SODIUM POLYSTYRENE SULFONATE

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
Oral Liquid Formulations
NOTE: Rectal administration is preferred over oral administration in neonates. Some products are contraindicated by the manufacturers for use in neonates.

-Separate sodium polystyrene sulfonate from other orally administered medications by at least 3 hours. For patients with gastroparesis or other conditions resulting in delayed emptying of food from the stomach into the small intestine, separate sodium polystyrene sulfonate from other orally administered medications by at least 6 hours. Sodium polystyrene sulfonate binds to many commonly prescribed oral medicines, decreasing the absorption and, therefore, the effectiveness of those oral medicines.

Commercially Available Suspension
-Shake well prior to administration.
-If necessary, administer into the stomach through a plastic tube.

Powdered Resin for Suspension
-Prior to administration, mix each dose of powdered resin in water or syrup to form a suspension. The amount of fluid usually ranges from 20 to 100 mL, depending on the dose. Alternatively, 3 to 4 mL of water/syrup can be used for each gram of resin.
-Shake well prior to administration.
-If necessary, administer into the stomach through a plastic tube.
-Storage: Each dose should be freshly prepared; store no longer than 24 hours.



Rectal Administration
Preparation
-Commercially Available Suspension: No further dilution is required.-Because the commercially available suspensions are hyperosmolar, do not use them in neonates. Sorbitol-free suspensions prepared from the powdered resin are preferred.

-Powdered Resin for Suspension: Mix each dose with an appropriate amount of an aqueous vehicle to form an emulsion.-For neonates, use non-sorbitol vehicles (e.g., water and normal saline).
-For small doses, mix with at least 2 to 3 mL aqueous vehicle per gram sodium polystyrene sulfonate. For doses of 30 to 50 g, mix each dose with at least 100 mL aqueous vehicle.


Administration
-Administer a cleansing enema before administering the sodium polystyrene sulfonate retention enema.
-The suspension should be approximately body temperature when administered; however, the manufacturer states that the resin itself should not be heated because heating may alter the resin's exchange properties.
-Instruct the patient to lie down on their left side with their lower leg extended and the upper leg flexed for support or place the patient in the knee-chest position.
-Gently insert a soft, rubber tube of age-appropriate size into the rectum for a distance that will place the tip well into the sigmoid colon. In adult patients, a tube size of 28-French and insertion distance of about 20 cm is recommended.
-Tape the tube in place.
-Shake the sodium polystyrene sulfonate suspension well.
-Administer the suspension through the tube by gravity. The particles should be kept suspended by gently agitating the suspension during administration. After administration is complete, flush the tube with an age-appropriate amount of fluid (50 to 100 mL is recommended for adults), clamp the tube, and leave in place. The suspension should be retained in the colon for at least 30 to 60 minutes or for several hours, if possible.
-After the retention enema is complete, administer a sodium-free cleansing enema warmed to body temperature to remove the resin. In adults, up to 2 quarts of fluid may be necessary. Constantly drain fluid through a Y-tube connection. If the enema contained sorbitol, particular attention should be paid to the cleansing enema to ensure proper removal.


Other Administration Route(s)
Addition of Sodium Polystyrene Sulfonate Powdered Resin to Infant Formula or Expressed Breast Milk (EBM)
NOTE: The addition of sodium polystyrene sulfonate to infant formula or breast milk is not an FDA-approved method of administration. Published data are limited and full clinical implications are unknown.
-Preparation takes about 1 hour; some institutions prepare batches up to 24 hours in advance.
-Mix the prescribed amount of sodium polystyrene sulfonate in the desired volume of formula/EBM and shake vigorously for 2 minutes.-Because some of the formula/EBM will be wasted during the decanting process, a larger volume than the intended volume for ingestion is required. As an example, one published protocol requires a 24-hour supply of formula/EBM plus 200 mL.

