ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following clinically significant adverse reactions are described elsewhere in the labeling: oSerious Hypersensitivity Reactions [see Warnings and Precautions (5.1)]oHypotension [see Warnings and Precautions (5.2)]oIron Overload [see Warnings and Precautions (5.3)]oMagnetic Resonance (MR) Imaging Test Interference [see Warnings and Precautions (5.4)]. oSerious Hypersensitivity Reactions [see Warnings and Precautions (5.1)]. oHypotension [see Warnings and Precautions (5.2)]. oIron Overload [see Warnings and Precautions (5.3)]. oMagnetic Resonance (MR) Imaging Test Interference [see Warnings and Precautions (5.4)]. The most common adverse reactions (>= 2%) are diarrhea, headache, nausea, dizziness, hypotension, constipation, and peripheral edema. (6.1) To report SUSPECTED ADVERSE REACTIONS with ferumoxytol injection, contact Sandoz Inc., at 1-800-525-8747, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.In clinical studies, 3,968 subjects were exposed to ferumoxytol. Of these subjects 31% were male and the median age was 54 years (range of 18 to 96 years).The data described below reflect exposure to ferumoxytol in 997 patients exposed to 1.02 course of ferumoxytol administered as two 510 mg intravenous (IV) doses: 992 subjects (99.5%) received at least complete dose of ferumoxytol and 946 subjects (94.9%) received complete doses. The mean cumulative IV Iron exposure was 993.80 +-119.085 mg.The safety of ferumoxytol was studied in randomized, multicenter, double-blind clinical trial in patients with IDA (IDA Trial 3), [see Clinical Studies (14.1)]. In this trial, patients were randomized to two intravenous infusions of 510 mg (1.02 g) of ferumoxytol (n=997), or two intravenous infusions of 750 mg (1.500 g) of ferric carboxymaltose (FCM) (n=1000). Both intravenous irons were infused over period of at least 15 minutes. Most patients received their second infusion of ferumoxytol and FCM 7(+1) days after Dose 1.The mean (SD) age of the study population (N=1997) was 55.2 (17.16) years. The majority of patients were female (76.1%), white (71.4%) and non-Hispanic (81.8%). The mean (SD) hemoglobin at baseline for all patients was 10.4 (1.5) g/dl.Serious adverse events were reported in 3.6% (71/1997) of ferumoxytol-and FCM-treated patients. The most common (>=2 subjects) serious AEs reported in ferumoxytol-treated patients were syncope, gastroenteritis, seizure, pneumonia, hemorrhagic anemia, and acute kidney injury. In FCM-treated patients the most common (>=2 subjects) serious AEs were syncope, cardiac failure congestive, angina pectoris, and atrial fibrillation.Adverse reactions related to ferumoxytol and reported by >= 1% of ferumoxytol-treated patients in IDA Trial are listed in Table 1.Table 1: Adverse Reactions to Ferumoxytol Reported in >=1% of IDA Patients in IDA Trial 3Adverse ReactionsFerumoxytol2 510 mg(N 997)%Ferric Carboxymaltose x 750 mg (N 1000)%Headache3.43.1Nausea1.83.4Dizziness1.51.6Fatigue1.51.2Diarrhea10.8Back Pain10.4In IDA Trial 3, adverse reactions leading to treatment discontinuation and occurring in >= ferumoxytol-treated patients included arthralgia (0.3%), dyspnea (0.3%), flushing (0.2%), chest discomfort (0.2%), chest pain (0.2%), nausea (0.2%), back pain (0.2%), dizziness (0.2%) and headache (0.2%). Across two clinical trials in patients with IDA (IDA Trial and 2), [see Clinical Studies (14.1)], patients were randomized to: two injections (rapid intravenous injection -prior method of administration no longer approved) of 510 mg of ferumoxytol (n=1,014), placebo (n=200), or five injections/infusions of 200 mg of iron sucrose (n=199). Most patients received their second ferumoxytol injection to days after the first injection. Adverse reactions related to ferumoxytol and reported by >= 1% of ferumoxytol-treated patients in these trials were similar to those seen in Trial 3. In Trials and 2, adverse reactions leading to treatment discontinuation and occurring in >= ferumoxytol-treated patients included hypersensitivity (0.6%), hypotension (0.3%), and rash (0.2%).In addition, total of 634 subjects enrolled in and completed participation in Phase open label extension study. Of these, 337 subjects met IDA treatment criteria and received ferumoxytol. Adverse reactions following this repeat ferumoxytol dosing were generally similar in type and frequency to those observed after the first two intravenous injections.Across three randomized clinical trials in patients with IDA and CKD (CKD Trials 1, 2, and 3), [see Clinical Studies (14.2)], total of 605 patients were exposed to two injections of 510 mg of ferumoxytol and total of 280 patients were exposed to 200 mg/day of oral iron for 21 days. Most patients received their second ferumoxytol injection to days after the first injection.Adverse reactions related to ferumoxytol and reported by >= 1% of ferumoxytol-treated patients in the CKD randomized clinical trials are listed in Table 2. Diarrhea (4%), constipation (2.1%) and hypertension (1%) have also been reported in ferumoxytol-treated patients.Table 2: Adverse Reactions to Ferumoxytol Reported in >=1% of Patients with IDA and CKD Trials 1, and 3Adverse ReactionsFerumoxytol2 510 mg(n 605)%Oral Iron (n 280)%Nausea3.17.5Dizziness2.61.8Hypotension2.50.4Peripheral Edema23.2Headache1.82.1Edema1.51.4Vomiting1.55Abdominal Pain1.31.4Chest Pain1.30.7Cough1.31.4Pruritus1.20.4Pyrexia10.7Back Pain10Muscle Spasms11.4Dyspnea11.1Rash10.4In these clinical trials in patients with IDA and CKD, adverse reactions leading to treatment discontinuation and occurring in >= ferumoxytol-treated patients included hypotension (0.4%), chest pain (0.3%), and dizziness (0.3%).Following completion of the controlled phase of the trials, 69 patients received two additional 510 mg intravenous injections of ferumoxytol (for total cumulative dose of 2.04 g). Adverse reactions following this repeat ferumoxytol dosing were similar in character and frequency to those observed following the first two intravenous injections.. 6.2 Postmarketing Experience. Because adverse reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.The following serious adverse reactions have been reported from the post-marketing experience with ferumoxytol: 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 ferumoxytol. Reactions have occurred following the first dose or subsequent doses of ferumoxytol.

