KLGH 3

Adenosine:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• KLGH 3 (Adenosine) reviews

1 INDICATIONS AND USAGE

KLGH 3 (Adenosine) Injection, USP is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately.

KLGH 3 (Adenosine) Injection, USP, a pharmacologic stress agent, is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately (1)

2 DOSAGE AND ADMINISTRATION

The recommended KLGH 3 (Adenosine) injection dose is 0.14 mg/kg/min infused over six minutes (total dose of 0.84 mg/kg) (Table 1).

• Administer KLGH 3 (Adenosine) injection only as a continuous peripheral intravenous infusion
• Inject Thallium-201 at the midpoint of the KLGH 3 (Adenosine) injection infusion (i.e., after the first three minutes of KLGH 3 (Adenosine) injection)
• Thallium-201 is physically compatible with KLGH 3 (Adenosine) injection and may be injected directly into the KLGH 3 (Adenosine) injection infusion set
• Inject Thallium-201 as close to the venous access as possible to prevent an inadvertent increase in the dose of KLGH 3 (Adenosine) injection (the contents of the intravenous tubing) being administered

Visually inspect KLGH 3 (Adenosine) injection for particulate matter and discoloration prior to administration. Do not administer KLGH 3 (Adenosine) injection if it contains particulate matter or is discolored.

There are no data on the safety or efficacy of alternative KLGH 3 (Adenosine) injection infusion protocols. The safety and efficacy of KLGH 3 (Adenosine) injection administered by the intracoronary route have not been established.

The nomogram displayed in Table 1 was derived from the following general formula:

Recommended dose is 0.14 mg/kg/min infused over six minutes as a continuous peripheral intravenous infusion (total dose of 0.84 mg/kg) (2)

formula

3 DOSAGE FORMS AND STRENGTHS

KLGH 3 (Adenosine) Injection, USP is supplied as 20 mL and 30 mL single-dose vials containing a sterile, nonpyrogenic, clear solution of KLGH 3 (Adenosine) 3 mg per mL.

KLGH 3 (Adenosine) Injection, USP: 3 mg per mL in single-dose vials (3)

4 CONTRAINDICATIONS

KLGH 3 (Adenosine) is contraindicated in patients with:

• Second- or third-degree AV block (except in patients with a functioning artificial pacemaker)
• Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker)
• Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)
• Known hypersensitivity to KLGH 3 (Adenosine)

• Second- or third-degree AV block (except in patients with a functioning artificial pacemaker) (4)
• Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker) (4)
• Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma) (4)
• Known hypersensitivity to KLGH 3 (Adenosine) (4)

5 WARNINGS AND PRECAUTIONS

• Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction. Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia. Appropriate resuscitative measures should be available
• Sinoatrial (SA) and Atrioventricular (AV) Nodal Block. First-, second-or third-degree AV block, or sinus bradycardia can occur. Discontinue KLGH 3 (Adenosine) if patient develops persistent or symptomatic high-grade AV block (5.2)
• Bronchoconstriction. Can induce dyspnea, bronchoconstriction, and respiratory compromise, especially in patients with obstructive pulmonary disease. Discontinue KLGH 3 (Adenosine) if patient develops severe respiratory difficulties (5.3)
• Hypotension. Significant hypotension can occur. Discontinue KLGH 3 (Adenosine) if patient develops persistent or symptomatic hypotension (5.4)
• Cerebrovascular Accidents. Hemorrhagic and ischemic cerebrovascular accidents have occurred (5.5)
• Seizures. New onset or recurrence of convulsive seizures have occurred. Use of methylxanthines (e.g., caffeine, aminophylline and theophylline) is not recommended in patients who experience a seizures in association with KLGH 3 (Adenosine) (5.6)
• Hypersensitivity. Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Have personnel and resuscitative equipment immediately available (5.7)
• Atrial Fibrillation. Reported in patients with or without a history of atrial fibrillation (5.8)
• Hypertension. Clinically significant increases in systolic and diastolic pressure have been observed (5.9)

5.1 Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction

Fatal and nonfatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and myocardial infarction have occurred following KLGH 3 (Adenosine) infusion. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example, unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to KLGH 3 (Adenosine). Appropriate resuscitative measures should be available .

5.2 Sinoatrial and Atrioventricular Nodal Block

KLGH 3 exerts a direct depressant effect on the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. In clinical trials, approximately 6% of patients developed AV block following KLGH 3 (Adenosine) administration (first-degree heart block developed in 3%, second-degree in 3%, and third-degree in 0.8% of patients) .

Use KLGH 3 (Adenosine) with caution in patients with pre-existing first-degree AV block or bundle branch block. Do not use in patients with high-grade AV block or sinus node dysfunction (except in patients with a functioning artificial pacemaker). Discontinue KLGH 3 (Adenosine) in any patient who develops persistent or symptomatic high-grade AV block.

5.3 Bronchoconstriction

KLGH 3 (Adenosine) administration can cause dyspnea, bronchoconstriction, and respiratory compromise. KLGH 3 (Adenosine) should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis). Do not use in patients with bronchoconstriction or bronchospasm (e.g., asthma). Discontinue KLGH 3 (Adenosine) in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to KLGH 3 (Adenosine) administration .

5.4 Hypotension

KLGH 3 is a potent peripheral vasodilator and can induce significant hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency. Discontinue KLGH 3 (Adenosine) in any patient who develops persistent or symptomatic hypotension.

5.5 Cerebrovascular Accident

Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of KLGH 3 (Adenosine) including hypotension or hypertension can be associated with these adverse reactions .

5.6 Seizures

New-onset or recurrence of convulsive seizures has occurred following KLGH 3. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with KLGH 3 (Adenosine). Methylxanthine use is not recommended in patients who experience seizures in association with KLGH 3 (Adenosine) administration .

