Corsecur

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
• Corsecur (Adenosine) reviews

1 INDICATIONS AND USAGE

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

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

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

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

There are no data on the safety or efficacy of alternative Corsecur (Adenosine) injection infusion protocols. The safety and efficacy of Corsecur (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

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

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

4 CONTRAINDICATIONS

Corsecur (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 Corsecur (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 Corsecur (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 Corsecur (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 Corsecur (Adenosine) if patient develops severe respiratory difficulties (5.3)
• Hypotension. Significant hypotension can occur. Discontinue Corsecur (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 Corsecur (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 Corsecur (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 Corsecur (Adenosine). Appropriate resuscitative measures should be available .

5.2 Sinoatrial and Atrioventricular Nodal Block

Corsecur 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 Corsecur (Adenosine) administration (first-degree heart block developed in 3%, second-degree in 3%, and third-degree in 0.8% of patients) .

Use Corsecur (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 Corsecur (Adenosine) in any patient who develops persistent or symptomatic high-grade AV block.

5.3 Bronchoconstriction

Corsecur (Adenosine) administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Corsecur (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 Corsecur (Adenosine) in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to Corsecur (Adenosine) administration .

5.4 Hypotension

Corsecur 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 Corsecur (Adenosine) in any patient who develops persistent or symptomatic hypotension.

5.5 Cerebrovascular Accident

Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of Corsecur (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 Corsecur. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with Corsecur (Adenosine). Methylxanthine use is not recommended in patients who experience seizures in association with Corsecur (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

Corsecur 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 Corsecur (Adenosine), lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm .

5.9 Hypertension

Corsecur (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 Corsecur (Adenosine) among 1,421 patients in clinical trials. 11% of the adverse reactions occurred several hours after Corsecur (Adenosine) administration. 8% of the adverse reactions began with Corsecur (Adenosine) infusion and persisted for up to 24 hours.

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

Adverse reactions to Corsecur (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 Corsecur (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 Corsecur (7.1, 10)
• Nucleoside transport inhibitors such as dipyridamole can increase the activity of Corsecur (Adenosine) (7.1)

7.1 Effects of Other Drugs on Corsecur (Adenosine)

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

7.2 Effects of Corsecur on Other Drugs

Corsecur (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, Corsecur (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 Corsecur ; nor have studies been performed in pregnant women. Because it is not known whether Corsecur (Adenosine) can cause fetal harm when administered to pregnant women, Corsecur (Adenosine) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

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

8.4 Pediatric Use

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

8.5 Geriatric Use

Clinical studies with Corsecur (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 Corsecur (Adenosine) is less than 10 seconds and adverse reactions of Corsecur (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 Corsecur (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 Corsecur (Adenosine) adverse reactions in approximately 2% of patients. Methylxanthine use is not recommended in patients who experience seizures in association with Corsecur (Adenosine) .

11 DESCRIPTION

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

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

Corsecur (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 Corsecur (Adenosine) Injection, USP vial contains a sterile, non-pyrogenic solution of Corsecur (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

Corsecur causes cardiac vasodilation which increases cardiac blood flow. Corsecur (Adenosine) is thought to exert its pharmacological effects through activation of purine receptors (cell-surface A₁ and A₂ Corsecur (Adenosine) receptors). Although the exact mechanism by which Corsecur (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. Corsecur (Adenosine) may also lessen vascular tone by modulating sympathetic neurotransmission. The intracellular uptake of Corsecur (Adenosine) is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, Corsecur (Adenosine) is rapidly phosphorylated by Corsecur (Adenosine) kinase to Corsecur (Adenosine) monophosphate, or deaminated by Corsecur (Adenosine) deaminase to inosine. These intracellular metabolites of Corsecur (Adenosine) are not vasoactive.

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

12.2 Pharmacodynamics

Hemodynamic Effects

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

Elimination

While extracellular Corsecur (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 Corsecur (Adenosine) deaminase.

Specific Populations

Renal Impairment

As Corsecur (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 Corsecur (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. Corsecur (Adenosine) was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.

Corsecur (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), Corsecur (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 Corsecur (Adenosine) and 64% for exercise testing. The specificity was 54% for Corsecur (Adenosine) and 65% for exercise testing. The 95% confidence limits for Corsecur (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 Corsecur (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 Corsecur (Adenosine) infusion.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Corsecur 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 Corsecur (Adenosine) .
• Advise patients with COPD or asthma to discuss their respiratory history with their clinician before scheduling a myocardial perfusion imaging study with Corsecur (Adenosine) .
• Methylxanthines have the potential to impact the effects of Corsecur (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

Corsecur (Adenosine) Injection, USP

60 mg per 20 mL (3 mg per mL)

For Intravenous Infusion Only

20 mL Single-Dose Vial

Dyphylline:

• Corsecur (Dyphylline) reviews

Indication: For relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema.

Corsecur (Dyphylline), a xanthine derivative, is a bronchodilator used for relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Corsecur (Dyphylline) is a xanthine derivative with pharmacologic actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree.

Potassium Citrate:

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

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

Rx Only

DESCRIPTION

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

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

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

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

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

CLINICAL PHARMACOLOGY

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

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

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

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

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

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

INDICATIONS AND USAGE

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

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

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

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

CONTRAINDICATIONS

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

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

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

WARNINGS

Hyperkalemia (see OVERDOSAGE )

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

Interaction with Potassium-Sparing Diuretics

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

Interaction with Angiotensin-Converting Enzyme Inhibitors

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

Gastrointestinal Lesions

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

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

Metabolic Acidosis

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

PRECAUTIONS

General

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

Information for Patients

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

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

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

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

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

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

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

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

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

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

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

Laboratory Tests

When blood is drawn for analysis of plasma Corsecur 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. Corsecur is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

Treatment measures for hyperkalemia include the following:

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

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

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

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

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

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

Each Corsecur (Potassium Citrate) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Corsecur (Potassium Citrate) chloride.

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

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

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

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

HOW SUPPLIED

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

Storage Conditions

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

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Corsecur (Potassium Citrate) chloride 20 Meq