-Place in refrigerator for at least 60 minutes. The mixture will settle, separating the sodium polystyrene sulfonate resin particulate from the formula/EBM.
-Using a large syringe, carefully decant the formula/EBM from the top of the container without disturbing the light brown particulate on the bottom of the container. The particulate contains the resin and bound potassium. Discard the formula/EBM and particulate remaining in the container.
-Transfer the decanted formula/EBM to an appropriate container and label properly.

Rare cases of acute bronchitis and/or broncho-pneumonia associated with inhalation of particles of polystyrene sulfonate have been noted in post-marketing reports. Position the patient carefully when administering the resin orally to minimize the risk of aspiration.

Cases of bowel necrosis have been associated with the use of sodium polystyrene sulfonate suspension enemas. Most cases reported the concomitant use of sorbitol or the use of a preparation containing sorbitol, which has led many clinicians to believe the events were more likely due to the hyperosmolar sorbitol content than the sodium polystyrene sulfonate. However, there have also been some reports of serious GI effects in patients who received sorbitol-free formulations. Although not all reported cases have occurred in the neonatal population, neonates, especially premature neonates, appear to be at higher risk, possibly due to their fragile intestinal mucosa. Hematochezia has been reported with the use of hypertonic sodium polystyrene sulfonate enemas (20% sorbitol was used as the vehicle for suspension) in premature neonates. In a review of 20 neonates, 4 (20%) experienced hematochezia temporally related to the use of the enemas. The episodes occurred in neonates that were < 29 weeks gestational age and < 1250 g birth weight. Sorbitol, the hyperosmolar suspending agent, was thought to contribute to the hematochezia. In another study of premature neonates with nonoliguric hyperkalemia, salbutamol intravenous infusion (n = 30) was compared to sodium polystyrene sulfonate (n = 15) 1 g/kg/dose PR every 4 hours; one case of intestinal perforation related to intestinal obstruction occurred in the sodium polystyrene sulfonate group and was felt to be treatment-related by the investigators. Necrotizing enterocolitis occurred in a 27 week (850 gram) anuric neonate receiving sorbitol-free sodium polystyrene sulfonate. Sodium polystyrene sulfonate 1 g/kg (0.85 grams) was suspended in water and given every 2 h rectally via a five french nasogastric tube for a total of 6.8 grams over 24 h. After 8 doses, hyperkalemia and anuria resolved. Although the neonate had not been enterally fed, at 8 days of life perforated necrotizing enterocolitis was diagnosed. Sodium polystyrene sulfonate crystals were found in mucosal and submucosal necrosis in intestinal wall specimens. Of note, preceding the renal failure, the patient developed group B Streptococcus sepsis, which may have compromised intestinal wall integrity prior to the patient receiving the sodium polystyrene sulfonate enemas. A 15 year old with chronic renal failure, seizure disorder, and chronic rejection of a living-related renal transplant who underwent transplant nephrectomy, received 3 sodium polystyrene sulfonate in sorbitol enemas over a 12-hour period. Thirty-six hours later, the patient developed significant abdominal symptoms and exploratory laparotomy showed necrosis of the entire colon without perforation.

