BRIEF SUMMARY OF PRESCRIBING INFORMATION MONOFERRIC ( ferric derisomaltose ) injection
INDICATION AND USAGE : Monoferric is an iron replacement product indicated for the treatment of iron deficiency anemia in adult patients :
• who have intolerance to oral iron or have had unsatisfactory response to oral iron .
• who have non-hemodialysis dependent chronic kidney disease .
DOSAGE AND ADMINISTRATION : For patients weighing 50 kg or more : Administer 1,000 mg of Monoferric by intravenous infusion over at least 20 minutes as a single dose . Repeat dose if iron deficiency anemia reoccurs .
For patients weighing less than 50 kg : Administer Monoferric as 20 mg / kg actual body weight by intravenous infusion over at least 20 minutes as a single dose . Repeat dose if iron deficiency anemia reoccurs .
The dosage of Monoferric is expressed in mg of elemental iron . Each mL of Monoferric contains 100 mg of elemental iron .
Only administer Monoferric when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions .
DOSAGE FORMS AND STRENGTHS : Monoferric is a sterile , dark brown , non-transparent aqueous solution available as :
• Injection : 1,000 mg iron / 10 mL ( 100 mg / mL ) single-dose vial
CONTRAINDICATIONS : Monoferric is contraindicated in patients with a history of serious hypersensitivity to Monoferric or any of its components . Reactions have included shock , clinically significant hypotension , loss of consciousness , and / or collapse .
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions : Serious hypersensitivity reactions , including anaphylactic-type reactions , some of which have been life-threatening and fatal , have been reported in patients receiving Monoferric . Patients may present with shock , clinically significant hypotension , loss of consciousness , and / or collapse . Monitor patients for signs and symptoms of hypersensitivity during and after Monoferric administration for at least 30 minutes and until clinically stable following completion of the infusion . Only administer Monoferric when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions . Monoferric is contraindicated in patients with prior serious hypersensitivity reactions to Monoferric or any of its components . In clinical trials in patients with IDA and CKD , serious or severe hypersensitivity were reported in 0.3 % ( 6 / 2008 ) of the Monoferric treated subjects . These included 3 events of hypersensitivity in 3 patients ; 2 events of infusion-related reactions in 2 patients and 1 event of asthma in one patient .
Iron Overload : Excessive therapy with parenteral iron can lead to excess iron storage and possibly iatrogenic hemosiderosis or hemochromatosis . Monitor the hematologic response ( hemoglobin and hematocrit ) and iron parameters ( serum ferritin and transferrin saturation ) during parenteral iron therapy . Do not administer Monoferric to patients with iron overload .
ADVERSE REACTIONS
Clinical Trials Experience : Because clinical trials are conducted under widely varying conditions , the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice .
The safety of Monoferric was evaluated in 3008 patients with iron deficiency anemia enrolled in two randomized , actively-controlled trials . Trial 1 enrolled adult patients with iron deficiency anemia with intolerance to oral iron or had an unsatisfactory response to oral iron with a clinical need for repletion of iron stores . Eligible subjects were required to have a baseline hemoglobin of ≤11g / dl , transferrin saturation ( TSAT ) < 20 % and serum ferritin level of < 100 ng / mL . Trial 2 enrolled adult patients with non-dialysis dependent chronic kidney disease . Eligible subjects also had to have serum ferritin ≤200 μg / L or ≤300 ng / mL if TSAT ≤30 %.
Trial 1 and Trial 2 : In the two randomized , actively-controlled clinical trials , Trials 1 and Trial 2 , patients were randomized in a 2:1 ratio to intravenous Monoferric ( n = 2008 ) or intravenous iron sucrose ( n = 1000 ) respectively . Monoferric was administered as a single intravenous infusion of 1000 mg diluted in 100 mL 0.9 % sodium chloride and given over approximately 20 minutes ( approximately 50 mg iron / min ). Iron sucrose was administered as 200 mg undiluted intravenous injections over approximately 2 – 5 minutes and repeated according to standard practice or physician choice up to a maximum of five times ( 1000 mg ) within the first two weeks starting at baseline .
The data described below reflect exposure to Monoferric in 2008 patients exposed to a 1000 mg single intravenous dose of Monoferric . The mean cumulative intravenous iron exposure was 984 mg .
Trial 1 included 1483 patients with iron deficiency anemia in the safety analysis that had intolerance to oral iron or have had unsatisfactory response to oral iron or with a clinical need for rapid repletion of iron stores . Trial 2 included 1525 patients in the safety analysis who had non-dialysis dependent CKD . The mean ( SD ) age of the combined study population was 56.4 ( 18.3 ) years . The majority of patients were women ( 75.7 %).
Adverse reactions were reported in 8.6 % ( 172 / 2008 ) of patients treated with Monoferric .
Adverse reactions related to treatment and reported by ≥1 % of the treated patients in the combined analysis of Trial 1 and 2 are listed in Table 1 .
Table 1 . Adverse Reactions ( ≥1 %) in Patients Receiving Monoferric in Clinical Trials 1 and 2
Monferric ( N = 2008 ) N (%)
Iron Sucrose ( N = 1000 ) N (%)
Adverse Reaction |
|
|
Nausea |
24 ( 1.2 ) |
11 ( 1.1 ) |
Rash |
21 ( 1 ) |
1 ( 0.1 ) |
Adjudicated serious or severe hypersensitivity reactions were reported in 6 / 2008 ( 0.3 %) patients in the Monoferric group .
Hypophosphatemia ( serum phosphate < 2.0 mg / dL ) was reported in 3.5 % of Monoferric-treated patients in Trials 1 & 2 .
Post-marketing Experience : 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 . The following adverse reactions have been most commonly reported from the post-marketing spontaneous reports with Monoferric :
Cardiac disorders : Tachycardia Gastrointestinal disorders : Abdominal pain , nausea and vomiting , constipation , diarrhea
General disorders and administration site conditions : Fatigue , pyrexia , chest pain , chills , Fishbane reaction , extravasation , influenza like symptoms , injection site reactions
Immune System disorders : Anaphylactic / anaphylactoid reaction , hypersensitivity Investigations : Hepatic enzymes increased Musculoskeletal and connective tissue disorders : Back pain , muscle spasms , arthralgia , myalgia
Nervous system disorders : Dizziness , headache , paresthesia , dysgeusia , seizure , loss of consciousness , syncope
Psychiatric disorders : Anxiety Respiratory , thoracic , and mediastinal disorders : Dyspnea , cough Skin and subcutaneous tissue disorders : Erythema , urticaria , discoloration skin , rash , pruritus , sweating Vascular disorders : Hypertension , hypotension , flushing , phlebitis
Extravasation of Monoferric at the injection site that may lead to irritation of the skin and potentially long lasting brown discoloration at the site of injection has also been reported .
USE IN SPECIFIC POPULATIONS
Pregnancy : There are no available data on Monoferric use in pregnant women to evaluate for a drug-associated risk of major birth defects , miscarriage , or adverse maternal or fetal outcomes . Published studies on the use of intravenous iron products in pregnant women have not reported an association with adverse developmental outcomes . However , these studies cannot establish or exclude the absence of any drug-related risk during pregnancy because the studies were not designed to assess for the risk of major birth defects . 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 .
Untreated iron deficiency anemia ( IDA ) in pregnancy is associated with adverse maternal outcomes such as post-partum anemia . Adverse pregnancy outcomes associated with IDA includes increased risk for preterm delivery and low birth weight .
Severe 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 Monoferric ) which may cause fetal bradycardia , especially during the second and third trimester .
Lactation : The available data on the use of Monoferric in lactating women demonstrate that iron is present in breast milk . However , the data do not inform the potential exposure of iron for the breastfed child or the effects on milk production . The developmental and health benefits of breastfeeding should be considered along with the mother ’ s clinical need for Monoferric in addition to any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition .
Pediatric Use : Safety and effectiveness have not been established in pediatric patients .
Geriatric Use : Of the 3934 patients in clinical studies of Monoferric , 29 % were 65 years and over , while 13 % were 75 years and over . No overall differences in safety or effectiveness were observed between these patients and younger subjects , and other reported clinical experience has not identified differences in responses between the elderly and younger patients , but greater sensitivity of some older individuals cannot be ruled out .
CLINICAL STUDIES : The safety and efficacy of Monoferric for treatment of iron deficiency anemia ( IDA ) were evaluated in two randomized , open-label , actively-controlled clinical trials performed in a total of 3050 patients with IDA of different etiology . Trial 1 included patients with IDA who had intolerance to oral iron or who had had unsatisfactory response to oral iron or for whom there was a clinical need for rapid repletion of iron stores . Trial 2 included patients with IDA who had non-dialysis dependent chronic kidney disease ( NDDCKD ). In these two 8-week trials , patients were randomized 2:1 to treatment with Monoferric or iron sucrose . Monoferric was intravenously administered as a single dose of 1000 mg . The efficacy of Monoferric was established based upon the change in Hb from baseline to Week 8 . In Trial 1 , the mean change in Hb from Baseline to Week 8 was 2.49 g / dL ( 2.41 ; 2.56 ) in the Monoferric group versus 2.49 g / dL ( 2.38 ; 2.59 ) in the IS group with an estimated difference of 0.00 ( 95 % CI -0.13 ; 0.13 ), non-inferiority confirmed . In Trial 2 , the mean change in Hb from Baseline to Week 8 was 1.22 g / dL ( 1.14 ; 1.31 ) in the Monoferric group versus 1.14 g / dL ( 1.03 ; 1.26 ) in the IS group with an estimated difference of 0.08 ( 95 % CI -0.06 ; 0.23 ), non-inferiority confirmed .
PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ).
Prior History of Allergies to Parenteral Iron Products : Question patients regarding any prior history of reactions to parenteral iron products .
Hypersensitivity Reactions : Advise patients to report any signs and symptoms of hypersensitivity that may develop during and following Monoferric administration , such as rash , itching , dizziness , dizziness , lightheadedness , swelling , and breathing problems .
Monoferric is manufactured under license from Pharmacosmos A / S , Denmark .
This is not all the risk information for Monoferric . Please see www . monoferric . com for Full Prescribing Information .
US-FDI-2000004 08 / 21