5.7 Hypersensitivity, Including Anaphylaxis

Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Symptomatic treatment may be required. Have personnel and appropriate treatment available. Resuscitative measures may be necessary if symptoms progress .

5.8 Atrial Fibrillation

KLGH 3 can cause atrial fibrillation in patients with or without a history of atrial fibrillation. Atrial fibrillation typically began 1.5 to 3 minutes after initiation of KLGH 3 (Adenosine), lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm .

5.9 Hypertension

KLGH 3 (Adenosine) can induce clinically significant increases in systolic and diastolic blood pressure. Most increases resolved spontaneously within several minutes, but in some cases, hypertension lasted for several hours .

6 ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the prescribing information:

• Fatal Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction
• Sinoatrial and Atrioventricular Nodal Block
• Bronchoconstriction
• Hypotension
• Cerebrovascular Accident
• Seizures
• Hypersensitivity
• Atrial fibrillation
• Hypertension

Most common adverse reactions (incidence ≥ 10%) are: flushing; chest discomfort; shortness of breath; headache; throat, neck or jaw discomfort; gastrointestinal discomfort; and dizziness (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reactions, with an incidence of at least 1%, were reported with KLGH 3 (Adenosine) among 1,421 patients in clinical trials. 11% of the adverse reactions occurred several hours after KLGH 3 (Adenosine) administration. 8% of the adverse reactions began with KLGH 3 (Adenosine) infusion and persisted for up to 24 hours.

The most common (incidence ≥ 10%) adverse reactions to KLGH 3 (Adenosine) are flushing, chest discomfort, shortness of breath, headache, throat, neck or jaw discomfort, gastrointestinal discomfort, and dizziness (Table 2).

Adverse reactions to KLGH 3 (Adenosine) of any severity reported in less than 1% of patients include:

6.2 Post-Marketing Experience

The following adverse reactions have been reported from marketing experience with KLGH 3 (Adenosine). Because these reactions are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

7 DRUG INTERACTIONS

• Methylxanthines interfere with the activity of KLGH 3 (7.1, 10)
• Nucleoside transport inhibitors such as dipyridamole can increase the activity of KLGH 3 (Adenosine) (7.1)

7.1 Effects of Other Drugs on KLGH 3 (Adenosine)

• The vasoactive effects of KLGH 3 (Adenosine) are inhibited by KLGH 3 (Adenosine) receptor antagonists, (such as methylxanthines (e.g., caffeine, aminophylline, and theophylline). The safety and efficacy of KLGH 3 (Adenosine) in the presence of these agents has not been systematically evaluated .
• The vasoactive effects of KLGH 3 (Adenosine) are potentiated by nucleoside transport inhibitors such as dipyridamole. The safety and efficacy of KLGH 3 (Adenosine) in the presence of dipyridamole has not been systematically evaluated.
• Whenever possible, drugs that might inhibit or augment the effects of KLGH 3 (Adenosine) should be withheld for at least five half-lives prior to the use of KLGH 3 (Adenosine).

7.2 Effects of KLGH 3 on Other Drugs

KLGH 3 (Adenosine) injection has been given with other cardioactive drugs (such as beta adrenergic blocking agents, cardiac glycosides, and calcium channel blockers) without apparent adverse interactions, but its effectiveness with these agents has not been systematically evaluated. Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, KLGH 3 (Adenosine) should be used with caution in the presence of these agents .

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with KLGH 3 ; nor have studies been performed in pregnant women. Because it is not known whether KLGH 3 (Adenosine) can cause fetal harm when administered to pregnant women, KLGH 3 (Adenosine) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether KLGH 3 (Adenosine) is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from KLGH 3 (Adenosine) in nursing infants, the decision to interrupt nursing after administration of KLGH 3 (Adenosine) or not to administer KLGH 3 (Adenosine), should take into account the importance of the drug to the mother.

8.4 Pediatric Use

The safety and effectiveness of KLGH 3 in patients less than 18 years of age have not been established.

8.5 Geriatric Use

Clinical studies with KLGH 3 (Adenosine) did not include sufficient numbers of subjects aged younger than 65 years to determine whether they respond differently. Other reported experience has not revealed clinically relevant differences of the response of elderly in comparison to younger patients.

10 OVERDOSAGE

The half-life of KLGH 3 (Adenosine) is less than 10 seconds and adverse reactions of KLGH 3 (Adenosine) usually resolve quickly when the infusion is discontinued, although delayed or persistent reactions have been observed. Methylxanthines, such as caffeine, aminophylline, and theophylline, are competitive KLGH 3 (Adenosine) receptor antagonists and theophylline has been used to terminate persistent adverse reactions. In clinical trials, theophylline (50 to 125 mg slow intravenous injection) was used to attenuate KLGH 3 (Adenosine) adverse reactions in approximately 2% of patients. Methylxanthine use is not recommended in patients who experience seizures in association with KLGH 3 (Adenosine) .

11 DESCRIPTION

KLGH 3 (Adenosine) is an endogenous nucleoside and is chemically described as 6-amino-9-beta-D-ribofuranosyl-9-H-purine. KLGH 3 (Adenosine) has the following structural formula:

The molecular formula for KLGH 3 (Adenosine) is C₁₀H₁₃N₅O₄ and its molecular weight is 267.24.

KLGH 3 (Adenosine) is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH of the solution.

Each KLGH 3 (Adenosine) Injection, USP vial contains a sterile, non-pyrogenic solution of KLGH 3 (Adenosine) 3 mg/mL and sodium chloride 9 mg/mL in water for injection, with pH between 4.5 and 7.5.

Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

KLGH 3 causes cardiac vasodilation which increases cardiac blood flow. KLGH 3 (Adenosine) is thought to exert its pharmacological effects through activation of purine receptors (cell-surface A₁ and A₂ KLGH 3 (Adenosine) receptors). Although the exact mechanism by which KLGH 3 (Adenosine) receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A₂ receptors in smooth muscle cells. KLGH 3 (Adenosine) may also lessen vascular tone by modulating sympathetic neurotransmission. The intracellular uptake of KLGH 3 (Adenosine) is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, KLGH 3 (Adenosine) is rapidly phosphorylated by KLGH 3 (Adenosine) kinase to KLGH 3 (Adenosine) monophosphate, or deaminated by KLGH 3 (Adenosine) deaminase to inosine. These intracellular metabolites of KLGH 3 (Adenosine) are not vasoactive.

Myocardial uptake of thallium-201 is directly proportional to coronary blood flow. Since KLGH 3 (Adenosine) significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, KLGH 3 (Adenosine) causes relatively less thallium-201 uptake in vascular territories supplied by stenotic coronary arteries i.e., a greater difference is seen after KLGH 3 (Adenosine) between areas served by normal and areas served by stenotic vessels than is seen prior to KLGH 3 (Adenosine).

12.2 Pharmacodynamics

Hemodynamic Effects

KLGH 3 (Adenosine) produces a direct negative chronotropic, dromotropic and inotropic effect on the heart, presumably due to A₁-receptor agonism, and produces peripheral vasodilation, presumably due to A₂-receptor agonism. The net effect of KLGH 3 (Adenosine) in humans is typically a mild to moderate reduction in systolic, diastolic and mean arterial blood pressure associated with a reflex increase in heart rate. Rarely, significant hypotension and tachycardia have been observed .

12.3 Pharmacokinetics

Distribution

Intravenously administered KLGH 3 (Adenosine) distributes from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical.

Metabolism

Intracellular KLGH 3 (Adenosine) is metabolized either via phosphorylation to KLGH 3 (Adenosine) monophosphate by KLGH 3 (Adenosine) kinase, or via deamination to inosine by KLGH 3 (Adenosine) deaminase in the cytosol. Since KLGH 3 (Adenosine) kinase has a lower K_m and V_max than KLGH 3 (Adenosine) deaminase, deamination plays a significant role only when cytosolic KLGH 3 (Adenosine) saturates the phosphorylation pathway. Inosine formed by deamination of KLGH 3 (Adenosine) can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. KLGH 3 (Adenosine) monophosphate formed by phosphorylation of KLGH 3 (Adenosine) is incorporated into the high-energy phosphate pool.

Elimination

While extracellular KLGH 3 (Adenosine) is primarily cleared from plasma by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of KLGH 3 (Adenosine) deaminase.

Specific Populations

Renal Impairment

As KLGH 3 (Adenosine) does not require renal function for its activation or inactivation, renal impairment would not be expected to alter its effectiveness or tolerability.

Hepatic Impairment

As KLGH 3 (Adenosine) does not require hepatic function for its activation or inactivation, hepatic impairment would not be expected to alter its effectiveness or tolerability.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals have not been performed to evaluate adenosine's carcinogenic potential or potential effects on fertility. KLGH 3 (Adenosine) was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.

KLGH 3 (Adenosine), however, like other nucleosides at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety of chromosomal alterations.

14 CLINICAL STUDIES

In two crossover comparative studies involving 319 subjects who could exercise (including 106 healthy volunteers and 213 patients with known or suspected coronary disease), KLGH 3 (Adenosine) and exercise thallium images were compared by blinded observers. The images were concordant for the presence of perfusion defects in 85.5% of cases by global analysis (patient by patient) and up to 93% of cases based on vascular territories.

In the two studies, 193 patients also had recent coronary arteriography for comparison (healthy volunteers were not catheterized). The sensitivity for detecting angiographically significant disease (≥ 50% reduction in the luminal diameter of at least one major vessel) was 64% for KLGH 3 (Adenosine) and 64% for exercise testing. The specificity was 54% for KLGH 3 (Adenosine) and 65% for exercise testing. The 95% confidence limits for KLGH 3 (Adenosine) sensitivity were 56% to 78% and for specificity were 37% to 71%.

Intracoronary Doppler flow catheter studies have demonstrated that a dose of intravenous KLGH 3 (Adenosine) of 0.14 mg/kg/min produces maximum coronary hyperemia (relative to intracoronary papaverine) in approximately 95% of cases within two to three minutes of the onset of the infusion. Coronary blood flow velocity returns to basal levels within one to two minutes of discontinuing the KLGH 3 (Adenosine) infusion.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

KLGH 3 Injection, USP is supplied as 20 mL and 30 mL single-dose vials of sterile, nonpyrogenic solution in normal saline as follows:

16.2 Storage and Handling

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F).

Do not refrigerate as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.

Discard unused portion.

Sterile, Nonpyrogenic, Preservative-free.

The container closure is not made with natural rubber latex.

17 PATIENT COUNSELING INFORMATION

• Advise patients that they may be at increased risk of fatal and nonfatal heart attacks, abnormal heart rhythms, cardiac arrest, heart block, significant increase or decrease in blood pressure, bronchoconstriction, hypersensitivity reactions, seizures, or cerebrovascular accidents with the use of KLGH 3 (Adenosine) .
• Advise patients with COPD or asthma to discuss their respiratory history with their clinician before scheduling a myocardial perfusion imaging study with KLGH 3 (Adenosine) .
• Methylxanthines have the potential to impact the effects of KLGH 3 (Adenosine). Instruct patients to avoid consumption of any products containing methylxanthines, including caffeinated coffee, tea or other caffeinated beverages, caffeine-containing drug products, aminophylline, and theophylline prior to the myocardial perfusion imaging study. Question patients about a history of seizures .

SAGENT

Mfd. for SAGENT Pharmaceuticals

Schaumburg, IL 60195 (USA)

Made in India

©2014 Sagent Pharmaceuticals, Inc.