Most adverse reactions that occur during sodium polystyrene sulfonate therapy are GI-related. Colonic necrosis after rectal administration is one of the most serious GI events (see bowel necrosis ADR content); however, other serious GI effects (GI bleeding, ischemic colitis, GI perforation, GI obstruction) have also been associated with sodium polystyrene sulfonate use. The majority of cases reported the concomitant use of sorbitol, and most patients had risk factors for GI events (e.g., prematurity, history of intestinal disease or surgery, hypovolemia, and renal insufficiency/failure). Gastric irritation can occur as well as anorexia, nausea, vomiting, and constipation, especially if large doses are given. Fecal impaction after rectal administration, particularly in pediatric patients, has been reported during post-marketing use, and bezoar formation has been reported after oral administration. To offset constipation, some commercial preparations of sodium polystyrene sulfonate contain a significant amount of sorbitol; however, sorbitol may also be associated with risks of serious adverse events (see bowel necrosis ADR content). Sorbitol emulsions occasionally cause diarrhea. Frequently, sorbitol causes cramping, abdominal pain, nausea, and vomiting. Cases of premature neonatal stomach and bowel opacification have been reported after administration of sodium polystyrene sulfonate ; oral administration is contraindicated in neonates. A 24-week gestational age (652 g birth weight) neonate received 1 g sodium polystyrene sulfonate via nasogastric tube every 4 hours and a single 1 g retention enema. On day 4, chest and abdominal radiographs showed opacification of the stomach and colon, which was not evident prior to sodium polystyrene sulfonate therapy. On abdominal radiograph, air surrounding the concretion within the stomach was noted. The patient died 7 days later. In a second case, a 630 g neonate received 0.6 g of sodium polystyrene sulfonate via nasogastric tube every 6 hours for elevated potassium. After administration, radiographs of the abdomen showed opacification of the stomach and bowel. The authors suggest that the premature infants' hypoactivity and bowel immaturity and hypomotility contributed to the precipitation of sodium polystyrene sulfonate in the stomach and to the increased water reabsorption in the colon, which increased the drug's radiographic density in the bowel. The authors also state that sodium polystyrene sulfonate's ability to bind intraluminal calcium may also contribute to the increased radiographic density. Another case series describes 5 extremely low-birth weight infants who developed radio opaque masses outlining the stomach after receiving either sodium polystyrene sulfonate or calcium polystyrene sulfonate orally. The masses were palpable in the left upper quadrant of the abdomen, and in 2 infants, the masses were identified as chalk-like concretions on autopsy.

Because the potassium-lowering ability of sodium polystyrene sulfonate is not precise, there is a risk of overcorrection and hypokalemia. In addition, the resin is not completely selective for potassium; other cations, such as calcium and magnesium, can also be lost during treatment, which can result in clinically significant hypocalcemia and/or hypomagnesemia. Serum potassium should be measured frequently within each 24 hour period; however, it should be noted that intracellular potassium depletion is not always accurately reflected by serum potassium concentrations. Clinical monitoring of the patient's mental status and electrocardiogram may also be helpful in detecting hypokalemia. Early signs of severe hypokalemia include irritable confusion and delayed thought process. Electrocardiographic changes (e.g., lengthened QT interval, widening, flattening, or inversion of the T wave, and prominent U waves) are also associated with severe hypokalemia. Cardiac arrhythmias (e.g., premature atrial, nodal, and ventricular contractions and supraventricular and ventricular tachycardias) can also occur. Late signs of hypokalemia include muscle weakness and even apnea. Because sodium polystyrene sulfonate exchanges sodium for potassium, therapy with sodium polystyrene sulfonate can introduce a significant sodium load, which may result in hypernatremia in susceptible patients. Patients who may be sensitive to changes in sodium status also warrant more frequent monitoring of sodium concentrations. Sodium polystyrene sulfonate has caused serious hypernatremia in extremely low birth weight infants. In one case, a premature neonate (25 weeks gestational age) was started on sodium polystyrene sulfonate 0.5 g/kg/dose rectally every 6 hours at 32 hours of life. After 8 hours, the potassium had begun to decrease, but the neonate developed hypernatremia (sodium = 167 mmol/L). After the fourth dose, sodium polystyrene sulfonate was stopped and a reduction in the sodium was observed. A second neonate born at 25 weeks gestational age started sodium polystyrene sulfonate 1 g/kg/dose every hour at 52 hours of life. After 24 hours of therapy, the potassium had decreased, but hypernatremia (sodium = 166 mmol/L) was present after only 4 hours of sodium polystyrene sulfonate treatment. Monitor all electrolytes carefully during therapy; supplementation/electrolyte replacement may be required. The manufacturer states that the colon should be irrigated with a non-sodium-containing solution after the retention enema is administered.

Sodium polystyrene sulfonate is contraindicated in patients with a history of hypersensitivity to polystyrene sulfonate resins.

Administer sodium polystyrene sulfonate 3 hours before or 3 hours after other orally administered medications to prevent sodium polystyrene sulfonate from binding to other oral medications, which may result in decreased gastrointestinal absorption and reduced efficacy of the bound drug. For patients with gastroparesis or other conditions resulting in delayed emptying of food from the stomach into the small intestine, separate sodium polystyrene sulfonate from other orally administered medications by at least 6 hours.

Because sodium polystyrene sulfonate may take several hours to lower serum potassium and the effect is variable, it is not appropriate monotherapy for the urgent treatment of severe hyperkalemia or for the correction of severe hyperkalemia associated with rapid tissue breakdown states (e.g. burns). Other treatment options, including dialysis, should also be considered in patients with severe hyperkalemia.

Sodium polystyrene sulfonate is contraindicated in patients with GI obstruction or obstructive bowel disease and neonates with reduced gut motility (postoperatively or drug induced). Some products are contraindicated by the manufacturer for use in neonates via any route; all products are contraindicated for oral administration neonates. Cases of concretion of the resin in the stomach and bowel have occurred after oral administration to neonates. In neonates, infants, and children, particular care should be observed with rectal administration; excessive dosage or inadequate dilution can result in impaction of the resin. Due to the risk of GI bleeding or colonic necrosis, particular care should be observed in premature neonates or low birth weight infants. In addition, when rectal sodium polystyrene sulfonate therapy is necessary in a neonate, do not use commercially available liquid preparations formulated with sorbitol because their hyperosmolality has been associated with intestinal hemorrhage in premature neonates; freshly compounded, sorbitol-free suspensions prepared from the powdered resin are preferred.

Sodium polystyrene sulfonate should only be used in patients with normal bowel function; avoid use in patients at risk for developing constipation or fecal impaction (i.e., those with a history of fecal impaction, chronic constipation, inflammatory bowel disease, ischemic colitis, previous bowel resection, or bowel obstruction). Do not use in post-operative patients who have not had a bowel movement post-surgery. Intestinal necrosis and other serious GI adverse events such as bleeding, ischemic colitis, and perforation have been reported in association with sodium polystyrene sulfonate. Concomitant use of sorbitol with sodium polystyrene sulfonate has been implicated in the majority cases of colonic necrosis. Additional sorbitol should not be used. Rectally administered hyperosmolar preparations containing high concentrations of sorbitol have been associated with intestinal hemorrhage in premature neonates; freshly compounded, sorbitol-free suspensions prepared from the powdered resin are preferred over commercially available suspensions containing sorbitol in this patient population. Premature neonates and patients with a history of intestinal disease or surgery, necrotizing enterocolitis, hypovolemia, and renal insufficiency, and/or renal failure may be at higher risk for intestinal necrosis. In the event of clinically significant constipation, discontinue treatment with sodium polystyrene sulfonate until normal bowel motion is resumed. Magnesium-containing laxatives or sorbitol should not be used for treatment of constipation.

Sodium polystyrene sulfonate reduces total body potassium and is contraindicated in patients with hypokalemia; monitor patients closely to avoid overcorrection. Keep in mind that intracellular potassium depletion is not always accurately reflected by serum potassium concentrations; clinical monitoring of the patient's mental status and electrocardiogram may also be helpful in detecting hypokalemia. Sodium polystyrene sulfonate is not completely selective for potassium; other cations, such as calcium and magnesium, can also be lost during treatment; therefore, use sodium polystyrene sulfonate therapy with caution in patients with hypocalcemia or hypomagnesemia. In addition, sodium polystyrene sulfonate should be used with caution in patients with hypernatremia or who require sodium restriction (i.e. severe congestive heart failure, severe hypertension, or marked edema) because administration of the resin can introduce a significant sodium load. In an effort to minimize the amount of sodium retained, ensure that adequate volumes of sodium-free cleansing enemas are used after rectal administration of sodium polystyrene sulfonate. Monitor all electrolytes carefully and correct using supplements or dosage adjustments as needed.

