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DRUGS & SUPPLEMENTS
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Niferex PM
What is the dose of the medication you are taking? |
Niferex PM uses
Niferex PM consists of Calcium Carbonate, Folic Acid, Iron (Iron Polysaccharide Complex), Vitamin A, Vitamin B1 (Thiamine Monohydrate), Vitamin B12 (Cyanocobalamin), Vitamin B2 (Riboflavin), Vitamin B3 (Niacinamide), Vitamin B6 (Pyridoxine Hydrochloride), Vitamin C (Sodium Ascorbate), Vitamin D2, Zinc Sulfate.Calcium Carbonate:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Niferex PM (Calcium Carbonate) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).
- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)
2 DOSAGE AND ADMINISTRATION
The recommended initial dose of Niferex PM (Calcium Carbonate) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.
- Starting dose is 2 capsules with each meal. (2)
- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)
3 DOSAGE FORMS AND STRENGTHS
Capsule: 667 mg Niferex PM (Calcium Carbonate) acetate capsule.
- Capsule: 667 mg Niferex PM (Calcium Carbonate) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting Niferex PM acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Niferex PM (Calcium Carbonate) acetate. (5.1)
- Hypercalcemia may aggravate digitalis toxicity. (5.2)
5.1 Hypercalcemia
Patients with end stage renal disease may develop hypercalcemia when treated with Niferex PM (Calcium Carbonate), including Niferex PM (Calcium Carbonate) acetate. Avoid the use of Niferex PM (Calcium Carbonate) supplements, including Niferex PM (Calcium Carbonate) based nonprescription antacids, concurrently with Niferex PM (Calcium Carbonate) acetate.
An overdose of Niferex PM (Calcium Carbonate) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Niferex PM (Calcium Carbonate) levels twice weekly. Should hypercalcemia develop, reduce the Niferex PM (Calcium Carbonate) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia
More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing Niferex PM (Calcium Carbonate) acetate therapy.
Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the Niferex PM (Calcium Carbonate) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.
Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of Niferex PM (Calcium Carbonate) acetate on the progression of vascular or soft tissue calcification has not been determined.
Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of Niferex PM (Calcium Carbonate) acetate; all cases resolved upon lowering the dose or discontinuing treatment.
Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.
5.2 Concomitant Use with Medications
Hypercalcemia may aggravate digitalis toxicity.
6 ADVERSE REACTIONS
Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].
- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)
- In clinical studies, patients have occasionally experienced nausea during Niferex PM (Calcium Carbonate) acetate therapy. (6)
To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a 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, Niferex PM (Calcium Carbonate) acetate has been generally well tolerated.
Niferex PM (Calcium Carbonate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Niferex PM (Calcium Carbonate) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.
| Preferred Term | Total adverse reactions reported for Niferex PM (Calcium Carbonate) acetate N=167 N (%) | 3 month, open label study of Niferex PM (Calcium Carbonate) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid Niferex PM (Calcium Carbonate) acetate N=69 | |
| Niferex PM (Calcium Carbonate) acetate N (%) | Placebo N (%) | |||
| Nausea | 6 (3.6) | 6 (6.1) | 0 (0) | 0 (0) |
| Vomiting | 4 (2.4) | 4 (4.1) | 0 (0) | 0 (0) |
| Hypercalcemia | 21 (12.6) | 16 (16.3) | 5 (7.2) | 0 (0) |
Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate Niferex PM (Calcium Carbonate) concentration could reduce the incidence and severity of Niferex PM (Calcium Carbonate) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.
6.2 Postmarketing Experience
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.
The following additional adverse reactions have been identified during post-approval of Niferex PM (Calcium Carbonate) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of Niferex PM acetate is characterized by the potential of Niferex PM (Calcium Carbonate) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Niferex PM (Calcium Carbonate) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between Niferex PM (Calcium Carbonate) acetate and most concomitant drugs. When administering an oral medication with Niferex PM (Calcium Carbonate) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after Niferex PM (Calcium Carbonate) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of Niferex PM (Calcium Carbonate) acetate.
- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)
- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after Niferex PM (Calcium Carbonate) acetate or consider monitoring blood levels of the drug. (7)
7.1 Ciprofloxacin
In a study of 15 healthy subjects, a co-administered single dose of 4 Niferex PM (Calcium Carbonate) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
Niferex PM acetate capsules contains Niferex PM (Calcium Carbonate) acetate. Animal reproduction studies have not been conducted with Niferex PM (Calcium Carbonate) acetate, and there are no adequate and well controlled studies of Niferex PM (Calcium Carbonate) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Niferex PM (Calcium Carbonate) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Niferex PM (Calcium Carbonate) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. Niferex PM (Calcium Carbonate) acetate treatment, as recommended, is not expected to harm a fetus if maternal Niferex PM (Calcium Carbonate) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of Niferex PM (Calcium Carbonate) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
Niferex PM Acetate Capsules contains Niferex PM (Calcium Carbonate) acetate and is excreted in human milk. Human milk feeding by a mother receiving Niferex PM (Calcium Carbonate) acetate is not expected to harm an infant, provided maternal serum Niferex PM (Calcium Carbonate) levels are appropriately monitored.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
Clinical studies of Niferex PM (Calcium Carbonate) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
10 OVERDOSAGE
Administration of Niferex PM (Calcium Carbonate) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
Niferex PM (Calcium Carbonate) acetate acts as a phosphate binder. Its chemical name is Niferex PM (Calcium Carbonate) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:
Each white opaque/blue opaque capsule contains 667 mg of Niferex PM (Calcium Carbonate) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Niferex PM (Calcium Carbonate), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.
