Comb I Homoeopathic

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Comb I Homoeopathic uses

Comb I Homoeopathic consists of Iron (Ferrous Phosphate), Magnesium Phosphate Dibasic, Potassium Sulfate.

Iron (Ferrous Phosphate):


1 INDICATIONS AND USAGE

Comb I Homoeopathic (Iron (Ferrous Phosphate)) is indicated for the treatment of Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency anemia in patients with chronic kidney disease (CKD).

Comb I Homoeopathic (Iron (Ferrous Phosphate)) is an Comb I Homoeopathic (Iron (Ferrous Phosphate)) replacement product indicated for the treatment of Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

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

Population Dose
Adult patients Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1) 100 mg slow intravenous injection or infusion
Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2) 200 mg slow intravenous injection or infusion
Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3) 300 mg or 400 mg intravenous infusion
Pediatric patients HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5) 0.5 mg/kg slow intravenous injection or infusion

2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)

Administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session. Comb I Homoeopathic (Iron (Ferrous Phosphate)) should be administered early during the dialysis session. The usual total treatment course of Comb I Homoeopathic (Iron (Ferrous Phosphate)) is 1000 mg. Comb I Homoeopathic (Iron (Ferrous Phosphate)) treatment may be repeated if Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency reoccurs.

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

Administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of Comb I Homoeopathic (Iron (Ferrous Phosphate)), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. Comb I Homoeopathic (Iron (Ferrous Phosphate)) treatment may be repeated if Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute Comb I Homoeopathic (Iron (Ferrous Phosphate)) in a maximum of 250 mL of 0.9% NaCl. Comb I Homoeopathic (Iron (Ferrous Phosphate)) treatment may be repeated if Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Comb I Homoeopathic (Iron (Ferrous Phosphate)) maintenance treatment

The dosing for Comb I Homoeopathic (Iron (Ferrous Phosphate)) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Comb I Homoeopathic (Iron (Ferrous Phosphate)) maintenance treatment: Administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Comb I Homoeopathic (Iron (Ferrous Phosphate)) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Comb I Homoeopathic (Iron (Ferrous Phosphate)) maintenance treatment

The dosing for Comb I Homoeopathic (Iron (Ferrous Phosphate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Comb I Homoeopathic (Iron (Ferrous Phosphate)) maintenance treatment: Administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Comb I Homoeopathic (Iron (Ferrous Phosphate)) treatment may be repeated if necessary.

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3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to Comb I Homoeopathic (Iron (Ferrous Phosphate))
  • Known hypersensitivity to Comb I Homoeopathic (Iron (Ferrous Phosphate)) (4)

5 WARNINGS AND PRECAUTIONS

  • Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Comb I Homoeopathic ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
  • Hypotension: Comb I Homoeopathic (Iron (Ferrous Phosphate)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Comb I Homoeopathic (Iron (Ferrous Phosphate)). (5.2)
  • Comb I Homoeopathic (Iron (Ferrous Phosphate)) Overload: Regularly monitor hematologic responses during Comb I Homoeopathic (Iron (Ferrous Phosphate)) therapy. Do not administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) to patients with Comb I Homoeopathic (Iron (Ferrous Phosphate)) overload. (5.3)

5.1 Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Comb I Homoeopathic (Iron (Ferrous Phosphate)). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop Comb I Homoeopathic (Iron (Ferrous Phosphate)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Comb I Homoeopathic (Iron (Ferrous Phosphate)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Comb I Homoeopathic (Iron (Ferrous Phosphate)) preparations occur within 30 minutes of the completion of the infusion .

5.2 Hypotension

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

5.3 Comb I Homoeopathic (Iron (Ferrous Phosphate)) Overload

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

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6 ADVERSE REACTIONS

The following serious adverse reactions associated with Comb I Homoeopathic ) are described in other sections .

  • The most common adverse reactions (≥2%) following the administration of Comb I Homoeopathic (Iron (Ferrous Phosphate)) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.

Adverse Reactions in Adults Patients with CKD

Adverse Reactions in Adult Patients with CKD

The frequency of adverse reactions associated with the use of Comb I Homoeopathic ) 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 Comb I Homoeopathic (Iron (Ferrous Phosphate)) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.


