ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. SPS(R) 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: oFecal impaction following rectal administration, particularly in children; oGastrointestinal concretions (bezoars) following oral administration; oIschemic colitis, gastrointestinal tract ulceration or necrosis which could lead to intestinal perforation; and oRare cases of acute bronchitis and/or bronchopneumonia associated with inhalation of particles of polystyrene sulfonate. To report suspected adverse reactions, contact CMP Pharma, Inc., toll free at 1-844-321-1443 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. oFecal impaction following rectal administration, particularly in children; oGastrointestinal concretions (bezoars) following oral administration; oIschemic colitis, gastrointestinal tract ulceration or necrosis which could lead to intestinal perforation; and oRare cases of acute bronchitis and/or bronchopneumonia associated with inhalation of particles of polystyrene sulfonate.

DESCRIPTION SECTION.

DESCRIPTION. Sodium Polystyrene Sulfonate Suspension USP (SPS(R) Suspension) can be administered orally or in an enema. It is cherry-flavored suspension containing 15 grams of cation-exchange resin (Sodium Polystyrene Sulfonate USP); 21.5 mL of Sorbitol Solution USP (equivalent to approximately 20 grams of Sorbitol); 0.18 mL (0.3%) of Alcohol per 60 mL of suspension. Also contains Purified Water USP; Propylene Glycol USP; Magnesium Aluminum Silicate NF; Sodium Saccharin USP; Methylparaben NF; Propylparaben NF; and flavor.Sodium polystyrene sulfonate is benzene, diethenyl-, polymer with ethenylbenzene, sulfonated, sodium salt and has the following structural formula: The sodium content of the suspension is 1500 mg (65 mEq) per 60 mL. It is brown, slightly viscous suspension with an in-vitro exchange capacity of approximately 3.1 mEq (in-vivo approximately mEq) of potassium per mL (1 gram) of suspension. It can be administered orally or in an enema.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. The average daily adult dose is 15 (60 mL) to 60 (240 mL) of suspension. This is best provided by administering 15 (60 mL) of SPS(R) Suspension one to four times daily. Each 60 mL of SPS(R) 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 resins actual sodium content is being delivered to the body.In smaller children and infants, lower doses should be employed by using as guide rate of mEq of potassium per gram of resin as the basis for calculation.SPS(R) Suspension may be introduced into the stomach through plastic tube and, if desired, given with diet appropriate for patient in renal failure.SPS(R) Suspension may also be given, although with less effective results, as an enema consisting (for adults) of 30 (120 mL) to 50 (200 mL) every six hours. The enema should be retained as long as possible and followed by cleansing enema. After an initial cleansing enema, soft, large size (French 28) rubber tube is inserted into the rectum for 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 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 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 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.SPS(R) Suspension should not be heated for to do so may alter the exchange properties of the resin.

DRUG INTERACTIONS SECTION.

Drug Interactions. Antacids. The simultaneous oral administration of sodium polystyrene sulfonate with nonabsorbable cation-donating antacids and laxatives may reduce the resins potassium exchange capability.. Nonabsorbable cation-donating antacids and laxatives. 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 patient with chronic hypocalcemia of renal failure who was given sodium polystyrene sulfonate with magnesium hydroxide as laxative.Intestinal obstruction due to concretions of aluminum hydroxide when used in combination with sodium polystyrene sulfonate has been reported.. Digitalis. The toxic effects of digitalis on the heart, especially various ventricular arrhythmias and A-V nodal dissociation, are likely to be exaggerated by hypokalemia, even in the face of serum digoxin concentrations in the normal range (See WARNINGS).. Sorbitol. Concomitant use of sorbitol with sodium polystyrene sulfonate has been implicated in cases of intestinal necrosis, which may be fatal (See WARNINGS).. Lithium. SPS(R) Suspension may decrease absorption of lithium.. Thyroxine. SPS(R) Suspension may decrease absorption of thyroxine.

PRECAUTIONS SECTION.

PRECAUTIONS. Caution is advised when sodium polystyrene sulfonate is administered to patients who cannot tolerate even small increase in sodium loads (i.e., severe congestive heart failure, severe hypertension, or marked edema). In such instances compensatory restriction of sodium intake from other sources may be indicated.Precautions should be taken to ensure the use of adequate volumes of sodium-free cleansing enemas after rectal administration.In the event of clinically significant constipation, treatment with SPS(R) Suspension should be discontinued until normal bowel motion is resumed (See WARNINGS, Intestinal Necrosis).. Drug Interactions. Antacids. The simultaneous oral administration of sodium polystyrene sulfonate with nonabsorbable cation-donating antacids and laxatives may reduce the resins potassium exchange capability.. Nonabsorbable cation-donating antacids and laxatives. 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 patient with chronic hypocalcemia of renal failure who was given sodium polystyrene sulfonate with magnesium hydroxide as laxative.Intestinal obstruction due to concretions of aluminum hydroxide when used in combination with sodium polystyrene sulfonate has been reported.. Digitalis. The toxic effects of digitalis on the heart, especially various ventricular arrhythmias and A-V nodal dissociation, are likely to be exaggerated by hypokalemia, even in the face of serum digoxin concentrations in the normal range (See WARNINGS).. Sorbitol. Concomitant use of sorbitol with sodium polystyrene sulfonate has been implicated in cases of intestinal necrosis, which may be fatal (See WARNINGS).. Lithium. SPS(R) Suspension may decrease absorption of lithium.. Thyroxine. SPS(R) Suspension may decrease absorption of thyroxine. Carcinogenesis, Mutagenesis, Impairment of Fertility. Studies have not been performed.. Pregnancy Category C. 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 pregnant woman or can affect reproduction capacity. Sodium polystyrene sulfonate should be given to pregnant woman only if clearly needed.. 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 sodium polystyrene sulfonate is administered to nursing woman.. Pediatric Use. The effectiveness of SPS(R) Suspension in pediatric patients has not been established. The use of SPS(R) Suspension is contraindicated in neonates and especially in premature infants. In children and neonates, particular care should be observed with rectal administration, as excessive dosage could result in impaction of the resin. Precautions should be taken to ensure the use of adequate volumes of sodium-free cleansing enemas after rectal administration.

WARNINGS SECTION.

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).oUse only in patients who have normal bowel function. Avoid use in patients who have not had bowel movement post-surgery. oAvoid 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).oDiscontinue use in patients who develop constipation.. oUse only in patients who have normal bowel function. Avoid use in patients who have not had bowel movement post-surgery. oAvoid 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).. oDiscontinue 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 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 patients clinical condition and electrocardiogram. Early clinical signs of severe hypokalemia include pattern of irritable confusion and delayed thought processes. Electrocardiographically, severe hypokalemia is often associated with lengthened Q-T interval, widening, flattening, or inversion of the wave, and prominent 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 patient with chronic hypocalcemia of renal failure who was given sodium polystyrene sulfonate with magnesium hydroxide as laxative (See PRECAUTIONS, Drug Interactions).