BOXED WARNING SECTION.

WARNING: RISK FOR SERIOUS HYPERSENSITIVITY/ANAPHYLAXIS REACTIONS. Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients receiving ferumoxytol. Initial symptoms may include hypotension, syncope, unresponsiveness, cardiac/cardiorespiratory arrest. oOnly administer ferumoxytol as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions[see Warnings and Precautions (5.1)].oObserve for signs or symptoms of hypersensitivity reactions during and for at least 30 minutes following ferumoxytol infusion including monitoring of blood pressure and pulse during and after ferumoxytol administration[see Warnings and Precautions (5.1)].oHypersensitivity reactions have occurred in patients in whom previous ferumoxytol dose was tolerated[see Warnings and Precautions (5.1)]. oOnly administer ferumoxytol as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions[see Warnings and Precautions (5.1)].. oObserve for signs or symptoms of hypersensitivity reactions during and for at least 30 minutes following ferumoxytol infusion including monitoring of blood pressure and pulse during and after ferumoxytol administration[see Warnings and Precautions (5.1)].. oHypersensitivity reactions have occurred in patients in whom previous ferumoxytol dose was tolerated[see Warnings and Precautions (5.1)]. WARNING: RISK FOR SERIOUS HYPERSENSITIVITY/ANAPHYLAXIS REACTIONSSee full prescribing information for complete boxed warning.Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients receiving ferumoxytol. Initial symptoms may include hypotension, syncope, unresponsiveness, cardiac/cardiorespiratory arrest.oOnly administer ferumoxytol as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. (5.1)oObserve for signs or symptoms of hypersensitivity reactions during and for at least 30 minutes following ferumoxytol infusion including monitoring of blood pressure and pulse during and after ferumoxytol administration. (5.1)oHypersensitivity reactions have occurred in patients in whom previous ferumoxytol dose was tolerated. (5.1). oOnly administer ferumoxytol as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. (5.1). oObserve for signs or symptoms of hypersensitivity reactions during and for at least 30 minutes following ferumoxytol infusion including monitoring of blood pressure and pulse during and after ferumoxytol administration. (5.1). oHypersensitivity reactions have occurred in patients in whom previous ferumoxytol dose was tolerated. (5.1).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Ferumoxytol was not tested for carcinogenic effects. In standard genotoxicity tests, ferumoxytol showed no evidence of mutagenic activity in an in vitro Ames test or clastogenic activity in either an in vitro chromosomal aberration assay or an in vivo micronucleus assay. No adverse effects on fertility or general reproductive performance were noted in animal studies. Ferumoxytol had no effect on male or female fertility or general reproductive function in rats. In pre and postnatal development study in rats, intravenous administration of ferumoxytol from gestation day until lactation day 20 at doses up to 60 mg/kg/day (approximately times the daily human dose based on body surface area comparisons assuming 60-kg person) had no effect on maternal delivery or numbers of liveborn offspring. Male offspring (F1) of pregnant rats (F0) administered ferumoxytol at dose of 60 mg/kg/day had delayed sexual maturation and decreased reproductive competence. Female offspring (F1) of pregnant rats (F0) administered ferumoxytol at doses of 30 mg/kg/day or 60 mg/kg/day had delayed sexual maturation and decreased reproductive competence. Doses of 30 mg/kg/day and 60 mg/kg/day are approximately and times the daily human dose based on body surface area comparisons assuming 60-kg person, respectively.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Ferumoxytol consists of superparamagnetic iron oxide that is coated with carbohydrate shell, which helps to isolate the bioactive iron from plasma components until the iron-carbohydrate complex enters the reticuloendothelial system macrophages of the liver, spleen and bone marrow. The iron is released from the iron-carbohydrate complex within vesicles in the macrophages. Iron then either enters the intracellular storage iron pool (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into hemoglobin.. 12.2 Pharmacodynamics. Cardiac ElectrophysiologyIn randomized, positive- and placebo-controlled, parallel-group study, healthy subjects received supratherapeutic regimen of ferumoxytol (1.02 given as two 510 mg doses within 24 hours), placebo or single dose of 400 mg moxifloxacin (positive control). Results demonstrated no effect of ferumoxytol on QT interval durations. No clinically meaningful effect of ferumoxytol on heart rate was observed.. 12.3 Pharmacokinetics. The pharmacokinetic (PK) behavior of ferumoxytol has been examined in healthy subjects and in patients with CKD stage 5D on hemodialysis. Ferumoxytol exhibited dose-dependent, capacity-limited elimination from plasma with half-life of approximately 15 hours in humans. The clearance (CL) was decreased by increasing the dose of ferumoxytol. Volume of distribution (Vd) was consistent with plasma volume, and the mean maximum observed plasma concentration (Cmax) and terminal half-life (t1/2) values increased with dose. The estimated values of CL and Vd following two 510 mg doses of ferumoxytol administered intravenously within 24 hours were 69.1 mL/hr and 3.16 L, respectively. The Cmax and time of maximum concentration (tmax) were 206 mcg/mL and 0.32 hr, respectively. Rate of infusion had no influence on ferumoxytol PK parameters. No gender differences in ferumoxytol PK parameters were observed. Ferumoxytol is not removed by hemodialysis.