A comparison of the rates of cisplatin (cDDP)--induced nephrotoxicity associated with sodium loading or sodium loading with forced diuresis as a preventative measure.

OBJECTIVE: To determine whether forced diuresis and sodium loading or sodium loading alone is better at preventing cisplatin-induced nephrotoxicity. METHODS: Records of 92 patients receiving cisplatin >40 mg/m(2) and sodium loading with or without mannitol were reviewed to determine the incidence of nephrotoxicity, average decline in creatinine clearance, degree of nephrotoxicity, time to resolution, rates of hospitalization, and electrolyte abnormalities among patients receiving sodium loading or sodium loading with forced diuresis. RESULTS: The mean cisplatin dose was 64.5 mg/m(2) with a majority of the subjects receiving treatment for lung cancer. The patients who received sodium loading experienced an average decline in creatinine clearance of 33.9 mL/min versus a decline of 38.9 mL/min in the group receiving forced diuresis and sodium loading (p = 0.09). Incidence of nephrotoxicity, rate of hospitalization and rates of hypokalemia or hypomagnesemia were similar between the groups. Time to resolution of nephrotoxicity was significantly different between the groups, although there were limitations in evaluating this outcome. Majority of the subjects in the sodium loading group experienced NCIC-TC Grade 0 nephrotoxicity, whereas half of the patients in the forced diuresis group experienced Grade 2 nephrotoxicity. CONCLUSION: We detected no difference in the prevention of cisplatin-induced nephrotoxicity when patients were treated with sodium loading alone or with sodium loading with mannitol. No differences were detected in average decrease in creatinine clearance, incidence of nephrotoxicity, or rates of hypomagnesemia and hypokalemia. The difference in time to resolution of toxicity appeared to be significant, however there were limitations in evaluating this outcome.

Safe administration of iron sucrose in a patient with a previous hypersensitivity reaction to ferric gluconate.

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.

Short-term stability of a new generic sodium ferric gluconate in complex with sucrose.

BACKGROUND: Sodium ferric gluconate in complex (SFG) is used to treat iron deficiency anemia in patients aged ≥6 years undergoing chronic hemodialysis and receiving supplemental epoetin therapy. Both the branded product (Ferrlecit, branded SFG) and a new generic version of sodium ferric gluconate in complex (Nulecit; generic SFG) are provided in 5 mL vials. SFG may be administered by slow intravenous (IV) injection of the undiluted product or by 1 h IV infusion after dilution in 100 mL 0.9% sodium chloride. This study evaluated the short-term stability of undiluted and diluted generic SFG at room temperature and under refrigeration. METHODS: Samples of generic SFG undiluted in 10 mL syringes or diluted in IV infusion bags containing 0.9% sodium chloride solution were stored at room temperature or under refrigerated conditions (2-8°C). Samples at room temperature were stored for ≤48 h if undiluted and for ≤24 h if diluted. All refrigerated samples were stored for ≤7 days. Parameters evaluated were elemental iron (Fe) concentration and SFG apparent molecular weight. All tests were performed on two lots of the generic product. RESULTS: Fe concentrations were identical in both lots and did not vary substantially over time under different conditions of storage or dilution. SFG apparent molecular weight varied across all samples from 306,000 to 354,000 Daltons, well within the range of 289,000 to 440,000 Daltons specified as the molecular weight in the FDA-approved prescribing information. CONCLUSION: Iron content and SFG apparent molecular weight were stable under all experimental conditions. Undiluted generic SFG was stable for ≥2 days at room temperature and ≥7 days under refrigerated conditions, and generic SFG diluted in IV infusion bags containing 0.9% sodium chloride solution was stable for ≥1 day at room temperature and ≥7 days under refrigerated conditions.

Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion: bioequivalence of a new generic product with the branded product in healthy volunteers.

OBJECTIVE: Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent. METHODS: In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG. RESULTS: Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%. CONCLUSIONS: A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

Iron replacement therapy in cancer-related anemia.

PURPOSE: The incidence, etiology, and management of cancer-related anemia is reviewed and the role of i.v. iron therapy in its treatment is described. SUMMARY: Between 30% and 90% of patients with cancer develop anemia due to direct effects of the disease, its treatment, underlying nutritional deficiencies, and the inflammation that characterizes chronic disease. Although the use of erythropoiesis-stimulating agents (ESAs) increases hemoglobin levels and decreases the need for transfusions, up to 50% of patients do not to respond to these drugs, usually due to the presence of absolute or functional iron deficiency. Multiple clinical trials have demonstrated that i.v. iron supplementation in patients with cancer-related anemia improves the response rate to ESAs, reduces the time to target hemoglobin levels, decreases ESA requirements, reduces costs, and is more efficacious than oral iron. These benefits are seen without increased toxicity. Nonetheless, i.v. iron remains underused in patients with cancer, partly due to misinformation and misinterpretation of the clinical nature of adverse events. CONCLUSION: Intravenous iron is underutilized in patients with cancer-related anemia. Based on published evidence, i.v. iron supplementation in patients with absolute or functional iron deficiency can improve patient responses to ESAs and reduce ESA requirements and may also reduce the need for transfusions and improve quality of life.

Extended-dosage-interval regimens of erythropoietic agents in chemotherapy-induced anemia.

PURPOSE: The safety and efficacy of extended-dosage-interval regimens of erythropoiesis-stimulating agents (ESAs) for managing chemotherapy-induced anemia (CIA) are reviewed. SUMMARY: Anemia is a frequent complication of chemotherapy. The ESAs epoetin alfa and darbepoetin alfa have been shown to safely and effectively manage CIA; comparable outcomes have been demonstrated between epoetin alfa 40,000 units once weekly and darbepoetin alfa 200 microg every two weeks. These commonly prescribed regimens necessitate extra clinic visits by cancer patients receiving cyclic chemotherapy. ESA administration can now often be synchronized with a three-week chemotherapy cycle because of the recent approval of darbepoetin alfa 500 microg every three weeks for CIA. However, in the Phase III trial providing the basis for this new dosage recommendation, more than 70% of patients required a 40% reduction in the dosage, resulting in an average dose of 375 microg every three weeks. The extended-dosage-interval regimens have not been associated with an increase in cardiovascular or thrombotic adverse events. Extended-dosage-interval regimens of epoetin alfa are under investigation and may provide additional alternatives. Synchronizing ESA therapy with scheduled chemotherapy visits would help minimize disruptions for patients and caregivers and improve the use of health care resources. CONCLUSION: Administration of darbepoetin alfa every three weeks offers the convenience of synchronization of treatment with 21-day-cycle chemotherapy in many patients with CIA. Extended-dosage-interval regimens for epoetin alfa are being investigated and show promise.