Iron carboxymaltose

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General
Non-proprietary name Iron carboxymaltose
other names

Iron (III) hydroxide oxide {4- O- poly [-α- D -glucopyranosyl (1 → 4)] - D-gluconate} hydrate

Molecular formula [FeO x (OH) y (H2O) z ] n [(C 6 H 10 O 5 ) m (C 6 H 12 O 7 ) l ] k , where n ~ 10 3 , m ~ 8, l ~ 11, and k ~ 4
External identifiers / databases
CAS number 9007-72-1
EC number 813-933-0
ECHA InfoCard 100.245.982
PubChem 86278165
DrugBank DB08917
Wikidata Q20817270
Drug information
ATC code

B03 AC

Drug class

Parenteral iron preparations

properties
Molar mass 788.44 g · mol -1
Physical state

liquid

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
08 - Dangerous to health 07 - Warning

Caution

H and P phrases H: 315-319-335-361-373
P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Iron carboxymaltose is a drug used for the parenteral treatment of iron deficiency / iron deficiency anemia . The active ingredient is a macromolecular complex , consisting of iron (III) hydroxide (trivalent iron, Fe 3+ ) and the complexing agent carboxymaltose .

application

Iron carboxymaltose is administered intravenously to patients with iron deficiency / iron deficiency anemia, for whom oral iron therapy is ineffective, ineffective, or impractical. Compared to oral iron therapy, intravenous iron therapy compensates for the iron deficiency more quickly and the anemia is usually corrected more quickly.

Iron carboxymaltose is only used when there is evidence of iron deficiency in the blood (e.g. low ferritin or low transferrin saturation ).

The medicine is in ampoules . Iron carboxymaltose can be administered as a bolus or as an infusion ; for an infusion, the contents of the ampoule are diluted with isotonic saline solution . There are upper limits for the single dose and the weekly dose. The total amount of iron to be administered can be calculated from the patient's hemoglobin value and body weight, using the Ganzoni formula.

Since the intravenous administration of iron preparations can in rare cases trigger acute hypersensitivity reactions of the immediate type ( anaphylactic reactions), the preparation may only be administered if medical specialists are available who can recognize and treat such hypersensitivity reactions immediately. Dextran, which was used in earlier iron preparations, is primarily responsible for the hypersensitivity reaction. Iron carboxymaltose does not contain dextran.

The active ingredient has been on the market since 2007 and is approved in over 70 countries. It is sold in Germany, Austria and Switzerland under the trade name Ferinject.

pharmacology

Mode of action

The active ingredient is absorbed into the reticulendothelial system in the blood via macrophages , mainly in the liver , where the iron is packed in storage iron (ferritin) or transport iron ( transferrin ) and thus the body for various functions, mainly for incorporation into hemoglobin in the red blood cells , can be made available. Hemoglobin transports oxygen from the lungs to the body's cells.

Pharmacodynamics

The utilization, resp. Uptake in the erythrocytes 24 days after administration of the iron administered intravenously via iron carboxmaltose was between 91 and 99% in patients with iron deficiency anemia and between 61 and 84% in renal anemia.

Pharmacokinetics

Following a single dose administration, maximum serum iron levels are reached after 15 to 70 minutes. The administered iron is rapidly eliminated from the blood plasma with a plasma half-life of between 7 and 12 hours. The average length of stay is 11 to 17 hours. Renal elimination is negligible.

Clinical efficacy and safety

The effectiveness and safety have been examined and documented in numerous clinical studies. Among other things, in dialysis patients, in patients with anemia in the context of chronic intestinal diseases, heart failure , kidney failure and in patients with postpartum anemia.

Efficacy studies

In patients with chronic heart failure and iron deficiency, an improvement in the Patient Global Assessment Score , the fatigue score and the quality of life was achieved. At the same time, there was a lower risk of inpatient hospitalization due to congestive heart failure. In women with symptomatic fatigue of unknown cause and iron deficiency, fatigue was reduced within a short time (7 days). In patients with chronic renal failure without dialysis , there was a delayed need for alternative therapies for the treatment of anemia ( blood transfusion , drugs that stimulate erythropoiesis ). An improvement in the comparable Hb values ​​was achieved in pregnant women (2nd and 3rd trimester ) with iron deficiency anemia. A faster and more frequent anemia correction and a better quality of life with iron carboxymaltose were found. The safety and tolerability of iron carboxmaltose in pregnant women and the fetus has been confirmed. In patients with Crohn's disease or ulcerative colitis and iron deficiency, more patients in the iron carboymaltose group compared to the iron sucrose group had an increased Hb value. The quality of life was improved in both groups and tolerability was comparable.

Contraindications and Precautions

If there is a known hypersensitivity to iron preparations, iron carboxmaltose, like all other parenteral iron preparations, must not be used. Iron supplements are not given for anemia that has a cause other than iron deficiency. Iron supplements are also not allowed to be administered in the case of known iron overload or iron utilization disorders.

As the drug has not been studied in children, it should not be given to children under 14 years of age.

Iron carboxymaltose must not be mixed with other medicinal products or given at the same time as oral iron. When administered as an infusion, the preparation may only be diluted with isotonic saline solution.

Side effects

The observed side effects with a frequency between 1 and 10% included headache , dizziness , increased blood pressure, nausea and local reaction at the infusion site. Rare side effects with a frequency between 0.1% and 1% included sensory disturbances, taste disturbances, plus increase, drop in blood pressure, flushes, muscle pain and abdominal pain , among others . Very rare side effects with a frequency between 0.1 and 0.01% include anaphylactic reactions, phlebitis , flatulence and flu-like symptoms.

