ferric-oxide--saccharated and Drug-Hypersensitivity

Parenteral iron replacement and maintenance are frequently required in hemodialysis patients. However, serious adverse events have been reported after single doses of some intravenous iron products. This multicenter phase IV clinical trial examined the safety of iron sucrose for the treatment of iron deficiency and for the maintenance of iron sufficiency in hemodialysis patients.. In this safety study, iron sucrose was given in two dosing regimens. Iron deficient patients were treated with intravenous iron sucrose, 100 mg, during 10 consecutive hemodialysis sessions (replacement regimen). Iron replete patients were given iron sucrose, 100 mg intravenous (iv) over 5 minutes, weekly for 10 weeks (maintenance regimen). At the end of each 10-dose cycle, iron status was reassessed, and dosing during the subsequent cycle was based on the adequacy of iron stores as per Dialysis Outcome Quality Initiative (K/DOQI) Guidelines. With each dosing regimen, adverse events, if any, were recorded and described.. Six hundred and sixty-five hemodialysis patients, including 80 who had experienced previous intolerance to other parenteral iron preparations, received a total of 8583 doses of iron sucrose. One hundred eighty-eight patients received more than one iv iron cycle (replacement, maintenance, or both). There were no serious or life-threatening drug-related adverse events.. Iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Drug Hypersensitivity; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Sepsis

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

Topics: Anemia, Iron-Deficiency; Blood Pressure; Drug Hypersensitivity; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Injections, Intravenous; Iron-Dextran Complex; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Topics: Anaphylaxis; Drug Hypersensitivity; Ferric Oxide, Saccharated; Humans; Iron; United States; United States Food and Drug Administration

Topics: Anaphylaxis; Drug Hypersensitivity; Ferric Oxide, Saccharated; Humans; Iron; United States; United States Food and Drug Administration

Severe hypersensitivity reactions (HSRs) such as anaphylaxis are of great clinical concern because of their life-threatening potential. The adverse events attributable to intravenous iron products include HSRs. An investigation by the European Medicines Agency presented in late 2013 resulted in the implementation of risk minimization measures (RMMs).. This study evaluated the number of severe HSRs reported for intravenous iron substances related to exposure for the 4-year periods before and after this implementation.. This was a retrospective pharmacoepidemiologic study with a case-population design. We obtained information from the safety surveillance database EudraVigilance on spontaneously reported severe HSRs using the Medical Dictionary for Regulatory Activities preferred terms "anaphylactic reaction/shock" and "anaphylactoid reaction/shock". Exposure was estimated using IQVIA MIDAS sales data in European economic area countries.. Reporting rates for individual products were heterogenous, and the implementation of RMMs appeared to have no clear impact. Reporting rates remained low for the full study period for iron sucrose (0.03-0.20) and ferric gluconate (0.02-0.14) and were higher at the beginning and lower at the end of the study period for ferric carboxymaltose (1.47-0.18). No clear trend was detected for iron dextran (range 0.22-2.80) and iron (III) isomaltoside 1000 (range 0-7.94).. Future research is needed to investigate whether the wide variability in reporting rates for severe HSRs associated with these intravenous iron products are due to potential differences in the safety profiles of these substances.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Europe; European Union; Female; Ferric Compounds; Ferric Oxide, Saccharated; Humans; Infusions, Intravenous; Iron Compounds; Middle Aged; Pharmacoepidemiology; Retrospective Studies; Young Adult

Topics: Anemia, Iron-Deficiency; Angioedema; Desensitization, Immunologic; Drug Hypersensitivity; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Glucaric Acid; Humans; Middle Aged; Sucrose; Urticaria

Topics: Adult; Drug Hypersensitivity; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Sucrose

Spontaneously-reported rates of adverse events (AEs) of intravenous (i.v.) iron products have not been compared since 2007. AEs in Europe (Eur) and North America (NA) have never been compared. New products have been marketed and many changes in prescribing habits have occurred since then, and the effect on AEs reporting is unclear. It was hypothesized that changing practices for i.v. iron products has caused changes in the rates of serious AEs and large differences exist between Eur and NA. Rates of AEs for three i.v. iron preparations (iron sucrose [IS], ferric gluconate [FG] and high and low MW iron dextran [HMWID, LMWID]) were compared by product and continent from January 1, 2003 to June 30, 2009 for selected countries in Eur and NA, using the Uppsala Monitoring Center's database. Rates of total, anaphylaxis and other serious allergic AEs were calculated as number of AEs divided by i.v. iron sales standardized to 100 mg dose equivalents (DEq) of iron. Quarterly sales (millions of 100 mg DEq of iron) increased from the first quarter 2003 to the end of the second quarter of 2009 by 1% for FG, 16% for IS and 2% for ID. Total AEs for NA plus Eur were similar for FG and IS, but total AEs were 6- to 7-fold higher for ID. Rates of anaphylaxis were 6- to 11-fold higher in Eur plus NA combined for ID than for IS or FG. In NA, there were substantially higher reports for total, anaphylaxis and other serious allergic AEs with FG compared to IS, whereas the reverse was the case in Eur. Odds ratios (OR) showed higher risks of anaphylaxis with FG in NA vs. Eur (OR = 4.40, P < 0.0001) and lower risks with IS (OR = 0.24, P < 0.0001). Odds of anaphylaxis with LMWID in Eur vs. FG and IS were 42.08 and 16.92 (both P < 0.0001), respectively. In NA, odds of anaphylaxis with ID vs. FG and IS were 2.36 and 17.73 (both P < 0.0001), respectively. Differences between NA and Eur may be related to varied treatment practices. ID had the highest rates of all types of AEs, and IS and FG had a continued trend for lowest rates of AEs.

