Kayexalate: Uses, Contraindications, Side Effects, Mechanism of Action, Administration and Precautions

Polystyrene sulfonates are polymers derived from polystyrene by adding sulfonate functional groups.

They are widely used as ion exchange resins to remove ions such as potassium, calcium and sodium from solutions in technical or medical applications.

Linear ionic polymers are generally soluble in water, while cross-linked materials (called resins) do not dissolve in water. These polymers are classified as polysalts and ionomers.

How does the Kayexalate work? What will you do for me?

Sodium polystyrene sulfonate belongs to the class of drugs called cation exchange resins. It is used to treat high levels of potassium in the blood ( hyperkalemia ).

It lowers the level of potassium in the blood by binding to potassium in the intestine. This drug may be available under various brand names and / or in several different forms.

No specific brand of this drug may be available on all forms or approved for all conditions discussed here.

Also, some forms of this drug cannot be used for all of the conditions discussed here.

Medical uses

Polystyrene sulfonate is generally supplied in the form of sodium or calcium. It is used as a potassium binder in acute and chronic kidney disease in people with hyperkalemia (abnormally high potassium levels in the blood).

However, it is not clear if it is medically beneficial and there are concerns about possible side effects when combined with sorbitol.

Polystyrene sulfonates are administered orally with a meal or rectally by retention enema.

Under the name tolevamer, a polystyrene sulfonate was investigated by Genzyme as a toxin binding agent for the treatment of Clostridium difficile-associated diarrhea (CDAD), but was never commercialized.

Kayexalate contraindications

The drug is contraindicated in patients with obstructive bowel disease and in newborn infants with reduced intestinal motility. Do not use this medicine if:

You are allergic to sodium polystyrene sulfonate or any part of the medicine. Have a serum potassium level lower than 5 mmol / L. You have obstructive bowel disease.

Side effects

Bowel disorders are common, such as loss of appetite, nausea, vomiting, and constipation. In rare cases, it has been associated with colonic necrosis.

Changes in electrolyte levels in the blood can occur, such as hypomagnesaemia, hypocalcemia, and hypokalemia.

Although most of the side effects listed below don’t happen very often, they can lead to serious problems if you don’t see your doctor or seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • Abdominal pain or bloating
  • Bleeding from the rectum
  • Bloody stools or bloody diarrhea.
  • Symptoms of low calcium levels (for example, abdominal cramps, irritability, muscle spasms).
  • Symptoms of low magnesium levels (eg, muscle weakness, irregular heartbeat, nausea, vomiting).
  • Symptoms of low potassium levels (eg, muscle weakness, irregular heartbeat, nausea, vomiting).
  • Symptoms of sodium retention (eg, bloating, excessive thirst).

Stop taking the medicine and seek immediate medical attention if any of the following occur:

  • Signs of an allergic reaction (such as difficulty breathing, hives, swelling of the face or throat).
  • Signs of stomach bleeding (for example, vomit that looks like coffee grounds, black, bloody, or tarry stools).
  • Symptoms of a blocked intestine (for example, abdominal pain, bloating, vomiting) symptoms of fecal impaction (for example, liquid leaky stools, stomach pain, feeling of needing to push, nausea, vomiting, loss of appetite).
  • Symptoms of a bowel tear (for example, abdominal pain, nausea, vomiting, fever).

Interactions

Polystyrene sulfonates can bind to various medications within the digestive tract and therefore decrease their absorption and effectiveness. Common examples include lithium, thyroxine, and digitalis.

There may be an interaction between sodium polystyrene sulfonate and any of the following:

  • Aluminum hydroxide.
  • Certain antacids (eg, magnesium hydroxide, calcium carbonate).
  • Digoxin.
  • Laxatives
  • Magnesium citrate.
  • Meloxicam.
  • Sorbitol.

If you are taking any of these medications, talk to your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

Stop taking one of the medications, switch one of the medications to another, change the way you are taking one or both medications, or leave everything as is.

In September 2017, the Food and Drug Administration (FDA) recommended separating the dose of polystyrene sulfonate from any other oral medication by at least three hours to avoid potential interactions.

Cases of intestinal necrosis have been reported when this polymer was combined with sorbitol.

Kayexalate Mechanism of Action

hyperkalemia

Polystyrene sulfonates release sodium or calcium ions in the stomach in exchange for hydrogen ions. When the resin reaches the large intestine, the hydrogen ions are exchanged for free potassium ions; the resin is then eliminated in the faeces.

