ferric-oxide--saccharated and Hypophosphatemia

Hypophosphatemia is a recognized side effect of treatment of iron deficiency anemias with injectable iron. We analyzed 35 clinical trials that used ferric carboxymaltose (FCM) or iron sucrose (IS). Hypophosphatemia prevalence ranged from 0 to 91.7%. FCM-induced a significant (P<0.001) greater hypophosphatemia prevalence and phosphatemia decrease than IS (52.0% [95% CI: 42.2-61.8%] vs. 7.7% [95% CI: -2.8 to 18.2%] and -1.12mmol/L [95% CI: -1.36 to -0.89mmol/L] vs. -0.13mmol/L [95% CI: -0.59 to 0.32mmol/L]). FCM-induced hypophosphatemia was dose-dependent. The nadir of hypophosphatemia was reached in almost all studies after 7 and 14days. Hypophosphatemia persisted at the end of the study in 53.8% of the reported studies that used FCM and lasted up to 6months. FCM-induced an increase in intact circulating fibroblast growth factor 23 and in renal phosphorus excretion while serum 1-25 dihydroxyvitamin D was decreased. Risk factors for hypophosphatemia after FCM therapy were low basal circulating phosphate or ferritin, low body weight, high glomerular filtration rate, serum parathyroid hormone or hemoglobin and age, whereas renal insufficiency was associated with a lower risk. In conclusion, hypophosphatemia is common after treatment with injectable iron, FCM being associated with a higher risk than IS and with disorders of phosphocalcium metabolism. Monitoring of blood phosphate and 1-25 dihydroxyvitamin D could be considered during FCM therapy.

Topics: Adult; Ferric Oxide, Saccharated; Humans; Hypophosphatemia; Iron; Phosphates

Fibroblast growth factor 23 (FGF23) is an essential hormone for phosphate metabolism. It has been shown that intravenous administration of some iron formulations including saccharated ferric oxide induces hypophosphatemic osteomalacia with high FGF23 levels. On the other hand, iron deficiency promotes FGF23 and induces hypophosphatemia in patients with autosomal dominant hypophosphatemic rickets (ADHR). While iron and phosphate metabolism is connected, the detailed mechanism of this connection remains to be clarified.

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Humans; Hypophosphatemia; Injections, Intravenous; Iron; Osteomalacia; Phosphates; Renal Insufficiency, Chronic; Rickets, Hypophosphatemic

Saccharaed ferric oxide (SFO)-induced osteomalacia develops when excessive SFO infusions are administrated to patients with anemia for prolonged periods for a few years. The small particles and almost neutral saccharide of SFO filter through the glomerular tufts into the renal tubules, resulting in impairment of proximal renal tubular function, particularly renal reabsorption of phosphate and 1alpha-hydroxylase activity, resulting in decreased serum levels of phosphorus and active vitamin D, both of which lead to development of hypophosphatemic osteomalacia. Furthermore, SFO, at concentrations attainable in serum, exacerbates the osteomalacia by inhibiting bone formation directly. In contrast to itai-itai disease, another iatrogenic osteomalacia due to cadmium nephropathy [44], the proximal renal tubular function impairment induced by SFO is reversible simply by discontinuing the nephrotoxin, which is followed by improvement of all the clinical manifestations, except bone deformities. So far, SFO-induced osteomalacia, that is, SFO-induced osteopathy due to nephropathy, has been reported only in Japan, probably due to the lax surveillance system of the health insurance scheme. All physicians who prescribe SFO should be aware of its severe adverse effects. We hope that such iatrogenic osteomalacia caused by abusive infusion of SFO will never again be reported in our country.

Topics: Aged; Anemia, Iron-Deficiency; Anemia, Refractory; Animals; Calcitriol; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Hypophosphatemia; Iatrogenic Disease; Kidney Diseases; Male; Middle Aged; Osteomalacia; Phosphates

