Sodium Polystyrene Sulfonate

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Continuing Education Activity

Sodium polystyrene sulfonate is a medication used in the management and treatment of hyperkalemia. This activity outlines and reviews the indications, mechanism of action, and contraindications for sodium polystyrene sulfonate in the treatment of hyperkalemia. Furthermore, this activity will highlight adverse event profile, dosing, pharmacodynamics, pharmacokinetics, and relevant interactions related to hyperkalemia management.


  • Identify the medically approved indications for sodium polystyrene sulfonate therapy.
  • Describe the mechanism of action of sodium polystyrene sulfonate.
  • Summarize the adverse effects of sodium polystyrene sulfonate.
  • Outline the importance of collaboration and coordination among the interprofessional team to enhance patient care when dosing and monitoring sodium polystyrene sulfonate to improve patient outcomes for patients receiving sodium polystyrene sulfonate.


Sodium polystyrene sulfonate (SPS) is approved by the Food and Drug Administration (FDA) for the treatment of hyperkalemia though it is not typically the first-line treatment.[1] A potassium level greater than 5 mEq/L qualifies as hyperkalemia. Hyperkalemia is often asymptomatic; however, it may cause fatigue, muscle cramps, muscle weakness, rarely paralysis. A high potassium level is associated with an increase in morbidity and mortality, especially K > 6.5 mEq/L can be fatal. Hence, prompt management is essential to avoid serious consequences. Sodium polystyrene sulfonate helps by removing extra potassium from the body. Due to its slow onset of action, it is a second-line agent in emergent situations. Data on the non-FDA-approved use of this drug is limited. This drug can also help to remove excess calcium, sodium from solutions in technical applications.[2][3][4][5][6][7]

Mechanism of Action

Sodium polystyrene sulfonate (SPS) is an insoluble polymer cation-exchange resin. After ingestion of the oral formulation or application through the rectal route, this resin exchanges sodium with potassium ions from the intestinal cells. Then the potassium binds with SPS, continues to move through the gastrointestinal tract, and is finally eliminated in the feces.[8][9] But sodium polystyrene sulfonate is not selective for potassium; it may bind with calcium and magnesium.[10] This drug begins its action within 2 to 24 hrs of its administration and continues its work up to 4 to 6 hours before it gets eliminated from the body through feces.[11] The exchange capacity of SPS is approximately 33% or 1 mEq of potassium per 1 gram of resin, and this number is not constant. It may be as low as 0.4 to 0.8 mEq/gram of SPS resin. Competition from other cations, especially sodium, calcium, and magnesium, contributes to this reduction of this exchange capacity.


Sodium polystyrene sulfonate can be administered either orally or rectally. It is available in oral suspension, oral powder formulation, and rectal enema formulation. Appropriate dosing of sodium polystyrene sulfonate is varying on the route of administration. Usually, the dose of sodium polystyrene sulfonate is between 15 g (60 mL) to 60 g (240 mL), and each 15 g of sodium polystyrene sulfonate can bind 15 mEq of potassium.[12] While using as an oral suspension, it should not be heated or should not be used along with heated foods or liquids because this may cause a decrease in the effectiveness of this drug. This drug should not be mixed with banana or orange juice (potassium-rich). SPS may impair the absorption of other orally administered medications and may lead to reduced efficacy, so other oral drugs should be administered at least 3 hours before or 3 hours after SPS therapy.

Patients with gastroparesis may require a longer period between SPS and other oral medications. When using an enema, the administration of a cleansing enema should be before administering sodium polystyrene sulfonate. It should be as warm as body temperature for rectal formulation. After administration, SPS should be retained in the colon for at least 30 to 60 min. After completing retention, irrigation should be done with a non-sodium colonic irrigant to remove the remaining resin. In the past, SPS used to be coadministered with sorbitol to reduce the chance of constipation, but in 2009, the FDA issued a warning against the concomitant use of SPS and sorbitol due to the occurrence of colonic necrosis and other serious GI side effects. Nowadays, the concurrent use of sorbitol is not recommended.[13] 


Resin powder should be stored at 25 degrees C (77 F); excursions permitted to 15 to 30 degrees C (59 to 86 F). After the preparation of suspension, it should be used within 24 hours.

Adverse Effects

Sodium polystyrene sulfonate has several side effects.[14][15] Some are mild and should eventually resolve spontaneously; others are serious and need urgent care. 

Mild Adverse Effect

  • Diarrhea
  • Nausea
  • Vomiting
  • Loss of appetite

Serious Side Effects

  • Ischemic colonic necrosis
  • Constipation 
  • Seizures
  • Confusion
  • Muscle weakness
  • Abdominal pain
  • Irregular heartbeat


SPS is contraindicated in the following conditions: 

  • Hypokalemia
  • Previous history of hypersensitivity to polystyrene sulfonate resins
  • Bowel Obstruction
  • Neonates with reduced gut motility


SPS can contribute to sodium overload and lead to fluid retention. Hence, SPS use requires caution in certain conditions such as congestive heart failure, severe hypertension, and marked edema. Clinicians should not use SPS in patients with abnormal bowel functions, such as bowel obstruction, Ileus, and postoperative patients. Using SPS in these patients may increase the risk of bowel ischemia, necrosis, and serious constipation.

Pregnancy and Lactation

SPS does not get absorbed systemically; thus, maternal use of SPS is not expected to cause harm to the fetus. Similarly, as it is not secreted through breast milk, breastfeeding is not expected to result in any particular risk to the newborn.


