Jagaplex Tablets

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Jagaplex Tablets uses

Jagaplex Tablets consists of Calcium Gluconate, Iron (Ferrous Fumarate), L-Lysine Hydrochloride, Magnesium Sulfate, Manganese (Manganese Sulfate), Vitamin A, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B3 (Niacinamide), Vitamin B6 (Pyridoxine Hydrochloride), Vitamin C, Vitamin D3, Vitamin E, Zinc Sulfate.

Calcium Gluconate:


1 INDICATIONS AND USAGE

Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate capsule.

- Capsule: 667 mg Jagaplex Tablets (Calcium Gluconate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

An overdose of Jagaplex Tablets (Calcium Gluconate) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Jagaplex Tablets (Calcium Gluconate) levels twice weekly. Should hypercalcemia develop, reduce the Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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, Jagaplex Tablets (Calcium Gluconate) acetate has been generally well tolerated.

Jagaplex Tablets (Calcium Gluconate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate

N=167

N (%)


3 month, open label study of Jagaplex Tablets (Calcium Gluconate) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Jagaplex Tablets (Calcium Gluconate) acetate

N=69


Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) concentration could reduce the incidence and severity of Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate: dizziness, edema, and weakness.

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7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Jagaplex Tablets (Calcium Gluconate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Jagaplex Tablets Acetate Capsules contains Jagaplex Tablets (Calcium Gluconate) acetate and is excreted in human milk. Human milk feeding by a mother receiving Jagaplex Tablets (Calcium Gluconate) acetate is not expected to harm an infant, provided maternal serum Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Jagaplex Tablets (Calcium Gluconate) acetate acts as a phosphate binder. Its chemical name is Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Jagaplex Tablets (Calcium Gluconate), 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.

Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Jagaplex Tablets (Calcium Gluconate) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Jagaplex Tablets (Calcium Gluconate) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate.

14 CLINICAL STUDIES

Effectiveness of Jagaplex Tablets (Calcium Gluconate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Jagaplex Tablets (Calcium Gluconate) 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


Jagaplex Tablets (Calcium Gluconate) (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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate is shown in the Table 3.


* ANOVA of Jagaplex Tablets (Calcium Gluconate) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Jagaplex Tablets (Calcium Gluconate) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Jagaplex Tablets (Calcium Gluconate) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Jagaplex Tablets (Calcium Gluconate) 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 Jagaplex Tablets (Calcium Gluconate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Iron (Ferrous Fumarate):


1 INDICATIONS AND USAGE

Jagaplex Tablets (Iron (Ferrous Fumarate)) is indicated for the treatment of Jagaplex Tablets (Iron (Ferrous Fumarate)) deficiency anemia in patients with chronic kidney disease (CKD).

Jagaplex Tablets (Iron (Ferrous Fumarate)) is an Jagaplex Tablets (Iron (Ferrous Fumarate)) replacement product indicated for the treatment of Jagaplex Tablets (Iron (Ferrous Fumarate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Jagaplex Tablets ) must only be administered intravenously either by slow injection or by infusion. The dosage of Jagaplex Tablets (Iron (Ferrous Fumarate)) is expressed in mg of elemental Jagaplex Tablets (Iron (Ferrous Fumarate)). Each mL contains 20 mg of elemental Jagaplex Tablets (Iron (Ferrous Fumarate)).

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 Jagaplex Tablets (Iron (Ferrous Fumarate)) 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. Jagaplex Tablets (Iron (Ferrous Fumarate)) should be administered early during the dialysis session. The usual total treatment course of Jagaplex Tablets (Iron (Ferrous Fumarate)) is 1000 mg. Jagaplex Tablets (Iron (Ferrous Fumarate)) treatment may be repeated if Jagaplex Tablets (Iron (Ferrous Fumarate)) deficiency reoccurs.

