FDA label 1a84ffdc-3950-43c7-bd3e-381e7d485f19

WARNINGS Hypersensitivity reactions have been reported with injectable iron products. See PRECAUTIONS .

ADVERSE REACTIONS Exposure to sodium ferric gluconate complex in sucrose injection has been documented in over 1,400 patients on hemodialysis. This population included 1,097 sodium ferric gluconate complex in sucrose injection-naïve patients who received a single-dose of sodium ferric gluconate complex in sucrose injection in a placebo-controlled, cross-over, post-marketing safety study. Undiluted sodium ferric gluconate complex in sucrose injection was administered over ten minutes (125 mg of elemental iron at 12.5 mg/min). No test dose was used. From a total of 1,498 sodium ferric gluconate complex in sucrose injection-treated patients in medical reports, North American trials, and post-marketing studies, twelve patients (0.8%) experienced serious reactions which precluded further therapy with sodium ferric gluconate complex in sucrose injection. Hypersensitivity Reactions See PRECAUTIONS . In the single-dose, post-marketing, safety study one patient experienced a life-threatening hypersensitivity reaction (diaphoresis, nausea, vomiting, severe lower back pain, dyspnea, and wheezing for 20 minutes) following sodium ferric gluconate complex in sucrose injection administration. Among 1,097 patients who received sodium ferric gluconate complex in sucrose injection in this study, there were 9 patients (0.8%) who had an adverse reaction that, in the view of the investigator, precluded further sodium ferric gluconate complex in sucrose injection administration (drug intolerance). These included one life-threatening reaction, six allergic reactions (pruritus x 2, facial flushing, chills, dyspnea/chest pain, and rash), and two other reactions (hypotension and nausea). Another 2 patients experienced (0.2%) allergic reactions not deemed to represent drug intolerance (nausea/malaise and nausea/dizziness) following sodium ferric gluconate complex in sucrose injection administration. Seventy-two (7.0%) of the 1,034 patients who had prior iron dextran exposure had a sensitivity to at least one form of iron dextran (INFeD ® or Dexferrum ® ). The patient who experienced a life-threatening adverse event following sodium ferric gluconate complex in sucrose injection administration during the study had a previous severe anaphylactic reaction to dextran in both forms (INFeD ® and Dexferrum ® ). The incidences of both drug intolerance and suspected allergic events following first dose sodium ferric gluconate complex in sucrose injection administration were 2.8% in patients with prior iron dextran sensitivity compared to 0.8% in patients without prior iron dextran sensitivity. In this study, 28% of the patients received concomitant angiotensin converting enzyme inhibitor (ACEi) therapy. The incidences of both drug intolerance or suspected allergic events following first dose sodium ferric gluconate complex in sucrose injection administration were 1.6% in patients with concomitant ACEi use compared to 0.7% in patients without concomitant ACEi use. The patient with a life-threatening event was not on ACEi therapy. One patient had facial flushing immediately on sodium ferric gluconate complex in sucrose injection exposure. No hypotension occurred and the event resolved rapidly and spontaneously without intervention other than drug withdrawal. In multiple dose Studies A and B, no fatal hypersensitivity reactions occurred among the 126 patients who received sodium ferric gluconate complex in sucrose injection. Sodium ferric gluconate complex in sucrose injection- associated hypersensitivity events in Study A resulting in premature study discontinuation occurred in three out of a total 88 (3.4%) sodium ferric gluconate complex in sucrose injection-treated patients. The first patient withdrew after the development of pruritus and chest pain following the test dose of sodium ferric gluconate complex in sucrose injection. The second patient, in the high-dose group, experienced nausea, abdominal and flank pain, fatigue and rash following the first dose of sodium ferric gluconate complex in sucrose injection. The third patient, in the low-dose group, experienced a “red blotchy rash” following the first dose of sodium ferric gluconate complex in sucrose injection. Of the 38 patients exposed to sodium ferric gluconate complex in sucrose injection in Study B, none reported hypersensitivity reactions. Many chronic renal failure patients experience cramps, pain, nausea, rash, flushing, and pruritus. In the postmarketing spontaneous reporting system, life-threatening hypersensitivity reactions have been reported rarely in patients receiving sodium ferric gluconate complex in sucrose injection. Hypertension See PRECAUTIONS . In the single dose safety study, post-administration hypotensive events were observed in 22/1,097 patients (2%) following sodium ferric gluconate complex in sucrose injection administration. Hypotension has also been reported following administration of sodium ferric gluconate complex in