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Iron Deficiency Anemia in Patients Who Are Intolerant to Oral Iron or Have Had Unsatisfactory Response to Oral Iron IDA-301 Trial (referred to as IDA Trial 1) (NCT 01114139), IDA-302 Trial (referred to as IDA Trial 2) (NCT 01114204) and IDA-304 Trial (referred to as IDA Trial 3) (NCT 02694978)The safety and efficacy of ferumoxytol in patients with iron deficiency anemia, regardless of etiology and history of unsatisfactory oral iron therapy or in whom oral iron could not be used, were assessed in two randomized, controlled clinical trials (IDA Trial and 2) with ferumoxytol administered as rapid intravenous injection (prior method of administration no longer approved). In IDA Trial 1, patients were randomized to treatment with ferumoxytol or placebo. In IDA Trial 2, patients were randomized to treatment with ferumoxytol or iron sucrose. Ferumoxytol (510 mg) and placebo were administered as two intravenous single dose injections over 3-8 days, and iron sucrose (200 mg) was administered as intravenous injections or infusions over period of 14 days.In IDA Trial 1, the mean age of patients was 45 years (range, 18 to 91); 89% were female; 56% were Caucasian, 25% were Black, 16% were Asian, and 3% were other races. In IDA Trial 2, the mean age of patients was 48 years (range, 18 to 89); 83% were female; 84% were Caucasian, 11% were Asian, 1% were Black, and 4% were other races.Table shows changes from baseline to Week in hemoglobin and transferrin saturation in IDA Trial and 2.Table 3: Changes from Baseline to Week in Hemoglobin (Hgb) and Transferrin Saturation in IDA Trial and (Intent to Treat Population)ENDPOINTIDA Trial 1IDA Trial 2FerumoxytolN 608PlaceboN 200FerumoxytolN 406Iron SucroseN 199Baseline Hgbmean (SD), g/dL8.9 (0.9)8.8 (0.9)8.9 (0.9)8.8 (1.0)Proportion of patients with Hgb Increase of >=2 g/dL at any time from Baseline to Week 5, %81.15.58481.4Treatment Difference (%, 95% CI)75.6p<=0.001 for main efficacy endpoint (71.2, 80)2.6(-3.9, 9.1)Mean change in Hgb from Baseline to Week mean (SD), g/dL2.6 (1.5)0.1 (0.9)2.9 (1.6)2.7 (1.3)Proportion of patients with Hgb >=12 g/dL at any time from Baseline to Week 5, %50.5366.748.2Baseline TSATmean (SD) %7 (12.9)5.4 (4.9)6.1 (9.9)5.5 (10.3)Mean change in TSAT from Baseline to Week mean (SD), 11.4 (15.1)0.4 (5.8)15.7 (16.8)11.9 (14.4)In IDA Trial 1, fatigue-related symptoms and impacts were assessed using patient reported outcome instrument, FACIT-Fatigue (score range from to 52 with higher scores indicating less fatigue). After weeks, ferumoxytol-treated patients reported greater improvement from baseline in the fatigue score (+11.7 +- 11.73 points) than did patients in the placebo arm (+6.8 +- 9.51 points) with treatment difference of 4.9 (95% CI: 3.08-6.71) points.The safety of ferumoxytol in IDA patients with history of unsatisfactory oral iron therapy or in whom oral iron could not be used was also assessed in another randomized, multicenter, double-blind safety clinical trial (IDA Trial 3). Patients were randomized in 1:1 ratio to either two infusions of 510 mg (1.020 g) of ferumoxytol (n=997) or two infusions of 750 mg (1.500 g) of ferric carboxymaltose (FCM) (n=1000). Both IV irons were infused over period of at least 15 minutes. Most patients received their second infusion of ferumoxytol or FCM 7(+1) days after the first infusion. This study included patients with any etiology of IDA including CKD excluding dialysis-dependent CKD.In IDA Trial 3, the mean age of patients was 55 years (range, 18 to 96); 76% were female; 71% were Caucasian, 24% were Black, 3% were Asian, and 2% were other races. The study met the primary endpoint to demonstrate non-inferiority to FCM with respect to the percentage of patients who experienced moderate-to-severe hypersensitivity reactions (including anaphylaxis) or moderate-to-severe hypotension (ferumoxytol: 0.6%; FCM: 0.7%; treatment difference: -0.1%; exact 95% confidence interval: -0.91% to +0.70%).Table shows the mean increase from baseline to week in hemoglobin (Hgb) per treatment (ferumoxytol x 510 mg; FCM x 750 mg) and per gram of iron administered (ferumoxytol 1.020 g; FCM 1.500 g) in IDA Trial 3. Table 4: Summary of Hemoglobin (Hgb) Changes per Treatment and per Gram of Iron Administered From Baseline to Week (Intent to Treat Population) in IDA Trial 3ENDPOINTFerumoxytol x 510mgN 997Ferric Carboxymaltose (FCM)2 750mg = 1000Baseline Hgbmean (SD); g/dL10.42 (1.48)10.39 (1.46)Mean change in Hgb from Baseline to Week per Gram of Iron Administeredmean (SD); g/dL1.35 (1.35)1.10 (1.05)Treatment Difference Per Gram of IronAdjusted for difference in baseline Hgb (%, 95% CI)0.26(0.17, 0.36)Mean change in Hgb from Baseline to Week mean (SD); g/dL1.38 (1.35)1.63 (1.54)Treatment Difference (%, 95% CI)-0.24 (-0.35, -0.13)In IDA Trial 3, the incidence of severe hypophosphatemia (defined by blood phosphorous of <0.6 mmol/L at week 2) in the patients receiving ferumoxytol (0.4% of patients) was less than those receiving FCM (38.7% of patients).. 14.2 Iron Deficiency Anemia in Patients with Chronic Kidney Disease Trial 62745-7 (referred to as CKD Trial 1) (NCT 00255437), Trial 62745-6 (referred to as CKD Trial 2) (NCT 00255424), and Trial 62745-5 (referred to as CKD Trial 3) (NCT 00233597).The safety and efficacy of ferumoxytol for the episodic treatment of iron deficiency anemia in patients with CKD were assessed in three randomized, open-label, controlled clinical trials (CKD Trial 1, and 3) where ferumoxytol was administered as rapid intravenous injection (prior method of administration no longer approved). These trials also included an uncontrolled, follow-up phase in which patients with persistent iron deficiency anemia could receive two additional 510 mg intravenous injections of ferumoxytol. The major efficacy results from the controlled phase of each study are shown in Table 5.In all three trials, patients with CKD and iron deficiency anemia were randomized to treatment with ferumoxytol or oral iron. Ferumoxytol was administered as two 510 mg undiluted intravenous injections and oral iron (ferrous fumarate) was administered as total daily dose of 200 mg elemental iron daily for 21 days. The major trial outcomes assessed