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

Administer Jagaplex Tablets (Iron (Ferrous Fumarate)) 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 Jagaplex Tablets (Iron (Ferrous Fumarate)), 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. Jagaplex Tablets (Iron (Ferrous Fumarate)) treatment may be repeated if Jagaplex Tablets (Iron (Ferrous Fumarate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Jagaplex Tablets (Iron (Ferrous Fumarate)) 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 Jagaplex Tablets (Iron (Ferrous Fumarate)) in a maximum of 250 mL of 0.9% NaCl. Jagaplex Tablets (Iron (Ferrous Fumarate)) treatment may be repeated if Jagaplex Tablets (Iron (Ferrous Fumarate)) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Jagaplex Tablets (Iron (Ferrous Fumarate)) maintenance treatment

The dosing for Jagaplex Tablets (Iron (Ferrous Fumarate)) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Jagaplex Tablets (Iron (Ferrous Fumarate)) maintenance treatment: Administer Jagaplex Tablets (Iron (Ferrous Fumarate)) 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. Jagaplex Tablets (Iron (Ferrous Fumarate)) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Jagaplex Tablets (Iron (Ferrous Fumarate)) maintenance treatment

The dosing for Jagaplex Tablets (Iron (Ferrous Fumarate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Jagaplex Tablets (Iron (Ferrous Fumarate)) maintenance treatment: Administer Jagaplex Tablets (Iron (Ferrous Fumarate)) 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. Jagaplex Tablets (Iron (Ferrous Fumarate)) treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental Jagaplex Tablets (Iron (Ferrous Fumarate)) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental Jagaplex Tablets (Iron (Ferrous Fumarate)) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental Jagaplex Tablets (Iron (Ferrous Fumarate)) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental Jagaplex Tablets (Iron (Ferrous Fumarate)) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental Jagaplex Tablets (Iron (Ferrous Fumarate)) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental Jagaplex Tablets (Iron (Ferrous Fumarate)) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to Jagaplex Tablets (Iron (Ferrous Fumarate))
  • Known hypersensitivity to Jagaplex Tablets (Iron (Ferrous Fumarate)) (4)

5 WARNINGS AND PRECAUTIONS

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

5.2 Hypotension

Jagaplex Tablets ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Jagaplex Tablets (Iron (Ferrous Fumarate)). Hypotension following administration of Jagaplex Tablets (Iron (Ferrous Fumarate)) may be related to the rate of administration and/or total dose administered .

5.3 Jagaplex Tablets (Iron (Ferrous Fumarate)) Overload

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

6 ADVERSE REACTIONS

The following serious adverse reactions associated with Jagaplex Tablets ) are described in other sections .

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

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 Jagaplex Tablets (Iron (Ferrous Fumarate)) maintenance treatment with Jagaplex Tablets (Iron (Ferrous Fumarate)) 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 Jagaplex Tablets (Iron (Ferrous Fumarate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Jagaplex Tablets (Iron (Ferrous Fumarate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Jagaplex Tablets (Iron (Ferrous Fumarate)) 2.0 mg/kg.

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

Safety and effectiveness of Jagaplex Tablets ) for Jagaplex Tablets (Iron (Ferrous Fumarate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

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

Jagaplex Tablets (Iron (Ferrous Fumarate)) has not been studied in patients younger than 2 years of age.

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

8.5 Geriatric Use

Clinical studies of Jagaplex Tablets (Iron (Ferrous Fumarate)) 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 Jagaplex Tablets (Iron (Ferrous Fumarate)), 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 Jagaplex Tablets (Iron (Ferrous Fumarate)) in humans. Excessive dosages of Jagaplex Tablets (Iron (Ferrous Fumarate)) may lead to accumulation of Jagaplex Tablets (Iron (Ferrous Fumarate)) in storage sites potentially leading to hemosiderosis. Do not administer Jagaplex Tablets (Iron (Ferrous Fumarate)) to patients with Jagaplex Tablets (Iron (Ferrous Fumarate)) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Jagaplex Tablets (Iron (Ferrous Fumarate)) 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

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

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

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

Jagaplex Tablets (Iron (Ferrous Fumarate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Jagaplex Tablets (Iron (Ferrous Fumarate)) 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 Jagaplex Tablets (Iron (Ferrous Fumarate)) sucrose.

Jagaplex Tablets (Iron (Ferrous Fumarate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Jagaplex Tablets (Iron (Ferrous Fumarate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Jagaplex Tablets (Iron (Ferrous Fumarate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Jagaplex Tablets (Iron (Ferrous Fumarate)) (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 Jagaplex Tablets ).

