Iron supplements

Iron supplements are supplements that can be prescribed by a doctor for a medical reason. Iron can also be a dietary supplement, which can be purchased in supermarkets etc. These two categories should not be confused.

The first iron pills were commonly known as Blaud's pills, which were named after P. Blaud of Beaucaire, the French physician who introduced and started the use of these medications as a treatment for patients with anemia.^[1]

Indications

Iron supplements are used in medicine to treat iron-deficiency anemia.

First, it must be clear that iron deficiency and not another factor (e.g. chronic, low-grade, undetected blood loss such as fecal occult blood) causes the anemia. Preventive measures must be discussed with the patient (for example when the patient is on a strict vegetarian diet because inorganic iron in plants has a lower bioavailability, or elderly patients with a poor diet).

Another indication for giving extra iron is the second and third trimester of pregnancy, generally in association with folic acid. Indeed, in some condition like growth, menstruation and pregnancy, the body's need for iron is increased. Supplements may be needed to reach RDA life goals.^[2]

Patients at risk of acute complications of iron supplementation may be candidates for blood transfusion, which decreases the need of iron for hemoglobin synthesis, and supplies additional iron when the transfused hemoglobin is degraded. Patients with anemia of chronic disease may benefit from erythropoietin.

Administration

Oral

Iron can be supplemented by the oral route using various pharmacological forms, such as iron(II) sulfate (this is the most common and cheapest salt, e.g. Feratab, Fer-Iron, Slow-FE,…) and in complex with gluconate, dextran, carbonyl iron, and other salts. Sometimes ascorbic acid is added for better absorption.

Heme iron polypeptide can be used when regular iron supplements such as ferrous sulfate or ferrous fumarate are not tolerated or absorbed. A clinical study demonstrated that HIP increased serum iron levels 23 times greater than ferrous fumarate on a milligram-per-milligram basis.^[3]

Another alternative is ferrous glycine sulfate or ferroglycine sulfate, has less gastrointestinal side-effects than standard preparations such as iron fumarate,^[4] but is more expensive. It is especially useful in iron deficiency anemia associated with autoimmune gastritis and Helicobacter pylori gastritis, where it generally has satisfactory effect.^[5]

Since iron stores in the body are generally depleted, and there is a limit to what the body can process (about 100mg per day) without iron poisoning, this is a chronic therapy which may take 3-6 months.

Parenteral

Parenteral iron therapy (intravenously or intramuscular) is only given when oral therapy has failed or oral absorption is seriously compromised (by illnesses, or when the patient cannot swallow) and benefit from oral therapy cannot be expected. Parenteral therapy is more expensive, has increased morbidity and might not be suitable during pregnancy. In cases of persistent iron deficiency (renal replacement therapy, inflammatory bowel disease), the benefits of parenteral iron far outweigh the risks.

One formulation of parenteral iron is iron dextran (trade names including Cosmofer, DexFerrum, Infed). A notable side effect is allergic reaction, which occurs in less than 1 on 100 treated patients,^[6] but may cause severe, sometimes fatal, complications, including loss of consciousness, collapse, difficulty breathing, hives, swelling, convulsions and severe low blood pressure (hypotension).^[7]

Iron saccharose (trade names including Venofer) has an occurrence of allergic reactions of less than 1 in 1000.^[8] A common side effect is taste changes, especially a metallic taste, occurring in between 1 in 10 and 1 in 100 treated patients.^[8]

Side effects

Side effects of therapy with iron are most often diarrhea or constipation and epigastric abdominal discomfort. Taken after a meal, side effects decrease, but there is an increased risk of interaction with other substances. Side effects are dose-dependent, and the dose may be adjusted.

The patient may notice that his/her stools become black. This is completely harmless, but patients must be warned about this to avoid unnecessary concern. When iron supplements are given in a liquid form, teeth may reversibly discolor (this can be avoided through the use of a straw). Intramuscular injection can be painful, and brown discoloration may be noticed.

Treatments with iron(II) sulfate have higher incidence of adverse events than iron(III)-hydroxide polymaltose complex (IPC)^[9][10][11] or iron bis-glycinate chelate.^[12][13]

Contraindications

Documented hypersensitivity and anemias without proper work-up (i.e., documentation of iron deficiency). Hypersensitivity reactions can be very dramatic if iron is administered intravenously.

Iron supplementation and infection risk

Because one of the functions of elevated ferritin (an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections. Replacement of iron stores is seldom such an emergency situation that it cannot wait for any such acute infection to be treated.

