Matol

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Matol uses

Matol consists of Iron (Ferrous Glycerophosphate), Magnesium (Magnesium Glycerophosphate), Potassium (Glycerophosphate Potassium), Potassium (Potassium Citrate), Potassium Iodide.

Iron (Ferrous Glycerophosphate):


1 INDICATIONS AND USAGE

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

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

2 DOSAGE AND ADMINISTRATION

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

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

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

Administer Matol (Iron (Ferrous Glycerophosphate)) 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 Matol (Iron (Ferrous Glycerophosphate)), 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. Matol (Iron (Ferrous Glycerophosphate)) treatment may be repeated if Matol (Iron (Ferrous Glycerophosphate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

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

2.4 Pediatric Patients with HDD-CKD for Matol (Iron (Ferrous Glycerophosphate)) maintenance treatment

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

For Matol (Iron (Ferrous Glycerophosphate)) maintenance treatment: Administer Matol (Iron (Ferrous Glycerophosphate)) 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. Matol (Iron (Ferrous Glycerophosphate)) treatment may be repeated if necessary.

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

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

For Matol (Iron (Ferrous Glycerophosphate)) maintenance treatment: Administer Matol (Iron (Ferrous Glycerophosphate)) 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. Matol (Iron (Ferrous Glycerophosphate)) treatment may be repeated if necessary.

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3 DOSAGE FORMS AND STRENGTHS

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

4 CONTRAINDICATIONS

  • Known hypersensitivity to Matol (Iron (Ferrous Glycerophosphate))
  • Known hypersensitivity to Matol (Iron (Ferrous Glycerophosphate)) (4)

5 WARNINGS AND PRECAUTIONS

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

5.2 Hypotension

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

5.3 Matol (Iron (Ferrous Glycerophosphate)) Overload

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

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6 ADVERSE REACTIONS

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

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

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

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

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

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

Matol (Iron (Ferrous Glycerophosphate)) has not been studied in patients younger than 2 years of age.

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

8.5 Geriatric Use

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

Toxicities in single-dose studies in mice and rats, at intravenous Matol (Iron (Ferrous Glycerophosphate)) 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

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

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

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

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

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

Matol (Iron (Ferrous Glycerophosphate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Matol (Iron (Ferrous Glycerophosphate)) (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 Matol ).

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 Matol (Iron (Ferrous Glycerophosphate)) treatment and 24 in the historical control group) with Matol (Iron (Ferrous Glycerophosphate)) deficiency anemia. Eligibility criteria for Matol (Iron (Ferrous Glycerophosphate)) 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.

Matol (Iron (Ferrous Glycerophosphate)) 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 Matol (Iron (Ferrous Glycerophosphate)), who were off intravenous Matol (Iron (Ferrous Glycerophosphate)) 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 Matol (Iron (Ferrous Glycerophosphate)) 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
Matol (Iron (Ferrous Glycerophosphate)) (n=69 Historical Control (n=18) Matol (Iron (Ferrous Glycerophosphate))

(n=73)

Historical Control

(n=18)

Matol (Iron (Ferrous Glycerophosphate))

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

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

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

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Matol (Iron (Ferrous Glycerophosphate)) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

Magnesium (Magnesium Glycerophosphate):



Matol (Magnesium (Magnesium Glycerophosphate)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Matol (Magnesium (Magnesium Glycerophosphate)) Sulfate Injection, USP is a sterile solution of Matol (Magnesium (Magnesium Glycerophosphate)) 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.

Matol (Magnesium (Magnesium Glycerophosphate)) 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

Matol (Magnesium (Magnesium Glycerophosphate)) (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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)). While there are large stores of Matol (Magnesium (Magnesium Glycerophosphate)) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Matol (Magnesium (Magnesium Glycerophosphate)) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Matol (Magnesium (Magnesium Glycerophosphate)) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) levels range from 1.5 to 2.5 mEq/liter.

As plasma Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)). Serum Matol (Magnesium (Magnesium Glycerophosphate)) concentrations in excess of 12 mEq/L may be fatal.

Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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. Matol (Magnesium (Magnesium Glycerophosphate)) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Matol (Magnesium (Magnesium Glycerophosphate)) Sulfate Injection, USP is suitable for replacement therapy in Matol (Magnesium (Magnesium Glycerophosphate)) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Matol (Magnesium (Magnesium Glycerophosphate)) (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), Matol (Magnesium (Magnesium Glycerophosphate)) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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. Matol (Magnesium (Magnesium Glycerophosphate)) sulfate should be used during pregnancy only if clearly needed. If Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Matol (Magnesium (Magnesium Glycerophosphate)).

Because Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) should be given until they return. Serum Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) intoxication in eclampsia.

50% Matol (Magnesium (Magnesium Glycerophosphate)) 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

Matol (Magnesium (Magnesium Glycerophosphate)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Matol (Magnesium (Magnesium Glycerophosphate)). CNS depression and peripheral transmission defects produced by Matol (Magnesium (Magnesium Glycerophosphate)) may be antagonized by calcium.

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

Cardiac Glycosides - Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) sulfate for more than 5 to 7 days.1-10 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Matol (Magnesium (Magnesium Glycerophosphate)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) is distributed into milk during parenteral Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Matol (Magnesium (Magnesium Glycerophosphate)) usually are the result of Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Matol (Magnesium (Magnesium Glycerophosphate)).

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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) Deficiency

In the treatment of mild Matol (Magnesium (Magnesium Glycerophosphate)) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Matol (Magnesium (Magnesium Glycerophosphate)) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) sulfate is 20 grams/48 hours and frequent serum Matol (Magnesium (Magnesium Glycerophosphate)) concentrations must be obtained. Continuous use of Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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, Matol (Magnesium (Magnesium Glycerophosphate)) 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

Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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

Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
  • Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
  • Santi MD, Henry GW, Douglas GL. Matol (Magnesium (Magnesium Glycerophosphate)) 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. Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
  • McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Matol (Magnesium (Magnesium Glycerophosphate)) 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 Matol (Magnesium (Magnesium Glycerophosphate)) 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% Matol (Magnesium (Magnesium Glycerophosphate)) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Matol (Magnesium (Magnesium Glycerophosphate)) 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

Potassium (Glycerophosphate Potassium):



Matol (Potassium (Glycerophosphate Potassium)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

Matol (Potassium (Glycerophosphate Potassium)) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Matol (Potassium (Glycerophosphate Potassium)) chloride, and the structural formula is KCl. Matol (Potassium (Glycerophosphate Potassium)) 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.

Matol (Potassium (Glycerophosphate Potassium)) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Matol (Potassium (Glycerophosphate Potassium)) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) chloride.

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

CLINICAL PHARMACOLOGY

The Matol (Potassium (Glycerophosphate Potassium)) ion is the principal intracellular cation of most body tissues. Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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.

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

Matol (Potassium (Glycerophosphate Potassium)) depletion will occur whenever the rate of Matol (Potassium (Glycerophosphate Potassium)) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Matol (Potassium (Glycerophosphate Potassium)) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Matol (Potassium (Glycerophosphate Potassium)) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Matol (Potassium (Glycerophosphate Potassium)) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) in the form of high Matol (Potassium (Glycerophosphate Potassium)) food or Matol (Potassium (Glycerophosphate Potassium)) chloride may be able to restore normal Matol (Potassium (Glycerophosphate Potassium)) levels.

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

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Matol (Potassium (Glycerophosphate Potassium)) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) salts may be indicated.

CONTRAINDICATIONS

Matol (Potassium (Glycerophosphate Potassium)) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Matol (Potassium (Glycerophosphate Potassium)) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Matol (Potassium (Glycerophosphate Potassium)) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)), the administration of Matol (Potassium (Glycerophosphate Potassium)) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Matol (Potassium (Glycerophosphate Potassium)) by the intravenous route but may also occur in patients given Matol (Potassium (Glycerophosphate Potassium)) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Matol (Potassium (Glycerophosphate Potassium)) salts in patients with chronic renal disease, or any other condition which impairs Matol (Potassium (Glycerophosphate Potassium)) excretion, requires particularly careful monitoring of the serum Matol (Potassium (Glycerophosphate Potassium)) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) retention by inhibiting aldosterone production. Matol (Potassium (Glycerophosphate Potassium)) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Matol (Potassium (Glycerophosphate Potassium)) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Matol (Potassium (Glycerophosphate Potassium)) 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. Matol (Potassium (Glycerophosphate Potassium)) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Matol (Potassium (Glycerophosphate Potassium)) chloride and thus to minimize the possibility of a high local concentration of Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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. Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) salt such as Matol (Potassium (Glycerophosphate Potassium)) bicarbonate, Matol (Potassium (Glycerophosphate Potassium)) citrate, Matol (Potassium (Glycerophosphate Potassium)) acetate, or Matol (Potassium (Glycerophosphate Potassium)) gluconate.