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 Jagaplex Tablets (Iron (Ferrous Fumarate)) treatment and 24 in the historical control group) with Jagaplex Tablets (Iron (Ferrous Fumarate)) deficiency anemia. Eligibility criteria for Jagaplex Tablets (Iron (Ferrous Fumarate)) 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.

Jagaplex Tablets (Iron (Ferrous Fumarate)) 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 Jagaplex Tablets (Iron (Ferrous Fumarate)), who were off intravenous Jagaplex Tablets (Iron (Ferrous Fumarate)) 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 Jagaplex Tablets (Iron (Ferrous Fumarate)) 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
Jagaplex Tablets (Iron (Ferrous Fumarate)) (n=69 Historical Control (n=18) Jagaplex Tablets (Iron (Ferrous Fumarate))

(n=73)

Historical Control

(n=18)

Jagaplex Tablets (Iron (Ferrous Fumarate))

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

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

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

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Jagaplex Tablets (Iron (Ferrous Fumarate)) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

L-Lysine Hydrochloride:


Jagaplex Tablets (L-Lysine Hydrochloride) (abbreviated as Lys or K) is an О±-amino acid with the chemical formula HO2CCH(CH2)4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it. Its codons are AAA and AAG.L-Lysine is a base, as are arginine and histidine. The Оµ-amino group often participates in hydrogen bonding and as a general base in catalysis. Common posttranslational modifications include methylation of the Оµ-amino group, giving methyl-, dimethyl-, and trimethyllysine. The latter occurs in calmodulin. Other posttranslational modifications include acetylation. Collagen contains hydroxylysine which is derived from lysine by lysyl hydroxylase. O-Glycosylation of lysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell.

Indication: Supplemental Jagaplex Tablets (L-Lysine Hydrochloride) has putative anti-herpes simplex virus activity. There is preliminary research suggesting that it may have some anti-osteoporotic activity.

Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems.

Magnesium Sulfate:



Jagaplex Tablets (Magnesium Sulfate)

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Jagaplex Tablets (Magnesium Sulfate) Injection, USP is a sterile solution of Jagaplex Tablets (Magnesium Sulfate) heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.

Jagaplex Tablets (Magnesium Sulfate), USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.

The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.

CLINICAL PHARMACOLOGY

Magnesium (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

As a nutritional adjunct in hyperalimentation, the precise mechanism of action for magnesium is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.

Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of magnesium. While there are large stores of magnesium present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral magnesium therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Magnesium is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma magnesium levels range from 1.5 to 2.5 mEq/liter.

As plasma magnesium rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of magnesium. Serum magnesium concentrations in excess of 12 mEq/L may be fatal.

Magnesium acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of magnesium poisoning are antagonized to some extent by intravenous administration of calcium.

Pharmacokinetics

With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. Magnesium is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Jagaplex Tablets (Magnesium Sulfate) Injection, USP is suitable for replacement therapy in magnesium deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum magnesium (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.

In total parenteral nutrition (TPN), Jagaplex Tablets (Magnesium Sulfate) may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Jagaplex Tablets (Magnesium Sulfate) Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.

WARNINGS

FETAL HARM: Continuous administration of Jagaplex Tablets (Magnesium Sulfate) beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Jagaplex Tablets (Magnesium Sulfate) should be used during pregnancy only if clearly needed. If Jagaplex Tablets (Magnesium Sulfate) is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of Jagaplex Tablets (Magnesium Sulfate) beyond 5 to 7 days may cause fetal abnormalities.

ALUMINUM TOXICITY: 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.

Parenteral use in the presence of renal insufficiency may lead to magnesium intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.

PRECAUTIONS

General

Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium.

Because magnesium is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum magnesium levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional magnesium should be given until they return. Serum magnesium levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when magnesium levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of magnesium intoxication in eclampsia.

50% Jagaplex Tablets (Magnesium Sulfate) Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.

