SODIUM POLYSTYRENE SULFONATE: 654 Adverse Event Reports & Safety Profile

DESCRIPTION Sodium Polystyrene Sulfonate Suspension USP (SPS ® Suspension) can be administered orally or in an enema. It is a 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 a 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 a brown, slightly viscous suspension with an in ‑ vitro exchange capacity of approximately 3.1 mEq ( in-vivo approximately 1 mEq) of potassium per 4 mL (1 gram) of suspension. It can be administered orally or in an enema.

Chemical

Structure

AND USAGE Sodium Polystyrene Sulfonate Powder, for Suspension is indicated for the treatment of hyperkalemia. Limitation of Use: Sodium Polystyrene Sulfonate Powder, for Suspension should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2)] .

Sodium Polystyrene Sulfonate

Powder, for Suspension is indicated for the treatment of hyperkalemia (1) . Limitation of Use: Sodium Polystyrene Sulfonate Powder, for Suspension should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action (1) .

DOSAGE AND ADMINISTRATION Suspension of this drug should be freshly prepared and not stored beyond 24 hours. The average daily adult dose of the resin is 15 g to 60 g. This is best provided by administering 15 g (approximately 4 level teaspoons) of sodium polystyrene sulfonate one to four times daily. One gram of sodium polystyrene sulfonate contains 4.1 mEq of sodium; one level teaspoon contains approximately 3.5 g of sodium polystyrene sulfonate and 15 mEq of sodium. (A heaping teaspoon may contain as much as 10 g to 12 g of sodium polystyrene sulfonate.) Since the in vivo efficiency of sodium-potassium exchange resins is approximately 33 percent, 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. Each dose should be given as a suspension in a small quantity of water or, for greater palatability, in syrup. The amount of fluid usually ranges from 20 mL to 100 mL, depending on the dose, or may be simply determined by allowing 3 mL to 4 mL per gram of resin. Healthcare professionals should follow full aspiration precautions when administering this product, such as placing and maintaining the patient in an upright position while the resin is being administered. The resin may be introduced into the stomach through a plastic tube and, if desired, mixed with a diet appropriate for a patient in renal failure. The resin may also be given, although with less effective results, in an enema consisting (for adults) of 30 g to 50 g every six hours. Each dose is administered as a warm emulsion (at body temperature) in 100 mL of aqueous vehicle. The emulsion should be agitated gently during administration. 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 in place. The resin is then suspended in the appropriate amount of aqueous vehicle at body temperature and introduced by gravity, while the particles are kept in suspension by stirring. The suspension is flushed with 50 mL 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. A somewhat thicker suspension may be used, but care should be taken that no paste is formed, because the latter has a greatly reduced exchange surface and will be particularly ineffective if deposited in the rectal ampulla. The suspension is kept in the sigmoid colon for several hours, if possible. Then, the colon is irrigated with nonsodium containing solution 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. While the use of sorbitol is not recommended, particular attention should be paid to this cleansing enema if sorbitol has been used. The intensity and duration of therapy depend upon the severity and resistance of hyperkalemia. Sodium polystyrene sulfonate should not be heated for to do so may alter the exchange properties of the resin.

Sodium Polystyrene Sulfonate Powder, for Suspension is contraindicated in patients with the following conditions:

• Hypersensitivity to polystyrene sulfonate resins
• Obstructive bowel disease
• Neonates with reduced gut motility
• Hypersensitivity to polystyrene sulfonate resins (4)
• Obstructive bowel disease (4)
• Neonates with reduced gut motility (4)

ADVERSE REACTIONS Sodium Polystyrene Sulfonate Suspension, USP 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 Burel Pharmaceuticals, LLC at 1-844-436-7010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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 sodium polystyrene sulfonate suspension with the patient in an upright position. Binding to Other Orally Administered Medications Sodium polystyrene sulfonate 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 sodium polystyrene sulfonate suspension. Patients with gastroparesis may require a 6 hour separation (see DOSAGE AND ADMINISTRATION and PRECAUTIONS, Drug Interactions ).

PRECAUTIONS Caution is advised when sodium polystyrene sulfonate is administered to patients who cannot tolerate even a 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 Sodium Polystyrene Sulfonate Suspension, USP should be discontinued until normal bowel motion is resumed (See WARNINGS, Intestinal Necrosis ).

Drug Interactions General

Interactions No formal drug interaction studies have been conducted in humans. Sodium polystyrene sulfonate suspension has the potential to bind other drugs. In in-vitro binding studies, sodium polystyrene sulfonate was shown to significantly bind the oral medications (n=6) that were tested. Decreased absorption of lithium and thyroxine have also been reported with co-administration of sodium polystyrene sulfonate. Binding of sodium polystyrene sulfonate suspension to other oral medications could cause decreased gastrointestinal absorption and loss of efficacy when taken close to the time sodium polystyrene sulfonate suspension is administered. Administer sodium polystyrene sulfonate suspension at least 3 hours before or 3 hours after other oral medications. Patients with gastroparesis may require a 6 hour separation. Monitor for clinical response and/or blood levels where possible.

Antacids

The simultaneous oral administration of sodium polystyrene sulfonate with nonabsorbable cation-donating antacids and laxatives may reduce the resin's 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 a patient with chronic hypocalcemia of renal failure who was given sodium polystyrene sulfonate with magnesium hydroxide as a 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 Sodium Polystyrene Sulfonate

Suspension, USP may decrease absorption of lithium.

Thyroxine Sodium Polystyrene Sulfonate

Suspension, USP may decrease absorption of thyroxine. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been performed.

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.

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 a nursing woman.

Pediatric Use

The effectiveness of Sodium Polystyrene Sulfonate Suspension, USP in pediatric patients has not been established. The use of Sodium Polystyrene Sulfonate Suspension, USP 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.

Drug Interactions General Interactions No formal drug interaction studies have been conducted in humans. Sodium polystyrene sulfonate suspension has the potential to bind other drugs. In in-vitro binding studies, sodium polystyrene sulfonate was shown to significantly bind the oral medications (n=6) that were tested. Decreased absorption of lithium and thyroxine have also been reported with co-administration of sodium polystyrene sulfonate. Binding of sodium polystyrene sulfonate suspension to other oral medications could cause decreased gastrointestinal absorption and loss of efficacy when taken close to the time sodium polystyrene sulfonate suspension is administered. Administer sodium polystyrene sulfonate suspension at least 3 hours before or 3 hours after other oral medications. Patients with gastroparesis may require a 6 hour separation. Monitor for clinical response and/or blood levels where possible.

Antacids

The simultaneous oral administration of sodium polystyrene sulfonate with nonabsorbable cation-donating antacids and laxatives may reduce the resin's 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 a patient with chronic hypocalcemia of renal failure who was given sodium polystyrene sulfonate with magnesium hydroxide as a 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 Sodium Polystyrene Sulfonate

Suspension, USP may decrease absorption of lithium.

Thyroxine Sodium Polystyrene Sulfonate

Suspension, USP may decrease absorption of thyroxine.