PRECAUTIONS

General

The diagnosis of Matol ) depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Matol (Potassium (Glycerophosphate Potassium)) depletion. In interpreting the serum Matol (Potassium (Glycerophosphate Potassium)) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Matol (Potassium (Glycerophosphate Potassium)) while acute acidosis per se can increase the serum Matol (Potassium (Glycerophosphate Potassium)) concentration into the normal range even in the presence of a reduced total body Matol (Potassium (Glycerophosphate Potassium)). The treatment of Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Matol (Potassium (Glycerophosphate Potassium)) 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 Matol ) 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. Matol ) is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

The normal Matol ) ion content of human milk is about 13 mEq per liter. Since oral Matol (Potassium (Glycerophosphate Potassium)) becomes part of the body Matol (Potassium (Glycerophosphate Potassium)) pool, so long as body Matol (Potassium (Glycerophosphate Potassium)) is not excessive, the contribution of Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) salts to persons with normal excretory mechanisms for Matol (Potassium (Glycerophosphate Potassium)) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) by the average adult is 50 to 100 mEq per day. Matol (Potassium (Glycerophosphate Potassium)) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Matol (Potassium (Glycerophosphate Potassium)) chloride.

Matol (Potassium (Glycerophosphate Potassium)) 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 Matol (Potassium (Glycerophosphate Potassium)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Matol (Potassium (Glycerophosphate Potassium)) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Matol (Potassium (Glycerophosphate Potassium)) 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

Matol (Potassium (Glycerophosphate Potassium)) chloride 20 Meq

Potassium (Potassium Citrate):



Matol (Potassium (Potassium Citrate)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

Matol (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Matol (Potassium (Potassium Citrate)) chloride, and the structural formula is KCl. Matol (Potassium (Potassium Citrate)) 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.

Matol (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Matol (Potassium (Potassium Citrate)) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) chloride.

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

CLINICAL PHARMACOLOGY

The Matol (Potassium (Potassium Citrate)) ion is the principal intracellular cation of most body tissues. Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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.

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

Matol (Potassium (Potassium Citrate)) depletion will occur whenever the rate of Matol (Potassium (Potassium Citrate)) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Matol (Potassium (Potassium Citrate)) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Matol (Potassium (Potassium Citrate)) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Matol (Potassium (Potassium Citrate)) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) in the form of high Matol (Potassium (Potassium Citrate)) food or Matol (Potassium (Potassium Citrate)) chloride may be able to restore normal Matol (Potassium (Potassium Citrate)) levels.

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

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Matol (Potassium (Potassium Citrate)) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) salts may be indicated.

CONTRAINDICATIONS

Matol (Potassium (Potassium Citrate)) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Matol (Potassium (Potassium Citrate)) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Matol (Potassium (Potassium Citrate)) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)), the administration of Matol (Potassium (Potassium Citrate)) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Matol (Potassium (Potassium Citrate)) by the intravenous route but may also occur in patients given Matol (Potassium (Potassium Citrate)) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Matol (Potassium (Potassium Citrate)) salts in patients with chronic renal disease, or any other condition which impairs Matol (Potassium (Potassium Citrate)) excretion, requires particularly careful monitoring of the serum Matol (Potassium (Potassium Citrate)) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) retention by inhibiting aldosterone production. Matol (Potassium (Potassium Citrate)) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Matol (Potassium (Potassium Citrate)) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Matol (Potassium (Potassium Citrate)) 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. Matol (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Matol (Potassium (Potassium Citrate)) chloride and thus to minimize the possibility of a high local concentration of Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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. Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) salt such as Matol (Potassium (Potassium Citrate)) bicarbonate, Matol (Potassium (Potassium Citrate)) citrate, Matol (Potassium (Potassium Citrate)) acetate, or Matol (Potassium (Potassium Citrate)) gluconate.

PRECAUTIONS

General

The diagnosis of Matol ) depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Matol (Potassium (Potassium Citrate)) depletion. In interpreting the serum Matol (Potassium (Potassium Citrate)) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Matol (Potassium (Potassium Citrate)) while acute acidosis per se can increase the serum Matol (Potassium (Potassium Citrate)) concentration into the normal range even in the presence of a reduced total body Matol (Potassium (Potassium Citrate)). The treatment of Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Matol (Potassium (Potassium Citrate)) 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 Matol ) 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. Matol ) is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

The normal Matol ) ion content of human milk is about 13 mEq per liter. Since oral Matol (Potassium (Potassium Citrate)) becomes part of the body Matol (Potassium (Potassium Citrate)) pool, so long as body Matol (Potassium (Potassium Citrate)) is not excessive, the contribution of Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) salts to persons with normal excretory mechanisms for Matol (Potassium (Potassium Citrate)) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) by the average adult is 50 to 100 mEq per day. Matol (Potassium (Potassium Citrate)) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Matol (Potassium (Potassium Citrate)) chloride.