Niferex PM (Calcium Carbonate) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.
12 CLINICAL PHARMACOLOGY
Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Niferex PM resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
Niferex PM (Calcium Carbonate) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Niferex PM (Calcium Carbonate) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered Niferex PM (Calcium Carbonate) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity, mutagenicity, or fertility studies have been conducted with Niferex PM (Calcium Carbonate) acetate.
14 CLINICAL STUDIES
Effectiveness of Niferex PM (Calcium Carbonate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Niferex PM (Calcium Carbonate) acetate solid oral dosage form.
Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.
The patients received Niferex PM (Calcium Carbonate) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.
The data presented in Table 2 demonstrate the efficacy of Niferex PM (Calcium Carbonate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Niferex PM (Calcium Carbonate) levels are also presented.
| * Ninety-one patients completed at least 6 weeks of the study. † ANOVA of difference in values at pre-study and study completion. ‡ Values expressed as mean ± SE. | |||||
| Parameter | Pre-Study | Week 4* | Week 8 | Week 12 | p-value† |
| Phosphorus (mg/dL)‡ | 7.4 ± 0.17 | 5.9 ± 0.16 | 5.6 ± 0.17 | 5.2 ± 0.17 | ≤0.01 |
| Niferex PM (Calcium Carbonate) (mg/dL)‡ | 8.9 ± 0.09 | 9.5 ± 0.10 | 9.7 ± 0.10 | 9.7 ± 0.10 | ≤0.01 |
There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Niferex PM (Calcium Carbonate) increased 9% during the study mostly in the first month of the study.
Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive Niferex PM (Calcium Carbonate) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.
The phosphate binding effect of Niferex PM (Calcium Carbonate) acetate is shown in the Table 3.
| * ANOVA of Niferex PM (Calcium Carbonate) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| Niferex PM (Calcium Carbonate) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| Niferex PM (Calcium Carbonate) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with Niferex PM (Calcium Carbonate) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Niferex PM (Calcium Carbonate) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
Niferex PM (Calcium Carbonate) Acetate Capsules
667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.
NDC 0615-2303-39: Blistercards of 30 Capsules
NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules
STORAGE
Store at 20° to 25°C (68° to 77°F).
17 PATIENT COUNSELING INFORMATION
Inform patients to take Niferex PM (Calcium Carbonate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Niferex PM (Calcium Carbonate) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].
Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after Niferex PM (Calcium Carbonate) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Folic Acid:
- Indications and usage
- Contraindications
- Precautions
- Adverse reactions
- Dosage and administration
- How supplied
- Storage
INDICATIONS AND USAGE
Niferex PM (Folic Acid)® is a prescription iron supplement indicated for use in improving the nutritional status of iron deficiency.
CONTRAINDICATIONS
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. |
PRECAUTIONS
Niferex PM (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.
ADVERSE REACTIONS
Allergic sensitization has been reported following both oral and parenteral administration of Niferex PM (Folic Acid) acid.
DOSAGE AND ADMINISTRATION
One tablet daily with or without food or as prescribed by a licensed healthcare provider with prescribing authority.
HOW SUPPLIED
Niferex PM (Folic Acid)® tablets are supplied in child-resistant bottles of 90 tablets (NDC 0037-6885-90)
KEEP OUT OF REACH OF CHILDREN.
STORAGE
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
Distributed by:
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.
Niferex PM (Folic Acid) and the BIFERA logo are registered trademarks and the Niferex PM (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
Iron (Iron Polysaccharide Complex):
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Niferex PM (Iron (Iron Polysaccharide Complex)) is indicated for the treatment of Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency anemia in patients with chronic kidney disease (CKD).
Niferex PM (Iron (Iron Polysaccharide Complex)) is an Niferex PM (Iron (Iron Polysaccharide Complex)) replacement product indicated for the treatment of Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency anemia in patients with chronic kidney disease (CKD). (1)
2 DOSAGE AND ADMINISTRATION
Niferex PM ) must only be administered intravenously either by slow injection or by infusion. The dosage of Niferex PM (Iron (Iron Polysaccharide Complex)) is expressed in mg of elemental Niferex PM (Iron (Iron Polysaccharide Complex)). Each mL contains 20 mg of elemental Niferex PM (Iron (Iron Polysaccharide Complex)).
| Population | Dose | |
| 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 |
2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)
Administer Niferex PM (Iron (Iron Polysaccharide Complex)) 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. Niferex PM (Iron (Iron Polysaccharide Complex)) should be administered early during the dialysis session. The usual total treatment course of Niferex PM (Iron (Iron Polysaccharide Complex)) is 1000 mg. Niferex PM (Iron (Iron Polysaccharide Complex)) treatment may be repeated if Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency reoccurs.
2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease
Administer Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)), 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. Niferex PM (Iron (Iron Polysaccharide Complex)) treatment may be repeated if Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency reoccurs.
2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease
Administer Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) in a maximum of 250 mL of 0.9% NaCl. Niferex PM (Iron (Iron Polysaccharide Complex)) treatment may be repeated if Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency reoccurs.
2.4 Pediatric Patients with HDD-CKD for Niferex PM (Iron (Iron Polysaccharide Complex)) maintenance treatment
The dosing for Niferex PM (Iron (Iron Polysaccharide Complex)) replacement treatment in pediatric patients with HDD-CKD has not been established.
For Niferex PM (Iron (Iron Polysaccharide Complex)) maintenance treatment: Administer Niferex PM (Iron (Iron Polysaccharide Complex)) 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. Niferex PM (Iron (Iron Polysaccharide Complex)) treatment may be repeated if necessary.
2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Niferex PM (Iron (Iron Polysaccharide Complex)) maintenance treatment
The dosing for Niferex PM (Iron (Iron Polysaccharide Complex)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.
For Niferex PM (Iron (Iron Polysaccharide Complex)) maintenance treatment: Administer Niferex PM (Iron (Iron Polysaccharide Complex)) 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. Niferex PM (Iron (Iron Polysaccharide Complex)) treatment may be repeated if necessary.
3 DOSAGE FORMS AND STRENGTHS
- 10 mL single-use vial / 200 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (20 mg/mL)
- 5 mL single-use vial / 100 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (20 mg/mL)
- 2.5 mL single-use vial / 50 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (20 mg/mL)
- 10 mL single-use vial / 200 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (20 mg/mL) (3)
- 5 mL single-use vial / 100 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (20 mg/mL) (3)
- 2.5 mL single-use vial / 50 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (20 mg/mL) (3)
4 CONTRAINDICATIONS
- Known hypersensitivity to Niferex PM (Iron (Iron Polysaccharide Complex))
- Known hypersensitivity to Niferex PM (Iron (Iron Polysaccharide Complex)) (4)
5 WARNINGS AND PRECAUTIONS
- Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Niferex PM ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Niferex PM (Iron (Iron Polysaccharide Complex)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
- Hypotension: Niferex PM (Iron (Iron Polysaccharide Complex)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Niferex PM (Iron (Iron Polysaccharide Complex)). (5.2)
- Niferex PM (Iron (Iron Polysaccharide Complex)) Overload: Regularly monitor hematologic responses during Niferex PM (Iron (Iron Polysaccharide Complex)) therapy. Do not administer Niferex PM (Iron (Iron Polysaccharide Complex)) to patients with Niferex PM (Iron (Iron Polysaccharide Complex)) overload. (5.3)
5.1 Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Niferex PM (Iron (Iron Polysaccharide Complex)). 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 Niferex PM (Iron (Iron Polysaccharide Complex)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Niferex PM (Iron (Iron Polysaccharide Complex)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Niferex PM (Iron (Iron Polysaccharide Complex)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Niferex PM (Iron (Iron Polysaccharide Complex)) preparations occur within 30 minutes of the completion of the infusion .
5.2 Hypotension
Niferex PM ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Niferex PM (Iron (Iron Polysaccharide Complex)). Hypotension following administration of Niferex PM (Iron (Iron Polysaccharide Complex)) may be related to the rate of administration and/or total dose administered .
5.3 Niferex PM (Iron (Iron Polysaccharide Complex)) Overload
Excessive therapy with parenteral Niferex PM (Iron (Iron Polysaccharide Complex)) can lead to excess storage of Niferex PM (Iron (Iron Polysaccharide Complex)) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Niferex PM (Iron (Iron Polysaccharide Complex)) require periodic monitoring of hematologic and Niferex PM (Iron (Iron Polysaccharide Complex)) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Niferex PM (Iron (Iron Polysaccharide Complex)) to patients with evidence of Niferex PM (Iron (Iron Polysaccharide Complex)) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose; do not perform serum Niferex PM (Iron (Iron Polysaccharide Complex)) measurements for at least 48 hours after intravenous dosing .
6 ADVERSE REACTIONS
The following serious adverse reactions associated with Niferex PM ) are described in other sections .
- The most common adverse reactions (≥2%) following the administration of Niferex PM (Iron (Iron Polysaccharide Complex)) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)
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 .
6.1 Adverse Reactions in Clinical Trials
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 Adults Patients with CKD
Adverse Reactions in Adult Patients with CKD
The frequency of adverse reactions associated with the use of Niferex PM ) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
| * EPO=Erythropoietin | |||||
| Adverse Reactions (Preferred Term) | HDD-CKD | NDD-CKD | PDD-CKD | ||
| Niferex PM (Iron (Iron Polysaccharide Complex)) | Niferex PM (Iron (Iron Polysaccharide Complex)) | Oral Niferex PM (Iron (Iron Polysaccharide Complex)) | Niferex PM (Iron (Iron Polysaccharide Complex)) | EPO* Only | |
| (N=231) | (N=139) | (N=139) | (N=75) | (N=46) | |
| % | % | % | % | % | |
| Subjects with any adverse reaction | 78.8 | 76.3 | 73.4 | 72.0 | 65.2 |
| Ear and Labyrinth Disorders | |||||
| Ear Pain | 0 | 2.2 | 0.7 | 0 | 0 |
| Eye Disorders | |||||
| Conjunctivitis | 0.4 | 0 | 0 | 2.7 | 0 |
| Gastrointestinal Disorders | |||||
| Abdominal pain | 3.5 | 1.4 | 2.9 | 4.0 | 6.5 |
| Diarrhea | 5.2 | 7.2 | 10.1 | 8.0 | 4.3 |
| Dysgeusia | 0.9 | 7.9 | 0 | 0 | 0 |
| Nausea | 14.7 | 8.6 | 12.2 | 5.3 | 4.3 |
| Vomiting | 9.1 | 5.0 | 8.6 | 8.0 | 2.2 |
| General Disorders and | |||||
| Administration Site Conditions | |||||
| Asthenia | 2.2 | 0.7 | 2.2 | 2.7 | 0 |
| Chest pain | 6.1 | 1.4 | 0 | 2.7 | 0 |
| Feeling abnormal | 3.0 | 0 | 0 | 0 | 0 |
| Infusion site pain or burning | 0 | 5.8 | 0 | 0 | 0 |
| Injection site extravasation | 0 | 2.2 | 0 | 0 | 0 |
| Peripheral edema | 2.6 | 7.2 | 5.0 | 5.3 | 10.9 |
| Pyrexia | 3.0 | 0.7 | 0.7 | 1.3 | 0 |
| Infections and Infestations | |||||
| Nasopharyngitis, Sinusitis, Upper respiratory tract infections, Pharyngitis | 2.6 | 2.2 | 4.3 | 16.0 | 4.3 |
| Injury, Poisoning and Procedural | |||||
| Complications | |||||
| Graft complication | 9.5 | 1.4 | 0 | 0 | 0 |
| Metabolism and Nutrition Disorders | |||||
| Fluid overload | 3.0 | 1.4 | 0.7 | 1.3 | 0 |
| Gout | 0 | 2.9 | 1.4 | 0 | 0 |
| Hyperglycemia | 0 | 2.9 | 0 | 0 | 2.2 |
| Hypoglycemia | 0.4 | 0.7 | 0.7 | 4.0 | 0 |
| Musculoskeletal and Connective | |||||
| Tissue Disorders | |||||
| Arthralgia | 3.5 | 1.4 | 2.2 | 4.0 | 4.3 |
| Back pain | 2.2 | 2.2 | 3.6 | 1.3 | 4.3 |
| Muscle cramp | 29.4 | 0.7 | 0.7 | 2.7 | 0 |
| Myalgia | 0 | 3.6 | 0 | 1.3 | 0 |
| Pain in extremity | 5.6 | 4.3 | 0 | 2.7 | 6.5 |
| Nervous System Disorders | |||||
| Dizziness | 6.5 | 6.5 | 1.4 | 1.3 | 4.3 |
| Headache | 12.6 | 2.9 | 0.7 | 4.0 | 0 |
| Respiratory, Thoracic and | |||||
| Mediastinal Disorders | |||||
| Cough | 3.0 | 2.2 | 0.7 | 1.3 | 0 |
| Dyspnea | 3.5 | 5.8 | 1.4 | 1.3 | 2.2 |
| Nasal congestion | 0 | 1.4 | 2.2 | 1.3 | 0 |
| Skin and Subcutaneous | |||||
| Tissue Disorders | |||||
| Pruritus | 3.9 | 2.2 | 4.3 | 2.7 | 0 |
| Vascular Disorders | |||||
| Hypertension | 6.5 | 6.5 | 4.3 | 8.0 | 6.5 |
| Hypotension | 39.4 | 2.2 | 0.7 | 2.7 | 2.2 |
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 Niferex PM (Iron (Iron Polysaccharide Complex)) therapy and were reported to be intolerant (defined as precluding further use of that Niferex PM (Iron (Iron Polysaccharide Complex)) product). When these patients were treated with Niferex PM (Iron (Iron Polysaccharide Complex)) there were no occurrences of adverse reactions that precluded further use of Niferex PM (Iron (Iron Polysaccharide Complex)) .
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
In a randomized, open-label, dose-ranging trial for Niferex PM (Iron (Iron Polysaccharide Complex)) maintenance treatment with Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 0.5 mg/kg, 53% (25/47) of the patients receiving Niferex PM (Iron (Iron Polysaccharide Complex)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Niferex PM (Iron (Iron Polysaccharide Complex)) 2.0 mg/kg.
A total of 5 (11%) subjects in the Niferex PM (Iron (Iron Polysaccharide Complex)) 0.5 mg/kg group, 10 (21%) patients in the Niferex PM (Iron (Iron Polysaccharide Complex)) 1.0 mg/kg group, and 10 (21%) patients in the Niferex PM (Iron (Iron Polysaccharide Complex)) 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%).
6.2 Adverse Reactions from 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.
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 Niferex PM (Iron (Iron Polysaccharide Complex)). 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) injection. Reactions have occurred following the first dose or subsequent doses of Niferex PM (Iron (Iron Polysaccharide Complex)). 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.
7 DRUG INTERACTIONS
Drug interactions involving Niferex PM (Iron (Iron Polysaccharide Complex)) have not been studied. However, Niferex PM (Iron (Iron Polysaccharide Complex)) may reduce the absorption of concomitantly administered oral Niferex PM (Iron (Iron Polysaccharide Complex)) preparations.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Niferex PM ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (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 Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose. Because animal reproductive studies are not always predictive of human response, Niferex PM (Iron (Iron Polysaccharide Complex)) should be used during pregnancy only if clearly needed.
8.3 Nursing Mothers
It is not known whether Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose is excreted in human milk. Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Niferex PM (Iron (Iron Polysaccharide Complex)) is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness of Niferex PM ) for Niferex PM (Iron (Iron Polysaccharide Complex)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.
Safety and effectiveness of Niferex PM (Iron (Iron Polysaccharide Complex)) for Niferex PM (Iron (Iron Polysaccharide Complex)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Niferex PM (Iron (Iron Polysaccharide Complex)) 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)]
Niferex PM (Iron (Iron Polysaccharide Complex)) has not been studied in patients younger than 2 years of age.
In a country where Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Niferex PM (Iron (Iron Polysaccharide Complex)) or any other drugs could be established.
8.5 Geriatric Use
Clinical studies of Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)), 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.
10 OVERDOSAGE
No data are available regarding overdosage of Niferex PM (Iron (Iron Polysaccharide Complex)) in humans. Excessive dosages of Niferex PM (Iron (Iron Polysaccharide Complex)) may lead to accumulation of Niferex PM (Iron (Iron Polysaccharide Complex)) in storage sites potentially leading to hemosiderosis. Do not administer Niferex PM (Iron (Iron Polysaccharide Complex)) to patients with Niferex PM (Iron (Iron Polysaccharide Complex)) overload.
Toxicities in single-dose studies in mice and rats, at intravenous Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
11 DESCRIPTION
Niferex PM (Iron (Iron Polysaccharide Complex)) (iron sucrose injection, USP), an Niferex PM (Iron (Iron Polysaccharide Complex)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Niferex PM (Iron (Iron Polysaccharide Complex)) (III)-hydroxide in sucrose for intravenous use. Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) polymerization and m is the number of sucrose molecules associated with the Niferex PM (Iron (Iron Polysaccharide Complex)) (III)-hydroxide.
Each mL contains 20 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) as Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose in water for injection. Niferex PM (Iron (Iron Polysaccharide Complex)) is available in 10 mL single-use vials (200 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) per 10 mL), 5 mL single-use vials (100 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Niferex PM ) is an aqueous complex of poly-nuclear Niferex PM (Iron (Iron Polysaccharide Complex)) (III)-hydroxide in sucrose. Following intravenous administration, Niferex PM (Iron (Iron Polysaccharide Complex)) is dissociated into Niferex PM (Iron (Iron Polysaccharide Complex)) and sucrose and the Niferex PM (Iron (Iron Polysaccharide Complex)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Niferex PM (Iron (Iron Polysaccharide Complex)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
12.2 Pharmacodynamics
Following intravenous administration, Niferex PM (Iron (Iron Polysaccharide Complex)) is dissociated into Niferex PM (Iron (Iron Polysaccharide Complex)) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose containing 100 mg of Niferex PM (Iron (Iron Polysaccharide Complex)), three times weekly for three weeks, significant increases in serum Niferex PM (Iron (Iron Polysaccharide Complex)) and serum ferritin and significant decreases in total Niferex PM (Iron (Iron Polysaccharide Complex)) binding capacity occurred four weeks from the initiation of Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose treatment.
12.3 Pharmacokinetics
In healthy adults administered intravenous doses of Niferex PM ), its Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Niferex PM (Iron (Iron Polysaccharide Complex)) containing 100 mg of Niferex PM (Iron (Iron Polysaccharide Complex)) labeled with 52Fe/59Fe in patients with Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency showed that a significant amount of the administered Niferex PM (Iron (Iron Polysaccharide Complex)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Niferex PM (Iron (Iron Polysaccharide Complex)) trapping compartment.
Following intravenous administration of Niferex PM (Iron (Iron Polysaccharide Complex)), Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose is dissociated into Niferex PM (Iron (Iron Polysaccharide Complex)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Niferex PM (Iron (Iron Polysaccharide Complex)) containing 1,510 mg of sucrose and 100 mg of Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose containing 500 to 700 mg of Niferex PM (Iron (Iron Polysaccharide Complex)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Niferex PM (Iron (Iron Polysaccharide Complex)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Niferex PM (Iron (Iron Polysaccharide Complex)) have not been studied.
Pharmacokinetics in Pediatric Patients
Pharmacokinetics in Pediatric Patients
In a single-dose PK study of Niferex PM (Iron (Iron Polysaccharide Complex)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Niferex PM (Iron (Iron Polysaccharide Complex)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Niferex PM (Iron (Iron Polysaccharide Complex)), the half-life of total serum Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
Niferex PM (Iron (Iron Polysaccharide Complex)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose.
Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.
Niferex PM (Iron (Iron Polysaccharide Complex)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (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.
14 CLINICAL STUDIES
Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Niferex PM ).
14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease (HDD–CKD)
Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Niferex PM (Iron (Iron Polysaccharide Complex)) treatment and 24 in the historical control group) with Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency anemia. Eligibility criteria for Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)), who were off intravenous Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 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. | ||||||
| Efficacy parameters | End of treatment | 2 week follow-up | 5 week follow-up | |||
| Niferex PM (Iron (Iron Polysaccharide Complex)) (n=69 | Historical Control (n=18) | Niferex PM (Iron (Iron Polysaccharide Complex)) (n=73) | Historical Control (n=18) | Niferex PM (Iron (Iron Polysaccharide Complex)) (n=71) | Historical Control (n=15) | |
| 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%).
14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease
Study B was a multicenter, open label study of Niferex PM (Iron (Iron Polysaccharide Complex)) in 23 patients with Niferex PM (Iron (Iron Polysaccharide Complex)) deficiency and HDD-CKD who had been discontinued from Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease
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 Niferex PM (Iron (Iron Polysaccharide Complex)). Exclusion criteria were similar to those in studies A and B. Niferex PM (Iron (Iron Polysaccharide Complex)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease
Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Niferex PM (Iron (Iron Polysaccharide Complex)) versus Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) (325 mg ferrous sulfate three times daily for 56 days); or Niferex PM (Iron (Iron Polysaccharide Complex)) (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 Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) group.
A statistically significantly greater proportion of Niferex PM (Iron (Iron Polysaccharide Complex)) subjects (35/79; 44.3%) compared to oral Niferex PM (Iron (Iron Polysaccharide Complex)) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).
14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease
Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Niferex PM (Iron (Iron Polysaccharide Complex)) to patients with PDD-CKD receiving an erythropoietin alone without Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) or Niferex PM (Iron (Iron Polysaccharide Complex)) (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 Niferex PM (Iron (Iron Polysaccharide Complex)) / 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 Niferex PM (Iron (Iron Polysaccharide Complex)) / 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 Niferex PM (Iron (Iron Polysaccharide Complex)) / 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%).
14.6 Study F: Niferex PM ) Maintenance Treatment Dosing in Pediatric Patients Ages 2 years and Older with Chronic Kidney Disease
Study F was a randomized, open-label, dose-ranging study for Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) (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 Niferex PM (Iron (Iron Polysaccharide Complex)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.
16 HOW SUPPLIED/storage and handling
16.1 How Supplied
Niferex PM ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)), each 5 mL vial contains 100 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)), and each 2.5 mL vial contains 50 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) (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 |
16.2 Stability and Storage
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: Niferex PM (Iron (Iron Polysaccharide Complex)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Niferex PM (Iron (Iron Polysaccharide Complex)) per mL, or undiluted (20 mg elemental Niferex PM (Iron (Iron Polysaccharide Complex)) 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: Niferex PM (Iron (Iron Polysaccharide Complex)), 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 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 Niferex PM (Iron (Iron Polysaccharide Complex)) 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.
17 PATIENT COUNSELING INFORMATION
Prior to Niferex PM (Iron (Iron Polysaccharide Complex)) administration:
- Question patients regarding any prior history of reactions to parenteral Niferex PM (Iron (Iron Polysaccharide Complex)) products
- Advise patients of the risks associated with Niferex PM (Iron (Iron Polysaccharide Complex))
- Advise patients to report any symptoms of hypersensitivity that may develop during and following Niferex PM (Iron (Iron Polysaccharide Complex)) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]
AMERICAN
REGENT, INC.
SHIRLEY, NY 11967
Niferex PM (Iron (Iron Polysaccharide Complex)) is manufactured under license from Vifor (International) Inc., Switzerland.
PremierProRx® is a trademark of Premier, Inc., used under license.
PREMIERProRx®
IN2340
MG #15727
Vitamin A:
- Dosage and administration
- Warning
- Clinical pharmacology
- Dietary supplementation
- Warnings
- Precautions
- Adverse reactions
- Dosage and administration
- How supplied
DOSAGE AND ADMINISTRATION
One tablet daily or as directed by a physician.
| Supplement Facts | ||
|---|---|---|
| Serving Size 1 Tablet Servings Per Container 100 | ||
| Amount Per Serving | % Daily Value | |
| Niferex PM (Vitamin A) | 2500 IU | 50% |
| Vitamin C | 60 mg | 100% |
| Vitamin D | 400 IU | 100% |
| Vitamin E | 15 IU | 50% |
| Thiamine | 1.05 mg | 70% |
| Riboflavin | 1.2 mg | 70% |
| Niacinamide | 13.5 mg | 68% |
| Vitamin B6 | 1.05 mg | 53% |
| Folic Acid | 0.3 mg | 75% |
| Vitamin B12 | 4.5 mcg | 75% |
| Fluoride | 0.25 mg | |
WARNING
KEEP OUT OF THE REACH OF CHILDREN.
In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.
Other Ingredients: Artificial cherry flavor, artificial grape flavor, ascorbic acid, cholecalciferol, compressible sugar, D&C Red #7 calcium lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, folic acid, magnesium stearate, microcrystalline cellulose, natural and artificial orange flavor, niacinamide, polyethylene glycol, pyridoxine HCl, riboflavin, sodium ascorbate, sodium fluoride, stearic acid, sucralose, thiamine HCl, Niferex PM (Vitamin A) acetate, vitamin B12 and vitamin E acetate.
Active ingredient for caries prophylaxis: Fluoride as sodium fluoride.
CLINICAL PHARMACOLOGY
Significant decrease in the incidence of dental caries can be linked to the fluoridation of the water supply (1ppm fluoride) during the period of tooth development.
Niferex PM (Vitamin A) Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride. Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the Hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite.
The reaction may be expressed by the equation:
| Ca10(PO4)6(OH2) + 2F- | Ca10 (PO4)6F2 + 2OH- |
| (Hydroxyapatite) | (Fluorapatite) |
Three stages of fluoride deposition in tooth enamel can be distinguished:
- Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.
- After enamel has been laid down, fluoride deposition continues in the surface enamel. Diffusion of fluoride from the surface inward is apparently restricted.
- After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts of saliva.
DIETARY SUPPLEMENTATION
Multivitamins with fluoride offer supplementation of the diet with 10 vitamins and fluoride.
WARNINGS
AS IN THE CASE OF ALL MEDICATIONS, KEEP OUT OF THE REACH OF CHILDREN. This tablet should be chewed. This product, as with all chewable tablets are not recommended for children under the age of 4 due to risk of choking.
PRECAUTIONS
The suggested dose of Niferex PM (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.
Before recommending Niferex PM (Vitamin A) Tablets
- Determine the fluoride content of the drinking water from all major sources
- Make sure the child is not receiving significant amounts of fluoride from other sources such as medications and swallowed toothpaste
- Periodically check to make sure that the child does not develop significant dental fluorosis.
ADVERSE REACTIONS
Allergic rash and other idiosyncrasies have been rarely reported.
To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1 (866) 592-6438 or FDA at 1 (800) 332-1088 or via the web at www.fda.gov/medwatch/index.html for voluntary reporting of adverse reactions.
DOSAGE AND ADMINISTRATION
One tablet daily or as directed by a physician.
HOW SUPPLIED
Niferex PM Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.
Niferex PM (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.
Niferex PM (Vitamin A) Tablets 1.0 mg are available as orange, red and purple chewable tablets imprinted with "153" in 100 tablet bottles.
STORAGE
Store at controlled room temperature 20ºC-25ºC (68º-77ºF), excursions permitted between 15º-30ºC (59º-86ºF).
Distributed by:
H2-Pharma, LLC
2010 Berry Chase Place
Montgomery, AL 36117
www.h2-pharma.com
1067084
61269-151-01
MultiVitamin
with Fluoride
Chewable Tablets
Rx
0.25 mg
MultiVitamin and Fluoride Supplement
Dietary Supplement
100 Tablets
H2pharma
Vitamin B12 (Cyanocobalamin):
Pharmacological action
Niferex PM ) refers to a group of water-soluble vitamins. It has high biological activity. Niferex PM (Vitamin B12 (Cyanocobalamin)) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.
Pharmacokinetics
After oral administration Niferex PM (Vitamin B12 (Cyanocobalamin)) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.
Why is Niferex PM ) prescribed?
Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of Niferex PM (Vitamin B12 (Cyanocobalamin)) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.
Dosage and administration
Niferex PM ) is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Niferex PM (Vitamin B12 (Cyanocobalamin)) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.
In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with Niferex PM (Vitamin B12 (Cyanocobalamin)) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.
When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.
Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.
When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.
In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.
When deficiency of Niferex PM (Vitamin B12 (Cyanocobalamin)) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.
Niferex PM (Vitamin B12 (Cyanocobalamin)) side effects, adverse reactions
CNS: rarely - a state of arousal.
Cardiovascular system: rarely - pain in the heart, tachycardia.
Allergic reactions: rarely - urticaria.
Niferex PM ) contraindications
Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.
Niferex PM ) using during pregnancy and breastfeeding
Cyanocobalamin can be used in pregnancy according to prescriptions.
Special instructions
When stenocardia should be used with caution in a single dose of Niferex PM ) 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.
Niferex PM (Vitamin B12 (Cyanocobalamin)) drug interactions
In an application of Niferex PM (Vitamin B12 (Cyanocobalamin)) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.
In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.
In an Niferex PM (Vitamin B12 (Cyanocobalamin)) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.
Cyanocobalamin may exacerbate allergic reactions caused by thiamine.
When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.
Pharmaceutical incompatibility
Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.
Vitamin C (Sodium Ascorbate):
Pharmacological action
Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. Niferex PM (Vitamin C (Sodium Ascorbate)) 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. Niferex PM (Vitamin C (Sodium Ascorbate)) 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).
Pharmacokinetics
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.
Why is Niferex PM ) prescribed?
For systemic use of Niferex PM (Vitamin C (Sodium Ascorbate)) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Niferex PM (Vitamin C (Sodium Ascorbate)); providing increased need for Niferex PM (Vitamin C (Sodium Ascorbate)) 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.
Dosage and administration
This medication administered orally, IM, IV, intravaginally.
For the prevention of deficiency conditions Niferex PM ) 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.
Niferex PM (Vitamin C (Sodium Ascorbate)) side effects, adverse reactions
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.
Niferex PM ) contraindications
Increased sensitivity to ascorbic acid.
Using during pregnancy and breastfeeding
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.
Special instructions
Niferex PM (Vitamin C (Sodium Ascorbate)) 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.
Niferex PM (Vitamin C (Sodium Ascorbate)) 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.
Niferex PM ) drug interactions
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 Niferex PM (Vitamin C (Sodium Ascorbate)) 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.
Niferex PM (Vitamin C (Sodium Ascorbate)) 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.
Niferex PM ) in case of emergency / overdose
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.
Vitamin D2:
Vitamin D (ergocalciferol-D2, cholecalciferol-D3, alfacalcidol) is a fat-soluble vitamin that helps your body absorb calcium and phosphorus. Having the right amount of vitamin D, calcium, and phosphorus is important for building and keeping strong bones. Vitamin D is used to treat and prevent bone disorders (such as rickets, osteomalacia). Vitamin D is made by the body when skin is exposed to sunlight. Sunscreen, protective clothing, limited exposure to sunlight, dark skin, and age may prevent getting enough vitamin D from the sun. Vitamin D with calcium is used to treat or prevent bone loss ( osteoporosis ). Vitamin D is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia ). It may be used in kidney disease to keep calcium levels normal and allow normal bone growth. Vitamin D drops (or other supplements ) are given to breast -fed infants because breast milk usually has low levels of vitamin D.
Zinc Sulfate:
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Drug abuse and dependence
- Overdosage
- Dosage and administration
- How supplied
INDICATIONS AND USAGE
Niferex PM (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Niferex PM (Zinc Sulfate) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.
CONTRAINDICATIONS
None known.
WARNINGS
Direct intramuscular or intravenous injection of Niferex PM (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.
Severe kidney disease may make it necessary to reduce or omit chromium and Niferex PM (Zinc Sulfate) doses because these elements are primarily eliminated in the urine.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
PRECAUTIONS
General
Do not use unless the solution is clear and the seal is intact.
Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Niferex PM (Zinc Sulfate) from a bolus injection. Administration of Niferex PM (Zinc Sulfate) in the absence of copper may cause a decrease in serum copper levels.
Laboratory Tests
Periodic determinations of serum copper as well as Niferex PM (Zinc Sulfate) are suggested as a guideline for subsequent Niferex PM (Zinc Sulfate) administration.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term animal studies to evaluate the carcinogenic potential of Niferex PM 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Niferex PM (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.
Pediatric Use
Pregnancy Category C. Animal reproduction studies have not been conducted with Niferex PM chloride. It is also not known whether Niferex PM (Zinc Sulfate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Niferex PM (Zinc Sulfate) chloride should be given to a pregnant woman only if clearly needed.
Geriatric Use
An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
None known.
DRUG ABUSE AND DEPENDENCE
None known.
OVERDOSAGE
Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Niferex PM (Zinc Sulfate) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Niferex PM (Zinc Sulfate) concentration of 207 mcg/dl. Symptoms abated within three hours.
Hyperamylasemia may be a sign of impending Niferex PM (Zinc Sulfate) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).
Death resulted from an overdosage in which 1683 mg Niferex PM (Zinc Sulfate) was delivered intravenously over the course of 60 hours to a 72 year old patient.
Symptoms of Niferex PM (Zinc Sulfate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Niferex PM (Zinc Sulfate) level of 4184 mcg/dl.
Calcium supplements may confer a protective effect against Niferex PM (Zinc Sulfate) toxicity.
DOSAGE AND ADMINISTRATION
Niferex PM (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Niferex PM (Zinc Sulfate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Niferex PM (Zinc Sulfate).
For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.
HOW SUPPLIED
Niferex PM (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).
Store at 20 to 25°C (68 to 77°F).
Revised: October, 2004
© Hospira 2004 EN-0488 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
10 mL Vial
Niferex PM (Zinc Sulfate)
1 mg/mL
Niferex PM (Zinc Sulfate) Chloride Inj., USP
Rx only
FOR I.V. USE ONLY AFTER DILUTION.
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
Niferex PM pharmaceutical active ingredients containing related brand and generic drugs:
Niferex PM available forms, composition, doses:
Niferex PM destination | category:
Niferex PM Anatomical Therapeutic Chemical codes:
Niferex PM pharmaceutical companies:
References
- Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."ZINC SULFATE TABLET [NATIONWIDE LABORATORIES, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."D-CAL (CALCIUM CARBONATE) TABLET, CHEWABLE [A&Z PHARMACEUTICAL INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming Niferex PM?Depending on the reaction of the Niferex PM after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Niferex PM 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 Niferex PM 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