sucrose injection in European case reports. Of the 226 renal dialysis patients exposed to sodium ferric gluconate complex in sucrose injection and reported in the literature, 3 (1.3%) patients experienced hypotensive events, which were accompanied by flushing in two. All completely reversed after one hour without sequelae. Transient hypotension may occur during dialysis. Administration of Nulecit TM may augment hypotension caused by dialysis. Among the 126 patients who received sodium ferric gluconate complex in sucrose injection in Studies A and B, one patient experienced a transient decreased level of consciousness without hypotension. Another patient discontinued treatment prematurely because of dizziness, lightheadedness, diplopia, malaise, and weakness without hypotension that resulted in a 3 to 4 hour hospitalization for observation following drug administration. The syndrome resolved spontaneously. Adverse Laboratory Changes No differences in laboratory findings associated with sodium ferric gluconate complex in sucrose injection were reported in North American clinical trials when normalized against a National Institute of Health database on laboratory findings in 1,100 hemodialysis patients. Most Frequent Adverse Reactions In the single-dose, post-marketing safety study, 11% of patients who received sodium ferric gluconate complex in sucrose injection and 9.4% of patients who received placebo reported adverse reactions. The most frequent adverse reactions following sodium ferric gluconate complex in sucrose injection were: hypotension (2%), nausea, vomiting and/or diarrhea (2%), pain (0.7%), hypertension (0.6%), allergic reaction (0.5%), chest pain (0.5%), pruritus (0.5%), and back pain (0.4%). Similar adverse reactions were seen following placebo administration. However, because of the high baseline incidence of adverse events in the hemodialysis patient population, insufficient number of exposed patients, and limitations inherent to the cross-over, single dose study design, no comparison of event rates between sodium ferric gluconate complex in sucrose injection and placebo treatments can be made. In multiple-dose Studies A and B, the most frequent adverse reactions following sodium ferric gluconate complex in sucrose injection were: Body as a Whole: injection site reaction (33%), chest pain (10%), pain (10%), asthenia (7%), headache (7%), abdominal pain (6%), fatigue (6%), fever (5%), malaise, infection, abscess, back pain, chills, rigors, arm pain, carcinoma, flu-like syndrome, sepsis. Nervous System: cramps (25%), dizziness (13%), paresthesias (6%), agitation, somnolence. Respiratory System: dyspnea (11%), coughing (6%), upper respiratory infections (6%), rhinitis, pneumonia. Cardiovascular System: hypotension (29%), hypertension (13%), syncope (6%), tachycardia (5%), bradycardia, vasodilatation, angina pectoris, myocardial infarction, pulmonary edema. Gastrointestinal System: nausea, vomiting and/or diarrhea (35%), anorexia, rectal disorder, dyspepsia, eructation, flatulence, gastrointestinal disorder, melena. Musculoskeletal System: leg cramps (10%), myalgia, arthralgia. Skin and Appendages: pruritus (6%), rash, increased sweating. Genitourinary System: urinary tract infection. Special Senses: conjunctivitis, abnormal vision, ear disorder. Metabolic and Nutritional Disorders: hyperkalemia (6%), generalized edema (5%), leg edema, peripheral edema, hypoglycemia, edema, hypervolemia, hypokalemia. Hematologic System: abnormal erythrocytes (11%), anemia, leukocytosis, lymphadenopathy. Other Adverse Reactions Observed During Clinical Trials: In the single-dose post-marketing safety study in 1,097 patients receiving sodium ferric gluconate complex in sucrose injection, the following additional events were reported in two or more patients: hypertonia, nervousness, dry mouth, and hemorrhage. Pediatric Patients: In a clinical trial of 66 iron-deficient pediatric hemodialysis patients, 6 to 15 years of age, inclusive, who were receiving a stable erythropoietin dosing regimen, the most common adverse events, whether or not related to study drug, occurring in ≥ 5%, regardless of treatment group, were: hypotension (35%), headache (24%), hypertension (23%), tachycardia (17%), vomiting (11%), fever (9%), nausea (9%), abdominal pain (9%), pharyngitis (9%), diarrhea (8%), infection (8%), rhinitis (6%), and thrombosis (6%). More patients in the higher dose group (3.0 mg/kg) than in the lower dose group (1.5 mg/kg) experienced the following adverse events: hypotension (41% vs. 28%), tachycardia (21% vs. 13%), fever (15% vs. 3%), headache (29% vs. 19%), abdominal pain (15% vs. 3%), nausea (12% vs. 6%), vomiting (12% vs. 9%), pharyngitis (12% vs. 6%), and rhinitis (9% vs. 3%). Postmarketing Surveillance: The following additional adverse reactions have been identified with the use of sodium ferric gluconate complex in sucrose injection from postmarketing spontaneous reports: dysgeusia, hypoesthesia, loss of consciousness, convulsion, skin discoloration, pallor, phlebitis, and shock. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.