Tolevamer is a medication developed to combat ''Clostridioides difficile'' associated diarrhea. It is a

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

polystyrene sulfonate Polystyrene sulfonates are a group of medications used to treat high blood potassium. Effects generally take hours to days. They are also used to remove potassium, calcium, and sodium from solutions in technical applications. Common side effec ...

. It was never marketed.

Mechanism of action

Tolevamer was designed to bind the

enterotoxin An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines. They can be chromosomally or plasmid encoded. They are heat labile (> 60 °C), of low molecular weight and water-soluble. Enterotoxins are frequently cy ...

s of ''Clostridioides difficile''. Since it has no antibiotic properties, it does not harm the

gut flora Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the g ...

. Early studies used the sodium salt, but it was soon replaced with the potassium sodium salt to prevent

hypokalaemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an ...

, which is often associated with diarrhea.

History

Termination of development

In early 2008, a noninferiority study versus

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously ( injection into a vein) to treat complicated skin infections, bloodstream infections, endocarditis, bone an ...

metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...

for ''Clostridioides difficile'' associated diarrhea (CDAD) found that about half of the patients in the tolevamer group did not complete the treatment, versus 25% in the vancomycin and 29% in the metronidazole groups. CDAD recurrence in patients reaching clinical success was reduced significantly by tolevamer (6% recurrence rate), vancomycin (18%), and metronidazole (19%). However, the good result of tolevamer is partly due to the high drop-out rate in this group. Since tolevamer did not reach its primary endpoint in this study, its development was halted.

References

Antidiarrhoeals Sulfonic acids Abandoned drugs {{antiinfective-drug-stub