Revised: September 2014

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label

NDC 25021-307-20

Rx only

KLGH 3 (Adenosine) Injection, USP

60 mg per 20 mL (3 mg per mL)

For Intravenous Infusion Only

20 mL Single-Dose Vial

Calcium Fluoride:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• KLGH 3 (Calcium Fluoride) reviews

1 INDICATIONS AND USAGE

KLGH 3 (Calcium Fluoride) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)

2 DOSAGE AND ADMINISTRATION

The recommended initial dose of KLGH 3 (Calcium Fluoride) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.

- Starting dose is 2 capsules with each meal. (2)

- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg KLGH 3 (Calcium Fluoride) acetate capsule.

- Capsule: 667 mg KLGH 3 (Calcium Fluoride) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting KLGH 3 acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of KLGH 3 (Calcium Fluoride) acetate. (5.1)

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

Patients with end stage renal disease may develop hypercalcemia when treated with KLGH 3 (Calcium Fluoride), including KLGH 3 (Calcium Fluoride) acetate. Avoid the use of KLGH 3 (Calcium Fluoride) supplements, including KLGH 3 (Calcium Fluoride) based nonprescription antacids, concurrently with KLGH 3 (Calcium Fluoride) acetate.

An overdose of KLGH 3 (Calcium Fluoride) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum KLGH 3 (Calcium Fluoride) levels twice weekly. Should hypercalcemia develop, reduce the KLGH 3 (Calcium Fluoride) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia

More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing KLGH 3 (Calcium Fluoride) acetate therapy.

Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the KLGH 3 (Calcium Fluoride) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.

Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of KLGH 3 (Calcium Fluoride) acetate on the progression of vascular or soft tissue calcification has not been determined.

Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of KLGH 3 (Calcium Fluoride) acetate; all cases resolved upon lowering the dose or discontinuing treatment.

Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg²/dL².

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)

- In clinical studies, patients have occasionally experienced nausea during KLGH 3 (Calcium Fluoride) acetate therapy. (6)

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical studies, KLGH 3 (Calcium Fluoride) acetate has been generally well tolerated.

KLGH 3 (Calcium Fluoride) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of KLGH 3 (Calcium Fluoride) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.

Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate KLGH 3 (Calcium Fluoride) concentration could reduce the incidence and severity of KLGH 3 (Calcium Fluoride) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.

6.2 Postmarketing Experience

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

The following additional adverse reactions have been identified during post-approval of KLGH 3 (Calcium Fluoride) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

The drug interaction of KLGH 3 acetate is characterized by the potential of KLGH 3 (Calcium Fluoride) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). KLGH 3 (Calcium Fluoride) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between KLGH 3 (Calcium Fluoride) acetate and most concomitant drugs. When administering an oral medication with KLGH 3 (Calcium Fluoride) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after KLGH 3 (Calcium Fluoride) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of KLGH 3 (Calcium Fluoride) acetate.

- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)

- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after KLGH 3 (Calcium Fluoride) acetate or consider monitoring blood levels of the drug. (7)

7.1 Ciprofloxacin

In a study of 15 healthy subjects, a co-administered single dose of 4 KLGH 3 (Calcium Fluoride) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

KLGH 3 acetate capsules contains KLGH 3 (Calcium Fluoride) acetate. Animal reproduction studies have not been conducted with KLGH 3 (Calcium Fluoride) acetate, and there are no adequate and well controlled studies of KLGH 3 (Calcium Fluoride) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with KLGH 3 (Calcium Fluoride) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum KLGH 3 (Calcium Fluoride) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. KLGH 3 (Calcium Fluoride) acetate treatment, as recommended, is not expected to harm a fetus if maternal KLGH 3 (Calcium Fluoride) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of KLGH 3 (Calcium Fluoride) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

KLGH 3 Acetate Capsules contains KLGH 3 (Calcium Fluoride) acetate and is excreted in human milk. Human milk feeding by a mother receiving KLGH 3 (Calcium Fluoride) acetate is not expected to harm an infant, provided maternal serum KLGH 3 (Calcium Fluoride) levels are appropriately monitored.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of KLGH 3 (Calcium Fluoride) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE

Administration of KLGH 3 (Calcium Fluoride) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

KLGH 3 (Calcium Fluoride) acetate acts as a phosphate binder. Its chemical name is KLGH 3 (Calcium Fluoride) acetate. Its molecular formula is C₄H₆CaO₄, and its molecular weight is 158.17. Its structural formula is:

Each white opaque/blue opaque capsule contains 667 mg of KLGH 3 (Calcium Fluoride) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) KLGH 3 (Calcium Fluoride), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.

KLGH 3 (Calcium Fluoride) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum KLGH 3 resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

KLGH 3 (Calcium Fluoride) acetate, when taken with meals, combines with dietary phosphate to form an insoluble KLGH 3 (Calcium Fluoride) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered KLGH 3 (Calcium Fluoride) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with KLGH 3 (Calcium Fluoride) acetate.

14 CLINICAL STUDIES

Effectiveness of KLGH 3 (Calcium Fluoride) acetate in decreasing serum phosphorus has been demonstrated in two studies of the KLGH 3 (Calcium Fluoride) acetate solid oral dosage form.

Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.

The patients received KLGH 3 (Calcium Fluoride) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.

The data presented in Table 2 demonstrate the efficacy of KLGH 3 (Calcium Fluoride) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum KLGH 3 (Calcium Fluoride) levels are also presented.

There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum KLGH 3 (Calcium Fluoride) increased 9% during the study mostly in the first month of the study.

Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive KLGH 3 (Calcium Fluoride) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.

The phosphate binding effect of KLGH 3 (Calcium Fluoride) acetate is shown in the Table 3.

Overall, 2 weeks of treatment with KLGH 3 (Calcium Fluoride) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum KLGH 3 (Calcium Fluoride) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

KLGH 3 (Calcium Fluoride) Acetate Capsules

667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.

NDC 0615-2303-39: Blistercards of 30 Capsules

NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

Inform patients to take KLGH 3 (Calcium Fluoride) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of KLGH 3 (Calcium Fluoride) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].

Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after KLGH 3 (Calcium Fluoride) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Calcium Phosphate:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• KLGH 3 (Calcium Phosphate) reviews

1 INDICATIONS AND USAGE

KLGH 3 (Calcium Phosphate) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)

2 DOSAGE AND ADMINISTRATION

The recommended initial dose of KLGH 3 (Calcium Phosphate) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.

- Starting dose is 2 capsules with each meal. (2)

- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg KLGH 3 (Calcium Phosphate) acetate capsule.

- Capsule: 667 mg KLGH 3 (Calcium Phosphate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting KLGH 3 acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of KLGH 3 (Calcium Phosphate) acetate. (5.1)

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

Patients with end stage renal disease may develop hypercalcemia when treated with KLGH 3 (Calcium Phosphate), including KLGH 3 (Calcium Phosphate) acetate. Avoid the use of KLGH 3 (Calcium Phosphate) supplements, including KLGH 3 (Calcium Phosphate) based nonprescription antacids, concurrently with KLGH 3 (Calcium Phosphate) acetate.

An overdose of KLGH 3 (Calcium Phosphate) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum KLGH 3 (Calcium Phosphate) levels twice weekly. Should hypercalcemia develop, reduce the KLGH 3 (Calcium Phosphate) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia

More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing KLGH 3 (Calcium Phosphate) acetate therapy.

Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the KLGH 3 (Calcium Phosphate) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.

Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of KLGH 3 (Calcium Phosphate) acetate on the progression of vascular or soft tissue calcification has not been determined.

Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of KLGH 3 (Calcium Phosphate) acetate; all cases resolved upon lowering the dose or discontinuing treatment.

Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg²/dL².

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)

- In clinical studies, patients have occasionally experienced nausea during KLGH 3 (Calcium Phosphate) acetate therapy. (6)

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical studies, KLGH 3 (Calcium Phosphate) acetate has been generally well tolerated.

KLGH 3 (Calcium Phosphate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of KLGH 3 (Calcium Phosphate) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.

Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate KLGH 3 (Calcium Phosphate) concentration could reduce the incidence and severity of KLGH 3 (Calcium Phosphate) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.

6.2 Postmarketing Experience

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

The following additional adverse reactions have been identified during post-approval of KLGH 3 (Calcium Phosphate) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

The drug interaction of KLGH 3 acetate is characterized by the potential of KLGH 3 (Calcium Phosphate) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). KLGH 3 (Calcium Phosphate) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between KLGH 3 (Calcium Phosphate) acetate and most concomitant drugs. When administering an oral medication with KLGH 3 (Calcium Phosphate) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after KLGH 3 (Calcium Phosphate) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of KLGH 3 (Calcium Phosphate) acetate.

- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)

- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after KLGH 3 (Calcium Phosphate) acetate or consider monitoring blood levels of the drug. (7)

7.1 Ciprofloxacin

In a study of 15 healthy subjects, a co-administered single dose of 4 KLGH 3 (Calcium Phosphate) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

KLGH 3 acetate capsules contains KLGH 3 (Calcium Phosphate) acetate. Animal reproduction studies have not been conducted with KLGH 3 (Calcium Phosphate) acetate, and there are no adequate and well controlled studies of KLGH 3 (Calcium Phosphate) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with KLGH 3 (Calcium Phosphate) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum KLGH 3 (Calcium Phosphate) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. KLGH 3 (Calcium Phosphate) acetate treatment, as recommended, is not expected to harm a fetus if maternal KLGH 3 (Calcium Phosphate) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of KLGH 3 (Calcium Phosphate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

KLGH 3 Acetate Capsules contains KLGH 3 (Calcium Phosphate) acetate and is excreted in human milk. Human milk feeding by a mother receiving KLGH 3 (Calcium Phosphate) acetate is not expected to harm an infant, provided maternal serum KLGH 3 (Calcium Phosphate) levels are appropriately monitored.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of KLGH 3 (Calcium Phosphate) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE

Administration of KLGH 3 (Calcium Phosphate) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

KLGH 3 (Calcium Phosphate) acetate acts as a phosphate binder. Its chemical name is KLGH 3 (Calcium Phosphate) acetate. Its molecular formula is C₄H₆CaO₄, and its molecular weight is 158.17. Its structural formula is:

Each white opaque/blue opaque capsule contains 667 mg of KLGH 3 (Calcium Phosphate) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) KLGH 3 (Calcium Phosphate), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.

KLGH 3 (Calcium Phosphate) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum KLGH 3 resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

KLGH 3 (Calcium Phosphate) acetate, when taken with meals, combines with dietary phosphate to form an insoluble KLGH 3 (Calcium Phosphate) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered KLGH 3 (Calcium Phosphate) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with KLGH 3 (Calcium Phosphate) acetate.

14 CLINICAL STUDIES

Effectiveness of KLGH 3 (Calcium Phosphate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the KLGH 3 (Calcium Phosphate) acetate solid oral dosage form.

Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.

The patients received KLGH 3 (Calcium Phosphate) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.

The data presented in Table 2 demonstrate the efficacy of KLGH 3 (Calcium Phosphate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum KLGH 3 (Calcium Phosphate) levels are also presented.

There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum KLGH 3 (Calcium Phosphate) increased 9% during the study mostly in the first month of the study.

Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive KLGH 3 (Calcium Phosphate) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.

The phosphate binding effect of KLGH 3 (Calcium Phosphate) acetate is shown in the Table 3.

Overall, 2 weeks of treatment with KLGH 3 (Calcium Phosphate) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum KLGH 3 (Calcium Phosphate) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

KLGH 3 (Calcium Phosphate) Acetate Capsules

667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.

NDC 0615-2303-39: Blistercards of 30 Capsules

NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

Inform patients to take KLGH 3 (Calcium Phosphate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of KLGH 3 (Calcium Phosphate) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].

Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after KLGH 3 (Calcium Phosphate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Ferrous Sulfate:

• Indications and usage
• Contraindications
• Precaution
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Storage
• KLGH 3 (Ferrous Sulfate) reviews

INDICATIONS AND USAGE

Non-pregnant Adults

For the treatment of iron deficiency and prevention of concomitant folic acid deficiency.

Pregnant Females

For the prevention and treatment of iron deficiency and to supply a maintenance dosage of folic acid.

CONTRAINDICATIONS

Contraindicated in patients with pernicious anemia and in the rare instance of hypersensitivity to folic acid. Hemochromatosis and hemosiderosis are contraindications to iron therapy.

PRECAUTION

Anemia is a manifestation that requires appropriate investigation to determine its cause or causes. Folic acid alone is unwarranted in the treatment of vitamin B₁₂ deficiency states such as pernicious anemia. Folic acid, especially in doses above 100 mcg daily may obscure pernicious anemia in that hematological remission may occur while neurological manifestations remain progressive. Concomitant parenteral therapy with vitamin B₁₂ may be necessary for adequate treatment of patients with a deficiency of vitamin B₁₂. Pernicious anemia is rare in women of childbearing age, and the likelihood of its occurrence along with pregnancy is reduced by the impairment of fertility associated with vitamin B₁₂ deficiency. In older patients and those with conditions tending to lead to vitamin B₁₂ depletion, serum B₁₂ levels should be regularly assessed during treatment.

Drug Interactions

Absorption of iron is inhibited by magnesium trisilicate and antacids containing carbonates. Since oral iron products interfere with absorption of oral tetracycline antibiotics, these products should not be taken within two hours of each other. Iron absorption may also be inhibited by the ingestion of milk or eggs.

Carcinogenesis

Adequate data are not available on long-term potential for carcinogenesis in animals and humans.

Pregnancy

Pregnancy Category A

Studies in pregnant women have not shown that the ingredients in KLGH 3 caplets formula increase the risk of fetal abnormalities if administered during pregnancy. If this product is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, KLGH 3 (Ferrous Sulfate) caplets should be used during pregnancy only if clearly needed.

Nursing Mothers

Folic acid and ascorbic acid are excreted in breast milk.

ADVERSE REACTIONS

Rarely, controlled-release iron produces gastrointestinal reactions, such as diarrhea or constipation. Administering the dose with meals will minimize these effects in the iron-sensitive patient. Allergic sensitization has been reported with both oral and parenteral administration of folic acid.

OVERDOSAGE

Signs and symptoms of iron toxicity, which may be delayed because the iron is in a controlled-release form, may include pallor and cyanosis, vomiting of blood, diarrhea, passage of dark-colored stool, shock, drowsiness and coma. In overdosage, efforts should be made to hasten the elimination of the caplets ingested. An emetic should be administered as soon as possible, followed by gastric lavage if indicated. Immediately following emesis, a large dose of saline cathartic should be used to speed passage through the intestinal tract. X-ray examination may then be considered to determine the position and number of caplets remaining in the gastrointestinal tract.

DOSAGE AND ADMINISTRATION

Adults, including Pregnant Females

The recommended dose is one (1) caplet daily on an empty stomach.

HOW SUPPLIED

KLGH 3 (Ferrous Sulfate) is supplied in bottles of 30 caplets.

Product Code: 13811-051-30

STORAGE

Store at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F).

Call your doctor about side effects. You may report side effects by calling 888 9 TRIGEN (888-987-4436).

KEEP OUT OF THE REACH OF CHILDREN.

R_x Only

All prescriptions using this product shall be pursuant to statutes as applicable. This is not an Orange Book product. There are no implied or explicit claims on therapeutic equivalence.

Manufactured for:

TRIGEN Laboratories, Inc., Sayreville, NJ 08872

www.trigenlab.com

Rev. 05/13

13811-051-30

R_x Only

KLGH 3 (Ferrous Sulfate)

Caplets

30 CAPLETS

TRIGEN

LABORATORIES

Magnesium Aspartate:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• KLGH 3 (Magnesium Aspartate) reviews

KLGH 3 (Magnesium Aspartate) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

KLGH 3 (Magnesium Aspartate) Sulfate Injection, USP is a sterile solution of KLGH 3 (Magnesium Aspartate) 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.

KLGH 3 (Magnesium Aspartate) 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

KLGH 3 (Magnesium Aspartate) (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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate). While there are large stores of KLGH 3 (Magnesium Aspartate) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral KLGH 3 (Magnesium Aspartate) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

KLGH 3 (Magnesium Aspartate) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) levels range from 1.5 to 2.5 mEq/liter.

As plasma KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate). Serum KLGH 3 (Magnesium Aspartate) concentrations in excess of 12 mEq/L may be fatal.

KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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. KLGH 3 (Magnesium Aspartate) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

KLGH 3 (Magnesium Aspartate) Sulfate Injection, USP is suitable for replacement therapy in KLGH 3 (Magnesium Aspartate) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum KLGH 3 (Magnesium Aspartate) (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), KLGH 3 (Magnesium Aspartate) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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. KLGH 3 (Magnesium Aspartate) sulfate should be used during pregnancy only if clearly needed. If KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate), their dosage should be adjusted with caution because of additive CNS depressant effects of KLGH 3 (Magnesium Aspartate).

Because KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) should be given until they return. Serum KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) intoxication in eclampsia.

50% KLGH 3 (Magnesium Aspartate) 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

KLGH 3 (Magnesium Aspartate) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate), their dosage should be adjusted with caution because of additive CNS depressant effects of KLGH 3 (Magnesium Aspartate). CNS depression and peripheral transmission defects produced by KLGH 3 (Magnesium Aspartate) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral KLGH 3 (Magnesium Aspartate) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) sulfate for more than 5 to 7 days.^1-10 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of KLGH 3 (Magnesium Aspartate) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) is distributed into milk during parenteral KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered KLGH 3 (Magnesium Aspartate) usually are the result of KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of KLGH 3 (Magnesium Aspartate).

