Kionex

INDICATIONS AND USAGE Kionex Suspension is indicated for the treatment of hyperkalemia.

DOSAGE AND ADMINISTRATION Administer Kionex Suspension at least 3 hours before or 3 hours after other oral medications. Patients with gastroparesis may require a 6 hour separation (see WARNINGS and PRECAUTIONS, Drug Interactions ). The average daily adult dose is 15 g (60 mL) to 60 g (240 mL) of suspension. This is best provided by administering 15 g (60 mL) of Kionex Suspension one to four times daily. Each 60 mL of Kionex Suspension contains 1500 mg (65 mEq) of sodium. Since the in-vivo efficiency of sodium-potassium exchange resins is approximately 33%, about one-third of the resin’s actual sodium content is being delivered to the body. In smaller children and infants, lower doses should be employed by using as a guide a rate of 1 mEq of potassium per gram of resin as the basis for calculation. Administer with patient in an upright position (see WARNINGS ). Kionex Suspension may be introduced into the stomach through a plastic tube and, if desired, given with a diet appropriate for a patient in renal failure. Kionex Suspension may also be given, although with less effective results, as an enema consisting (for adults) of 30 g (120 mL) to 50 g (200 mL) every six hours. The enema should be retained as long as possible and followed by a cleansing enema. After an initial cleansing enema, a soft, large size (French 28) rubber tube is inserted into the rectum for a distance of about 20 cm, with the tip well into the sigmoid colon, and taped into place. The suspension is introduced at body temperature by gravity. The suspension is flushed with 50 or 100 mL of fluid, following which the tube is clamped and left in place. If back leakage occurs, the hips are elevated on pillows or a knee-chest position is taken temporarily. The suspension is kept in the sigmoid colon for several hours, if possible. Then the colon is irrigated with a sodium-free cleansing enema at body temperature in order to remove the resin. Two quarts of flushing solution may be necessary. The returns are drained constantly through a Y tube connection. Particular attention should be paid to this cleansing enema, because sorbitol is present in the vehicle. The intensity and duration of therapy depend upon the severity and resistance of hyperkalemia. Kionex Suspension should not be heated for to do so may alter the exchange properties of the resin.

CONTRAINDICATIONS Kionex Suspension is contraindicated in the following conditions: patients with hypokalemia, patients with a history of hypersensitivity to polystyrene sulfonate resins, obstructive bowel disease, oral or rectal administration in neonates (see PRECAUTIONS ).

WARNINGS Intestinal Necrosis Cases of intestinal necrosis, which may be fatal, and other serious gastrointestinal adverse events (bleeding, ischemic colitis, perforation) have been reported in association with sodium polystyrene sulfonate use. The majority of these cases reported the concomitant use of sorbitol. Risk factors for gastrointestinal adverse events were present in many of the cases including prematurity, history of intestinal disease or surgery, hypovolemia, and renal insufficiency and failure. Concomitant administration of additional sorbitol is not recommended (see PRECAUTIONS, Drug Interactions ). • Use only in patients who have normal bowel function. Avoid use in patients who have not had a bowel movement post-surgery. • Avoid use in patients who are at risk for developing constipation or impaction (including those with history of impaction, chronic constipation, inflammatory bowel disease, ischemic colitis, vascular intestinal atherosclerosis, previous bowel resection, or bowel obstruction). • Discontinue use in patients who develop constipation. Alternative Therapy in Severe Hyperkalemia Since the effective lowering of serum potassium with sodium polystyrene sulfonate may take hours to days, treatment with this drug alone may be insufficient to rapidly correct severe hyperkalemia associated with states of rapid tissue breakdown (e.g., burns and renal failure) or hyperkalemia so marked as to constitute a medical emergency. Therefore, other definitive measures, including dialysis, should always be considered and may be imperative. Hypokalemia Serious potassium deficiency can occur from sodium polystyrene sulfonate therapy. The effect must be carefully controlled by frequent serum potassium determinations within each 24 hour period. Since intracellular potassium deficiency is not always reflected by serum potassium levels, the level at which treatment with sodium polystyrene sulfonate should be discontinued must be determined individually for each patient. Important aids in making this determination are the patient’s clinical condition and electrocardiogram. Early clinical signs of severe hypokalemia include a pattern of irritable confusion and delayed thought processes. Electrocardiographically, severe hypokalemia is often associated with a lengthened Q-T interval, widening, flattening, or inversion of the T wave, and prominent U waves. Also, cardiac arrhythmias may occur, such as premature atrial, nodal, and ventricular contractions, and supraventricular and ventricular tachycardias. The toxic effects of digitalis are likely to be exaggerated. Marked hypokalemia can also be manifested by severe muscle weakness, at times extending into frank paralysis. Electrolyte Disturbances Like all cation-exchange resins, sodium polystyrene sulfonate is not totally selective (for potassium) in its actions, and small amounts of other cations such as magnesium and calcium can also be lost during treatment. Accordingly, patients receiving sodium polystyrene sulfonate should be monitored for all applicable electrolyte disturbances. Systemic Alkalosis Systemic alkalosis has been reported after cation-exchange resins were administered orally in combination with nonabsorbable cation-donating antacids and laxatives such as magnesium hydroxide and aluminum carbonate. Magnesium hydroxide should not be administered with sodium polystyrene sulfonate. One case of grand mal seizure has been reported in a patient with chronic hypocalcemia of renal failure who was given sodium polystyrene sulfonate with magnesium hydroxide as a laxative (see PRECAUTIONS, Drug Interactions ). Risk of Aspiration Cases of acute bronchitis or bronchopneumonia caused by inhalation of sodium polystyrene sulfonate particles has been reported. Patients with impaired gag reflex, altered level of consciousness, or patients prone to regurgitation may be at increased risk. Administer Kionex Suspension with the patient in an upright position. Binding to Other Orally Administered Medications Kionex Suspension may bind orally administered medications, which could decrease their gastrointestinal absorption and lead to reduced efficacy. Administer other oral medications at least 3 hours before or 3 hours after Kionex Suspension. Patients with gastroparesis may require a 6 hour separation (see DOSAGE AND ADMINISTRATION and PRECAUTIONS, Drug Interactions ).

ADVERSE REACTIONS Kionex Suspension may cause some degree of gastric irritation. Anorexia, nausea, vomiting, and constipation may occur especially if high doses are given. Also, hypokalemia, hypocalcemia, hypomagnesemia and significant sodium retention, and their related clinical manifestations, may occur (see WARNINGS ). Occasionally diarrhea develops. Large doses in elderly individuals may cause fecal impaction (see PRECAUTIONS ). Rare instances of intestinal necrosis have been reported. Intestinal obstruction due to concretions of aluminum hydroxide, when used in combination with sodium polystyrene sulfonate, has been reported. The following events have been reported from worldwide post marketing experience: • Fecal impaction following rectal administration, particularly in children; • Gastrointestinal concretions (bezoars) following oral administration; • Ischemic colitis, gastrointestinal tract ulceration or necrosis which could lead to intestinal perforation; and • Rare cases of acute bronchitis and/or bronchopneumonia associated with inhalation of particles of polystyrene sulfonate (see WARNINGS ). To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pregnancy Animal reproduction studies have not been conducted with sodium polystyrene sulfonate. It is also not known whether sodium polystyrene sulfonate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium polystyrene sulfonate should be given to a pregnant woman only if clearly needed.