Oral iron as treatment for iron deficiency: Should it always be the first choice?

Jericó Alba, Carlos; García Erce, José Antonio

doi:10.1016/j.medcle.2018.03.024

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However this may be insufficient or ineffective in different clinical situations, especially when a rapid repletion of iron deposits is required to stimulate erythropoiesis, correct secondary anaemia and reduce transfusion risk, or in patients affected by chronic inflammatory diseases in which the capacity for duodenal iron absorption is significantly reduced.<a class="elsevierStyleCrossRef" href="#bib0030">1</a>A large number of commercial oral iron formulations are available, with ferrous salts being considered the first line of choice over ferric salts, due to their apparent superior bioavailability at a lower cost. However, we are unaware of the existence of randomised clinical trials that have clearly demonstrated these pharmacokinetic differences or changes in the incidence of adverse effects. Similarly, although there are no studies to confirm the most suitable daily dose, the common recommendation is 100–200mg of elemental iron per day, as shown in different clinical guidelines and drug agency recommendations. These recommended daily doses greatly exceed the absorptive capacity of the intestine for iron, that is (10–20mg a day) and additionally it causes a marked increase in digestive side effects, such as abdominal pain, diarrhoea or constipation, as a result of the greater elimination of non-absorbed iron salts. In this respect, several recent studies, although all were observational, have recommended the use of lower doses of oral iron (40–80mg per day), dividing the dose so as to administer it twice a day, and even recommending the administration of this dose every other day. This can thus maximise absorption by reducing the effect of the absorbed iron on the hepcidin expression, improving the adherence to treatment and reducing gastrointestinal adverse effects.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>In addition, the intake of foods that are very common in our environment, such as coffee, milk and phytates (present in whole grains and legumes), and which are frequently taken at breakfast, markedly reduce the absorption of oral iron. The same happens with commonly used drugs, such as proton pump inhibitors, antacids or tetracyclines. Therefore the usual recommendation is to take oral iron preparations separate to foods and drugs to favour their absorption. However this is an accepted fact that is not clearly proven, and it is associated with a marked increase in gastrointestinal adverse effects.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>Another point to consider about oral iron treatment is the possible confusion between its digestive side effects and the symptoms of pathologies that associate iron deficiency, such as inflammatory bowel disease, or the interference of the elimination of the non-absorbed remains of iron salts in diagnostic or therapeutic digestive endoscopic studies, or with the detection of blood remains in patients with digestive pathologies that associate recurrent haemorrhaging, such as intestinal angiodysplasias.Finally, the evaluation of the efficacy of oral iron treatment is of great importance, as an increase of 1–2g/dL of haemoglobin at 2–4 weeks of treatment is expected, if treatment is complied with. Failure to respond to the treatment in the case of confirmed iron deficiency makes a study of the causes of this refractoriness mandatory, and rather than increasing the dose of ferrous salt or changing the oral iron preparation, perhaps i/v iron treatment could be considered as an alternative.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Therefore, oral iron may be the first therapeutic option for iron deficiency in patients with mild-moderate iron deficiency anaemia, who do not have previous intolerance nor refractoriness to oral iron. However, in various clinical situations that present iron deficiency, with or without anaemia, treatment with i/v iron becomes the most appropriate option for treatment.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> In this regard, the possible although very infrequent adverse reactions to i/v iron should be taken into account.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> But with a correct selection of patients, and with the i/v iron administered according to the drug agency recommendations, the reluctance of professionals to use i/v iron when indicated should be reduced.<a class="elsevierStyleCrossRef" href="#bib0050">5</a>AuthorshipShared authorship.Conflict of interestsDr. Jericó Alba: He has given lectures and received fees as a consultant for Bial, Vifor Pharma España and Zambon.Dr. García Erce: He has given lectures, chaired conference panels and seminars and organised courses with scholarships or financing for Alexion, Amgen, Braun, Celgene, Ferrer, GSK, Inmucor, Jansen, Novartis, Octapharma, Sanofi, Sandoz, Terumo, Vifor, Zambon." 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"identificador" => "fn0005" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Uso del hierro intravenoso en la clínica actual" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D. Beneitez Pastor" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2018" "volumen" => "150" "paginaInicial" => "188" "paginaFinal" => "190" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aportaciones acerca del uso de hierro intravenoso" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.M. Prieto de Paula" 1 => "S. Franco Hidalgo" 2 => "M. Martín Asenjo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medcli.2017.10.013" "Revista" => array:2 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2017" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current misconceptions in diagnosis and management of iron deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Muñoz" 1 => "S. Gómez-Ramírez" 2 => "M. Besser" 3 => "M. Pavía" 4 => "F. Gomollón" 5 => "G.M. Liumbruno" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2450/2017.0113-17" "Revista" => array:6 [ "tituloSerie" => "Blood Transfus" "fecha" => "2017" "volumen" => "15" "paginaInicial" => "422" "paginaFinal" => "437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28880842" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How I treat unexplained refractory iron deficiency anemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Hershko" 1 => "C. Camaschella" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2013-10-512624" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2014" "volumen" => "123" "paginaInicial" => "326" "paginaFinal" => "333" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24215034" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sobre la seguridad de las formulaciones de hierro intravenoso" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Muñoz Gómez" 1 => "S. Gómez Ramírez" 2 => "J.A. 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