A multicenter, randomized, open-label, phase III study was conducted to compare the efficacy and safety of intravenous ferric derisomaltose (FDI) versus saccharated ferric oxide (SFO) in Japanese patients with iron deficiency anemia associated with menorrhagia. FDI can be administered as a single dose up to 1000 mg, whereas SFO has a maximum single dose of 120 mg. The primary endpoint, which was the maximum change in hemoglobin concentration from baseline, was noninferior for the FDI group compared with the SFO group. The incidence of treatment-emergent adverse events was lower in the FDI group (66.2%) than in the SFO group (90.8%). Notably, the incidence of serum phosphorus level < 2.0 mg/dL was significantly lower in the FDI group (8.4%) than in the SFO group (83.2%), and severe hypophosphatemia (≤ 1.0 mg/dL) occurred in 6.7% of SFO‑treated patients compared with none in the FDI group. The percentage of patients who achieved the cumulative total iron dose during the 8-week treatment period was higher in the FDI group (92.8%) than in the SFO group (43.2%). The study met its primary endpoint, and also demonstrated the tolerability of a high dose of FDI per infusion, with a lower incidence of hypophosphatemia.

Topics: Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Hemoglobins; Humans; Hypophosphatemia; Iron; Iron Deficiencies; Menorrhagia; Phosphorus

Intravenous (IV) administration of iron is considered a safe and efficacious treatment for iron deficiency anemia (IDA), recommended in patients requiring rapid replenishment of iron, or intolerant or unresponsive to oral administration of iron. Recent randomized controlled trials (RCTs) have shown high incidence of hypophosphatemia after administration of two IV iron preparations: saccharated ferric oxide (SFO) and ferric carboxymaltose (FCM). The present study aimed to conduct matching-adjusted indirect comparison (MAIC) of hypophosphatemia incidence with these iron formulations and ferric derisomaltose (FDI) based on data from head-to-head RCTs conducted in Japan.. A MAIC of hypophosphatemia incidence was conducted on the basis of data from two head-to-head RCTs. The relative odds of hypophosphatemia with FDI versus SFO were obtained from patient-level data from a recent RCT and adjusted for cumulative iron dose, while parametric models of serum phosphate levels from a separate RCT were used to estimate the relative odds of hypophosphatemia with FCM with SFO. An anchored MAIC was then conducted comparing FDI with FCM.. The adjusted odds of experiencing hypophosphatemia were significantly lower with FDI than SFO [odds ratio (OR) of 0.02; 95% confidence interval (CI) 0.01-0.05]. The parametric models of serum phosphate from the RCT comparing FCM with SFO provided an estimated OR of 1.17 for the incidence of hypophosphatemia with FCM versus SFO. Combining the two estimates in the MAIC showed that the odds of experiencing hypophosphatemia would be 52.5 (95% CI 27.7-99.4) times higher with FCM than FDI in patients with IDA associated with heavy menstrual bleeding in Japan.. Direct comparison of patient-level data and a MAIC from two RCTs in Japanese patients with heavy menstrual bleeding indicated that hypophosphatemia is less frequent in patients treated with FDI than those with FCM or SFO. Results are in agreement with RCTs comparing FDI and FCM in patients with various etiologies conducted in the USA and Europe.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; East Asian People; Female; Ferric Oxide, Saccharated; Humans; Hypophosphatemia; Incidence; Iron; Menorrhagia; Phosphates; Randomized Controlled Trials as Topic

Iron deficiency is common following bariatric surgery, and treatment with intravenous iron is often required. This post hoc analysis of data from two randomized, open-label, multicenter trials evaluated the efficacy and safety of ferric derisomaltose (FDI; formerly iron isomaltoside 1000) versus iron sucrose (IS) over 4 weeks in adults with iron deficiency anemia (IDA) resulting from prior bariatric surgery.. Data were pooled for participants who received FDI or IS in the PROVIDE or FERWON-IDA trials for the treatment of IDA post bariatric surgery. Efficacy outcomes included changes in hemoglobin (Hb) and iron parameters; safety outcomes included the incidence of adverse drug reactions (ADRs), serious or severe hypersensitivity reactions (HSRs), and hypophosphatemia.. The analysis included 159 patients. Mean (standard deviation) cumulative iron doses were 1199 (± 347) mg for FDI and 937 (± 209) mg for IS. Compared with IS, FDI resulted in a faster and more pronounced Hb response, and a higher proportion of responders (Hb level increase ≥ 2 g/dL from baseline) at all time points. The incidence of ADRs was similar with FDI and IS (15.1% and 18.2%, respectively), with no serious ADRs or serious or severe HSRs reported. The incidence of hypophosphatemia was low and similar in both treatment groups, with no cases of severe hypophosphatemia observed.. In patients with IDA resulting from bariatric surgery, FDI produced a faster and more pronounced Hb response than IS. Both FDI and IS were well tolerated.