Laboratory Tests

Jagaplex Tablets (Magnesium Sulfate) injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of magnesium is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium. CNS depression and peripheral transmission defects produced by magnesium may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Jagaplex Tablets (Magnesium Sulfate) and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Jagaplex Tablets (Magnesium Sulfate) should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat magnesium toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Jagaplex Tablets (Magnesium Sulfate) can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of Jagaplex Tablets (Magnesium Sulfate) for more than 5 to 7 days.1-10 Jagaplex Tablets (Magnesium Sulfate) injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.

Nonteratogenic Effects

When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of magnesium toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Jagaplex Tablets (Magnesium Sulfate) is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Jagaplex Tablets (Magnesium Sulfate) outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Nursing Mothers

Since magnesium is distributed into milk during parenteral Jagaplex Tablets (Magnesium Sulfate) administration, the drug should be used with caution in nursing women.

Geriatrics

Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum magnesium should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered magnesium usually are the result of magnesium intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to Jagaplex Tablets (Magnesium Sulfate) therapy for eclampsia has been reported.

OVERDOSAGE

Magnesium intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of magnesium intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of magnesium.

For Treatment of Overdose

Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.

Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

DOSAGE AND ADMINISTRATION

Dosage of Jagaplex Tablets (Magnesium Sulfate) must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of Jagaplex Tablets (Magnesium Sulfate) in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.

In Magnesium Deficiency

In the treatment of mild magnesium deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of magnesium (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of magnesium per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.

In Hyperalimentation

In total parenteral nutrition, maintenance requirements for magnesium are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.

In Pre-eclampsia or Eclampsia

In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of Jagaplex Tablets (Magnesium Sulfate). Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum magnesium level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of Jagaplex Tablets (Magnesium Sulfate) is 20 grams/48 hours and frequent serum magnesium concentrations must be obtained. Continuous use of Jagaplex Tablets (Magnesium Sulfate) in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Jagaplex Tablets (Magnesium Sulfate) is 1 gram to 2 grams given intravenously.

For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.

In paroxysmal atrial tachycardia, magnesium should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.

For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.

Incompatibilities

Jagaplex Tablets (Magnesium Sulfate) in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.

It has been reported that magnesium may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED

Jagaplex Tablets (Magnesium Sulfate) Injection, USP is supplied in single-dose containers as follows:


NDC No.


Container


Total

Amount


Concentration


mEq

Mg++/mL


0409-1754-10


Ansyr

Plastic Syringe


5 g/10 mL


50%


4 mEq/mL


Do not administer unless solution is clear and container is undamaged. Discard unused portion.

Store at 20 to 25°C (68 to 77°F).

REFERENCES

  • Yokoyama K, Takahashi N, Yada Y. Prolonged maternal magnesium administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
  • Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal magnesium toxicity. J. Perinatol. 2006; 26(6):371-4.
  • Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of Jagaplex Tablets (Magnesium Sulfate) tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
  • Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received magnesium sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
  • Matsuda Y, Maeda Y, Ito M, et al. Effect of Jagaplex Tablets (Magnesium Sulfate) treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
  • Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous Jagaplex Tablets (Magnesium Sulfate) therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
  • Santi MD, Henry GW, Douglas GL. Jagaplex Tablets (Magnesium Sulfate) treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
  • Holcomb WL, Shackelford GD, Petrie RH. Magnesium tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
  • Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
  • Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with Jagaplex Tablets (Magnesium Sulfate) infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
  • McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Jagaplex Tablets (Magnesium Sulfate) treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
  • Riaz M, Porat R, Brodsky NL, et al. The effects of maternal Jagaplex Tablets (Magnesium Sulfate) treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% Jagaplex Tablets (Magnesium Sulfate) 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Jagaplex Tablets (Magnesium Sulfate) Injection, USP

5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)

MUST BE DILUTED FOR INTRAVENOUS USE.

For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Manganese (Manganese Sulfate):


INDICATIONS AND USAGE

Jagaplex Tablets (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN).

Administration helps to maintain Jagaplex Tablets (Manganese (Manganese Sulfate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Jagaplex Tablets (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is contraindicated as the acidic pH of the solution (pH 2.0) may cause considerable tissue irritation.