* EPO=Erythropoietin

Adverse Reactions

(Preferred Term)

HDD-CKD NDD-CKD PDD-CKD
Comb I Homoeopathic (Iron (Ferrous Phosphate)) Comb I Homoeopathic (Iron (Ferrous Phosphate)) Oral Comb I Homoeopathic (Iron (Ferrous Phosphate)) Comb I Homoeopathic (Iron (Ferrous Phosphate)) EPO* Only
(N=231) (N=139) (N=139) (N=75) (N=46)
% % % % %
Subjects with any adverse reaction 78.8 76.3 73.4 72.0 65.2
Ear and Labyrinth Disorders
Ear Pain 0 2.2 0.7 0 0
Eye Disorders
Conjunctivitis 0.4 0 0 2.7 0
Gastrointestinal Disorders
Abdominal pain 3.5 1.4 2.9 4.0 6.5
Diarrhea 5.2 7.2 10.1 8.0 4.3
Dysgeusia 0.9 7.9 0 0 0
Nausea 14.7 8.6 12.2 5.3 4.3
Vomiting 9.1 5.0 8.6 8.0 2.2
General Disorders and
Administration Site Conditions
Asthenia 2.2 0.7 2.2 2.7 0
Chest pain 6.1 1.4 0 2.7 0
Feeling abnormal 3.0 0 0 0 0
Infusion site pain or burning 0 5.8 0 0 0
Injection site extravasation 0 2.2 0 0 0
Peripheral edema 2.6 7.2 5.0 5.3 10.9
Pyrexia 3.0 0.7 0.7 1.3 0
Infections and Infestations
Nasopharyngitis, Sinusitis, Upper

respiratory tract infections, Pharyngitis

2.6 2.2 4.3 16.0 4.3
Injury, Poisoning and Procedural
Complications
Graft complication 9.5 1.4 0 0 0
Metabolism and Nutrition Disorders
Fluid overload 3.0 1.4 0.7 1.3 0
Gout 0 2.9 1.4 0 0
Hyperglycemia 0 2.9 0 0 2.2
Hypoglycemia 0.4 0.7 0.7 4.0 0
Musculoskeletal and Connective
Tissue Disorders
Arthralgia 3.5 1.4 2.2 4.0 4.3
Back pain 2.2 2.2 3.6 1.3 4.3
Muscle cramp 29.4 0.7 0.7 2.7 0
Myalgia 0 3.6 0 1.3 0
Pain in extremity 5.6 4.3 0 2.7 6.5
Nervous System Disorders
Dizziness 6.5 6.5 1.4 1.3 4.3
Headache 12.6 2.9 0.7 4.0 0
Respiratory, Thoracic and
Mediastinal Disorders
Cough 3.0 2.2 0.7 1.3 0
Dyspnea 3.5 5.8 1.4 1.3 2.2
Nasal congestion 0 1.4 2.2 1.3 0
Skin and Subcutaneous
Tissue Disorders
Pruritus 3.9 2.2 4.3 2.7 0
Vascular Disorders
Hypertension 6.5 6.5 4.3 8.0 6.5
Hypotension 39.4 2.2 0.7 2.7 2.2

One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous Comb I Homoeopathic (Iron (Ferrous Phosphate)) therapy and were reported to be intolerant (defined as precluding further use of that Comb I Homoeopathic (Iron (Ferrous Phosphate)) product). When these patients were treated with Comb I Homoeopathic (Iron (Ferrous Phosphate)) there were no occurrences of adverse reactions that precluded further use of Comb I Homoeopathic (Iron (Ferrous Phosphate)) .

Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)

Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)

In a randomized, open-label, dose-ranging trial for Comb I Homoeopathic (Iron (Ferrous Phosphate)) maintenance treatment with Comb I Homoeopathic (Iron (Ferrous Phosphate)) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving Comb I Homoeopathic (Iron (Ferrous Phosphate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Comb I Homoeopathic (Iron (Ferrous Phosphate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Comb I Homoeopathic (Iron (Ferrous Phosphate)) 2.0 mg/kg.

A total of 5 (11%) subjects in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) 0.5 mg/kg group, 10 (21%) patients in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) 1.0 mg/kg group, and 10 (21%) patients in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).