Description: Sodium polystyrene sulfonate is a cation-exchange resin used in the treatment of hyperkalemia. Each gram of resin can remove roughly 3 mEq of potassium in vitro, but because sodium polystyrene sulfonate can bind other cations, the actual amount of potassium removed in vivo is closer to 1 mEq per gram of drug. Due to the sodium-potassium exchange and sodium content in the sodium polystyrene sulfonate products, sodium retention may occur. Hypernatremia has been reported in extremely low birth weight infants after treatment with sodium polystyrene sulfonate. Sodium polystyrene sulfonate exerts its effects over several hours; it is inappropriate for the acute treatment of life-threatening hyperkalemia. Cases of concretion of the resin in the stomach and bowel have occurred after oral administration to neonates; therefore, oral administration is contraindicated in neonates. Rectal administration of sorbitol-containing products has been associated with colonic necrosis and intestinal hemorrhage in neonates; therefore, freshly compounded, sorbitol-free suspensions prepared from the powdered resin are preferred in this age group. Due to the risks associated with sodium polystyrene sulfonate therapy in neonates and inferior efficacy, other treatments for hyperkalemia (e.g., insulin with glucose) should be used as first-line therapy in this population. Although data is limited, some practitioners have used sodium polystyrene sulfonate to remove potassium from formula or expressed milk prior to consumption, eliminating the risk of resin ingestion in young patients with renal impairment. Sodium polystyrene sulfonate is FDA-approved for use in pediatric patients as young as infants. Some labels carry a contraindication for use in neonates by any route, and others are contraindicated for use in neonates by the oral route only.

General dosing information
-The in vivo exchange capacity is approximately 1 mEq of potassium per 1 g sodium polystyrene sulfonate; however, efficiency is variable.
-One gram of sodium polystyrene sulfonate powder or suspension contains approximately 100 mg (4.1 meq) sodium.
-The in vivo efficiency of sodium-potassium exchange resins is approximately 33%. On average, approximately one-third of the resin's sodium content is delivered to the body.

