 2 weeks, but commonly caused reductions in serum phosphate (although none of these was clinically symptomatic). Parenteral iron caused elevations in hepcidin sustained to 4 weeks post-injection. Patients stated they would be prepared to receive the treatment again.
CONCLUSION
CONCLUSIONS
Rapid injection of undiluted ferric carboxymaltose is well tolerated and could provide an approach to treat patients in the ambulatory setting.
Substances chimiques
Ferric Compounds
0
ferric carboxymaltose
6897GXD6OE
Maltose
69-79-4
Iron
E1UOL152H7
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1304-1311Subventions
Organisme : Vifor Pharma
Informations de copyright
© 2021 Royal Australasian College of Physicians.
Références
Gupta PM, Hamner HC, Suchdev PS, Flores-Ayala R, Mei Z. Iron status of toddlers, nonpregnant females, and pregnant females in the United States. Am J Clin Nutr 2017; 106: 1640S-6S.
Salvin HE, Pasricha SR, Marks DC, Speedy J. Iron deficiency in blood donors: a national cross-sectional study. Transfusion 2014; 54: 2434-44.
Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One 2015; 10: e0117383.
Pasricha S-R, Flecknoe-Brown SC, Allen KJ, Gibson PR, McMahon LP, Olynyk JK et al. Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust 2010; 193: 525-32.
Radhika AG, Sharma AK, Perumal V, Sinha A, Sriganesh V, Kulshreshtha V et al. Parenteral versus oral iron for treatment of iron deficiency Anaemia during pregnancy and post-partum: a systematic review. J Obstet Gynaecol India 2019; 69: 13-24.
Lewkowitz AK, Gupta A, Simon L, Sabol BA, Stoll C, Cooke E et al. Intravenous compared with oral iron for the treatment of iron-deficiency anemia in pregnancy: a systematic review and meta-analysis. J Perinatol 2019; 39: 519-32.
Bonovas S, Fiorino G, Allocca M, Lytras T, Tsantes A, Peyrin-Biroulet L et al. Intravenous versus oral iron for the treatment of anemia in inflammatory bowel disease: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2016; 95: e2308.
Geisser P, Rumyantsev V. Pharmacodynamics and safety of ferric carboxymaltose: a multiple-dose study in patients with iron-deficiency anaemia secondary to a gastrointestinal disorder. Arzneimittelforschung 2010; 60: 373-85.
Girelli D, Ugolini S, Busti F, Marchi G, Castagna A. Modern iron replacement therapy: clinical and pathophysiological insights. Int J Hematol 2018; 107: 16-30.
Byrne D. Administering Intravenous Iron in General Practice. Adelaide: GPEx Limited; 2016.
Evstatiev R, Marteau P, Iqbal T, Khalif IL, Stein J, Bokemeyer B et al. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology 2011; 141: 846-53 e1-2.
Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009; 361: 2436-48.
Roger SD, Gaillard CA, Bock AH, Carrera F, Eckardt KU, Van Wyck DB et al. Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial. Nephrol Dial Transplant 2017; 32: 1530-9.
Favrat B, Balck K, Breymann C, Hedenus M, Keller T, Mezzacasa A et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women - PREFER a randomized, placebo-controlled study. PLoS One 2014; 9: e94217.
Breymann C, Milman N, Mezzacasa A, Bernard R, Dudenhausen J, investigators F-A. Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP). J Perinat Med 2017; 45: 443-53.
Damineni SC, Thunga S. IV ferric carboxymaltose vs oral iron in the treatment of post-partum iron deficiency anaemia. J Clin Diagn Res 2016; 10: QC08-10.
Australian Register of Therapeutic Goods. Australian Product Information - Ferinject® (Ferric Carboxymaltose) Solution for Injection, Vol. 2019. Canberra: Therapeutic Goods Administration; 2019.
U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). V4.03. Washington, DC: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2009.
Bregman DB, Goodnough LT. Experience with intravenous ferric carboxymaltose in patients with iron deficiency anemia. Ther Adv Hematol 2014; 5: 48-60.
Medicinewise NPS. Ferinject - Ferric carboxymaltose. Consumer medicine information (CMI) leaflet. In: Consumer Medicine Information, Vol. 2019. Surry Hills, NSW: NPS Medicinewise; 2019.
Adkinson NF, Strauss WE, Macdougall IC, Bernard KE, Auerbach M, Kaper RF et al. Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: a randomized trial. Am J Hematol 2018; 93: 683-90.
Klein K, Asaad S, Econs M, Rubin JE. Severe FGF23-based hypophosphataemic osteomalacia due to ferric carboxymaltose administration. BMJ Case Rep 2018; 2018: bcr-2017-222851.
Fang W, McMahon LP, Bloom S, Garg M. Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose. JGH Open 2019; 3: 438-40.
Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight 2018; 3: e124486.
AMAG Pharmaceuticals. Dosing and Administration. In: Feraheme® Ferumoxytol Injection, Vol. 2019. Waltham, MA: AMAG Pharmaceuticals; 2019.
Karki NR, Auerbach M. Single total dose infusion of ferumoxytol (1020 mg in 30 minutes) is an improved method of administration of intravenous iron. Am J Hematol 2019; 94: E229-31.
Detlie TE, Lindstrom JC, Jahnsen ME, Finnes E, Zoller H, Moum B et al. Incidence of hypophosphatemia in patients with inflammatory bowel disease treated with ferric carboxymaltose or iron isomaltoside. Aliment Pharmacol Ther 2019; 50: 397-406.
Agency EM. Intravenous Iron-Containing Medicinal Products, Vol. 2019. London: European Medicines Agency; 2013.
Wray K, Allen A, Evans E, Fisher C, Premawardhena A, Perera L et al. Hepcidin detects iron deficiency in Sri Lankan adolescents with a high burden of hemoglobinopathy: a diagnostic test accuracy study. Am J Hematol 2017; 92: 196-203.
Pasricha SR, Atkinson SH, Armitage AE, Khandwala S, Veenemans J, Cox SE et al. Expression of the iron hormone hepcidin distinguishes different types of anemia in African children. Sci Transl Med 2014; 6: 235re3.
Eypasch E, Lefering R, Kum CK, Troidl H. Probability of adverse events that have not yet occurred: a statistical reminder. BMJ 1995; 311: 619-20.