the change in hemoglobin from baseline to Day 35. CKD Trial and enrolled patients with non-dialysis dependent CKD and CKD Trial enrolled patients who were undergoing hemodialysis.In CKD Trial 1, the mean age of patients was 66 years (range, 23 to 95); 60% were female; 65% were Caucasian, 32% were Black, and 2% were other races. In the ferumoxytol and oral iron groups, 42% and 44% of patients, respectively, were receiving erythropoiesis stimulating agents (ESAs) at baseline.In CKD Trial 2, the mean age of patients was 65 years (range, 31 to 96); 61% were female; 58% were Caucasian, 35% were Black, and 7% were other races. In the ferumoxytol and oral iron groups, 36% and 43% of patients, respectively, were receiving ESAs at baseline.In CKD Trial 3, the mean age of patients was 60 years (range, 24 to 87); 43% were female; 34% were Caucasian, 59% were Black, and 7% were other races. All patients were receiving ESAs. Table shows the Baseline and mean change to Day 35 in hemoglobin (Hgb, g/dL), transferrin saturation (TSAT, %) and ferritin (ng/mL) in each treatment group for Trial 1, 2, and 3. Table 5:Changes from Baseline to Day 35 in Hemoglobin (Hgb), Transferrin Saturation and Ferritin (Intent to Treat Population) in CKD Trials 1, and 3ENDPOINTCKD Trial 1Non-DialysisCKD Trial 2Non-DialysisCKD Trial 3DialysisFerumoxytolN 226Oral IronN 77FerumoxytolN 228Oral IronN 76Ferumoxytol = 114Oral IronN 116Baseline Hgbmean (SD), g/dL9.9 (0.8)9.9 (0.7)10 (0.7)10 (0.8)10.6 (0.7)10.7(0.6)Hgb change from Baseline at Day 35 mean (SD), g/dL1.2p<=0.001 for main efficacy endpoint (1.3)0.5 (1.0)0.8 (1.2)0.2 (1)1 (1.1)0.5 (1.1)Baseline TSAT mean (SD), 9.8 (5.4)10.4 (5.2)11.3 (6.1)10.1 (5.5)15.7(7.2)15.9 (6.3)TSAT change from Baseline at Day 35 mean (SD), %9.2 (9.4)0.3 (4.7)9.8 (9.2)1.3 (6.4)6.4 (12.6)0.6 (8.3)Baseline ferritin mean (SD), ng/mL 123.7 (125.4)146.2 (136.3)146.1 (173.6)143.5 (144.9)340.5 (159.1)357.6 (171.7)Ferritin change from Baseline at Day 35 mean (SD), ng/mL 300.7 (214.9)0.3 (82)381.7 (278.6)6.9 (60.1)233.9 (207)-59.2 (106.2)Following completion of the controlled phase of each of the Phase trials, patients who were iron deficient and anemic could receive two additional 510 mg intravenous injections of ferumoxytol for total cumulative dose of 2.04 g. Overall, 69 patients received two additional 510 mg intravenous injections of ferumoxytol, and on Day 35 following these additional injections, the majority of these patients (70%) experienced an increase in hemoglobin and iron parameters (TSAT and ferritin). The mean change (+-SD) in hemoglobin level from the retreatment baseline for patients with an increase in hemoglobin was 0.86 (+- 0.68) g/dL and was 0.5 (+- 0.8) g/dL for all patients.In randomized, controlled clinical trial of 162 IDA patients with CKD (92 Non-Dialysis and 70 on Dialysis), mean change in hemoglobin from Baseline to Week was 0.71 +-1.03 g/dL for ferumoxytol-treated patients and 0.61 +-0.97 g/dL for iron sucrose-treated patients.. Table 5:Changes from Baseline to Day 35 in Hemoglobin (Hgb), Transferrin Saturation and Ferritin (Intent to Treat Population) in CKD Trials 1, and 3.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Ferumoxytol is contraindicated in patients with:oKnown hypersensitivity to ferumoxytol or any of its components [see Warnings and Precautions (5.1)].oHistory of allergic reaction to any intravenous iron product [see Warnings and Precautions (5.1)].. oKnown hypersensitivity to ferumoxytol or any of its components [see Warnings and Precautions (5.1)].. oHistory of allergic reaction to any intravenous iron product [see Warnings and Precautions (5.1)].. oKnown hypersensitivity to ferumoxytol or any of its components. (4)oHistory of allergic reaction to any intravenous iron product. (4). oKnown hypersensitivity to ferumoxytol or any of its components. (4). oHistory of allergic reaction to any intravenous iron product. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Ferumoxytol is an iron replacement product containing ferumoxytol for intravenous infusion. Ferumoxytol is non-stoichiometric magnetite (superparamagnetic iron oxide) coated with polyglucose sorbitol carboxymethylether. The overall colloidal particle size is 17 to 31 nm in diameter. The chemical formula of ferumoxytol is Fe5874O8752-C11719H18682O9933Na414 with an apparent molecular weight of 750 kDa.Ferumoxytol injection is sterile aqueous colloidal product that is formulated with mannitol. It is reddish brown liquid, and is provided in single-dose vials containing 510 mg of elemental iron. Each mL of the sterile colloidal solution of ferumoxytol injection contains 30 mg of elemental iron and 44 mg of mannitol, and 30 mg polyglucose sorbitol carboxymethylether. The formulation is isotonic with an osmolality of 270 to 330 mOsm/kg. The product contains no preservatives, and has pH of to 8.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. The recommended dose of ferumoxytol injection is an initial 510 mg dose followed by second 510 mg dose to days later. Administer ferumoxytol as an intravenous infusion in 50 to 200 mL 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP over at least 15 minutes. Administer while the patient is in reclined or semi-reclined position. Ferumoxytol injection does not contain antimicrobial preservatives. Discard unused portion. Ferumoxytol injection, when added to intravenous infusion bags containing either 0.9% Sodium Chloride Injection, USP (normal saline), or 5% Dextrose Injection, USP, at concentrations of to mg elemental iron per mL, should be used immediately but may be stored at controlled room temperature (25C +- 2C) for up to hours or refrigerated (2 to C) for up to 48 hoursThe dosage is expressed in terms of mg of elemental iron, with each mL of ferumoxytol containing 30 mg of elemental iron. Evaluate the hematologic response (hemoglobin, ferritin, iron and transferrin saturation) at least one month following the second ferumoxytol infusion. The recommended ferumoxytol injection dose may be