Detail-Document #240811 −This Detail-Document accompanies the related article published in− PHARMACIST’S LETTER / PRESCRIBER’S LETTER August 2008 ~ Volume 24 ~ Number 240811 Comparison of Oral Iron Supplements A new iron supplement product in the U.S. called Ferralet 90 is adding to the confusion surrounding the numerous oral iron supplements on the market. Ferralet 90 is a combination product containing carbonyl iron, B12, vitamin C, folic acid, and docusate and it is marketed as a prescription product. No oral iron dietary supplements are approved by the FDA, but manufacturers can choose to market their products as prescription only.8 There are two main iron salts forms (ferric and ferrous irons) and numerous formulations (e.g., amino-acid chelates, carbonyl iron, polysaccharide-iron complex, combination products, extended-release products, etc) available in the U.S. and Canada. All dietary iron has to be reduced to the ferrous form to enter the mucosal cells; therefore ferrous iron is absorbed three times more readily than the ferric form. Anecdotal claims that sustained-release iron preparations cause fewer gastrointestinal side effects have not been well substantiated.1,2 There is some evidence that controlled-release iron preparation causes less nausea and epigastric pain than conventional ferrous sulfate, but the discontinuation rates are similar.3 Theoretically, once-daily dosing can improve compliance. However, extended-release or enteric-coated formulations have been found to transport iron past the duodenum and proximal jejunum, thereby reducing the absorption of iron.1,2 Vitamin C is added to some products to enhance iron absorption. About 200 mg is needed to increase absorption of 30 mg of elemental iron.1 However, doses of 500 mg to 1000 mg only increase iron absorption by about 10%.2 Most iron preparations containing vitamin C don’t have a sufficient amount of vitamin C to substantially affect iron absorption.1,2 In general, iron supplements should be taken on an empty stomach since food can decrease absorption by 40% to 50%. GI side effects such as nausea and abdominal pain occur more frequently as the quantity of soluble elemental iron in contact with the stomach and duodenum increases. Higher iron doses also increase the occurrence of constipation.1,10 Therefore, there should be no difference in GI tolerance when an equal quantity of elemental iron is administered regardless of the form of iron salt.2 A chart summarizing the differences among the various iron formulations is included. Comparison of Oral Iron Salts and Formulations Formulation Carbonyl iron (U.S. Only) Brand Names Feosol with Carbonyl Iron, Ferracap, Ferralet 90 Icar, Iron chews, etc. % Elemental Iron 1,2(w/w) 100 Dosage Forms Tablets, chewable tablets, suspension Comments • • • • • • Consists of microparticles of highly purified elemental iron; not an iron salt.1 Provides the highest amount of elemental iron. Dissolves in gastric secretion and is converted to hydrochloride salt prior to absorption in the stomach.1 Absorption rate is slow, which permits continued release of iron for 1 to 2 days.4 Less toxic than iron salts.4,5 Requires much higher dosage to cause toxicity compared to ferrous sulfate.4,5 More. . . Copyright © 2008 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #240811: Page 2 of 4) Formulation Cont. Ferric ammonium citrate4 Brand Names % Elemental Iron 1,2(w/w) Iron Citrate 18 Dosage Forms Capsules (U.S. & Canada) Comments • • • • Ferrous bisglycinate4 (U.S. Only) Bluebonnet Chelated Iron Albion, Amino Acid Chelate Ferrochel, etc. 20 Capsules, tablets • • • • Ferrous fumarate Ferrous gluconate FerroSequels time-release tablets, Nephro-Fer, Ferretts, Repliva, etc. Canada: Palafer, Neo Fer Pediafer, etc. Fergon, Floradix, etc. Canada: ApoFerrous Gluconate, etc. 33 (Please note Repliva contains two types of iron) 12 Tablets, chewable tablets Tablets • • • • • Most commonly used ferric salt.4 Requires reduction to ferrous form in the intestinal lumen.4 Less bioavailable than ferrous salts.4 Less poisoning potential since the GI tract has limited capacity to reduce it to ferrous form. An iron-amino acid chelate. Relatively high bioavailability. Theoretically, the conjugation of ferrous iron with amino acid prevents the