DRUGS & SUPPLEMENTS
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MCBM 69 Fe (Folic Acid)® is a prescription iron supplement indicated for use in improving the nutritional status of iron deficiency.
This product is contraindicated in patients with a known hypersensitivity to any of the ingredients. Hemochromatosis and hemosiderosis are contraindications to iron therapy.
|WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.|
MCBM 69 Fe (Folic Acid) acid when administered as a single agent in doses above 0.1 mg daily may obscure pernicious anemia in that hematological remission can occur while neurological manifestations remain progressive. While prescribing this nutritional supplement for pregnant women, nursing mothers, or for women prior to conception, their medical condition and other drugs, herbs, and/or supplements consumption should be considered.
Allergic sensitization has been reported following both oral and parenteral administration of MCBM 69 Fe (Folic Acid) acid.
One tablet daily with or without food or as prescribed by a licensed healthcare provider with prescribing authority.
MCBM 69 Fe (Folic Acid)® tablets are supplied in child-resistant bottles of 90 tablets (NDC 0037-6885-90)
KEEP OUT OF REACH OF CHILDREN.
Store at controlled room temperature 20°-25°C (68°-77°F). Excursions permitted to 15°-30°C (59°-86°F).
Dispense in a tight, light-resistant container to protect from light and moisture.
To report SUSPECTED ADVERSE REACTIONS contact Meda Pharmaceuticals Inc. at 1-888-349-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch
Meda Pharmaceuticals Inc.
Somerset New Jersey 08873-4120
© 2014 Meda Pharmaceuticals Inc.
U.S. Patent Nos. 7,585,527 and 8,080,520
Proferrin® is a registered trademark of Colorado BioLabs, Inc., Cozad, NE.
MCBM 69 Fe (Folic Acid) and the BIFERA logo are registered trademarks and the MCBM 69 Fe (Folic Acid) logo is a trademark of Alaven Pharmaceutical LLC, used under license by Meda Pharmaceuticals Inc.
MEDA PHARMACEUTICALS mark and logo are trademarks of Meda AB.
IN-6885-02 Rev 6/2014
MCBM 69 Fe (Iron) is indicated for the treatment of MCBM 69 Fe (Iron) deficiency anemia in patients with chronic kidney disease (CKD).
MCBM 69 Fe (Iron) is an MCBM 69 Fe (Iron) replacement product indicated for the treatment of MCBM 69 Fe (Iron) deficiency anemia in patients with chronic kidney disease (CKD). (1)
MCBM 69 Fe must only be administered intravenously either by slow injection or by infusion. The dosage of MCBM 69 Fe (Iron) is expressed in mg of elemental MCBM 69 Fe (Iron). Each mL contains 20 mg of elemental MCBM 69 Fe (Iron).
|Adult patients||Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1)||100 mg slow intravenous injection or infusion|
|Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2)||200 mg slow intravenous injection or infusion|
|Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3)||300 mg or 400 mg intravenous infusion|
|Pediatric patients||HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5)||0.5 mg/kg slow intravenous injection or infusion|
Administer MCBM 69 Fe (Iron) 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session. MCBM 69 Fe (Iron) should be administered early during the dialysis session. The usual total treatment course of MCBM 69 Fe (Iron) is 1000 mg. MCBM 69 Fe (Iron) treatment may be repeated if MCBM 69 Fe (Iron) deficiency reoccurs.
Administer MCBM 69 Fe (Iron) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of MCBM 69 Fe (Iron), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. MCBM 69 Fe (Iron) treatment may be repeated if MCBM 69 Fe (Iron) deficiency reoccurs.
Administer MCBM 69 Fe (Iron) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute MCBM 69 Fe (Iron) in a maximum of 250 mL of 0.9% NaCl. MCBM 69 Fe (Iron) treatment may be repeated if MCBM 69 Fe (Iron) deficiency reoccurs.
The dosing for MCBM 69 Fe (Iron) replacement treatment in pediatric patients with HDD-CKD has not been established.