For the treatment of hyperkalemia:
Oral dosage:
Neonates: Oral administration is contraindicated.
Infants, Children, and Adolescents: 1 g/kg/dose (Max: 15 g/dose) PO every 6 hours as needed to correct hyperkalemia. FDA-approved labeling recommends using an exchange rate of 1 mEq of potassium per gram of resin as the basis for calculating the dosage for infants and small children. Because efficacy is variable, carefully monitor serum electrolytes to determine appropriateness of dosage and duration of therapy.
Rectal dosage:
Neonates*: Insulin with glucose is preferred over treatment with rectal cation-resin in pre-term neonates. Some products are contraindicated by the manufacturer for use in neonates. Individual doses of 0.5 to 1 g/kg/dose PR have been recommended. The frequency of administration depends on the severity of hyperkalemia and patient response; every 6 hours as needed is recommended in other age groups. To minimize the risk of impaction, use the lowest effective dose, properly dilute the powder for suspension, and after the enema is complete, adequately irrigate using a sodium-free cleansing fluid to ensure full recovery of the resin. Sodium polystyrene sulfonate 1 g/kg/dose PR every 4 hours has been studied; however, the authors concluded that early continuous regular insulin infusion therapy for the treatment of non-oliguric hyperkalemia in very low birth weight infants is more effective than sodium polystyrene sulfonate. If sodium polystyrene sulfonate therapy is necessary, do not use commercially available liquid formulations containing sorbitol because their hyperosmolality has been associated with intestinal hemorrhage in premature neonates; freshly compounded suspensions prepared from the powdered resin are preferred.
Infants, Children, and Adolescents: 1 g/kg/dose (Max: 50 g/dose) PR every 6 hours as needed to correct hyperkalemia. FDA-approved labeling recommends using an exchange rate of 1 mEq of potassium per gram of resin as the basis for calculating the dosage for infants and small children. The usual adult dose is 30 to 50 g/dose. Because efficacy is variable, carefully monitor serum electrolytes to determine appropriateness of dosage and duration of therapy.
-for the reduction of bioavailable potassium content in infant formula or expressed breast milk*:
Extracorporeal dosage (to be added to infant formula or expressed breast milk):
Neonates and Infants: Limited data are available; the ideal dosage has not been established. A dosage of 0.5 to 1 g sodium polystyrene sulfonate powder per 100 mL formula/breast milk appears to be a common initial dosage range used. One small study (n = 13, patient weights 2.4 to 7.5 kg) reports doses of 0.4 to 1.5 g per 100 mL formula/breast milk; 6 of the 13 patients received a starting dose of 1 g/100 mL. Authors from another study suggest an initial dose of 5 mL of sodium polystyrene powder (measured as leveled powder in a medicine cup) per 770 mL formula (this dose corresponds to about 0.5 to 0.65 g per 100 mL formula, depending on the brand of sodium polystyrene sulfonate used). When mixed with infant formula or breast milk, sodium polystyrene sulfonate binds with potassium in exchange for sodium, lowering the bioavailable potassium content and leaving the formula rich in sodium. After binding has occurred and the resin particulate has settled to the bottom, the ingestible formula/breast milk is decanted off of the top. The sodium polystyrene sulfonate resin is not ingested by the infant. Because the resin can alter other electrolytes (e.g. binds with calcium, magnesium, and phosphate and increases the sodium content in the milk), careful monitoring of all electrolytes is necessary. Supplementation of some electrolytes may be required. Pretreatment of formula or breast milk with sodium polystyrene sulfate resulted in a 24% decrease in serum potassium concentrations (mean: 6.3 to 4.8 mEq/L, p < 0.0001) in 13 infants (age: 1.4 to 33 weeks) with nonoliguric hyperkalemia within 48 hours of treatment initiation; hyperkalemia resolved in all subjects within 72 hours of initiation. There was a significant difference in before and after calcium (10.7 to 10 mg/dL) and creatinine (2 to 1.9 mg/dL) concentrations, but not other electrolytes.

Maximum Dosage Limits:
Specific maximum dosage information is not available for pediatric patients; however, commonly used maximum doses are 15 g/dose PO and 50 g/dose PR. Individualize dosage based on careful monitoring of serum potassium concentrations and other clinical parameters in all patient populations.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Sodium polystyrene sulfonate (SPS) is a non-absorbed, cation-exchange polymer indicated for the treatment of hyperkalemia. The drug can be administered either orally or as a retention enema. Once in the gastrointestinal lumen, the insoluble resin swells allowing for the sodium contained within the polymer to be exchanged for potassium and other cations dissolved within the gastrointestinal tract; this action occurs primarily in the large intestine. The potassium that is now bound to the polymer continues through the colon and is eventually eliminated in the feces. By binding and eliminating free potassium from the gastrointestinal lumen, SPS reduces serum potassium concentrations. The in vivo exchanges ratio is estimated to be approximately 1 meq of potassium for each gram of SPS administered. However, drug efficacy is unpredictable, as competition from other cations (i.e., calcium and magnesium) may reduce the potassium exchange capacity to as low as 0.4 meq per gram of SPS.

Sodium polystyrene sulfonate has a delayed onset of action (1 to 2 hours); therefore, the drug is not indicated as an emergency treatment for severe or life-threatening hyperkalemia. Alternative treatment options may include dialysis, insulin with 5% dextrose (15 to 30 minutes), nebulized albuterol (15 to 30 minutes), and intravenous furosemide (15 minutes to 1 hour).

Pharmacokinetics: Sodium polystyrene sulfonate is administered orally or rectally. It is not absorbed after administration; therefore, it does not distribute in the body and is not metabolized. The cationically modified resin is excreted in the feces. The resin's onset of action is typically within a few hours.

Affected cytochrome P450 isoenzymes: none