iron from forming insoluble ferric hydroxide in the small intestine. May be less likely to cause GI intolerance than ferrous sulfate, ferrous gluconate, or ferrous fumerate.5 Similar efficacy and tolerability as ferrous sulfate. Moderately soluble in water. Almost tasteless.4 Repliva also contains Sumalate (ferrous asparto glycinate) a which is a chelated iron. Similar efficacy and tolerability as ferrous sulfate.1,2 More. . . Copyright © 2008 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #240811: Page 3 of 4) Formulation Cont. Ferrous sulfate Ferrous sulfate, dried Heme-iron polypeptide Brand Names % Elemental Iron 1,2(w/w) Dosage Forms Feosol with Ferrous Sulfate, FeroSul, Fer-In-Sol, Fer-GenSol, etc. 20 Oral solution, tablets, enteric-coated tablets, filmcoated tablets • Formulation of choice for treatment of iron-deficiency anemia given its general tolerability, effectiveness, and low cost.1,2 30 Capsules, tablets, extendedrelease tablets • Formulation of choice for treatment of iron-deficiency anemia given its general tolerability, effectiveness, and low cost.1,2 Capsules • Hemaglobin extracted from porcine red blood cells.7 More bioavailable than iron salts.7 Well-tolerated. Heme iron is classified as a medical food rather than a supplement, because it is derived from a food (animal) source. Canada: Fero Grad, Fer-In-Sol, Ferodan, etc. Feratab, Slow FE, etc. Canada: Slow FE Proferrin ES, Proferrin Forte 1006 • • • Canada: Proferrin Polysaccharide Niferex, -iron complex Niferex-150, Ferrex 150, etc. Canada: Triferexx Comments 1009 Capsules, solution, filmcoated tablets • • • Ferric iron is complexed to hydrolyzed starch, making it tasteless and odorless. Similar bioavailability as ferrous sulfate. Promoted to cause less GI irritation, but the claim is unproven. a. Theoretically, chelated irons are better tolerated and absorbed compared to other forms of iron. Refer to ferrous bisglycinate regarding details of chelated irons. Note that there are no clinical trials to prove that ferrous asparto glycinate (Sumalate) is better tolerated or absorbed than other forms of iron.11 Users of this document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and Internet links in this article were current as of the date of publication. More. . . Copyright © 2008 by Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com (Detail-Document #240811: Page 4 of 4) Project Leader in preparation of this DetailDocument: Wan-Chih Tom, Pharm.D. References 1. 2. 3. 4. 5. McEvoy GK, ed. AHFS Drug Information. Iron preparations, oral. AHFS 2007 Drug Information. Bethesda, MD: American Society of HealthSystems Pharmacists, Inc; 2007, 1410-7. Bolinger AM, Korman NR. Chapter 49. Anemias. In: Koda-Kimball MA, Young LY, Eds. Applied th Therapeutics: The Clinical Use of Drugs. 4 ed. Vancouver, WA: Applied Therapeutics , Inc. 1990: 1051-68. McDiarmid T, Johnson ED. Clinical inquiries. Are any oral iron formulations better tolerated than ferrous sulfate? J Fam Pract 2002;51(6):576. Nagpal J, Choudhury P. Iron formulations in pediatric practice. Indian Pediatr 2004:41:807-15. Anon. Product Review: iron supplements. ConsumerLab.com. May 5, 2008. 6. Personal communication. Sonia. Medical Information Dept. Colorado Biolabs, Inc. Cozad, NE 69130. June 2008. 7. Seligman PA, Moore GM, Schleicher RB. Clinical studies of HIP: An oral heme-iron product. Nutrition Research 2000;20:1279-86. 8. Personal communication. S. Cianci. Center for Food Safety and Applied Nutrition. FDA. May 1, 2008. 9. Personal communication. Michelle. Medical Information Dept. Ther-Rx Corp. Bridgeton, MO 63044. June 2008. 10. Jellin M, Gregory PJ, et al. Iron monograph. Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. (Accessed July 18, 2008). 11. Personal communication. Nathan. Medical Information Department. Ther-Rx Corp. Bridgeton, MO 63044. (July 23, 2008). Cite this Detail-Document as follows: Comparison of oral iron supplements. Pharmacist’s Letter/Prescriber’s Letter 2008;24(8):240811. Evidence and Advice You Can Trust… 3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright © 2008 by Therapeutic Research Center Subscribers to Pharmacist’s Letter and Prescriber’s Letter can get Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com or www.prescribersletter.com