View source for Tolevamer

{{Drugbox
| drug_name         = Tolevamer (free acid)
| IUPAC_name        = Poly(styrol-4-sulfonic acid)
| image             = Tolevamer structure.svg
| width             = 100
| CAS_number        = 28210-41-5
| CAS_supplemental  =
| ATC_prefix        = none
| ATC_suffix        = 
| ATC_supplemental  = 
| PubChem           = 
| DrugBank          = 
| chemical_formula  = (C<sub>8</sub>H<sub>8</sub>O<sub>3</sub>S)<sub>n</sub>
| molecular_weight  =  
| smiles            = 
| bioavailability   = not significantly absorbed from the gut
| protein_bound     = 
| metabolism        = not metabolised
| elimination_half-life = 
| excretion         = N/A
| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US      =  <!-- A / B            / C / D / X -->
| pregnancy_category=  
| legal_AU =  <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA =  <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK =  <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US =  <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status      = development terminated
| routes_of_administration = oral
}}

'''Tolevamer''' is a [[toxin]] binding [[polymer]] that was investigated by [[Genzyme]] for the treatment of ''[[Clostridium difficile]]'' associated diarrhoea (CDAD).

==Background==
''Clostridium difficile'' is a major cause of hospital-acquired diarrhoea, affecting about 300,000 patients in the U.S. alone. CDAD typically occurs after treatment with [[antibiotic]]s which disrupt the [[gut flora]], allowing ''C. difficile'' to proliferate in the gut and release [[enterotoxin]]s which lead to diarrhoea. CDAD is usually treated with the antibiotics [[vancomycin]], [[metronidazole]] or both. This therapy yields good results but has the disadvantage of further disrupting the flora.<ref name="ÖAZ">{{cite journal
 | author = H. Spreitzer
 | date = September 24, 2007
 | title = Neue Wirkstoffe - Tolevamer
 | journal = Österreichische Apothekerzeitung
 | issue = 20/2007
 | pages = 955
 | language = German
 }}</ref>

==Mechanism of action==
Tolevamer was designed to bind the enterotoxins rather than attack ''C. difficile'' directly. Since it has no antibiotic properties, it does not harm the gut flora. Early studies used the [[sodium]] salt, but it was soon replaced with the [[potassium]] sodium salt to prevent [[hypokalaemia]] which is often associated with diarrhoea.<ref name="ÖAZ" /><ref name="Drugs of the Future">{{cite journal
 | author = Wang, Y, Serradell, N, Rosa, E, Bolos, J
 | title = Tolevamer Potassium Sodium
 | journal = Drugs of the Future
 | year = 2007
 | volume = 32
 | issue = 6
 | pages = 501–505
 | doi = 10.1358/dof.2007.032.06.1108513
 }}</ref>

==Dosage==
Six grams of tolevamer potassium sodium were applied per day, but up to 15 g were tolerated well by most patients.<ref name="Drugs of the Future" />

==Termination of development==
In early 2008, a noninferiority study versus vancomycin or metronidazole found that about half of the patient 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, the development was halted.<ref>[http://www.medscape.com/viewarticle/573449 Medscape.com: Tolevamer Less Effective Than Standard Therapies for ''C difficile''–Associated Diarrhea]</ref>

== References ==
{{Reflist}}

[[Category:Antidiarrhoeals]]
[[Category:2Fix]]