Feraheme administration may cause serious hypersensitivity reactions and hypotension [ see Warnings and Precautions (5.1),(5.2) ]. In clinical studies, 1,726 subjects were exposed to Feraheme; 1,562 of these had CKD and 164 did not have CKD. Of these subjects 46% were male and the median age was 63 years (range of 18 to 96 years). Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice. The most common adverse reactions (≥ 2%) following the administration of Feraheme are diarrhea, nausea, dizziness, hypotension, constipation, and peripheral edema. (6.1) To report SUSPECTEDwith Feraheme, contact AMAG Pharmaceuticals, Inc. at 1-877-411-2510, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Adverse Reactions in Clinical Studies Across the three randomized clinical trials [Trial 1, 2, and 3, see Clinical Studies (14) ], a total of 605 patients were exposed to two injections of 510 mg of Feraheme and a total of 280 patients were exposed to 200 mg/day of oral iron for 21 days. Most patients received their second Feraheme injection 3 to 8 days after the first injection. Adverse reactions related to Feraheme and reported by ≥ 1% of Feraheme-treated patients in the randomized clinical trials are listed in Table 1. Diarrhea (4.0%), constipation (2.1%) and hypertension (1.0%) have also been reported in Feraheme-treated patients. Table 1: Adverse Reactions to Feraheme Reported in ≥1% of Patients with CKD Adverse Reactions Feraheme 2 x 510 mg (n = 605) Oral Iron (n = 280) Nausea 3.1% 7.5% Dizziness 2.6% 1.8% Hypotension 2.5% 0.4% Peripheral Edema 2.0% 3.2% Headache 1.8% 2.1% Edema 1.5% 1.4% Vomiting 1.5% 5.0% Abdominal Pain 1.3% 1.4% Chest Pain 1.3% 0.7% Cough 1.3% 1.4% Pruritus 1.2% 0.4% Pyrexia 1.0% 0.7% Back Pain 1.0% 0% Muscle Spasms 1.0% 1.4% Dyspnea 1.0% 1.1% Rash 1.0% 0.4% In clinical trials, adverse reactions leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included hypotension, infusion site swelling, increased serum ferritin level, chest pain, diarrhea, dizziness, ecchymosis, pruritus, chronic renal failure, and urticaria. Following completion of the controlled phase of the trials, 69 patients received two additional 510 mg intravenous injections of Feraheme (for a total cumulative dose of 2.04 g). Adverse reactions following this repeat Feraheme dosing were similar in character and frequency to those observed following the first two intravenous injections. In a placebo-controlled, cross-over trial, 713 patients with CKD received a single 510 mg dose of Feraheme. Adverse reactions reported by these patients were similar in character and frequency to those observed in other clinical trials. 6.2 Postmarketing Experience Because adverse 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. The following serious adverse reactions have been reported from the post-marketing experience with Feraheme: fatal, life-threatening, and serious anaphylactic-type reactions, cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, unresponsiveness, loss of consciousness, tachycardia/rhythm abnormalities, angioedema, ischemic myocardial events, congestive heart failure, pulse absent, and cyanosis. These adverse reactions have usually occurred within 30 minutes after the administration of Feraheme. Reactions have occurred following the first dose or subsequent doses of Feraheme.