readministered to patients with persistent or recurrent iron deficiency anemia.For patients receiving hemodialysis, administer ferumoxytol once the blood pressure is stable and the patient has completed at least one hour of hemodialysis. Monitor for signs and symptoms of hypotension following each ferumoxytol infusion.Allow at least 30 minutes between administration of ferumoxytol and administration of other medications that could potentially cause serious hypersensitivity reactions and/or hypotension, such as chemotherapeutic agents or monoclonal antibodies.Inspect parenteral drug products visually for the absence of particulate matter and discoloration prior to administration.. oThe recommended dose of ferumoxytol is an initial 510 mg dose followed by second 510 mg dose to days later. (2)oAdminister ferumoxytol as an intravenous infusion in 50 to 200 mL 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP over at least 15 minutes. (2). oThe recommended dose of ferumoxytol is an initial 510 mg dose followed by second 510 mg dose to days later. (2). oAdminister ferumoxytol as an intravenous infusion in 50 to 200 mL 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP over at least 15 minutes. (2).

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Ferumoxytol Injection is available in single-dose vials. Each vial contains 510 mg of elemental iron in 17 mL (30 mg per ml).. Injection: 510 mg iron per 17 mL (30 mg per mL) in single-dose vials. (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Drug-drug interaction studies with ferumoxytol were not conducted. Ferumoxytol may reduce the absorption of concomitantly administered oral iron preparations.

GERIATRIC USE SECTION.

8.5 Geriatric Use. In controlled clinical trials, 833 patients >= 65 years of age were treated with ferumoxytol. No overall differences in safety and efficacy were observed between older and younger patients in these trials, but greater sensitivity of older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of ferumoxytol may have more severe outcomes. The potential risks and benefits of ferumoxytol administration should be carefully considered in these patients [see Dosage and Administration (2), Warnings and Precautions (5.1), and Clinical Studies (14)].

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Ferumoxytol is indicated for the treatment of iron deficiency anemia (IDA) in adult patients:owho have intolerance to oral iron or have had unsatisfactory response to oral iron orowho have chronic kidney disease (CKD).. owho have intolerance to oral iron or have had unsatisfactory response to oral iron or. owho have chronic kidney disease (CKD).. Ferumoxytol is an iron replacement product indicated for the treatment of iron deficiency anemia (IDA) in adult patients:owho have intolerance to oral iron or have had unsatisfactory response to oral iron (1) orowho have chronic kidney disease (CKD). (1). owho have intolerance to oral iron or have had unsatisfactory response to oral iron (1) or. owho have chronic kidney disease (CKD). (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Patient Information)Prior History of Allergies to Parenteral Iron ProductsQuestion patients regarding any prior history of allergies to parenteral iron products [see Warnings and Precautions (5.1)]. Hypersensitivity Reactions Advise patients to immediately report any symptoms of hypersensitivity that may develop during and following ferumoxytol administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions( 5.1 )]. Manufactured in Slovenia by Lek Pharmaceuticals d.d forSandoz Inc., Princeton, NJ 08540.

LACTATION SECTION.

8.2 Lactation Risk SummaryThere are no data on the presence of ferumoxytol in human milk, the effects on the breastfed child, or the effects on milk production. Ferumoxytol has been detected in the milk of lactating rats. However, due to species-specific differences in lactation physiology, the clinical relevance of these data are not clear. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for ferumoxytol and any potential adverse effects on the breastfed child from ferumoxytol or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Ferumoxytol consists of superparamagnetic iron oxide that is coated with carbohydrate shell, which helps to isolate the bioactive iron from plasma components until the iron-carbohydrate complex enters the reticuloendothelial system macrophages of the liver, spleen and bone marrow. The iron is released from the iron-carbohydrate complex within vesicles in the macrophages. Iron then either enters the intracellular storage iron pool (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into hemoglobin.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Ferumoxytol was not tested for carcinogenic effects. In standard genotoxicity tests, ferumoxytol showed no evidence of mutagenic activity in an in vitro Ames test or clastogenic activity in either an in vitro chromosomal aberration assay or an in vivo micronucleus assay. No adverse effects on fertility or general reproductive performance were noted in animal studies. Ferumoxytol had no effect on male or female fertility or general reproductive function in rats. In pre and postnatal development study in rats, intravenous administration of ferumoxytol from gestation day until lactation day 20 at doses up to 60 mg/kg/day (approximately times the daily human dose based on body surface area comparisons assuming 60-kg person) had no effect on maternal delivery or numbers of liveborn offspring. Male offspring (F1) of pregnant rats (F0) administered ferumoxytol at dose of 60 mg/kg/day had delayed sexual maturation and decreased reproductive competence. Female offspring (F1) of pregnant rats (F0) administered ferumoxytol at doses of 30 mg/kg/day or 60 mg/kg/day had delayed sexual maturation and decreased reproductive competence. Doses of 30 mg/kg/day and 60 mg/kg/day are approximately and times the daily human dose based on body surface area comparisons assuming 60-kg person, respectively.

OVERDOSAGE SECTION.

10 OVERDOSAGE. Limited data are available regarding overdosage of ferumoxytol in humans. Excessive dosages of ferumoxytol may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer ferumoxytol to patients with iron overload [Warnings and Precautions (5.3)]. Ferumoxytol is not removed by hemodialysis.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. NDC 0781-3154-01Ferumoxytol Injection510 mg elemental iron Per 17 mL (30 mg/mL)For Intravenous Use onlySingle-Dose Vial Discard Unused PortionRx onlySANDOZ. Label.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of ferumoxytol in pediatric patients (less than 18 years old) have not been established.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Cardiac ElectrophysiologyIn randomized, positive- and placebo-controlled, parallel-group study, healthy subjects received supratherapeutic regimen of ferumoxytol (1.02 given as two 510 mg doses within 24 hours), placebo or single dose of 400 mg moxifloxacin (positive control). Results demonstrated no effect of ferumoxytol on QT interval durations. No clinically meaningful effect of ferumoxytol on heart rate was observed.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. The pharmacokinetic (PK) behavior of ferumoxytol has been examined in healthy subjects and in patients with CKD stage 5D on hemodialysis. Ferumoxytol exhibited dose-dependent, capacity-limited elimination from plasma with half-life of approximately 15 hours in humans. The clearance (CL) was decreased by increasing the dose of ferumoxytol. Volume of distribution (Vd) was consistent with plasma volume, and the mean maximum observed plasma concentration (Cmax) and terminal half-life (t1/2) values increased with dose. The estimated values of CL and Vd following two 510 mg doses of ferumoxytol administered intravenously within 24 hours were 69.1 mL/hr and 3.16 L, respectively. The Cmax and time of maximum concentration (tmax) were 206 mcg/mL and 0.32 hr, respectively. Rate of infusion had no influence on ferumoxytol PK parameters. No gender differences in ferumoxytol PK parameters were observed. Ferumoxytol is not removed by hemodialysis.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryLimited available data with ferumoxytol use in pregnant women are insufficient to inform drug associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with untreated iron deficiency anemia (IDA) in pregnancy as well as risks to the fetus associated with maternal severe hypersensitivity reactions (see Clinical Considerations). In animal studies, administration of ferumoxytol to pregnant rabbits during organogenesis caused adverse developmental outcomes including fetal malformations and decreased fetal weights at maternally toxic doses of times the estimated human daily dose.The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively.Clinical ConsiderationsDisease-associated maternal and/or embryo/fetal riskUntreated iron deficiency anemia (IDA) in pregnancy is associated with adverse maternal outcomes such as post-partum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.Fetal/Neonatal adverse reactionsSevere adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as ferumoxytol) which may cause fetal bradycardia, especially during the second and third trimester.DataAnimal DataAdministration of ferumoxytol during organogenesis, at doses of 31.6 mg Fe/kg/day in rats and16.5 mg Fe/kg/day in rabbits, did not result in maternal or fetal effects. These doses are approximately times the estimated human daily dose based on body surface area. In rats, administration of ferumoxytol during organogenesis at maternally toxic dose of 100 mg Fe/kg/day, approximately times the estimated human daily dose based on body surface area, caused decrease in fetal weights. In rabbits, administration of ferumoxytol during organogenesis at maternally toxic dose of 45 mg Fe/kg/day, approximately times the estimated human daily dose based on body surface area, was associated with external and soft tissue fetal malformations and decreased fetal weights.

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATIONFerumoxytol Injection (FER-ue-MOX-i-tol)What is the most important information should know about ferumoxytol injectionFerumoxytol injection may cause serious side effects including:oSerious allergic reactions that can lead to death. Serious allergic reactions have happened in people after receiving the first dose of ferumoxytol injection or after receiving additional doses in people who did not previously have an allergic reaction. If you have history of allergies to many different medicines, you may have an increased risk of serious allergic reactions to ferumoxytol injection. Tell your healthcare provider or get medical help right away if you get any of these signs or symptoms: rashitchingdizziness or lightheadednessswelling of the tongue or throatwheezing or trouble breathing See What are the possible side effects of ferumoxytol injection for more information about side effects.What is ferumoxytol injectionFerumoxytol injection is prescription medicine used to treat iron deficiency anemia in adults who have:ointolerance to oral iron or who have not responded well to treatment with oral iron orochronic kidney disease (CKD).It is not known if ferumoxytol injection is safe and effective in children less than 18 years of age. Who should not receive ferumoxytol injection Do not receive ferumoxytol injection if you:oare allergic to ferumoxytol injection or any of the ingredients in ferumoxytol injection. See the end of this leaflet for complete list of ingredients in ferumoxytol injection.ohave had an allergic reaction to any iron medicine given into your vein by intravenous (IV) infusion.Before receiving ferumoxytol injection, tell your healthcare provider about all of your medical conditions, including if you:ohave allergies to many different medicines.ohave iron overloadohave low blood pressure (hypotension).oare pregnant or plan to become pregnant. It is not known if ferumoxytol injection will harm your unborn baby.oare breastfeeding or plan to breastfeed. It is not known if ferumoxytol passes into your breast milk. You and your healthcare provider should decide if you will receive ferumoxytol injection or breastfeed.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive ferumoxytol injection oFerumoxytol injection will be given to you into your vein by intravenous (IV) infusion over at least 15 minutes by your healthcare provider. You will receive ferumoxytol injection in doses to days apart.oYour healthcare provider will watch you during and for at least 30 minutes after you receive ferumoxytol injection.What are the possible side effects of ferumoxytol injection Ferumoxytol injection can cause serious side effects, including:oSee What is the most important information should know about ferumoxytol injectionoLow blood pressure (hypotension) is common side effect of ferumoxytol injection and can sometimes be serious. Your healthcare provider will check you for signs and symptoms of hypotension after each ferumoxytol infusion.oIron overload. Your healthcare provider will do blood tests to check your iron levels during treatment with ferumoxytol injection. The most common side effects of ferumoxytol injection include: diarrhea, headache, nausea, dizziness, constipation, and swelling of your legs, feet, arms, or hands.These are not all of the possible side effects of ferumoxytol injection. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of ferumoxytol injection.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about ferumoxytol injection that is written for health professionals.What are the ingredients in ferumoxytol injectionActive ingredient: ferumoxytolInactive ingredient: mannitolManufactured in Slovenia by Lek Pharmaceuticals d.d forSandoz Inc., Princeton, NJ 08540For more information, call 1-800-525-8747. The Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 09/2020. oSerious allergic reactions that can lead to death. Serious allergic reactions have happened in people after receiving the first dose of ferumoxytol injection or after receiving additional doses in people who did not previously have an allergic reaction. If you have history of allergies to many different medicines, you may have an increased risk of serious allergic reactions to ferumoxytol injection. Tell your healthcare provider or get medical help right away if you get any of these signs or symptoms: rashitchingdizziness or lightheadednessswelling of the tongue or throatwheezing or trouble breathing rash. itching. dizziness or lightheadedness. swelling of the tongue or throat. wheezing or trouble breathing. ointolerance to oral iron or who have not responded well to treatment with oral iron or. ochronic kidney disease (CKD).. oare allergic to ferumoxytol injection or any of the ingredients in ferumoxytol injection. See the end of this leaflet for complete list of ingredients in ferumoxytol injection.. ohave had an allergic reaction to any iron medicine given into your vein by intravenous (IV) infusion.. ohave allergies to many different medicines.. ohave iron overload. ohave low blood pressure (hypotension).. oare pregnant or plan to become pregnant. It is not known if ferumoxytol injection will harm your unborn baby.. oare breastfeeding or plan to breastfeed. It is not known if ferumoxytol passes into your breast milk. You and your healthcare provider should decide if you will receive ferumoxytol injection or breastfeed.. oFerumoxytol injection will be given to you into your vein by intravenous (IV) infusion over at least 15 minutes by your healthcare provider. You will receive ferumoxytol injection in doses to days apart.. oYour healthcare provider will watch you during and for at least 30 minutes after you receive ferumoxytol injection.. oSee What is the most important information should know about ferumoxytol injection. oLow blood pressure (hypotension) is common side effect of ferumoxytol injection and can sometimes be serious. Your healthcare provider will check you for signs and symptoms of hypotension after each ferumoxytol infusion.. oIron overload. Your healthcare provider will do blood tests to check your iron levels during treatment with ferumoxytol injection. The Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 09/2020.

SPL UNCLASSIFIED SECTION.

5.1 Serious Hypersensitivity Reactions. Fatal and serious hypersensitivity reactions including anaphylaxis, presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, or unresponsiveness have occurred in patients receiving ferumoxytol. Other adverse reactions potentially associated with hypersensitivity have occurred (pruritus, rash, urticaria, and wheezing). These reactions have occurred following the first dose or subsequent doses in patients in whom previous ferumoxytol dose was tolerated. Patients with history of multiple drug allergies may have greater risk of anaphylaxis with parenteral iron products. Carefully consider the potential risks and benefits before administering ferumoxytol to these patients. Only administer ferumoxytol as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Closely observe patients for signs and symptoms of hypersensitivity including monitoring of blood pressure and pulse during and after ferumoxytol administration for at least 30 minutes and until clinically stable following completion of each infusion [see Adverse Reactions (6.2)]. In clinical study in patients with IDA, regardless of etiology, hypersensitivity reactions were reported in 0.4% (4/997) of subjects receiving ferumoxytol administered as intravenous infusion over at least 15 minutes. These included one patient with severe hypersensitivity reaction and three patients with moderate hypersensitivity reactions.In clinical studies predominantly in patients with IDA and CKD, serious hypersensitivity reactions were reported in 0.2% (4/1,806) of subjects receiving ferumoxytol (administered as rapid intravenous injection prior method of administration no longer approved). Other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria or wheezing) were reported in 3.5% (63/1,806) of these subjects. In the post-marketing experience, fatal and serious anaphylactic type reactions presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, and unresponsiveness have been reported. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of ferumoxytol may have more severe outcomes [see Boxed Warning, Adverse Reactions (6.2) and Use in Specific Populations (8.5)].