6.2 Adverse Reactions from Post-Marketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.

The following adverse reactions have been identified during post-approval use of Comb I Homoeopathic (Iron (Ferrous Phosphate)). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.

Symptoms associated with Comb I Homoeopathic (Iron (Ferrous Phosphate)) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of Comb I Homoeopathic (Iron (Ferrous Phosphate)) injection. Reactions have occurred following the first dose or subsequent doses of Comb I Homoeopathic (Iron (Ferrous Phosphate)). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.

Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.

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7 DRUG INTERACTIONS

Drug interactions involving Comb I Homoeopathic (Iron (Ferrous Phosphate)) have not been studied. However, Comb I Homoeopathic (Iron (Ferrous Phosphate)) may reduce the absorption of concomitantly administered oral Comb I Homoeopathic (Iron (Ferrous Phosphate)) preparations.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Comb I Homoeopathic ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose. Because animal reproductive studies are not always predictive of human response, Comb I Homoeopathic (Iron (Ferrous Phosphate)) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

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

8.4 Pediatric Use

Safety and effectiveness of Comb I Homoeopathic ) for Comb I Homoeopathic (Iron (Ferrous Phosphate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Comb I Homoeopathic (Iron (Ferrous Phosphate)) for Comb I Homoeopathic (Iron (Ferrous Phosphate)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Comb I Homoeopathic (Iron (Ferrous Phosphate)) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]

Comb I Homoeopathic (Iron (Ferrous Phosphate)) has not been studied in patients younger than 2 years of age.

In a country where Comb I Homoeopathic (Iron (Ferrous Phosphate)) is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received Comb I Homoeopathic (Iron (Ferrous Phosphate)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Comb I Homoeopathic (Iron (Ferrous Phosphate)) or any other drugs could be established.

8.5 Geriatric Use

Clinical studies of Comb I Homoeopathic (Iron (Ferrous Phosphate)) did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of Comb I Homoeopathic (Iron (Ferrous Phosphate)), 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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10 OVERDOSAGE

No data are available regarding overdosage of Comb I Homoeopathic (Iron (Ferrous Phosphate)) in humans. Excessive dosages of Comb I Homoeopathic (Iron (Ferrous Phosphate)) may lead to accumulation of Comb I Homoeopathic (Iron (Ferrous Phosphate)) in storage sites potentially leading to hemosiderosis. Do not administer Comb I Homoeopathic (Iron (Ferrous Phosphate)) to patients with Comb I Homoeopathic (Iron (Ferrous Phosphate)) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.

11 DESCRIPTION

Comb I Homoeopathic (Iron (Ferrous Phosphate)) (iron sucrose injection, USP), an Comb I Homoeopathic (Iron (Ferrous Phosphate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Comb I Homoeopathic (Iron (Ferrous Phosphate)) (III)-hydroxide in sucrose for intravenous use. Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:

[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)

where: n is the degree of Comb I Homoeopathic (Iron (Ferrous Phosphate)) polymerization and m is the number of sucrose molecules associated with the Comb I Homoeopathic (Iron (Ferrous Phosphate)) (III)-hydroxide.

Each mL contains 20 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) as Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose in water for injection. Comb I Homoeopathic (Iron (Ferrous Phosphate)) is available in 10 mL single-use vials (200 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) per 10 mL), 5 mL single-use vials (100 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

In healthy adults administered intravenous doses of Comb I Homoeopathic ), its Comb I Homoeopathic (Iron (Ferrous Phosphate)) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The Comb I Homoeopathic (Iron (Ferrous Phosphate)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Comb I Homoeopathic (Iron (Ferrous Phosphate)) containing 100 mg of Comb I Homoeopathic (Iron (Ferrous Phosphate)) labeled with 52Fe/59Fe in patients with Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency showed that a significant amount of the administered Comb I Homoeopathic (Iron (Ferrous Phosphate)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Comb I Homoeopathic (Iron (Ferrous Phosphate)) trapping compartment.