It has also been shown that intravenous administration of iron carboxymaltose leads to transient (temporary) hypophosphataemia in approx. 40% of cases .

Trade names

Iron carboxymaltose is sold under the name Ferinject .

Web links

Individual evidence

  1. ↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A label derived from a self-classification by the distributor of (2S, 3S, 4S, 5R) -4 - [(2R, 3R, 4R, 5S, 6R) -5 - [(2R, 3R, 4R, 5S, 6R) -3,4-dihydroxy-6- (hydroxymethyl) -5 - [(2R, 3R, 4S, 5S, 6R) -3,4,5-trihydroxy-6- (hydroxymethyl) oxan-2-yl] oxyoxan-2 -yl] oxy-3,4-dihydroxy-6- (hydroxymethyl) oxan-2-yl] oxy-2,3,5,6-tetrahydroxyhexanoate; iron (3 +); oxygen (2 -); hydroxide; hydrate im Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on June 19, 2018.
  2. ↑ S. Beshara, J. Sorensen, M. Lubberink, V. Tolmachev, B. Långström, G. Antoni, BG Danielson, H. Lundqvist: Pharmacokinetics and red cell utilization of 52 Fe / 59 Fe-labeled iron Polymaltose in anemic patients using positron emission tomography. In: British Journal of Hematology . Volume 120, Number 5, March 2003, pp. 853-859, PMID 12614222 .
  3. ↑ P. Geisser, J. Banké-Bochita: Pharmacokinetics, safety and tolerability of intravenous ferric carboxymaltose: a dose-escalation study in volunteers with mild iron-deficiency anemia. In: drug research. Volume 60, number 6a, 2010, pp. 362-372, doi: 10.1055 / s-0031-1296301 , PMID 20648928 .
  4. ↑ S. Kulnigg, S. Stoinov, V. Simanenkov, LV Dudar, W. Karnafel, LC Garcia, AM Sambuelli, G. D'Haens, C. Gasche: A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. In: The American Journal of Gastroenterology . Volume 103, Number 5, 2008, pp. 1182-1192, doi: 10.1111 / j.1572-0241.2007.01744.x , PMID 18371137 .
  5. ↑ P. Ponikowski, DJ van Veldhuisen, J. Comin-Colet, G. Ertl, M. Komajda, V. Mareev, T. McDonagh, A. Parkhomenko, L. Tavazzi, V. Levesque, C. Mori, B. Roubert , G. Filippatos, F. Ruschitzka, SD Anker: Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency †. In: European Heart Journal . Volume 36, Number 11, 2015, pp. 657–668, doi: 10.1093 / eurheartj / ehu385 , PMID 25176939 , PMC 4359359 (free full text).
  6. ^ A b I. C. Macdougall, AH Bock, F. Carrera, KU Eckardt, C. Gaillard, D. Van Wyck, B. Roubert, JG Nolen, SD Roger: FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anemia. In: Nephrology, Dialysis, Transplantation . Volume 29, number 11, 2014, pp. 2075-2084, doi: 10.1093 / ndt / gfu201 , PMID 24891437 , PMC 4209879 (free full text).
  7. ^ MH Seid, RJ Derman, JB Baker, W. Banach, C. Goldberg, R. Rogers: Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trial. In: American Journal of Obstetrics and Gynecology . Volume 199, Number 4, October 2008, pp. 435.e1-435.e7, doi: 10.1016 / j.ajog.2008.07.046 , PMID 18928998 .
  8. ↑ P. Ponikowski, DJ van Veldhuisen, J. Comin-Colet, G. Ertl, M. Komajda, V. Mareev, T. McDonagh, A. Parkhomenko, L. Tavazzi, V. Levesque, C. Mori, B. Roubert , G. Filippatos, F. Ruschitzka, SD Anker: Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency †. In: European Heart Journal. Volume 36, Number 11, 2015, pp. 657–668, doi: 10.1093 / eurheartj / ehu385 , PMID 25176939 , PMC 4359359 (free full text).
  9. ↑ B. Favrat, K. Balck, C. Breymann, M. Hedenus, T. Keller, A. Mezzacasa, C. Gasche: Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women - PREFER a randomized, placebo -controlled study. In: PloS one . Volume 9, number 4, 2014, p. E94217, doi: 10.1371 / journal.pone.0094217 , PMID 24751822 , PMC 3994001 (free full text).
  10. ↑ C. Breymann, N. Milman, A. Mezzacasa, R. Bernard, J. Dudenhausen: Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP). In: Journal of Perinatal Medicine. 2016, doi: 10.1515 / jpm-2016-0050 , PMID 27278921 .
  11. ↑ R. Evstatiev, P. Marteau, T. Iqbal, IL Khalifa, J., B. Bokemeyer, IV Chopey, FS Gutzwiller, L. Riopel, C. Gasche: FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. In: Gastroenterology. Volume 141, number 3, September 2011, pp. 846-853.e1, doi: 10.1053 / j.gastro.2011.06.005 , PMID 21699794 .
  12. ↑ Ferinject. In: compendium.ch. HCI Solutions AG, accessed on April 10, 2017 .
  13. ↑ Robert Stöhr, Lukas Sandstede, Gunnar H. Heine, Nikolaus Marx, Vincent Brandenburg: High-Dose Ferric Carboxymaltose in Patients With HFrEF Induces Significant Hypophosphatemia . In: Journal of the American College of Cardiology . tape 71 , no. May 19 , 2018, p. 2270–2271 , doi : 10.1016 / j.jacc.2018.03.448 .
  14. ^ Henning Schneider: The obstetrics. Springer-Verlag, 2016, ISBN 978-3-662-45064-2 , p. 505.