Liver and/or biliary tract dysfunction may require omission or reduction of copper and Jagaplex Tablets (Manganese (Manganese Sulfate)) doses because these elements are primarily eliminated in the bile.

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 solution is clear and seal is intact.

Jagaplex Tablets ) 0.1 mg/mL (Manganese Chloride Injection, USP) 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.

Laboratory Tests

Serum Jagaplex Tablets (Manganese (Manganese Sulfate)) levels can be measured periodically at the discretion of the investigator. Because of the low serum concentration normally present, samples will usually be analyzed by a reference laboratory.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Jagaplex Tablets ) 0.1 mg/mL (Manganese 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 Jagaplex Tablets (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) additive is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Pregnancy Category C.

Animal reproduction studies have not been conducted with Jagaplex Tablets (Manganese (Manganese Sulfate)) chloride. It is also not known whether Jagaplex Tablets (Manganese (Manganese Sulfate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Jagaplex Tablets (Manganese (Manganese Sulfate)) chloride should be given to a pregnant woman only if clearly indicated.

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

Jagaplex Tablets (Manganese (Manganese Sulfate)) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Jagaplex Tablets (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) contains 0.1 mg manganese/mL and is administered intravenously only after dilution. The additive should be administered in a volume of fluid not less than 100 mL. For the adult receiving TPN, the suggested additive dosage for Jagaplex Tablets (Manganese (Manganese Sulfate)) is 0.15 to 0.8 mg/day (1.5 to 8 mL/day). For pediatric patients, a dosage of 2 to 10 mcg manganese/kg/day (0.02 to 0.1 mL/kg/day) is recommended.

Periodic monitoring of Jagaplex Tablets (Manganese (Manganese Sulfate)) plasma levels is suggested as a guideline for subsequent administration.

Parenteral products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. (See PRECAUTIONS .)

HOW SUPPLIED

Jagaplex Tablets (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is supplied in 10 mL Plastic Vials (NDC No. 0409-4091-01).

Store at 20 to 25°C (68 to 77°F)

Revised: November, 2009

Printed in USA EN-2320

Hospira, Inc., Lake Forest, IL 60045 USA

RL-0104


Vitamin A:


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
Jagaplex Tablets (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 Daily Value not established

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, Jagaplex Tablets (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.

Jagaplex Tablets (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 Jagaplex Tablets (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Jagaplex Tablets (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

Jagaplex Tablets Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.

Jagaplex Tablets (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.

Jagaplex Tablets (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:


Pharmacological action

Jagaplex Tablets refers to a group of water-soluble vitamins. It has high biological activity. Jagaplex Tablets (Vitamin B12) 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 Jagaplex Tablets (Vitamin B12) 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 Jagaplex Tablets 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 Jagaplex Tablets (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Jagaplex Tablets is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Jagaplex Tablets (Vitamin B12) 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 Jagaplex Tablets (Vitamin B12) 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 Jagaplex Tablets (Vitamin B12) 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.

Jagaplex Tablets (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

Cardiovascular system: rarely - pain in the heart, tachycardia.

Allergic reactions: rarely - urticaria.

Jagaplex Tablets contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Jagaplex Tablets 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 Jagaplex Tablets 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.

Jagaplex Tablets (Vitamin B12) drug interactions

In an application of Jagaplex Tablets (Vitamin B12) 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 Jagaplex Tablets (Vitamin B12) 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:


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. Jagaplex Tablets (Vitamin C) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. Jagaplex Tablets (Vitamin C) has antioxidant properties.

With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).

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 Jagaplex Tablets prescribed?

For systemic use of Jagaplex Tablets (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Jagaplex Tablets (Vitamin C); providing increased need for Jagaplex Tablets (Vitamin C) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.

For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

For the prevention of deficiency conditions Jagaplex Tablets 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.

Jagaplex Tablets (Vitamin C) 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.

Jagaplex Tablets 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

Jagaplex Tablets (Vitamin C) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.

Patients with high content body iron should apply ascorbic acid in minimal doses.

Jagaplex Tablets (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.

The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.

Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.

It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.

Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.

Jagaplex Tablets 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 Jagaplex Tablets (Vitamin C) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.

Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.

Jagaplex Tablets (Vitamin C) in an application with warfarin may decrease effects of warfarin.

With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.

In an application with tetracycline is increased excretion of ascorbic acid in the urine.

There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.

May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.

Jagaplex Tablets 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 E:


A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.

Indication: Jagaplex Tablets (Vitamin E), known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.

Jagaplex Tablets (Vitamin E) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Jagaplex Tablets (Vitamin E) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Jagaplex Tablets (Vitamin E) is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Jagaplex Tablets (Vitamin E) is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a Jagaplex Tablets (Vitamin E) deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A Jagaplex Tablets (Vitamin E) deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that Jagaplex Tablets (Vitamin E) may help prevent or delay coronary heart disease. Antioxidants such as Jagaplex Tablets (Vitamin E) help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of Jagaplex Tablets (Vitamin E) have been linked to increased incidence of breast and colon cancer.

Zinc Sulfate:


INDICATIONS AND USAGE

Jagaplex Tablets (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 Jagaplex Tablets (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 Jagaplex Tablets (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 Jagaplex Tablets (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 Jagaplex Tablets (Zinc Sulfate) from a bolus injection. Administration of Jagaplex Tablets (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 Jagaplex Tablets (Zinc Sulfate) are suggested as a guideline for subsequent Jagaplex Tablets (Zinc Sulfate) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Jagaplex Tablets 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 Jagaplex Tablets (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 Jagaplex Tablets chloride. It is also not known whether Jagaplex Tablets (Zinc Sulfate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Jagaplex Tablets (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 Jagaplex Tablets (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 Jagaplex Tablets (Zinc Sulfate) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending Jagaplex Tablets (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 Jagaplex Tablets (Zinc Sulfate) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Jagaplex Tablets (Zinc Sulfate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Jagaplex Tablets (Zinc Sulfate) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Jagaplex Tablets (Zinc Sulfate) toxicity.

DOSAGE AND ADMINISTRATION

Jagaplex Tablets (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 Jagaplex Tablets (Zinc Sulfate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Jagaplex Tablets (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

Jagaplex Tablets (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

Jagaplex Tablets (Zinc Sulfate)

1 mg/mL

Jagaplex Tablets (Zinc Sulfate) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Jagaplex Tablets 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.


Jagaplex Tablets 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.


Jagaplex Tablets 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.


Jagaplex Tablets 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.


Jagaplex Tablets 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."MAGNESIUM SULFATE INJECTION, SOLUTION [HOSPIRA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."CALCIUM GLUCONATE TABLET [WEST-WARD PHARMACEUTICALS CORP.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."ZINC SULFATE TABLET [NATIONWIDE LABORATORIES, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Jagaplex Tablets?

Depending on the reaction of the Jagaplex Tablets after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Jagaplex Tablets 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 Jagaplex Tablets 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 Jagaplex Tablets, 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 Jagaplex Tablets 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.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Three visitors reported frequency of use

How often in a day do you take the medicine?
Are you taking the Jagaplex Tablets drug as prescribed by the doctor?

Few medications can be taken Twice in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sdrugs.com website users about the frequency of taking the drug Jagaplex Tablets is mentioned below.
Visitors%
Twice in a day1
33.3%
Once in a day1
33.3%
4 times in a day1
33.3%

One visitor reported doses

What is the dose of Jagaplex Tablets drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 51-100mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
51-100mg1
100.0%

Two visitors reported time for results

What is the time duration Jagaplex Tablets drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 3 month to notice the result from using Jagaplex Tablets drug. The time needed to show improvement in health condition after using the medicine Jagaplex Tablets need not be same for all the users. It varies based on other factors.
Visitors%
3 month1
50.0%
1 week1
50.0%

One visitor reported administration

The drugs are administered in various routes, like oral or injection form. They are administered before food or after food. How are you taking Jagaplex Tablets drug, before food or after food?
Click here to find out how other users of our website are taking it. For any doubts or queries on how and when the medicine is administered, contact your health care provider immediately.
Visitors%
Empty stomach1
100.0%

Three visitors reported age

Visitors%
46-601
33.3%
> 601
33.3%
30-451
33.3%

Visitor reviews


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

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