Following intravenous administration of Comb I Homoeopathic (Iron (Ferrous Phosphate)), Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose is dissociated into Comb I Homoeopathic (Iron (Ferrous Phosphate)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Comb I Homoeopathic (Iron (Ferrous Phosphate)) containing 1,510 mg of sucrose and 100 mg of Comb I Homoeopathic (Iron (Ferrous Phosphate)) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Comb I Homoeopathic (Iron (Ferrous Phosphate)) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose containing 500 to 700 mg of Comb I Homoeopathic (Iron (Ferrous Phosphate)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Comb I Homoeopathic (Iron (Ferrous Phosphate)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Comb I Homoeopathic (Iron (Ferrous Phosphate)) have not been studied.

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

In a single-dose PK study of Comb I Homoeopathic (Iron (Ferrous Phosphate)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Comb I Homoeopathic (Iron (Ferrous Phosphate)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Comb I Homoeopathic (Iron (Ferrous Phosphate)), the half-life of total serum Comb I Homoeopathic (Iron (Ferrous Phosphate)) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.

Comb I Homoeopathic (Iron (Ferrous Phosphate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose.

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

Comb I Homoeopathic (Iron (Ferrous Phosphate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.

14 CLINICAL STUDIES

Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Comb I Homoeopathic ).

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 Comb I Homoeopathic (Iron (Ferrous Phosphate)) treatment and 24 in the historical control group) with Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency anemia. Eligibility criteria for Comb I Homoeopathic (Iron (Ferrous Phosphate)) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.

Comb I Homoeopathic (Iron (Ferrous Phosphate)) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with Comb I Homoeopathic (Iron (Ferrous Phosphate)), who were off intravenous Comb I Homoeopathic (Iron (Ferrous Phosphate)) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.

Patients in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.


**p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates.


Efficacy

parameters

End of treatment 2 week follow-up 5 week follow-up
Comb I Homoeopathic (Iron (Ferrous Phosphate)) (n=69 Historical Control (n=18) Comb I Homoeopathic (Iron (Ferrous Phosphate))

(n=73)

Historical Control

(n=18)

Comb I Homoeopathic (Iron (Ferrous Phosphate))

(n=71)

Historical

Control

(n=15)

Hemoglobin (g/dL) 1.0 ± 0.12** 0.0 ± 0.21 1.3 ± 0.14** -0.6 ± 0.24 1.2 ± 0.17* -0.1 ± 0.23
Hematocrit (%) 3.1 ± 0.37** -0.3 ± 0.65 3.6 ± 0.44** -1.2 ± 0.76 3.3 ± 0.54 0.2 ± 0.86

Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).

14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease

Study B was a multicenter, open label study of Comb I Homoeopathic (Iron (Ferrous Phosphate)) in 23 patients with Comb I Homoeopathic (Iron (Ferrous Phosphate)) deficiency and HDD-CKD who had been discontinued from Comb I Homoeopathic (Iron (Ferrous Phosphate)) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.

All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.

14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease

Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral Comb I Homoeopathic (Iron (Ferrous Phosphate)). Exclusion criteria were similar to those in studies A and B. Comb I Homoeopathic (Iron (Ferrous Phosphate)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Comb I Homoeopathic (Iron (Ferrous Phosphate)) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.

The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.

14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease

Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Comb I Homoeopathic (Iron (Ferrous Phosphate)) versus Comb I Homoeopathic (Iron (Ferrous Phosphate)) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral Comb I Homoeopathic (Iron (Ferrous Phosphate)) (325 mg ferrous sulfate three times daily for 56 days); or Comb I Homoeopathic (Iron (Ferrous Phosphate)) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral Comb I Homoeopathic (Iron (Ferrous Phosphate)) group.

A statistically significantly greater proportion of Comb I Homoeopathic (Iron (Ferrous Phosphate)) subjects (35/79; 44.3%) compared to oral Comb I Homoeopathic (Iron (Ferrous Phosphate)) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).

14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease

Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Comb I Homoeopathic (Iron (Ferrous Phosphate)) to patients with PDD-CKD receiving an erythropoietin alone without Comb I Homoeopathic (Iron (Ferrous Phosphate)) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no Comb I Homoeopathic (Iron (Ferrous Phosphate)) or Comb I Homoeopathic (Iron (Ferrous Phosphate)) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.

Patients in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with Comb I Homoeopathic (Iron (Ferrous Phosphate)) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).

