Sunday, 3 May 2020

Dose of intravenous Inj FCM as IV therapy-How much Inj FCM is too much??


Any member using 1500 mg Inj FCM  as a single dose eiher in puerperium or women with menorrhagia with moderate to severe anemia with documented low serum Fe, low Ferritin and high TIBC?? ??

Iron is an essential element and its balance must be maintained for proper physiologic functioning. Blood loss, a major cause of iron deficiency, is highly prevalent  A) women  with menorrhagia left untreated for long time B) patients with chronic occult gastrointestinal (GI) blood .However, there is no point in denying that therapeutic management of IDA is focused primarily on repletion of iron stores . While iron deficient individuals without inflammation may respond to oral iron therapy, administration of IV iron is beneficial in many patient populations, including those with inflammation resulting, from variety of   systemic diseaes., from kidney disease, heart failure, or rheumatological diseases, patients who cannot tolerate oral iron, and patients who are noncompliant with oral iron therapy

Iron intolerance :-Even under the best of circumstances, oral iron is not well tolerated, and patients are often nonadherent for a variety of reasons, including intolerable side effects and the need for multiple daily doses .The frequently poor absorption of oral iron, moreover, can contribute to suboptimal patient response.
The hepcidin response in anemic patients having inflammatory conditions, such as inflammatory bowel disease (IBD), inhibits GI absorption of oral iron .Moreover, hepcidin impacts iron homeostasis in patients with concurrent inflammation (e.g., repressed recycling of iron from the reticuloendothelial system and sequestration in bone marrow); this may limit both oral and IV iron supplementation and may serve to explain why such patients remain iron deficient despite multiple courses of therapy . Despite these recommendations, in many clinical situations the treatment of IDA with IV iron has not been limited to a cumulative dose of 1000 mg. In oncology patients, for example, the National Comprehensive Cancer Network (NCCN) states that if the calculated dose exceeds 1000 mg, the remaining dose may be given after 4 weeks if the Hb response is inadequate Additionally, in two randomized controlled trials involving IV iron supplementation in oncology patients, a total of up to 3000 mg iron was administered in weekly doses of 100 mg . In another prospective, randomized, controlled trial, patients with chemotherapy-related anemia received cumulative doses of IV iron ranging from 1000 to 3000 mg .
Q.1. What is the consensus of the most appropriate iron deficit repletion dosing in patients with IDA.  Ans:   Currently, there is no consensus regarding the most appropriate iron deficit repletion dosing in patients with IDA, partly because the iron dosing selected for virtually all trials has been based largely on clinical judgment, clinical guidelines in nephrology, or best estimates from past results . But is it possible to administer of a higher cumulative dose of IV iron than what is typically administered, with the goal of providing clinicians with practical, evidence-based guidance for determining iron dosing requirements in a wide range of patients with IDA. 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). 
Guidelines for the management of IDA in inflammatory bowel disease (IBD), moreover, recommend IV iron as the preferred route of administration and state that anemic IBD patients rarely present with total iron deficits below 1000 mg. These guidelines recommend use of the Ganzoni formula to estimate iron replacement needs, and in controlled trials, up to 3600 mg of iron sucrose has been administered safely (up to TSAT >50%) .  Congruent with evidence reported in the international IBD guidelines, many states that cumulative doses up to 3600 mg of IV iron may be administered safely in these patients(IBD cases) .

Q. 2: The classification of types of iron complexes used in I V route??  Ans: The reactivity of each complex correlates inversely with its molecular weight; larger complexes are less prone to release significant amounts of labile iron or react directly with transferrin .Type I complexes such as iron dextran preparations or FCM have a high molecular weight and a high structural homogeneity and thereby deliver iron from the complex to transferrin in a regulated way via macrophage endocytosis and subsequent controlled export . To help determine the optimal means of administering these higher doses, it is important to note that the degradation kinetics, and therefore the safety, of parenteral iron products are directly related to the molecular weight and stability of the iron complex
Complexes can be generally classified as A) labile or B) robust (kinetic variability, i.e., how fast the ligands coordinated to the iron can be exchanged) and weak or strong (thermodynamic variability, i.e., how strongly the ligands are bound to the iron and thus how much energy is required to dissociate a ligand from the iron) or any intermediate state
 They also bind iron tightly as nonionic polynuclear iron(III) hydroxide and do not release large amounts of iron ions into the blood. Such complexes can be administered intravenously and are clinically well tolerated even when administered at high doses. For less stable iron complexes, the maximum single doses are significantly lower and the administration times are drastically longer
Q. 4. What is FCM?? Ans: FCM is a stable type I polynuclear iron(III) hydroxide carbohydrate complex that prevents the partial release of iron to serum ferritin observed with IS(iron sucrose) , allowing administration of high doses, since this iron is available only via reticuloendothelial processing .
FCM can be administered as a single 750 mg dose via a slow IV push injection over 7.5 minutes or as an IV infusion over at least 15 minutes. The second dose is administered at least 7 days later for a recommended cumulative dose of 1500 mg iron. But use of high doses reduces the number of infusions, enabling the possibility of cost reductions compared to multiple administrations

Q. 5. Can we administer I V iron in Cancer related anemic patients?? Many also believe that more routine use of IV iron for CRA(Cancer-related anemia )  and chemotherapy-induced anemia (CIA Cancer-related anemia ) is appropriate in view of existing evidence. Oncology patients whose CIA is treated with ESAs, furthermore, respond better to IV iron therapy than to oral supplementation . Mixed anemia is a diagnosis of exclusion without a therapeutic trial of iron.
Q. 6. Can we administer 1500 mg Inj FCM  in severe Fe deficient men/ wmen to avoid repeated visits?? I V iron in higher doses??  Recently few researchers have suggested that suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in the majority of patients with IDA and that a dose of 1500 mg is closer to the actual iron deficit in these patients. Additionally, 1500 mg of iron resulted in a more rapid, robust Hb response, allowed more patients to reach target Hb levels, and required a longer mean time to retreatment with additional IV iron compared to 1000 mg of iron. They belive that 1500 mg of IV iron is more suitable for iron repletion in many patients with IDA compared to the commonly utilized dose of 1000 mg of IV iron. . In some studies  multiple-dose, phase II/III study of IDA patients with GI disorders, mean total cumulative doses of 1800 mg IV iron were administered /Clinical evidence also indicates that iron requirements of 1000 to 1500 mg or higher may be required in patients with NDD-CKD to attain target ferritin and Hb levels, up to 1600 mg may be required in obstetric patients, and as much as 2000 mg may be needed in patients with heavy or abnormal menstrual bleeding

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