Ferric maltol

Ferric maltol
Clinical data
Trade names	Accrufer, Feraccru
AHFS/Drugs.com	Monograph
License data	US DailyMed: Ferric_maltol;
Routes of; administration	By mouth
Drug class	Hematologic agents
ATC code	B03AB10 (WHO) ;
Legal status
Legal status	UK: POM (Prescription only); US: ℞-only; EU: Rx-only; In general: ℞ (Prescription only);
Pharmacokinetic data
Metabolism	Glucuronidation (maltol)
Elimination half-life	0.7 hrs (maltol)
Excretion	Urine (maltol)
Identifiers
	IUPAC name Iron(3+) tris(2-methyl-4-oxo-4H-pyran-3-olate);
CAS Number	33725-54-1;
PubChem CID	169535;
DrugBank	DB876;
ChemSpider	148265;
UNII	MA10QYF1Z0;
KEGG	D10833;
CompTox Dashboard (EPA)	DTXSID10955335 ;
Chemical and physical data
Formula	C18H15FeO9
Molar mass	431.154 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C(=O)C=CO1)[O-].CC1=C(C(=O)C=CO1)[O-].CC1=C(C(=O)C=CO1)[O-].[Fe+3];
	InChI InChI=1S/3C6H6O3.Fe/c31-4-6(8)5(7)2-3-9-4;/h32-3,8H,1H3;/q;;;+3/p-3; Key:AHPWLYJHTFAWKI-UHFFFAOYSA-K;

Ferric maltol, sold under the brand names Accrufer (US) and Feraccru (EU), is an iron containing medication for the treatment of adults with low iron stores. It is taken by mouth.^[2]^[4]

Contraindications

Structure of Fe(maltol-H)₃.^[5] Color code: red = O, gray = C, blue = Fe.

The drug is contraindicated in people with hereditary hemochromatosis and other kinds of iron overload, as well as those repeatedly receiving blood transfusions^[6] and are therefore also at risk of developing iron overload.

Side effects

The most common side effects are flatulence (in 5% of people taking the drug), diarrhea (4%), constipation (4%), stool color change (4%), nausea (3%), vomiting (3%), and abdominal discomfort, bloating and pain (1%).^[2]^[7] Ferric maltol may cause serious side effects including increased risk of inflammatory bowel disease flare and iron overload in the body.^[2]

Interactions

No systematic interaction studies with ferric maltol have been conducted. Food reduces its uptake from the gut, as do calcium and magnesium salts and tetracycline antibiotics. Conversely, iron inhibits the uptake of many drugs, such as bisphosphonates, tetracycline antibiotics, quinolone antibiotics, levothyroxin, and levodopa. Combining the drug with intravenous iron can result in fast release of iron into the blood, potentially leading to low blood pressure or even collapse.^[6]

Dimercaprol in combination with iron is toxic for the kidneys. The antibiotic chloramphenicol interferes with incorporation of iron into red blood cells and with iron excretion. Furthermore, iron can reduce the blood pressure lowering effects of methyldopa.^[6]

Maltol is metabolized by the enzyme UGT1A6. It is not known whether inhibitors of this enzyme increase maltol concentrations in the body.^[6]

Pharmacology

Mechanism of action

Ferric maltol acts as a source of iron, which is essential for oxygen transport in the blood and other processes in the human body.^[8]

Pharmacokinetics

The substance is a complex of iron with maltol, which is absorbed from the gut and then dissociates, releasing iron and maltol separately into the bloodstream. Iron is bound to transferrin and reaches its highest concentrations in the blood plasma one to three hours after ingestion. It is also bound to ferritin for storage. Maltol reaches its highest plasma concentrations after 1 to 1.5 hours. It is quickly metabolized to the glucuronide by UGT1A6 and eliminated via the urine with a biological half-life of 0.7 hours. 40–60% are excreted in the glucuronidized form.^[6]^[7]

History

Ferric maltol was approved for medical use in the European Union in February 2016.^[4]

Ferric maltol was approved for medical use in the United States in July 2019,^[3]^[9] based on evidence from three clinical trials (trial 1/NCT01252221, trial 2/NCT01340872,^[10] and trial 3/NCT02968368^[11]).^[2] All 295 participants had low iron stores in the body and consequent iron deficiency anemia. In the first two trials low iron was caused by participants' inflammatory bowel disease (IBD) and in the last trial, by long standing (chronic) kidney disease.^[2] Trials were conducted at 79 sites in Europe and the United States.^[2]

References

^ "Feraccru 30mg hard capsules - Summary of Product Characteristics (SmPC)". electronic medicines compendium (emc). 7 February 2019. Archived from the original on 23 November 2019. Retrieved 23 November 2019.
^ ^a ^b ^c ^d ^e ^f ^g "Drug Trials Snapshots: Accrufer". U.S. Food and Drug Administration (FDA). 15 August 2019. Archived from the original on 23 November 2019. Retrieved 23 November 2019. This article incorporates text from this source, which is in the public domain.
^ ^a ^b "Drug Approval Package: Accrufer". U.S. Food and Drug Administration (FDA). 14 August 2019. Archived from the original on 23 November 2019. Retrieved 23 November 2019. This article incorporates text from this source, which is in the public domain.
^ ^a ^b ^c "Feraccru EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 23 November 2019. Retrieved 23 November 2019. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ Ahmet MT, Frampton CS, Silver J (1988). "A Potential Iron Pharmaceutical Composition for the Treatment of Iron-Deficiency Anaemia. The Crystal and Molecular Structure of mer-tris-(3-Hydroxy-2-methyl-4H-pyran-4-onato)iron(III)". Journal of the Chemical Society, Dalton Transactions (5): 1159. doi:10.1039/DT9880001159.
^ ^a ^b ^c ^d ^e "Feraccru: EPAR – Product Information" (PDF). European Medicines Agency. 25 February 2020. Archived (PDF) from the original on 11 April 2020. Retrieved 29 July 2020.
^ ^a ^b Ferric maltol Professional Drug Facts. Accessed 29 July 2020.
^ Maton A, Hopkins J, McLaughlin CW, Johnson S, Warner MQ, LaHart D, et al. (1993). Human Biology and Health. Englewood Cliffs, New Jersey, US: Prentice Hall. ISBN 978-0139811760.
^ "Accrufer (ferric maltol) FDA Approval History". Drugs.com. 25 July 2019. Archived from the original on 1 August 2019. Retrieved 23 November 2019.
^ Clinical trial number NCT01340872 for "Safety and Efficacy Study of Oral Ferric Iron To Treat Iron Deficiency Anaemia in Quiescent Ulcerative Colitis (AEGIS-1) (AEGIS-1)" at ClinicalTrials.gov
^ Clinical trial number NCT02968368 for "Study With Oral Ferric Maltol for the Treatment of Iron Deficiency Anemia in Subjects With Chronic Kidney Disease (AEGIS-CKD)" at ClinicalTrials.gov