Matol (Potassium (Potassium Citrate)) 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 Matol (Potassium (Potassium Citrate)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Matol (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Matol (Potassium (Potassium Citrate)) 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

Matol (Potassium (Potassium Citrate)) chloride 20 Meq

Potassium Iodide:



Matol (Potassium Iodide) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

Matol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Matol (Potassium Iodide) chloride, and the structural formula is KCl. Matol (Potassium Iodide) 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.

Matol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Matol (Potassium Iodide) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Matol (Potassium Iodide) 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 Matol (Potassium Iodide) chloride.

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

CLINICAL PHARMACOLOGY

The Matol (Potassium Iodide) ion is the principal intracellular cation of most body tissues. Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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.

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

Matol (Potassium Iodide) depletion will occur whenever the rate of Matol (Potassium Iodide) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Matol (Potassium Iodide) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Matol (Potassium Iodide) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Matol (Potassium Iodide) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) in the form of high Matol (Potassium Iodide) food or Matol (Potassium Iodide) chloride may be able to restore normal Matol (Potassium Iodide) levels.

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

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Matol (Potassium Iodide) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) salts may be indicated.

CONTRAINDICATIONS

Matol (Potassium Iodide) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Matol (Potassium Iodide) 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 Matol (Potassium Iodide) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Matol (Potassium Iodide) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Matol (Potassium Iodide) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Matol (Potassium Iodide) 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 Matol (Potassium Iodide), the administration of Matol (Potassium Iodide) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Matol (Potassium Iodide) by the intravenous route but may also occur in patients given Matol (Potassium Iodide) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Matol (Potassium Iodide) salts in patients with chronic renal disease, or any other condition which impairs Matol (Potassium Iodide) excretion, requires particularly careful monitoring of the serum Matol (Potassium Iodide) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Matol (Potassium Iodide) 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 Matol (Potassium Iodide) retention by inhibiting aldosterone production. Matol (Potassium Iodide) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Matol (Potassium Iodide) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Matol (Potassium Iodide) 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. Matol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Matol (Potassium Iodide) chloride and thus to minimize the possibility of a high local concentration of Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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. Matol (Potassium Iodide) 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 Matol (Potassium Iodide) salt such as Matol (Potassium Iodide) bicarbonate, Matol (Potassium Iodide) citrate, Matol (Potassium Iodide) acetate, or Matol (Potassium Iodide) gluconate.

PRECAUTIONS

General

The diagnosis of Matol depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Matol (Potassium Iodide) depletion. In interpreting the serum Matol (Potassium Iodide) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Matol (Potassium Iodide) while acute acidosis per se can increase the serum Matol (Potassium Iodide) concentration into the normal range even in the presence of a reduced total body Matol (Potassium Iodide). The treatment of Matol (Potassium Iodide) 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 Matol (Potassium Iodide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Matol (Potassium Iodide) 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 Matol 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. Matol is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

The normal Matol ion content of human milk is about 13 mEq per liter. Since oral Matol (Potassium Iodide) becomes part of the body Matol (Potassium Iodide) pool, so long as body Matol (Potassium Iodide) is not excessive, the contribution of Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) salts to persons with normal excretory mechanisms for Matol (Potassium Iodide) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) by the average adult is 50 to 100 mEq per day. Matol (Potassium Iodide) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Matol (Potassium Iodide) 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 Matol (Potassium Iodide) 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 Matol (Potassium Iodide) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Matol (Potassium Iodide) chloride.

Matol (Potassium Iodide) 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 Matol (Potassium Iodide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Matol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Matol (Potassium Iodide) 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

Matol (Potassium Iodide) chloride 20 Meq

Matol 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.


Matol 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.


Matol 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.


Matol 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.


Matol 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."THYROSHIELD (POTASSIUM IODIDE) SOLUTION [FLEMING & COMPANY, PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."POTASSIUM IODIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "Potassium". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Matol?

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

One visitor reported useful

How is the drug Matol useful in reducing or relieving the symptoms? How useful is it?
According to the survey conducted by the website sdrugs.com, there are variable results and below are the percentages of the users that say the medicine is useful to them and that say it is not helping them much. It is not ideal to continue taking the medication if you feel it is not helping you much. Contact your healthcare provider to check if there is a need to change the medicine or if there is a need to re-evaluate your condition. The usefulness of the medicine may vary from patient to patient, depending on the other diseases he is suffering from and slightly depends on the brand name.
Visitors%
Not useful1
100.0%

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

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Visitor reported age

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

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