Some studies have found that iron supplementation can lead to an increase in infectious disease morbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrhea overall and enteropathogen shedding. Iron deficiency protects against infection by creating an unfavorable environment for bacterial growth. Nevertheless, while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as Salmonella typhimurium or Entamoeba histolytica. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases; however this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection.

Interactions

Iron forms an insoluble complex with several other drugs, resulting in decreased absorption of both iron and the other drug. Examples include tetracycline, penicillamine, methyldopa, levodopa, bisphosphonates and quinolones. The same can occur with elements in food, such as calcium. Absorption of iron is better at a low pH (an acid environment), and resorption is decreased if there is a simultaneous intake of antacids, phosphates, etc.

Tannins from foods, such as tea and saw palmetto, reduce absorption of iron.

Taken after a meal, there are fewer side effects but there is also less absorption because of interaction and pH alteration. Generally, an interval of 2-3h between the iron intake and that of other drugs seems advisable.

Precautions

Children who ingest tablets may become intoxicated, in which case they should be taken to an emergency department. Some formulations (like carbonyl-iron) may be safer.

Follow-up

Follow-up is needed to ensure compliance and to detect adequate response to therapy. If not, this may indicate another cause of anemia. Haematocrit, reticulocyte percentage, MCV, MCH and MCHC (the latter three being signs of microcytic anemia) should increase.

See also

• Human iron metabolism
• Proferrin
• Geritol
• iron deficiency
• iron deficiency anemia

References

1. ^ Robinson, Victor, Ph.C., M.D. (editor) (1939). "P. Blaud of Beaucaire, Blaud's Pills for Anemia, Iron pills, Iron". The Modern Home Physician, A New Encyclopedia of Medical Knowledge. WM. H. Wise & Company (New York). , page 435.
2. ^ Dietary Supplement Fact Sheet: Iron - U.S. National Institutes of Health, Office of Dietary Supplements.
3. ^ Seligman, et al., Nutritional Research 2000; Vol. 20, No 9:1279-1286.
4. ^ Aronstam, A.; Aston, D. (1982). "A comparative trial of a controlled-release iron tablet preparation ('Ferrocontin' Continus) and ferrous fumarate tablets". Pharmatherapeutica 3 (4): 263–267. PMID 7146040.  edit
5. ^ Hershko, C.; Ianculovich, M.; Souroujon, M. (2007). "Decreased Treatment Failure Rates following Duodenal Release Ferrous Glycine Sulfate in Iron Deficiency Anemia Associated with Autoimmune Gastritis and Helicobacter pylori Gastritis". Acta Haematologica 118 (1): 19–26. doi:10.1159/000101701. PMID 17426393.  edit
6. ^ Cosmofer in FASS (drug formulary), translated from Swedish "Allergiska reaktioner (förekommer hos færre än 1 av 100 behandlade patienter) "
7. ^ Drugs.com > iron dextran Version: 1.05. Revision Date: 12/15/2010
8. ^ ^{a b} Venofer in FASS (drug formulary), translated from Swedish "Allergiska reaktioner (inträffar hos färre än 1 av 1 000 patienter)" and "Vanliga (inträffar hos färre än 1 av 10 patienter): Tillfälliga smakförändringar (speciellt metallsmak)."
9. ^ Geisser P (2007). "Safety and efficacy of iron(III)-hydroxide polymaltose complex / a review of over 25 years experience". Arzneimittelforschung 57 (6A): 439–52. PMID 17691594. 
10. ^ Toblli JE, Brignoli R (2007). "Iron(III)-hydroxide polymaltose complex in iron deficiency anemia / review and meta-analysis". Arzneimittelforschung 57 (6A): 431–8. PMID 17691593. 
11. ^ Saha L, Pandhi P, Gopalan S, Malhotra S, Saha PK (2007). "Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulfate in the treatment of iron deficiency anemia in pregnant women". MedGenMed 9 (1): 1. PMC 1924983. PMID 17435611. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1924983. 
12. ^ Szarfarc SC, de Cassana LM, Fujimori E, Guerra-Shinohara EM, de Oliveira IM (2001). "Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women". Arch Latinoam Nutr 51 (1 Suppl 1): 42–7. PMID 11688081. 
13. ^ Ashmead SD (2001). "The chemistry of ferrous bis-glycinate chelate". Arch Latinoam Nutr 51 (1 Suppl 1): 7–12. PMID 11688084.