Fluindione and drug reaction with eosinophilia and systemic symptoms: an unrecognised adverse effect?

PURPOSE: Fluindione is an oral vitamin K antagonist (indanedione derivative) exclusively marketed in France and Luxembourg, known to have immuno-allergic adverse effects such as hepatitis, fever or interstitial nephritis. A few cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with fluindione. The aim of the present study was to investigate fluindione-induced DRESS cases reported in France and to describe their characteristics. METHODS: We searched for potential cases of DRESS with fluindione reported in the French pharmacovigilance database since 2000. RESULTS: Thirty-six cases of DRESS were included and concerned 17 women and 19 men. The mean age was 65 years (median: 68 years, range: 28-95 years). Kidneys and liver were the most frequent organs involved. Thirty-five cases were serious. In 5 cases, the effect was life-threatening. Most of the patients recovered. Fluindione was the only medicine suspected in 26 cases. Skin patch tests, performed in 10 cases, were positive with fluindione in 9 cases. CONCLUSIONS: Fluindione is not known to be a frequent cause of DRESS. However, the number of reports found is probably underestimated. The seriousness of DRESS, as all immuno-allergic adverse effects, contraindicates fluindione reintroduction. Coumarinic derivatives are the alternatives in patients who need oral anticoagulant treatment.

[Oral vitamin B12: Efficacy and safety data in 31 patients with pernicious anemia and food-cobalamin malabsorption]. / Efficacité et tolérance de la vitamine B12 par voie orale chez 31 patients avec une maladie de Biermer ou une maldigestion des cobalamines alimentaires.

OBJECTIVE: The aim of this study is to validate the efficacy and safety of oral cobalamin therapy in the treatment of cobalamin deficiency related to various causes. PATIENT AND METHOD: It's a retrospective study, including 31 patients with documented cobalamin deficiency related to food-cobalamin malabsorption (n=20) and pernicious anemia (n=11). These patients were treated at least for 3 months with oral cyanocobalamin, between 125 to 1000microg per day. Serum cobalamin levels and hematological parameters were compared before and after the therapy and in relation with the nature of cobalamin deficiency. Safety data were also recorded. RESULTS: After 3 months of therapy, the serum cobalamin levels have significantly increased in all the patients, with a mean of +161.6±79.3pg/mL in the food-cobalamin malabsorption group (P<0,00005) and +136.7±67.4pg/mL in the pernicious anemia group (P<0,0001). Hematological parameters have been normalized in 90 % of the patients, independently of the cause of the cobalamin deficiency. Only 1 patient presented an urticarial reaction. CONCLUSION: This study confirms the efficacy and safety of oral cobalamin therapy in food-cobalamin malabsorption and also in case of pernicious anemia.

[Food-cobalamin syndrome]. / Syndrome de non-dissociation de la vitamine B12 de ses proteines porteuses ou de maldigestion des cobalamines alimentaires.

Food-cobalamin malabsorption is a new well-characterized syndrome. In association with pernicious anemia, it is the leading etiology of cobalamin deficiency in adult, especially in elderly patient. Currently, it is an exclusion diagnosis that requires a well-codified clinical strategy for diagnosis. There are several causes of food-cobalamin malabsorption, mainly gastric disorders and drugs (metformin and anti-acid drugs). Current treatment modality includes oral cobalamin administration with lower doses than in pernicious anemia. Studies are in the way to better characterize the food-cobalamin malabsorption in a clinical practice perspective and to validate the usefulness of oral cobalamin therapy.

Cobalamin deficiency in elderly patients: a personal view.

Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age) but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. In the elderly, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well documented but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.