Topics: Adult; Anemia, Iron-Deficiency; Bariatric Surgery; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Hemoglobins; Humans; Hypophosphatemia; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Saccharated ferric oxide has been shown to lead to elevation of fibroblast growth factor 23, hypophosphatemia, and, consequently, osteomalacia. Moreover, mineral imbalance is often observed in patients with short-bowel syndrome to some degree.. A 62-year-old woman with short-bowel syndrome related with multiple resections of small intestines due to Crohn disease received regular intravenous administration of saccharated ferric oxide. Over the course of treatment, she was diagnosed with tetany, which was attributed to hypocalcemia. Additional assessments of the patient revealed not only hypocalcemia, but also hypophosphatemia, hypomagnesemia, osteomalacia, and a high concentration of fibroblast growth factor 23 (314 pg/mL).. We diagnosed her with mineral imbalance-induced osteomalacia due to saccharated ferric oxide and short-bowel syndrome.. Magnesium replacement therapy and discontinuation of saccharated ferric oxide alone.. These treatments were able to normalize her serum mineral levels and increase her bone mineral density.. This case suggests that adequate evaluation of serum minerals, including phosphate and magnesium, during saccharated ferric oxide administration may be necessary, especially in patients with short-bowel syndrome.

Topics: Bone Density; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Hematinics; Humans; Hypocalcemia; Hypophosphatemia; Magnesium; Magnesium Deficiency; Middle Aged; Osteomalacia; Short Bowel Syndrome; Treatment Outcome; Withholding Treatment

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Hypophosphatemia; Low Back Pain; Magnetic Resonance Imaging; Middle Aged; Osteomalacia; Pelvic Pain; Remission Induction; Treatment Outcome

Topics: Aged; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Hematinics; Humans; Hypophosphatemia; Male; Osteomalacia

Fibroblast growth factor 23 (FGF23) is a humoral factor that is produced by osteocytes and regulates phosphate and vitamin D metabolism. Several hypophosphatemic diseases including X-linked, autosomal dominant and autosomal recessive hypophosphatemic rickets/osteomalacia and tumor-induced rickets/osteomalacia are caused by excess actions of FGF23. These diseases are characterized by hypophosphatemia associated with impaired proximal tubular phosphate reabsorption and inappropriately low serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels for hypophosphatemia. Saccharated ferric oxide is widely used in Japan for iron-deficiency anemia. While it has been shown that saccharated ferric oxide induces hypophosphatemic osteomalacia, the mechanism of this hypophosphatemia remains to be clarified. We here describe three hypophosphatemic patients caused by intravenous administration of saccharated ferric oxide. Hypophosphatemia in these patients were associated with impaired renal tubular phosphate reabsorption, rather low serum 1,25(OH)(2)D and high FGF23 levels. All these biochemical features improved by the cessation of saccharated ferric oxide. These results indicate that hypophosphatemia caused by saccharated ferric oxide is another form of FGF23-related hypophosphatemia.

Topics: Adult; Aged, 80 and over; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Humans; Hypophosphatemia; Injections, Intravenous; Male; Middle Aged

An 81-year-old woman was hospitalised because of pneumonia in December 1989. In February 1991, an iliac bone biopsy was performed on the suspicion of disturbed bone metabolism due to chronic renal failure. Since she developed anemia due to continuous bleeding from the surgical wounds, saccharated iron oxide was administered beginning in March. Hypophosphatemia was noted 23 days after the beginning of administration. Due to the possibility of osteomalacia, active vitamin D was given but the hypophosphatemia persisted. Following an EDTA-2 Na load test performed to evaluate the reabsorption of phosphorus in the renal tubules, it was considered that the patient had a functional disorder of the parathyroid glands and that reabsorption of phosphorus was interrupted in the renal tubules. Furthermore, abnormal distributions of phosphorus seemed to occur in the same areas where sucrose was metabolized and iron was stored. Therefore, it was considered that these abnormalities induced hypophosphatemia following the intravenous administration of saccharated iron oxide. In addition to these actions, the possibility remained that phosphate absorption was inhibited in the small intestine by calcium lactate.

Topics: Aged; Aged, 80 and over; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Hypophosphatemia; Injections, Intravenous