Since SPS is not selective for potassium ions, other electrolyte imbalances may occur while using SPS in hyperkalemic patients. Patients should be monitored carefully for the signs and symptoms of other electrolyte abnormalities such as hypokalemia,  hypomagnesemia, and hypocalcemia. Hypokalemia may be associated with cardiac arrhythmias and severe muscle weakness. Hypokalemia may be evident as prolongation of the QT interval, T-wave inversions, prominent U waves (an extra upward wave after the T-wave) in Electrocardiogram (ECG). Some patients may present with significant symptoms of rebound hyperkalemia, which may be evident in ECG as a tall peaked T wave. 

Hypomagnesemia can present with muscle weakness and potentiate hypokalemia. Hypocalcemia presents with tremors, muscle weakness, tetany, and rarely, seizures.


Prolong use of Sodium polystyrene sulfonate can be attributed to several toxicities, including hypomagnesemia, hypocalcemia, sodium load, and colonic necrosis. Toxicity may occur to a greater extent with the concomitant administration of aluminum hydroxide, which may cause intestinal obstruction. Hypokalemia associated with SPS use may also increase the adverse effects of digitalis.[14][9] Excessive SPS use may also cause sodium load, potentially precipitating worsening hypertension and congestive heart failure symptoms.

Enhancing Healthcare Team Outcomes

SPS is usually prescribed by clinicians, including primary care providers, PAs or NPs, or internists. Since the drug can cause several side effects and is related to several toxicities, all interprofessional healthcare team members should be familiar with its pharmacology. They must be aware of its side effects and toxicities. A proper history and physical examination should take place before the initiation of SPS in any patient. Interprofessional discussion with nephrology, pharmacists, and nursing staff is prudent when considering using SPS as the primary line of therapy for hyperkalemia. The team should monitor the signs-symptoms of toxicity regularly and be ready to initiate any necessary measures if any complications occur. Upon successful management, this interprofessional team should educate the patients about dosing, side effects, and warning signs which may arise in the future. This approach will result in better patient outcomes with fewer adverse events. [Level 5]

Article Details

Article Author

Sajedur Rahman

Article Editor:

Rachana Marathi


7/5/2021 5:19:06 PM



Lehnhardt A,Kemper MJ, Pathogenesis, diagnosis and management of hyperkalemia. Pediatric nephrology (Berlin, Germany). 2011 Mar;     [PubMed PMID: 21181208]


Acker CG,Johnson JP,Palevsky PM,Greenberg A, Hyperkalemia in hospitalized patients: causes, adequacy of treatment, and results of an attempt to improve physician compliance with published therapy guidelines. Archives of internal medicine. 1998 Apr 27;     [PubMed PMID: 9570179]


Moore ML,Bailey RR, Hyperkalaemia in patients in hospital. The New Zealand medical journal. 1989 Oct 25;     [PubMed PMID: 2812582]


Shapiro S,Slone D,Lewis GP,Jick H, Fatal drug reactions among medical inpatients. JAMA. 1971 Apr 19;     [PubMed PMID: 5107928]


Paice B,Gray JM,McBride D,Donnelly T,Lawson DH, Hyperkalaemia in patients in hospital. British medical journal (Clinical research ed.). 1983 Apr 9;     [PubMed PMID: 6404388]


Kraft MD,Btaiche IF,Sacks GS,Kudsk KA, Treatment of electrolyte disorders in adult patients in the intensive care unit. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2005 Aug 15;     [PubMed PMID: 16085929]


Nakamura T,Fujisaki T,Miyazono M,Yoshihara M,Jinnouchi H,Fukunari K,Awanami Y,Ikeda Y,Hashimoto K,Yamasaki M,Nonaka Y,Fukuda M,Kishi T,Ikeda Y, Risks and Benefits of Sodium Polystyrene Sulfonate for Hyperkalemia in Patients on Maintenance Hemodialysis. Drugs in R     [PubMed PMID: 30097847]


Gruy-Kapral C,Emmett M,Santa Ana CA,Porter JL,Fordtran JS,Fine KD, Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease. Journal of the American Society of Nephrology : JASN. 1998 Oct;     [PubMed PMID: 9773794]


Sterns RH,Rojas M,Bernstein P,Chennupati S, Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? Journal of the American Society of Nephrology : JASN. 2010 May;     [PubMed PMID: 20167700]


KLINGENSMITH WC Jr,ELKINTON JR, Cation exchange resin in the treatment of congestive heart failure. II. Clinical effectiveness and chemical complications during prolonged periods of use. Circulation. 1952 Jun;     [PubMed PMID: 14936180]


Kessler C,Ng J,Valdez K,Xie H,Geiger B, The use of sodium polystyrene sulfonate in the inpatient management of hyperkalemia. Journal of hospital medicine. 2011 Mar;     [PubMed PMID: 21387549]


Chaitman M,Dixit D,Bridgeman MB, Potassium-Binding Agents for the Clinical Management of Hyperkalemia. P     [PubMed PMID: 26765867]


Nguyen T,Ondrik D,Zhufyak O,To W,He S, Hyperkalemia and potential pitfalls of sodium polystyrene sulfonate. JAAPA : official journal of the American Academy of Physician Assistants. 2015 Mar;     [PubMed PMID: 25710403]


Harel Z,Harel S,Shah PS,Wald R,Perl J,Bell CM, Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. The American journal of medicine. 2013 Mar;     [PubMed PMID: 23321430]


Lepage L,Dufour AC,Doiron J,Handfield K,Desforges K,Bell R,Vallée M,Savoie M,Perreault S,Laurin LP,Pichette V,Lafrance JP, Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD. Clinical journal of the American Society of Nephrology : CJASN. 2015 Dec 7;     [PubMed PMID: 26576619]