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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) Deficiency

In the treatment of mild KLGH 3 (Magnesium Aspartate) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of KLGH 3 (Magnesium Aspartate) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) sulfate is 20 grams/48 hours and frequent serum KLGH 3 (Magnesium Aspartate) concentrations must be obtained. Continuous use of KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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, KLGH 3 (Magnesium Aspartate) 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

KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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

KLGH 3 (Magnesium Aspartate) Sulfate Injection, USP is supplied in single-dose containers as follows:

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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
• Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
• Santi MD, Henry GW, Douglas GL. KLGH 3 (Magnesium Aspartate) 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. KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
• McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of KLGH 3 (Magnesium Aspartate) 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 KLGH 3 (Magnesium Aspartate) 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% KLGH 3 (Magnesium Aspartate) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% KLGH 3 (Magnesium Aspartate) 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

Magnesium Sulfate:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• KLGH 3 (Magnesium Sulfate) reviews

KLGH 3 (Magnesium Sulfate)

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

KLGH 3 (Magnesium Sulfate) Injection, USP is a sterile solution of KLGH 3 (Magnesium Sulfate) heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).

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

KLGH 3 (Magnesium Sulfate), USP heptahydrate is chemically designated MgSO₄ - 7H₂O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.

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

CLINICAL PHARMACOLOGY

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

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

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

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

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

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

Pharmacokinetics

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

INDICATIONS AND USAGE

KLGH 3 (Magnesium Sulfate) Injection, USP is suitable for replacement therapy in magnesium deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum magnesium (Mg⁺⁺) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca⁺⁺) level is normal (4.3 to 5.3 mEq/liter) or elevated.

In total parenteral nutrition (TPN), KLGH 3 (Magnesium Sulfate) may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

KLGH 3 (Magnesium Sulfate) Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

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

WARNINGS

FETAL HARM: Continuous administration of KLGH 3 (Magnesium Sulfate) beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. KLGH 3 (Magnesium Sulfate) should be used during pregnancy only if clearly needed. If KLGH 3 (Magnesium Sulfate) is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of KLGH 3 (Magnesium Sulfate) beyond 5 to 7 days may cause fetal abnormalities.

ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

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

PRECAUTIONS

General

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

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

50% KLGH 3 (Magnesium Sulfate) Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.

Laboratory Tests

KLGH 3 (Magnesium Sulfate) injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of magnesium is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

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

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral KLGH 3 (Magnesium Sulfate) and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - KLGH 3 (Magnesium Sulfate) should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat magnesium toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

KLGH 3 (Magnesium Sulfate) can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of KLGH 3 (Magnesium Sulfate) for more than 5 to 7 days.^1-10 KLGH 3 (Magnesium Sulfate) injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.

Nonteratogenic Effects

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

Labor and Delivery

Continuous administration of KLGH 3 (Magnesium Sulfate) is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of KLGH 3 (Magnesium Sulfate) outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Nursing Mothers

Since magnesium is distributed into milk during parenteral KLGH 3 (Magnesium Sulfate) administration, the drug should be used with caution in nursing women.

Geriatrics

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

ADVERSE REACTIONS

The adverse effects of parenterally administered magnesium usually are the result of magnesium intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to KLGH 3 (Magnesium Sulfate) therapy for eclampsia has been reported.

OVERDOSAGE

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

For Treatment of Overdose

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

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

DOSAGE AND ADMINISTRATION

Dosage of KLGH 3 (Magnesium Sulfate) must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of KLGH 3 (Magnesium Sulfate) in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

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

In Magnesium Deficiency

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

In Hyperalimentation

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

In Pre-eclampsia or Eclampsia

In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of KLGH 3 (Magnesium Sulfate). Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum magnesium level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of KLGH 3 (Magnesium Sulfate) is 20 grams/48 hours and frequent serum magnesium concentrations must be obtained. Continuous use of KLGH 3 (Magnesium Sulfate) in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of KLGH 3 (Magnesium Sulfate) is 1 gram to 2 grams given intravenously.

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

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

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

Incompatibilities

KLGH 3 (Magnesium Sulfate) in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

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

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

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

HOW SUPPLIED

KLGH 3 (Magnesium Sulfate) Injection, USP is supplied in single-dose containers as follows:

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

Store at 20 to 25°C (68 to 77°F).

REFERENCES

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

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% KLGH 3 (Magnesium Sulfate) 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% KLGH 3 (Magnesium Sulfate) Injection, USP

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

MUST BE DILUTED FOR INTRAVENOUS USE.

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

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Potassium Aspartate:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• KLGH 3 (Potassium Aspartate) reviews

KLGH 3 (Potassium Aspartate) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The KLGH 3 (Potassium Aspartate) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of KLGH 3 (Potassium Aspartate) chloride containing 1500 mg of microencapsulated KLGH 3 (Potassium Aspartate) chloride, USP equivalent to 20 mEq of KLGH 3 (Potassium Aspartate) in a tablet.

These formulations are intended to slow the release of KLGH 3 (Potassium Aspartate) so that the likelihood of a high localized concentration of KLGH 3 (Potassium Aspartate) chloride within the gastrointestinal tract is reduced.

KLGH 3 (Potassium Aspartate) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is KLGH 3 (Potassium Aspartate) chloride, and the structural formula is KCl. KLGH 3 (Potassium Aspartate) 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.

KLGH 3 (Potassium Aspartate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated KLGH 3 (Potassium Aspartate) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) chloride.

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

CLINICAL PHARMACOLOGY

The KLGH 3 (Potassium Aspartate) ion is the principal intracellular cation of most body tissues. KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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.