14.6 Study F: Comb I Homoeopathic ) 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 Comb I Homoeopathic (Iron (Ferrous Phosphate)) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of Comb I Homoeopathic (Iron (Ferrous Phosphate)) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received Comb I Homoeopathic (Iron (Ferrous Phosphate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Comb I Homoeopathic (Iron (Ferrous Phosphate)) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the Comb I Homoeopathic (Iron (Ferrous Phosphate)) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.

16 HOW SUPPLIED/storage and handling

16.1 How Supplied

Comb I Homoeopathic ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)), each 5 mL vial contains 100 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)), and each 2.5 mL vial contains 50 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) (20 mg/mL).

NDC-0517-2310-05 200 mg/10 mL Single-Use Vial Packages of 5
NDC-0517-2310-10 200 mg/10 mL Single-Use Vial Packages of 10
NDC-0517-2340-01 100 mg/5 mL Single-Use Vial Individually Boxed
NDC-0517-2340-10 100 mg/5 mL Single-Use Vial Packages of 10
NDC-0517-2340-25 100 mg/5 mL Single-Use Vial Packages of 25
NDC-0517-2340-99 100 mg/5 mL Single-Use Vial Packages of 10
NDC-0517-2325-10 50 mg/2.5 mL Single-Use Vial Packages of 10
NDC-0517-2325-25 50 mg/2.5 mL Single-Use Vial Packages of 25

16.2 Stability and Storage

Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.

Syringe Stability: Comb I Homoeopathic (Iron (Ferrous Phosphate)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) per mL, or undiluted (20 mg elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).

Intravenous Admixture Stability: Comb I Homoeopathic (Iron (Ferrous Phosphate)), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental Comb I Homoeopathic (Iron (Ferrous Phosphate)) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).

Do not dilute to concentrations below 1 mg/mL.

Do not mix Comb I Homoeopathic (Iron (Ferrous Phosphate)) with other medications or add to parenteral nutrition solutions for intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.

17 PATIENT COUNSELING INFORMATION

Prior to Comb I Homoeopathic (Iron (Ferrous Phosphate)) administration:

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Comb I Homoeopathic (Iron (Ferrous Phosphate)) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

Potassium Sulfate:



Comb I Homoeopathic (Potassium Sulfate) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Comb I Homoeopathic (Potassium Sulfate) chloride containing 1500 mg of microencapsulated Comb I Homoeopathic (Potassium Sulfate) chloride, USP equivalent to 20 mEq of Comb I Homoeopathic (Potassium Sulfate) in a tablet.

These formulations are intended to slow the release of Comb I Homoeopathic (Potassium Sulfate) so that the likelihood of a high localized concentration of Comb I Homoeopathic (Potassium Sulfate) chloride within the gastrointestinal tract is reduced.

Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Comb I Homoeopathic (Potassium Sulfate) chloride, and the structural formula is KCl. Comb I Homoeopathic (Potassium Sulfate) chloride, USP occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol.

Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Comb I Homoeopathic (Potassium Sulfate) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended release of Comb I Homoeopathic (Potassium Sulfate) chloride.

Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.

CLINICAL PHARMACOLOGY

The Comb I Homoeopathic (Potassium Sulfate) ion is the principal intracellular cation of most body tissues. Comb I Homoeopathic (Potassium Sulfate) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.

The intracellular concentration of Comb I Homoeopathic (Potassium Sulfate) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.

Comb I Homoeopathic (Potassium Sulfate) is a normal dietary constituent and under steady-state conditions the amount of Comb I Homoeopathic (Potassium Sulfate) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Comb I Homoeopathic (Potassium Sulfate) is 50 to 100 mEq per day.

Comb I Homoeopathic (Potassium Sulfate) depletion will occur whenever the rate of Comb I Homoeopathic (Potassium Sulfate) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Comb I Homoeopathic (Potassium Sulfate) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Comb I Homoeopathic (Potassium Sulfate) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Comb I Homoeopathic (Potassium Sulfate) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Comb I Homoeopathic (Potassium Sulfate) depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.

If Comb I Homoeopathic (Potassium Sulfate) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental Comb I Homoeopathic (Potassium Sulfate) in the form of high Comb I Homoeopathic (Potassium Sulfate) food or Comb I Homoeopathic (Potassium Sulfate) chloride may be able to restore normal Comb I Homoeopathic (Potassium Sulfate) levels.