STORAGE AND HANDLING SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1 How Supplied. Ferumoxytol injection is available in single-dose vials in the following package sizes (Table 6).Table 6: Ferumoxytol Packaging DescriptionNDC CodeDose/Total volume per vialVials/CartonNDC 0781-3154-01510 mg/17 mL1NDC 0781-3154-95510 mg/17 mL10. 16.2 Stability and Storage. Store at 20 to 25C (68 to 77F). Excursions permitted to 15 to 30C (59 to 86F) [See USP Controlled Room Temperature]. Store in the original package to protect from light. Do not freeze.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryLimited available data with ferumoxytol use in pregnant women are insufficient to inform drug associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with untreated iron deficiency anemia (IDA) in pregnancy as well as risks to the fetus associated with maternal severe hypersensitivity reactions (see Clinical Considerations). In animal studies, administration of ferumoxytol to pregnant rabbits during organogenesis caused adverse developmental outcomes including fetal malformations and decreased fetal weights at maternally toxic doses of times the estimated human daily dose.The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively.Clinical ConsiderationsDisease-associated maternal and/or embryo/fetal riskUntreated iron deficiency anemia (IDA) in pregnancy is associated with adverse maternal outcomes such as post-partum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.Fetal/Neonatal adverse reactionsSevere adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as ferumoxytol) which may cause fetal bradycardia, especially during the second and third trimester.DataAnimal DataAdministration of ferumoxytol during organogenesis, at doses of 31.6 mg Fe/kg/day in rats and16.5 mg Fe/kg/day in rabbits, did not result in maternal or fetal effects. These doses are approximately times the estimated human daily dose based on body surface area. In rats, administration of ferumoxytol during organogenesis at maternally toxic dose of 100 mg Fe/kg/day, approximately times the estimated human daily dose based on body surface area, caused decrease in fetal weights. In rabbits, administration of ferumoxytol during organogenesis at maternally toxic dose of 45 mg Fe/kg/day, approximately times the estimated human daily dose based on body surface area, was associated with external and soft tissue fetal malformations and decreased fetal weights. 8.2 Lactation Risk SummaryThere are no data on the presence of ferumoxytol in human milk, the effects on the breastfed child, or the effects on milk production. Ferumoxytol has been detected in the milk of lactating rats. However, due to species-specific differences in lactation physiology, the clinical relevance of these data are not clear. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for ferumoxytol and any potential adverse effects on the breastfed child from ferumoxytol or from the underlying maternal condition.. 8.4 Pediatric Use. The safety and effectiveness of ferumoxytol in pediatric patients (less than 18 years old) have not been established.. 8.5 Geriatric Use. In controlled clinical trials, 833 patients >= 65 years of age were treated with ferumoxytol. No overall differences in safety and efficacy were observed between older and younger patients in these trials, but greater sensitivity of older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of ferumoxytol may have more severe outcomes. The potential risks and benefits of ferumoxytol administration should be carefully considered in these patients [see Dosage and Administration (2), Warnings and Precautions (5.1), and Clinical Studies (14)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. oGreater risk of anaphylaxis in patients with multiple drug allergies. (5.1)oHypotension: Ferumoxytol may cause hypotension. Monitor for signs and symptoms of hypotension following each administration of ferumoxytol. (5.2)oIron Overload: Regularly monitor hematologic responses during ferumoxytol therapy. Do not administer ferumoxytol to patients with iron overload. (5.3)oMagnetic Resonance Imaging Test Interference: Ferumoxytol can alter magnetic resonance imaging (MRI) studies. (5.4). oGreater risk of anaphylaxis in patients with multiple drug allergies. (5.1). oHypotension: Ferumoxytol may cause hypotension. Monitor for signs and symptoms of hypotension following each administration of ferumoxytol. (5.2). oIron Overload: Regularly monitor hematologic responses during ferumoxytol therapy. Do not administer ferumoxytol to patients with iron overload. (5.3). oMagnetic Resonance Imaging Test Interference: Ferumoxytol can alter magnetic resonance imaging (MRI) studies. (5.4). 5.1 Serious Hypersensitivity Reactions. Fatal and serious hypersensitivity reactions including anaphylaxis, presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, or unresponsiveness have occurred in patients receiving ferumoxytol. Other adverse reactions potentially associated with hypersensitivity have occurred (pruritus, rash, urticaria, and wheezing). These reactions have occurred following the first dose or subsequent doses in patients in whom previous ferumoxytol dose was tolerated. Patients with history of multiple drug allergies may have greater risk of anaphylaxis with parenteral iron products. Carefully consider the potential risks and benefits before administering ferumoxytol to these patients. Only administer ferumoxytol as an intravenous infusion over at least 15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Closely observe patients for signs and symptoms of hypersensitivity including monitoring of blood pressure and pulse during and after ferumoxytol administration for at least 30 minutes and until clinically stable following completion of each infusion [see Adverse Reactions (6.2)]. In clinical study in patients with IDA, regardless of etiology, hypersensitivity reactions were reported in 0.4% (4/997) of subjects receiving ferumoxytol administered as intravenous infusion over at least 15 minutes. These included one patient with severe hypersensitivity reaction and three patients with moderate hypersensitivity reactions.In clinical studies predominantly in patients with IDA and CKD, serious hypersensitivity reactions were reported in 0.2% (4/1,806) of subjects receiving ferumoxytol (administered as rapid intravenous injection prior method of administration no longer approved). Other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria or wheezing) were reported in 3.5% (63/1,806) of these subjects. In the post-marketing experience, fatal and serious anaphylactic type reactions presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, and unresponsiveness have been reported. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of ferumoxytol may have more severe outcomes [see Boxed Warning, Adverse Reactions (6.2) and Use in Specific Populations (8.5)]. 5.2 Hypotension. Ferumoxytol may cause clinically significant hypotension.In clinical study with ferumoxytol in patients with IDA, regardless of etiology, moderate hypotension was reported in 0.2% (2/997) of subjects receiving ferumoxytol administered as intravenous infusion over at least 15 minutes.In clinical studies in patients with IDA and CKD, hypotension was reported in 1.9% (35/1,806) of subjects, including three patients with serious hypotensive reactions, who had received ferumoxytol as rapid intravenous injection (prior method of administration no longer approved).Hypotension has also been reported in the post-marketing experience [see Adverse Reactions (6.2)]. Monitor patients for signs and symptoms of hypotension following each ferumoxytol administration [see Dosage and Administration (2) and Warnings and Precautions (5.1)]. 5.3 Iron Overload. Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. Regularly monitor the hematologic response during parenteral iron therapy [see Dosage and Administration (2)]. Do not administer ferumoxytol to patients with iron overload.In the 24 hours following administration of ferumoxytol, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in the ferumoxytol complex.. 5.4 Magnetic Resonance (MR) Imaging Test Interference. Administration of ferumoxytol may transiently affect the diagnostic ability of MR imaging. Conduct anticipated MR imaging studies prior to the administration of ferumoxytol. Alteration of MR imaging studies may persist for up to months following the last ferumoxytol dose. If MR imaging is required within months after ferumoxytol administration, use T1- or proton density-weighted MR pulse sequences to minimize the ferumoxytol effects; MR imaging using T2-weighted pulse sequences should not be performed earlier than weeks after the administration of ferumoxytol. Maximum alteration of vascular MR imaging is anticipated to be evident for to days following ferumoxytol administration [see Clinical Pharmacology (12.3)]. Ferumoxytol will not interfere with X-ray, computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), ultrasound or nuclear medicine imaging.