Topics: Anaphylaxis; Drug Hypersensitivity; Europe; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Iron Compounds; Iron-Dextran Complex; North America; Odds Ratio; United States; United States Food and Drug Administration

This study aimed to assess the safety and efficacy of iron sucrose in hemodialysis (HD) patients with documented hypersensitivity reactions to iron dextran. Of 205 HD patients who received low molecular weight iron dextran, 15 (7.3%) patients developed documented hypersensitivity reactions. The patients were treated with iron sucrose (100 mg administered as an intravenous push over 5-10 minutes once a week) for 8 weeks. Complete blood count, serum iron, serum ferritin, and parathyroid hormone were measured at the beginning and at the end of the study (except parathyroid hormone). All patients received subcutaneous erythropoietin at a constant dose of 5000 IU twice weekly unless a change was required. All the patients completed the study period and none of them developed hypersensitivity reactions to iron sucrose. The mean hematocrit increased from 23.8% to 32.27% (p < 0.0001), the mean serum ferritin from 185 ng/mL to 599 ng/mL (p < 0.0001), and the mean serum iron from 29.3 ng/dL to 76.8 ng/dL (p = 0.01). We conclude that iron sucrose is safe and effective in HD patients with documented hypersensitivity reactions to low molecular weight iron dextran.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Dialysis Solutions; Drug Hypersensitivity; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Hematinics; Humans; Iron-Dextran Complex; Male; Middle Aged; Renal Dialysis; Treatment Outcome; Young Adult

A 67-year-old woman with iron deficiency anemia required parenteral iron therapy and was treated with intravenous ferric gluconate. She tolerated the first dose, but after the second dose, she developed a tingling feeling all over her body, along with swelling in her hands and feet, and a rash with hives over most of her body. It was thought that she had likely experienced a hypersensitivity reaction to ferric gluconate. The decision was made to continue therapy; however, two modifications were made. The patient was given dexamethasone, diphenhydramine, and ibuprofen 1 hour before administering the third dose, and the infusion time was prolonged by 1 hour. Approximately 45 minutes after the infusion was completed, the patient developed hives on her arms and legs. At the patient's next clinic visit, it was decided that continuation of parenteral iron repletion was necessary, and the decision was made to attempt a challenge with iron sucrose. The patient was given dexamethasone 8 mg to be taken the night before and the morning of treatment. She successfully completed the iron repletion therapy with iron sucrose. Three parenteral iron products are available in the United States: iron dextran, sodium ferric gluconate complex, and iron sucrose. Iron dextran, the oldest of these products, carries the highest risk for hypersensitivity reactions. Available data suggest that either iron sucrose or ferric gluconate can be safely administered to patients with known hypersensitivity to iron dextran. Our patient's experience implies that it may be possible to safely administer iron sucrose to a patient with hypersensitivity to ferric gluconate. This finding has clinical implications and warrants confirmation in a larger population.

Topics: Aged; Anemia, Iron-Deficiency; Drug Hypersensitivity; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hispanic or Latino; Humans; Infusions, Intravenous; Injections, Intravenous; Self Administration; Treatment Outcome

Parenteral iron therapy is an accepted adjunctive management of anaemia in kidney disease. Newer agents may have fewer severe hypersensitivity adverse events (AE) compared with iron dextrans (ID). The rate of type 1 AE to iron sucrose (IS) and sodium ferric gluconate (SFG) relative to ID is unclear. We used the US Food and Drug Administration's Freedom of Information (FOI) surveillance database to compare the type 1 AE profiles for the three intravenous iron preparations available in the United States.. We tabulated reports received by the FOI database between January 1997 and September 2002, and calculated 100 mg dose equivalents for the treated population for each agent. We developed four clinical categories describing hypersensitivity AE (anaphylaxis, anaphylactoid reaction, urticaria and angioedema) and an algorithm describing anaphylaxis, for specific analyses.. All-event reporting rates were 29.2, 10.5 and 4.2 reports/million 100 mg dose equivalents, while all-fatal-event reporting rates were 1.4, 0.6 and 0.0 reports/million 100 mg dose equivalents for ID, SFG and IS, respectively. ID had the highest reporting rates in all four clinical categories and the anaphylaxis algorithm. SFG had intermediate reporting rates for urticaria, anaphylactoid reaction and the anaphylaxis algorithm, and a zero reporting rate for the anaphylaxis clinical category. IS had either the lowest or a zero reporting rate in all clinical categories/algorithm.. These findings confirm a higher risk for AE, especially serious type 1 reactions, with ID therapy than with newer intravenous iron products and also suggest that IS carries the lowest risk for hypersensitivity reactions.

Topics: Adverse Drug Reaction Reporting Systems; Algorithms; Anaphylaxis; Drug Hypersensitivity; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Retrospective Studies; Severity of Illness Index; Sucrose; United States