In rare circumstances (eg, patients with renal tubular acidosis) Comb I Homoeopathic (Potassium Sulfate) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Comb I Homoeopathic (Potassium Sulfate) replacement should be accomplished with Comb I Homoeopathic (Potassium Sulfate) salts other than the chloride, such as Comb I Homoeopathic (Potassium Sulfate) bicarbonate, Comb I Homoeopathic (Potassium Sulfate) citrate, Comb I Homoeopathic (Potassium Sulfate) acetate, or Comb I Homoeopathic (Potassium Sulfate) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Comb I Homoeopathic (Potassium Sulfate) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Comb I Homoeopathic (Potassium Sulfate) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.

1. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.

2. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, eg, digitalized patients or patients with significant cardiac arrhythmias.

The use of Comb I Homoeopathic (Potassium Sulfate) salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum Comb I Homoeopathic (Potassium Sulfate) should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with Comb I Homoeopathic (Potassium Sulfate) salts may be indicated.

CONTRAINDICATIONS

Comb I Homoeopathic (Potassium Sulfate) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Comb I Homoeopathic (Potassium Sulfate) concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) (see OVERDOSAGE ).

Controlled-release formulations of Comb I Homoeopathic (Potassium Sulfate) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Comb I Homoeopathic (Potassium Sulfate) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Comb I Homoeopathic (Potassium Sulfate) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Comb I Homoeopathic (Potassium Sulfate) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

WARNINGS

Hyperkalemia (see OVERDOSAGE )

In patients with impaired mechanisms for excreting Comb I Homoeopathic (Potassium Sulfate), the administration of Comb I Homoeopathic (Potassium Sulfate) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Comb I Homoeopathic (Potassium Sulfate) by the intravenous route but may also occur in patients given Comb I Homoeopathic (Potassium Sulfate) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Comb I Homoeopathic (Potassium Sulfate) salts in patients with chronic renal disease, or any other condition which impairs Comb I Homoeopathic (Potassium Sulfate) excretion, requires particularly careful monitoring of the serum Comb I Homoeopathic (Potassium Sulfate) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Comb I Homoeopathic (Potassium Sulfate) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.

Interaction with Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some Comb I Homoeopathic (Potassium Sulfate) retention by inhibiting aldosterone production. Comb I Homoeopathic (Potassium Sulfate) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Comb I Homoeopathic (Potassium Sulfate) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Comb I Homoeopathic (Potassium Sulfate) chloride are associated with an increased frequency of small bowel lesions (40-50 per 100,000 patient years) compared to sustained release wax matrix formulations (less than one per 100,000 patient years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax matrix or enteric-coated products is not available. Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Comb I Homoeopathic (Potassium Sulfate) chloride and thus to minimize the possibility of a high local concentration of Comb I Homoeopathic (Potassium Sulfate) near the gastrointestinal wall.

Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after 1 week of solid oral Comb I Homoeopathic (Potassium Sulfate) chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax matrix and microencapsulated dosage forms. In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of a wax matrix controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (ie, 96 mEq per day in divided doses of Comb I Homoeopathic (Potassium Sulfate) chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (ie, non-fasting, no anticholinergic agent, smaller doses) under which controlled-release Comb I Homoeopathic (Potassium Sulfate) chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations. Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq should be discontinued immediately and the possibility of ulceration, obstruction, or perforation should be considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Comb I Homoeopathic (Potassium Sulfate) salt such as Comb I Homoeopathic (Potassium Sulfate) bicarbonate, Comb I Homoeopathic (Potassium Sulfate) citrate, Comb I Homoeopathic (Potassium Sulfate) acetate, or Comb I Homoeopathic (Potassium Sulfate) gluconate.

PRECAUTIONS

General

The diagnosis of Comb I Homoeopathic depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Comb I Homoeopathic (Potassium Sulfate) depletion. In interpreting the serum Comb I Homoeopathic (Potassium Sulfate) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Comb I Homoeopathic (Potassium Sulfate) while acute acidosis per se can increase the serum Comb I Homoeopathic (Potassium Sulfate) concentration into the normal range even in the presence of a reduced total body Comb I Homoeopathic (Potassium Sulfate). The treatment of Comb I Homoeopathic (Potassium Sulfate) depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.

Information for Patients

Physicians should consider reminding the patient of the following: To take each dose with meals and with a full glass of water or other liquid. To take each dose without crushing, chewing, or sucking the tablets. If those patients are having difficulty swallowing whole tablets, they may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:

    1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).

    2. Allow approximately 2 minutes for the tablet(s) to disintegrate.

    3. Stir for about half a minute after the tablet(s) has disintegrated.

    4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.

    5. Add another 1 fluid ounce of water, swirl, and consume immediately.

    6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.


Aqueous suspension of Comb I Homoeopathic (Potassium Sulfate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.

To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.

Laboratory Tests

When blood is drawn for analysis of plasma Comb I Homoeopathic it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.

Drug Interactions

Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Comb I Homoeopathic is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Comb I Homoeopathic (Potassium Sulfate) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal Comb I Homoeopathic ion content of human milk is about 13 mEq per liter. Since oral Comb I Homoeopathic (Potassium Sulfate) becomes part of the body Comb I Homoeopathic (Potassium Sulfate) pool, so long as body Comb I Homoeopathic (Potassium Sulfate) is not excessive, the contribution of Comb I Homoeopathic (Potassium Sulfate) chloride supplementation should have little or no effect on the level in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Comb I Homoeopathic (Potassium Sulfate) Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the 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.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; and it may be useful to monitor renal function.

ADVERSE REACTIONS

One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS ). The most common adverse reactions to oral Comb I Homoeopathic (Potassium Sulfate) salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals or reducing the amount taken at one time.

OVERDOSAGE

The administration of oral Comb I Homoeopathic (Potassium Sulfate) salts to persons with normal excretory mechanisms for Comb I Homoeopathic (Potassium Sulfate) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Comb I Homoeopathic (Potassium Sulfate) is administered too rapidly intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum Comb I Homoeopathic (Potassium Sulfate) concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).

Treatment measures for hyperkalemia include the following:

  • Patients should be closely monitored for arrhythmias and electrolyte changes.
  • Elimination of foods and medications containing Comb I Homoeopathic (Potassium Sulfate) and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.
  • Intravenous calcium gluconate if the patient is at no risk of developing digitalis toxicity.
  • Intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10-20 units of crystalline insulin per 1,000 mL.
  • Correction of acidosis, if present, with intravenous sodium bicarbonate.
  • Use of exchange resins, hemodialysis, or peritoneal dialysis.

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum Comb I Homoeopathic (Potassium Sulfate) concentration can produce digitalis toxicity.

The extended release feature means that absorption and toxic effects may be delayed for hours.

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

The usual dietary intake of Comb I Homoeopathic (Potassium Sulfate) by the average adult is 50 to 100 mEq per day. Comb I Homoeopathic (Potassium Sulfate) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Comb I Homoeopathic (Potassium Sulfate) from the total body store.

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of Comb I Homoeopathic (Potassium Sulfate) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Comb I Homoeopathic (Potassium Sulfate) chloride.

Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:
    • Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
    • Allow approximately 2 minutes for the tablet(s) to disintegrate.
    • Stir for about half a minute after the tablet(s) has disintegrated.
    • Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
    • Add another 1 fluid ounce of water, swirl, and consume immediately.
    • Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.

Aqueous suspension of Comb I Homoeopathic (Potassium Sulfate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Comb I Homoeopathic (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.

Storage Conditions

Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Comb I Homoeopathic (Potassium Sulfate) chloride 20 Meq

Comb I Homoeopathic 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.


Comb I Homoeopathic 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.


Comb I Homoeopathic 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.


Comb I Homoeopathic 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.


Comb I Homoeopathic 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. "Potassium". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  2. "Iron". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "Iron". http://www.drugbank.ca/drugs/DB0159... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Comb I Homoeopathic?

Depending on the reaction of the Comb I Homoeopathic after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Comb I Homoeopathic 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 Comb I Homoeopathic 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 Comb I Homoeopathic, 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 Comb I Homoeopathic consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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

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