The net effect is to decrease the amount of potassium available for absorption into the blood and to increase the amount that is excreted through the stool. The effect is a reduction in potassium levels in the body.

Clostridium difficile associated diarrhea (CDDA)

Tolevamer was designed to bind enterotoxins rather than directly attack Clostridium difficile. As it does not have antibiotic properties, it does not harm the intestinal flora.

The first studies used sodium salt, but it was soon replaced with potassium sodium salt to prevent hypokalemia, which is often associated with diarrhea.

Production and chemical structure

Polystyrene sulfonic acid has the idealized formula (CH2CHC6H4SO3H) n. The material is prepared by sulfonation of polystyrene:

  • (CH2CHC6H5) n + n SO3 → (CH2CHC6H4SO3H) n

There are several methods for this conversion, which can lead to a variable degree of sulfonation. Polystyrene is generally cross-linked, which prevents the polymer from dissolving.

Since the sulfonic acid group (SO3H) is strongly acidic, this polymer neutralizes bases. In this way, various salts of the polymer can be prepared, leading to sodium, calcium, and other salts:

  • (CH2CHC6H4SO3H) n + n NaOH → (CH2CHC6H4SO3Na) n + n H2O

These ion-containing polymers are called ionomers.

Alternative sulfonation methods

Double substitutions of phenyl rings are known to occur, even with conversions well below 100%.

Crosslinking reactions are also found, where the condensation of two sulfonic acid groups produces a sulfonyl crosslinking.

On the other hand, the use of milder conditions like acetyl sulfate leads to incomplete sulfonation.

Recently, radical atom transfer polymerization (PRTA) of protected styrene sulfonates has been reported, leading to well-defined linear polymers, as well as more complicated molecular architectures.

History

Completion of tolevamer development

In early 2008, a non-inferiority study with vancomycin or metronidazole for Clostridium difficile-associated diarrhea (CDAD).

It found that approximately half of the patients in the tolevamer group did not complete treatment, compared with 25% in the vancomycin and 29% in the metronidazole groups.

Recurrence of Clostridium difficile-associated diarrhea in clinically successful patients was significantly reduced with tolevamer (6% recurrence rate), vancomycin (18%), and metronidazole (19%). However, the good outcome of tolevamer is partly due to the high attrition rate in this group.

Since tolevamer did not reach its primary end point in this study, its development was halted.

Chemical uses

Polystyrene sulfonates are useful because of their ion exchange properties.

Water softening

Softening of the water is accomplished by filtering hard water through a bed of the cross-linked polystyrene sulfonate sodium form.

Hard ions such as calcium (Ca2 +) and magnesium (Mg2 +) adhere to sulfonate groups, displacing sodium ions. The resulting solution of sodium ions softens.

Other uses

Sodium polystyrene sulfonate is used as a superplasticizer in cement, as a dye enhancing agent for cotton, and as proton exchange membranes in fuel cell applications.

In its acid form, the resin is used as a solid acid catalyst in organic synthesis.

In what form (s) does this medicine come?

Light brown, to brown, finely ground sodium polystyrene sulfonate powder. The sodium content is approximately 4.1 mmol (100 mg) per gram.

How should I use this medicine?

  • Oral : The average adult dose is 15 grams taken 1 to 4 times a day. Each dose should be mixed in 45 ml to 60 ml of water or syrup. Do not mix it with orange juice or fruit that contains potassium. Doses for children are based on body weight.
  • Rectal : the recommended dose for adults is 30 to 50 grams administered 1 or 2 times a day (at 6-hour intervals). Doses for children are based on body weight.

If your doctor has recommended a different dose than those listed here, do not change the way you take the medicine without consulting your doctor. It is important to use this medicine exactly as prescribed by your doctor.

Sodium polystyrene sulfonate should not be administered orally to newborns or rectally to newborns with slow movement through the intestines.

Are there other precautions or warnings for Kayexalate?

These factors can affect the way you should use this medicine.

Increased Sodium Levels : Sodium polystyrene sulfonate can cause an increase in sodium levels.

If you have congestive heart failure, high blood pressure, kidney problems, or swelling of the ankles, feet, legs, or hands, discuss with your doctor how this medication may affect your medical condition and if special monitoring is required.

Low Potassium Levels – Sodium polystyrene sulfonate can cause low potassium levels. Tell your doctor if you experience symptoms of low potassium, such as confusion, irregular heartbeats, and muscle weakness or cramps.

Pregnancy : The safety and efficacy of using this medication during pregnancy have not been established.

Children and Babies : Newborns should not take sodium polystyrene sulfonate by mouth.