KLGH 3 (Potassium Aspartate) is a normal dietary constituent and under steady-state conditions the amount of KLGH 3 (Potassium Aspartate) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of KLGH 3 (Potassium Aspartate) is 50 to 100 mEq per day.

KLGH 3 (Potassium Aspartate) depletion will occur whenever the rate of KLGH 3 (Potassium Aspartate) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of KLGH 3 (Potassium Aspartate) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of KLGH 3 (Potassium Aspartate) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. KLGH 3 (Potassium Aspartate) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) in the form of high KLGH 3 (Potassium Aspartate) food or KLGH 3 (Potassium Aspartate) chloride may be able to restore normal KLGH 3 (Potassium Aspartate) levels.

In rare circumstances (eg, patients with renal tubular acidosis) KLGH 3 (Potassium Aspartate) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients KLGH 3 (Potassium Aspartate) replacement should be accomplished with KLGH 3 (Potassium Aspartate) salts other than the chloride, such as KLGH 3 (Potassium Aspartate) bicarbonate, KLGH 3 (Potassium Aspartate) citrate, KLGH 3 (Potassium Aspartate) acetate, or KLGH 3 (Potassium Aspartate) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE KLGH 3 (Potassium Aspartate) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) salts may be indicated.

CONTRAINDICATIONS

KLGH 3 (Potassium Aspartate) supplements are contraindicated in patients with hyperkalemia since a further increase in serum KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. KLGH 3 (Potassium Aspartate) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of KLGH 3 (Potassium Aspartate) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate), the administration of KLGH 3 (Potassium Aspartate) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given KLGH 3 (Potassium Aspartate) by the intravenous route but may also occur in patients given KLGH 3 (Potassium Aspartate) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of KLGH 3 (Potassium Aspartate) salts in patients with chronic renal disease, or any other condition which impairs KLGH 3 (Potassium Aspartate) excretion, requires particularly careful monitoring of the serum KLGH 3 (Potassium Aspartate) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) retention by inhibiting aldosterone production. KLGH 3 (Potassium Aspartate) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of KLGH 3 (Potassium Aspartate) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of KLGH 3 (Potassium Aspartate) 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. KLGH 3 (Potassium Aspartate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated KLGH 3 (Potassium Aspartate) chloride and thus to minimize the possibility of a high local concentration of KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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. KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) salt such as KLGH 3 (Potassium Aspartate) bicarbonate, KLGH 3 (Potassium Aspartate) citrate, KLGH 3 (Potassium Aspartate) acetate, or KLGH 3 (Potassium Aspartate) gluconate.

PRECAUTIONS

General

The diagnosis of KLGH 3 depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for KLGH 3 (Potassium Aspartate) depletion. In interpreting the serum KLGH 3 (Potassium Aspartate) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body KLGH 3 (Potassium Aspartate) while acute acidosis per se can increase the serum KLGH 3 (Potassium Aspartate) concentration into the normal range even in the presence of a reduced total body KLGH 3 (Potassium Aspartate). The treatment of KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending KLGH 3 (Potassium Aspartate) 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 KLGH 3 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. KLGH 3 is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with KLGH 3 (Potassium Aspartate) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that KLGH 3 (Potassium Aspartate) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal KLGH 3 ion content of human milk is about 13 mEq per liter. Since oral KLGH 3 (Potassium Aspartate) becomes part of the body KLGH 3 (Potassium Aspartate) pool, so long as body KLGH 3 (Potassium Aspartate) is not excessive, the contribution of KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) salts to persons with normal excretory mechanisms for KLGH 3 (Potassium Aspartate) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) by the average adult is 50 to 100 mEq per day. KLGH 3 (Potassium Aspartate) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of KLGH 3 (Potassium Aspartate) chloride.

KLGH 3 (Potassium Aspartate) 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 KLGH 3 (Potassium Aspartate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending KLGH 3 (Potassium Aspartate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

KLGH 3 (Potassium Aspartate) 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

KLGH 3 (Potassium Aspartate) chloride 20 Meq

Procaine Hydrochloride:

• KLGH 3 (Procaine Hydrochloride) reviews

Indication: Used as a local anesthetic primarily in oral surgery

KLGH 3 (Procaine Hydrochloride) is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. KLGH 3 (Procaine Hydrochloride) (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. KLGH 3 (Procaine Hydrochloride) is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into the urine.

Zinc Oxide:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• KLGH 3 (Zinc Oxide) reviews

INDICATIONS AND USAGE

KLGH 3 (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain KLGH 3 (Zinc Oxide) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of KLGH 3 (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and KLGH 3 (Zinc Oxide) doses because these elements are primarily eliminated in the urine.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General

Do not use unless the solution is clear and the seal is intact.

Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of KLGH 3 (Zinc Oxide) from a bolus injection. Administration of KLGH 3 (Zinc Oxide) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as KLGH 3 (Zinc Oxide) are suggested as a guideline for subsequent KLGH 3 (Zinc Oxide) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of KLGH 3 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when KLGH 3 (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with KLGH 3 chloride. It is also not known whether KLGH 3 (Zinc Oxide) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. KLGH 3 (Zinc Oxide) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg KLGH 3 (Zinc Oxide) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum KLGH 3 (Zinc Oxide) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending KLGH 3 (Zinc Oxide) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg KLGH 3 (Zinc Oxide) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of KLGH 3 (Zinc Oxide) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum KLGH 3 (Zinc Oxide) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against KLGH 3 (Zinc Oxide) toxicity.

DOSAGE AND ADMINISTRATION

KLGH 3 (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of KLGH 3 (Zinc Oxide) blood levels is suggested for patients receiving more than the usual maintenance dosage level of KLGH 3 (Zinc Oxide).

For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.

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

HOW SUPPLIED

KLGH 3 (Zinc Oxide) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004

© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

KLGH 3 (Zinc Oxide)

1 mg/mL

KLGH 3 (Zinc Oxide) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA