Original Title: Guides et normes: traitement au fer intraveineux chez l’adulte

Authors' objectives: Iron deficiency is responsible for nearly half of all cases of anemia. Although oral iron can be used to treat iron deficiency in many cases, it may sometimes be necessary to administer intravenous (IV) iron. Several specialties, in addition to hematology and family medicine, need to use IV iron in their practice, including nephrology, gastroenterology, cardiology and obstetrics/gynecology. Midwives are also authorized to prescribe IV iron. Three IV iron formulations are available in Canada and are on the list of drugs covered by Québec’s public prescription drug insurance plan: iron sucrose, ferric gluconate complex and ferric derisomaltose (also called iron isomaltoside 1000). However, the conditions of use, i.e., the dosages and the methods of preparation (dilution) and administration, differ according to the type of iron. Currently, the practice is not standardized across the province, and some outpatient settings do not have standardized information concerning the administration of one or more IV iron formulations, which can result in disruptions in services and treatment delays for some patients. In addition, the risk of severe allergic reactions is the main concern with IV iron administration, but this risk is considered low with the formulations other than iron dextran, which is no longer marketed in Canada. The Institut national d’excellence en santé et en services sociaux (INESSS) was asked by the Direction nationale des soins et services infirmiers (DNSSI) of the Ministère de la Santé et des Services sociaux (MSSS) to carry out work on initiating intravenous iron therapy. The objective of this work was to identify the best clinical practices for initiating intravenous iron, particularly with regard to the indications and conditions of use for the different available formulations, in order to support clinicians in their prescribing, administration and follow-up.

Authors' results and conclusions: RESULTS: For the purpose of this work, 25 documents whose methodological quality was deemed adequate in terms of scientific rigour were used. Of these, six concerned the general population, while four were specific to cancer, two to chronic kidney disease, four to pregnancy and postpartum, five to gastrointestinal disorders, three to heart failure and one to liver resection. In addition, 12 documents (individual prescriptions and protocols) from institutions in the health and social services system were identified and reviewed. According to the information gathered, IV iron is used in many different clinical conditions, both in hospitalized and non-hospitalized patients. Between 2018 and 2020, for persons insured by Québec’s public prescription drug insurance plan, IV iron was prescribed primarily by family physicians, nephrologists, gastroenterologists, internists, hematologists, oncologists and obstetricians/gynecologists. It should generally be preferred when iron deficiency is associated with anemia, except preoperatively or in heart failure cases, where its use, if there is no anemia, is more widely recognized by clinicians. The ferritin cut-off value for defining iron deficiency can vary according to certain clinical conditions, being along a continuum between absolute deficiency and relative deficiency. In addition to being an alternative option when oral iron is ineffective or poorly tolerated, there are several clinical conditions that may, in themselves, warrant the immediate use of IV iron. However, certain situations should be borne in mind when deciding to prescribe IV iron, namely, a history of anaphylactic reaction, the use of IV iron during pregnancy or breastfeeding, and the presence of an infection. General ferritin and transferrin saturation benchmarks have been proposed for determining whether a patient has iron deficiency and assessing the effectiveness of the treatment of iron deficiency in the general population. As for the choice of IV iron formulation, any of them can be used in most of the indications, but single-dose IV iron may be advantageous in an outpatient setting in situations where it is important to quickly replenish iron stores while at the same time avoiding travel for the patient and limiting the amount of time spent in the clinic. The proportion of prescriptions for single-dose IV iron for those insured under the RPAM has, in fact, increased in the past three years, as have the annual costs associated with this formulation. Severe reactions during IV iron administration are very rare with the different formulations currently on the market. Infusion reactions can nonetheless occur (e.g., Fishbane reaction or isolated symptoms) but are sometimes incorrectly assessed as severe reactions. Therefore, in the interest of patient safety, we have proposed generally slow administration rates to limit potential reactions that might occur during infusion and set out the steps to be taken for each type of reaction (allergic, Fishbane or isolated symptoms) and the safe administration conditions that should be met regardless of the setting in which IV iron is to be administered. CONCLUSION: While not a substitute for clinical judgment, the recommendations made and the Québec national medical protocol (NMP) and accompanying preprinted individual prescription template should help harmonize prescribing practices and address concerns about the risk of allergic reactions as opposed to Fishbane reactions or isolated symptoms. These tools should also facilitate the administration of IV iron by nurses by providing clinical benchmarks and guidelines that can be used regardless of the setting in which it is administered. However, the practice changes that might ensue will depend on the dissemination of the clinical tools, the decision by institutions and family medicine groups, via their electronic health records, to implement a preprinted individual prescription, adherence to the practice changes, and the uptake of the recommendations by the health professionals concerned. Lastly, the advisability of updating the recommendations will be determined in four years from the date of publication on the basis of the advances in scientific data, the clinical practice changes, and the listing or delisting of the drugs.

Authors' methods: This work is based on a review of the best available scientific data, as assessed by the authors of clinical practice guidelines and clinical guidance documents, which were supplemented with the experiential knowledge of different stakeholders through an informal deliberative process. The Régie de l’assurance maladie du Québec (RAMQ)’s clinical administrative databases were queried in order to provide a summary portrait of the use of the different IV iron formulations and of the medical specialties that prescribe IV iron in practice in Québec to persons insured under Québec’s public prescription drug insurance plan (RPAM). The systematic search for guidance documents and guidelines was conducted across several databases and covered the period from 2017 to 2021. In November 2021, INESSS checked with organizations, learned societies and agencies regarding the topic of this work to see if any new items had been published since then. Publications were selected according to predefined exclusion and inclusion criteria, and the methodological quality of those selected was assessed with validated tools. These steps were carried out independently by two scientific professionals. Recommendations and relevant data were then extracted by one professional and validated by the other. The results were presented in tables and summarized in the form of a narrative synthesis. Clinicians’ perspectives regarding the current practice, taking into account data from the selected publications, contextual issues and other important information, were collected with the help of the members of the advisory committee, which consisted of individuals with different specialties and expertise, key informers from other medical specialties not represented on the committee, external reviewers and future users, and summarized in the form of a narrative synthesis. Following the knowledge triangulation, preliminary proposals for key clinical information for decision-making and clinical recommendations were drawn up and shared for a first iteration with the advisory committee’s members. Two additional iterations were necessary before the majority of the committee members gave their approval. During these discussions, the members were also invited to provide feedback on the applicability, acceptability and potential impact of the clinical recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/thematiques/medicaments/protocoles-medicaux-nationaux-et-ordonnances-associees/protocoles-medicaux-nationaux-et-ordonnances-associees/traitement-au-fer-intraveineux-chez-ladulte.html

Year Published: 2022

URL for published report: https://www.inesss.qc.ca/thematiques/medicaments/protocoles-medicaux-nationaux-et-ordonnances-associees/protocoles-medicaux-nationaux-et-ordonnances-associees/traitement-au-fer-intraveineux-chez-ladulte.html

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec