Celloid Compounds Sodical Plus

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Celloid Compounds Sodical Plus uses

Celloid Compounds Sodical Plus consists of Calcium Phosphate, Iron (Ferrous Phosphate), Sodium Phosphate Dibasic.

Calcium Phosphate:


1 INDICATIONS AND USAGE

Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate capsule.

- Capsule: 667 mg Celloid Compounds Sodical Plus (Calcium Phosphate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Celloid Compounds Sodical Plus acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate), including Celloid Compounds Sodical Plus (Calcium Phosphate) acetate. Avoid the use of Celloid Compounds Sodical Plus (Calcium Phosphate) supplements, including Celloid Compounds Sodical Plus (Calcium Phosphate) based nonprescription antacids, concurrently with Celloid Compounds Sodical Plus (Calcium Phosphate) acetate.

An overdose of Celloid Compounds Sodical Plus (Calcium Phosphate) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Celloid Compounds Sodical Plus (Calcium Phosphate) levels twice weekly. Should hypercalcemia develop, reduce the Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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.

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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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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, Celloid Compounds Sodical Plus (Calcium Phosphate) acetate has been generally well tolerated.

Celloid Compounds Sodical Plus (Calcium Phosphate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate

N=167

N (%)


3 month, open label study of Celloid Compounds Sodical Plus (Calcium Phosphate) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Celloid Compounds Sodical Plus (Calcium Phosphate) acetate

N=69


Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) concentration could reduce the incidence and severity of Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate: dizziness, edema, and weakness.

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7 DRUG INTERACTIONS

The drug interaction of Celloid Compounds Sodical Plus acetate is characterized by the potential of Celloid Compounds Sodical Plus (Calcium Phosphate) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Celloid Compounds Sodical Plus (Calcium Phosphate) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between Celloid Compounds Sodical Plus (Calcium Phosphate) acetate and most concomitant drugs. When administering an oral medication with Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

Celloid Compounds Sodical Plus acetate capsules contains Celloid Compounds Sodical Plus (Calcium Phosphate) acetate. Animal reproduction studies have not been conducted with Celloid Compounds Sodical Plus (Calcium Phosphate) acetate, and there are no adequate and well controlled studies of Celloid Compounds Sodical Plus (Calcium Phosphate) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Celloid Compounds Sodical Plus (Calcium Phosphate) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Celloid Compounds Sodical Plus (Calcium Phosphate) 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. Celloid Compounds Sodical Plus (Calcium Phosphate) acetate treatment, as recommended, is not expected to harm a fetus if maternal Celloid Compounds Sodical Plus (Calcium Phosphate) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of Celloid Compounds Sodical Plus (Calcium Phosphate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Celloid Compounds Sodical Plus Acetate Capsules contains Celloid Compounds Sodical Plus (Calcium Phosphate) acetate and is excreted in human milk. Human milk feeding by a mother receiving Celloid Compounds Sodical Plus (Calcium Phosphate) acetate is not expected to harm an infant, provided maternal serum Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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.

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10 OVERDOSAGE

Administration of Celloid Compounds Sodical Plus (Calcium Phosphate) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Celloid Compounds Sodical Plus (Calcium Phosphate) acetate acts as a phosphate binder. Its chemical name is Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Celloid Compounds Sodical Plus (Calcium Phosphate), 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.

Celloid Compounds Sodical Plus (Calcium Phosphate) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Celloid Compounds Sodical Plus resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Celloid Compounds Sodical Plus (Calcium Phosphate) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Celloid Compounds Sodical Plus (Calcium Phosphate) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Celloid Compounds Sodical Plus (Calcium Phosphate) 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.

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13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Celloid Compounds Sodical Plus (Calcium Phosphate) acetate.

14 CLINICAL STUDIES

Effectiveness of Celloid Compounds Sodical Plus (Calcium Phosphate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Celloid Compounds Sodical Plus (Calcium Phosphate) 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


Celloid Compounds Sodical Plus (Calcium Phosphate) (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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate is shown in the Table 3.


* ANOVA of Celloid Compounds Sodical Plus (Calcium Phosphate) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Celloid Compounds Sodical Plus (Calcium Phosphate) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Celloid Compounds Sodical Plus (Calcium Phosphate) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


Overall, 2 weeks of treatment with Celloid Compounds Sodical Plus (Calcium Phosphate) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Celloid Compounds Sodical Plus (Calcium Phosphate) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Celloid Compounds Sodical Plus (Calcium Phosphate) 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 Celloid Compounds Sodical Plus (Calcium Phosphate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Iron (Ferrous Phosphate):


1 INDICATIONS AND USAGE

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is indicated for the treatment of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency anemia in patients with chronic kidney disease (CKD).

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is an Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) replacement product indicated for the treatment of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Celloid Compounds Sodical Plus ) must only be administered intravenously either by slow injection or by infusion. The dosage of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is expressed in mg of elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)). Each mL contains 20 mg of elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)).

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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) should be administered early during the dialysis session. The usual total treatment course of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is 1000 mg. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) treatment may be repeated if Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency reoccurs.

2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease

Administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), 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. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) treatment may be repeated if Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) in a maximum of 250 mL of 0.9% NaCl. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) treatment may be repeated if Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) maintenance treatment

The dosing for Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) maintenance treatment: Administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) maintenance treatment

The dosing for Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) maintenance treatment: Administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate))
  • Known hypersensitivity to Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (4)

5 WARNINGS AND PRECAUTIONS

  • Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Celloid Compounds Sodical Plus ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
  • Hypotension: Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)). (5.2)
  • Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) Overload: Regularly monitor hematologic responses during Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) therapy. Do not administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) to patients with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)). 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) preparations occur within 30 minutes of the completion of the infusion .

5.2 Hypotension

Celloid Compounds Sodical Plus ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)). Hypotension following administration of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) may be related to the rate of administration and/or total dose administered .

5.3 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) Overload

Excessive therapy with parenteral Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) can lead to excess storage of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) require periodic monitoring of hematologic and Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) to patients with evidence of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose; do not perform serum Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) measurements for at least 48 hours after intravenous dosing .

6 ADVERSE REACTIONS

The following serious adverse reactions associated with Celloid Compounds Sodical Plus ) are described in other sections .

  • The most common adverse reactions (≥2%) following the administration of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus ) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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
Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) Oral Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) therapy and were reported to be intolerant (defined as precluding further use of that Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) product). When these patients were treated with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) there were no occurrences of adverse reactions that precluded further use of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) .

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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) maintenance treatment with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 2.0 mg/kg.

A total of 5 (11%) subjects in the Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 0.5 mg/kg group, 10 (21%) patients in the Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 1.0 mg/kg group, and 10 (21%) patients in the Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)). 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) injection. Reactions have occurred following the first dose or subsequent doses of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)). 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) have not been studied. However, Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) may reduce the absorption of concomitantly administered oral Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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, Celloid Compounds Sodical Plus ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose. Because animal reproductive studies are not always predictive of human response, Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose is excreted in human milk. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Celloid Compounds Sodical Plus ) for Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) for Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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)]

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) has not been studied in patients younger than 2 years of age.

In a country where Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) or any other drugs could be established.

8.5 Geriatric Use

Clinical studies of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) in humans. Excessive dosages of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) may lead to accumulation of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) in storage sites potentially leading to hemosiderosis. Do not administer Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) to patients with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (iron sucrose injection, USP), an Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (III)-hydroxide in sucrose for intravenous use. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) polymerization and m is the number of sucrose molecules associated with the Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (III)-hydroxide.

Each mL contains 20 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) as Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose in water for injection. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is available in 10 mL single-use vials (200 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) per 10 mL), 5 mL single-use vials (100 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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

Celloid Compounds Sodical Plus ) is an aqueous complex of poly-nuclear Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (III)-hydroxide in sucrose. Following intravenous administration, Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is dissociated into Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) and sucrose and the Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.

12.2 Pharmacodynamics

Following intravenous administration, Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is dissociated into Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose containing 100 mg of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), three times weekly for three weeks, significant increases in serum Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) and serum ferritin and significant decreases in total Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) binding capacity occurred four weeks from the initiation of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose treatment.

12.3 Pharmacokinetics

In healthy adults administered intravenous doses of Celloid Compounds Sodical Plus ), its Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) containing 100 mg of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) labeled with 52Fe/59Fe in patients with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency showed that a significant amount of the administered Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) trapping compartment.

Following intravenous administration of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose is dissociated into Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) containing 1,510 mg of sucrose and 100 mg of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose containing 500 to 700 mg of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) have not been studied.

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

In a single-dose PK study of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), the half-life of total serum Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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.

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose.

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (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 Celloid Compounds Sodical Plus ).

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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) treatment and 24 in the historical control group) with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency anemia. Eligibility criteria for Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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.

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), who were off intravenous Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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
Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (n=69 Historical Control (n=18) Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate))

(n=73)

Historical Control

(n=18)

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate))

(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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) in 23 patients with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) deficiency and HDD-CKD who had been discontinued from Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)). Exclusion criteria were similar to those in studies A and B. Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) versus Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (325 mg ferrous sulfate three times daily for 56 days); or Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) group.

A statistically significantly greater proportion of Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) subjects (35/79; 44.3%) compared to oral Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) to patients with PDD-CKD receiving an erythropoietin alone without Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) or Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) / 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) / 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) / 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: Celloid Compounds Sodical Plus ) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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

Celloid Compounds Sodical Plus ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), each 5 mL vial contains 100 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), and each 2.5 mL vial contains 50 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) (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: Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) per mL, or undiluted (20 mg elemental Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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: Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)), 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) 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 Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) administration:

  • Question patients regarding any prior history of reactions to parenteral Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) products
  • Advise patients of the risks associated with Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate))
  • Advise patients to report any symptoms of hypersensitivity that may develop during and following Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Celloid Compounds Sodical Plus (Iron (Ferrous Phosphate)) is manufactured under license from Vifor (International) Inc., Switzerland.

PremierProRx® is a trademark of Premier, Inc., used under license.

PREMIERProRx®

IN2340

MG #15727

Celloid Compounds Sodical Plus pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Celloid Compounds Sodical Plus available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Celloid Compounds Sodical Plus destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Celloid Compounds Sodical Plus Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Celloid Compounds Sodical Plus pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."CALCIUM: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "Calcium". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "Calcium phosphate". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Celloid Compounds Sodical Plus?

Depending on the reaction of the Celloid Compounds Sodical Plus after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Celloid Compounds Sodical Plus 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 Celloid Compounds Sodical Plus 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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Review

sdrugs.com conducted a study on Celloid Compounds Sodical Plus, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Celloid Compounds Sodical Plus consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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