For MCBM 69 Fe (Iron) maintenance treatment: Administer MCBM 69 Fe (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. MCBM 69 Fe (Iron) treatment may be repeated if necessary.
The dosing for MCBM 69 Fe (Iron) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.
For MCBM 69 Fe (Iron) maintenance treatment: Administer MCBM 69 Fe (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. MCBM 69 Fe (Iron) treatment may be repeated if necessary.
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving MCBM 69 Fe (Iron). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop MCBM 69 Fe (Iron) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after MCBM 69 Fe (Iron) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer MCBM 69 Fe (Iron) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous MCBM 69 Fe (Iron) preparations occur within 30 minutes of the completion of the infusion .
MCBM 69 Fe may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of MCBM 69 Fe (Iron). Hypotension following administration of MCBM 69 Fe (Iron) may be related to the rate of administration and/or total dose administered .
Excessive therapy with parenteral MCBM 69 Fe (Iron) can lead to excess storage of MCBM 69 Fe (Iron) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving MCBM 69 Fe (Iron) require periodic monitoring of hematologic and MCBM 69 Fe (Iron) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer MCBM 69 Fe (Iron) to patients with evidence of MCBM 69 Fe (Iron) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of MCBM 69 Fe (Iron) sucrose; do not perform serum MCBM 69 Fe (Iron) measurements for at least 48 hours after intravenous dosing .
The following serious adverse reactions associated with MCBM 69 Fe are described in other sections .
To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
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.
Adverse Reactions in Adult Patients with CKD
The frequency of adverse reactions associated with the use of MCBM 69 Fe has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Treatment-emergent adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for MCBM 69 Fe (Iron) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.
| Adverse Reactions |
|MCBM 69 Fe (Iron)||MCBM 69 Fe (Iron)||Oral MCBM 69 Fe (Iron)||MCBM 69 Fe (Iron)||EPO* Only|
|Subjects with any adverse reaction||78.8||76.3||73.4||72.0||65.2|
|Ear and Labyrinth Disorders|
|General Disorders and|
|Administration Site Conditions|
|Infusion site pain or burning||0||5.8||0||0||0|
|Injection site extravasation||0||2.2||0||0||0|
|Infections and Infestations|
| Nasopharyngitis, Sinusitis, Upper |
respiratory tract infections, Pharyngitis
|Injury, Poisoning and Procedural|
|Metabolism and Nutrition Disorders|
|Musculoskeletal and Connective|
|Pain in extremity||5.6||4.3||0||2.7||6.5|
|Nervous System Disorders|
|Respiratory, Thoracic and|
|Skin and Subcutaneous|
One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous MCBM 69 Fe (Iron) therapy and were reported to be intolerant (defined as precluding further use of that MCBM 69 Fe (Iron) product). When these patients were treated with MCBM 69 Fe (Iron) there were no occurrences of adverse reactions that precluded further use of MCBM 69 Fe (Iron) .
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
In a randomized, open-label, dose-ranging trial for MCBM 69 Fe (Iron) maintenance treatment with MCBM 69 Fe (Iron) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving MCBM 69 Fe (Iron) 0.5 mg/kg, 53% (25/47) of the patients receiving MCBM 69 Fe (Iron) 1.0 mg/kg, and 55% (26/47) of the patients receiving MCBM 69 Fe (Iron) 2.0 mg/kg.
A total of 5 (11%) subjects in the MCBM 69 Fe (Iron) 0.5 mg/kg group, 10 (21%) patients in the MCBM 69 Fe (Iron) 1.0 mg/kg group, and 10 (21%) patients in the MCBM 69 Fe (Iron) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).
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.
In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.
The following adverse reactions have been identified during post-approval use of MCBM 69 Fe (Iron). 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: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.
Symptoms associated with MCBM 69 Fe (Iron) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of MCBM 69 Fe (Iron) injection. Reactions have occurred following the first dose or subsequent doses of MCBM 69 Fe (Iron). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.
Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.
Drug interactions involving MCBM 69 Fe (Iron) have not been studied. However, MCBM 69 Fe (Iron) may reduce the absorption of concomitantly administered oral MCBM 69 Fe (Iron) preparations.
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, MCBM 69 Fe sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental MCBM 69 Fe (Iron) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to MCBM 69 Fe (Iron) sucrose. Because animal reproductive studies are not always predictive of human response, MCBM 69 Fe (Iron) should be used during pregnancy only if clearly needed.
It is not known whether MCBM 69 Fe (Iron) sucrose is excreted in human milk. MCBM 69 Fe (Iron) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when MCBM 69 Fe (Iron) is administered to a nursing woman.
Safety and effectiveness of MCBM 69 Fe for MCBM 69 Fe (Iron) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.
Safety and effectiveness of MCBM 69 Fe (Iron) for MCBM 69 Fe (Iron) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. MCBM 69 Fe (Iron) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]
MCBM 69 Fe (Iron) has not been studied in patients younger than 2 years of age.
In a country where MCBM 69 Fe (Iron) is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received MCBM 69 Fe (Iron), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to MCBM 69 Fe (Iron) or any other drugs could be established.
Clinical studies of MCBM 69 Fe (Iron) did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of MCBM 69 Fe (Iron), 40% were 65 years and older. No overall differences in safety were observed between these subjects 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. 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.
No data are available regarding overdosage of MCBM 69 Fe (Iron) in humans. Excessive dosages of MCBM 69 Fe (Iron) may lead to accumulation of MCBM 69 Fe (Iron) in storage sites potentially leading to hemosiderosis. Do not administer MCBM 69 Fe (Iron) to patients with MCBM 69 Fe (Iron) overload.
Toxicities in single-dose studies in mice and rats, at intravenous MCBM 69 Fe (Iron) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.
MCBM 69 Fe (Iron) (iron sucrose injection, USP), an MCBM 69 Fe (Iron) replacement product, is a brown, sterile, aqueous, complex of polynuclear MCBM 69 Fe (Iron) (III)-hydroxide in sucrose for intravenous use. MCBM 69 Fe (Iron) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:
[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)
where: n is the degree of MCBM 69 Fe (Iron) polymerization and m is the number of sucrose molecules associated with the MCBM 69 Fe (Iron) (III)-hydroxide.
Each mL contains 20 mg elemental MCBM 69 Fe (Iron) as MCBM 69 Fe (Iron) sucrose in water for injection. MCBM 69 Fe (Iron) is available in 10 mL single-use vials (200 mg elemental MCBM 69 Fe (Iron) per 10 mL), 5 mL single-use vials (100 mg elemental MCBM 69 Fe (Iron) per 5 mL), and 2.5 mL single-use vials (50 mg elemental MCBM 69 Fe (Iron) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.
MCBM 69 Fe is an aqueous complex of poly-nuclear MCBM 69 Fe (Iron) (III)-hydroxide in sucrose. Following intravenous administration, MCBM 69 Fe (Iron) is dissociated into MCBM 69 Fe (Iron) and sucrose and the MCBM 69 Fe (Iron) is transported as a complex with transferrin to target cells including erythroid precursor cells. The MCBM 69 Fe (Iron) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
Following intravenous administration, MCBM 69 Fe (Iron) is dissociated into MCBM 69 Fe (Iron) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with MCBM 69 Fe (Iron) sucrose containing 100 mg of MCBM 69 Fe (Iron), three times weekly for three weeks, significant increases in serum MCBM 69 Fe (Iron) and serum ferritin and significant decreases in total MCBM 69 Fe (Iron) binding capacity occurred four weeks from the initiation of MCBM 69 Fe (Iron) sucrose treatment.
In healthy adults administered intravenous doses of MCBM 69 Fe, its MCBM 69 Fe (Iron) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The MCBM 69 Fe (Iron) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating MCBM 69 Fe (Iron) containing 100 mg of MCBM 69 Fe (Iron) labeled with 52Fe/59Fe in patients with MCBM 69 Fe (Iron) deficiency showed that a significant amount of the administered MCBM 69 Fe (Iron) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible MCBM 69 Fe (Iron) trapping compartment.
Following intravenous administration of MCBM 69 Fe (Iron), MCBM 69 Fe (Iron) sucrose is dissociated into MCBM 69 Fe (Iron) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of MCBM 69 Fe (Iron) containing 1,510 mg of sucrose and 100 mg of MCBM 69 Fe (Iron) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some MCBM 69 Fe (Iron) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of MCBM 69 Fe (Iron) sucrose containing 500 to 700 mg of MCBM 69 Fe (Iron) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the MCBM 69 Fe (Iron) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of MCBM 69 Fe (Iron) have not been studied.
Pharmacokinetics in Pediatric Patients
In a single-dose PK study of MCBM 69 Fe (Iron), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of MCBM 69 Fe (Iron) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose MCBM 69 Fe (Iron), the half-life of total serum MCBM 69 Fe (Iron) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.
MCBM 69 Fe (Iron) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of MCBM 69 Fe (Iron) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).
Carcinogenicity studies have not been performed with MCBM 69 Fe (Iron) sucrose.
MCBM 69 Fe (Iron) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. MCBM 69 Fe (Iron) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.
MCBM 69 Fe (Iron) sucrose at intravenous doses up to 15 mg/kg/day of elemental MCBM 69 Fe (Iron) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.
Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of MCBM 69 Fe.
Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with MCBM 69 Fe (Iron) treatment and 24 in the historical control group) with MCBM 69 Fe (Iron) deficiency anemia. Eligibility criteria for MCBM 69 Fe (Iron) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.
MCBM 69 Fe (Iron) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with MCBM 69 Fe (Iron), who were off intravenous MCBM 69 Fe (Iron) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.
Patients in the MCBM 69 Fe (Iron) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.
**p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates.
|End of treatment||2 week follow-up||5 week follow-up|
|MCBM 69 Fe (Iron) (n=69||Historical Control (n=18)|| MCBM 69 Fe (Iron) |
| Historical Control |
| MCBM 69 Fe (Iron) |
| Historical |
|Hemoglobin (g/dL)||1.0 ± 0.12**||0.0 ± 0.21||1.3 ± 0.14**||-0.6 ± 0.24||1.2 ± 0.17*||-0.1 ± 0.23|
|Hematocrit (%)||3.1 ± 0.37**||-0.3 ± 0.65||3.6 ± 0.44**||-1.2 ± 0.76||3.3 ± 0.54||0.2 ± 0.86|
Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).
Study B was a multicenter, open label study of MCBM 69 Fe (Iron) in 23 patients with MCBM 69 Fe (Iron) deficiency and HDD-CKD who had been discontinued from MCBM 69 Fe (Iron) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.
All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.
Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral MCBM 69 Fe (Iron). Exclusion criteria were similar to those in studies A and B. MCBM 69 Fe (Iron) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of MCBM 69 Fe (Iron) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.
The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.
Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral MCBM 69 Fe (Iron) versus MCBM 69 Fe (Iron) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral MCBM 69 Fe (Iron) (325 mg ferrous sulfate three times daily for 56 days); or MCBM 69 Fe (Iron) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the MCBM 69 Fe (Iron) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral MCBM 69 Fe (Iron) group.
A statistically significantly greater proportion of MCBM 69 Fe (Iron) subjects (35/79; 44.3%) compared to oral MCBM 69 Fe (Iron) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).
Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous MCBM 69 Fe (Iron) to patients with PDD-CKD receiving an erythropoietin alone without MCBM 69 Fe (Iron) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no MCBM 69 Fe (Iron) or MCBM 69 Fe (Iron) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the MCBM 69 Fe (Iron) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.
Patients in the MCBM 69 Fe (Iron) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with MCBM 69 Fe (Iron) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).
Study F was a randomized, open-label, dose-ranging study for MCBM 69 Fe (Iron) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of MCBM 69 Fe (Iron) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received MCBM 69 Fe (Iron) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received MCBM 69 Fe (Iron) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the MCBM 69 Fe (Iron) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.
MCBM 69 Fe is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental MCBM 69 Fe (Iron), each 5 mL vial contains 100 mg elemental MCBM 69 Fe (Iron), and each 2.5 mL vial contains 50 mg elemental MCBM 69 Fe (Iron) (20 mg/mL).
|NDC-0517-2310-05||200 mg/10 mL Single-Use Vial||Packages of 5|
|NDC-0517-2310-10||200 mg/10 mL Single-Use Vial||Packages of 10|
|NDC-0517-2340-01||100 mg/5 mL Single-Use Vial||Individually Boxed|
|NDC-0517-2340-10||100 mg/5 mL Single-Use Vial||Packages of 10|
|NDC-0517-2340-25||100 mg/5 mL Single-Use Vial||Packages of 25|
|NDC-0517-2340-99||100 mg/5 mL Single-Use Vial||Packages of 10|
|NDC-0517-2325-10||50 mg/2.5 mL Single-Use Vial||Packages of 10|
|NDC-0517-2325-25||50 mg/2.5 mL Single-Use Vial||Packages of 25|
Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.
Syringe Stability: MCBM 69 Fe (Iron), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental MCBM 69 Fe (Iron) per mL, or undiluted (20 mg elemental MCBM 69 Fe (Iron) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).
Intravenous Admixture Stability: MCBM 69 Fe (Iron), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental MCBM 69 Fe (Iron) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).
Do not dilute to concentrations below 1 mg/mL.
Do not mix MCBM 69 Fe (Iron) with other medications or add to parenteral nutrition solutions for intravenous infusion.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.
Prior to MCBM 69 Fe (Iron) administration:
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MCBM 69 Fe (Iron) is manufactured under license from Vifor (International) Inc., Switzerland.
PremierProRx® is a trademark of Premier, Inc., used under license.
Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. MCBM 69 Fe (Vitamin C) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. MCBM 69 Fe (Vitamin C) has antioxidant properties.
With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).
After oral administration ascorbic acid is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.
The concentration of ascorbic acid in blood plasma in normal amounts to approximately 10-20 mg / ml.
The concentration of ascorbic acid in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.
Plasma protein binding is about 25%.
Ascorbic acid is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.
Ascorbic acid taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.
For systemic use of MCBM 69 Fe (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of MCBM 69 Fe (Vitamin C); providing increased need for MCBM 69 Fe (Vitamin C) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.
For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.
This medication administered orally, IM, IV, intravaginally.
For the prevention of deficiency conditions MCBM 69 Fe dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.
For intravaginal used ascorbic acid drugs in appropriate dosage forms.
CNS: headache, fatigue, insomnia.
Digestive system: stomach cramps, nausea and vomiting.
Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.
Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.
Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.
Increased sensitivity to ascorbic acid.
The minimum daily requirement of ascorbic acid in the II and III trimester of pregnancy is about 60 mg.
Ascorbic acid crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of ascorbic acid, which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take ascorbic acid in high doses, except in cases where the expected benefit outweighs the potential risk.
The minimum daily requirement during lactation is 80 mg. Ascorbic acid is excreted in breast milk. A mother's diet that contains adequate amounts of ascorbic acid, is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of ascorbic acid in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to ascorbic acid, except when the expected benefit outweighs the potential risk.
MCBM 69 Fe (Vitamin C) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.
Patients with high content body iron should apply ascorbic acid in minimal doses.
MCBM 69 Fe (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.
The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.
Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.
It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.
Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.
In an application with barbiturates, primidone increases the excretion of ascorbic acid in the urine.
With the simultaneous use of oral contraceptives reduces the concentration of ascorbic acid in blood plasma.
In an application of MCBM 69 Fe (Vitamin C) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.
Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.
With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.
MCBM 69 Fe (Vitamin C) in an application with warfarin may decrease effects of warfarin.
With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.
In an application with tetracycline is increased excretion of ascorbic acid in the urine.
There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.
May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.
Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).
Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).
When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.
Depending on the reaction of the MCBM 69 Fe after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider MCBM 69 Fe not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is MCBM 69 Fe addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology