Colestilan
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| Surname | Colestilan | ||||||||
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IUPAC : 2- (chloromethyl) oxirane-2-methyl-1 H -imidazole copolymer |
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| CAS number | 95522-45-5 | ||||||||
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| Mechanism of action |
Phosphate binding in the gastrointestinal tract so that the entire compound can be excreted |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||
Colestilan is a drug from the group of phosphate binders that is used in dialysis patients to reduce high blood phosphate levels ( hyperphosphataemia ), the greatest risk factor for mortality from chronic kidney disease.
Colestilan is a non-absorbable polymer that binds phosphate and other anions from food in the gastrointestinal tract. In contrast to most other phosphate binders, it contains neither aluminum nor calcium, the long-term administration of which can be associated with considerable health risks such as encephalopathy or atherosclerosis .
pharmacology
Colestilan is a polymer-based anion exchange resin that cannot be absorbed by the body. Due to its positive charge, it binds the phosphate anions released from food in the gastrointestinal tract and is then excreted. Colestilan is able to bind phosphate in a wide pH range between 3 and 11. In addition, other anions such as. B. Bile acids bound to colestilan.
Dosage form
Colestilan is available in a dosage of one gram as a film-coated tablet and as granules in sachets with 2 or 3 grams content.
application areas
Colestilan has been approved in the EU since April 2013 for the treatment of hyperphosphatemia in adult patients with chronic kidney disease (CKD stage 5D) who are receiving hemodialysis or peritoneal dialysis. Colestilan has been approved in Japan for the treatment of hypercholesterolemia since 1999.
effectiveness
Colestilan's phosphate-binding efficacy and safety have been tested in 21 Phase I-III clinical trials , including studies in over 1,400 patients with advanced renal impairment and hyperphosphatemia . It was shown that the active ingredient can significantly reduce the serum phosphate level and the calcium phosphate ion product.
The studies also showed additional effects on other metabolic parameters. Colestilan significantly reduced the LDL cholesterol level from a dose of 6 g per day without influencing the HDL cholesterol. The uric acid levels also decreased compared to a placebo . Colestilan also apparently has a positive influence on HbA1c values that are too high : While it led to a reduction of up to 0.9% in patients with HbA1c above 7.0%, it had a normal effect of less than 6 on non-diabetics 0% no decrease.
The National Association of Statutory Health Insurance Physicians sees no proven additional benefit in the treatment of hyperphosphataemia in adults with chronic kidney disease compared to sevelamer or lanthanum carbonate . In the legally required benefit assessment after market entry in Germany, the Federal Joint Committee found that an additional benefit had not been proven.
Side effects
The side effects of colestilan are dose-dependent and usually mild to moderate. The most common side effects, which occur in up to 10% of all patients, are nausea , vomiting , constipation , diarrhea , abdominal pain and indigestion.
Early benefit assessment
In Germany, since 2011, newly approved drugs with new active ingredients must be subjected to an " early benefit assessment " by the Federal Joint Committee (G-BA) in accordance with Section 35a SGB V if the pharmaceutical manufacturer wants to achieve a higher sales price than just the fixed amount . Only if there is an additional benefit can the pharmaceutical manufacturer negotiate a price with the umbrella association of statutory health insurance companies. The dossier evaluations, on the basis of which the G-BA makes its decisions, are created by the Institute for Quality and Efficiency in Health Care (IQWiG) .
In the 2013 early benefit assessment, colestilan was compared with calcium-containing phosphate binders or sevelamer or lanthanum carbonate for the treatment of hyperphosphataemia in adults with stage 5 chronic kidney disease who are undergoing hemodialysis or peritoneal dialysis. According to the G-BA decision, an additional benefit compared to this ACT is not proven.
Trade names
Colestilan is manufactured by Mitsubishi Tanabe Pharma .
BindRen (D, A, CH), Cholebine (JP)
Individual evidence
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ a b c d Specialist information BindRen ® , Mitsubishi Pharma Deutschland GmbH, July 2014.
- ^ Block GA et al .: Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. In: Kidney Int . 2005; 68, pp. 1815-1824.
- ↑ Mudge, DW et al .: Do aluminum-based phosphate binders continue to have a role in contemporary nephrology practice? In: BMC Nephrol. 2011; 12, p. 20.
- ↑ Bushinsky, DA: Contribution of intestine, bone, kidney, and dialysis to ex-tracellular fluid calcium content. In: Clin J Am Soc Nephrol. 2010; 5 (Suppl 1), p. 12.
- ↑ a b Shantouf RS et al .: Total and individual coronary artery calcium scores as in-dependent predictors of mortality in hemodialysis patients. In: Am J Nephrol. 2010; 31, pp. 419-425.
- ↑ Locatelli F et al .: In: Effect of MCI-196 on serum phosphate and cholesterol levels in haemodialysis patients with hyperphosphataemia: a double-blind, randomized, placebo-controlled study. In: Nephrol Dial Transplant. 2010; 25, pp. 574-581.
- ↑ a b Hertel JE et al .: In: J Am Soc Nephrol. 2010; 21 (Abstracts Issue), Abstract F-PO1862.
- ↑ Dimkovic N: In: Nephrol Dial Transplant. 2012; 27 (Suppl 2), abstract SAP575.
- ^ Locatelli F et al .: In: J Am Soc Nephrol. 2011; 22 (Abstracts Issue), Abstract FR-OR185.
- ↑ a b Wanner C et al .: In: J Am Soc Nephrol. 2012; 23 (Abstracts Issue), Abstract FR-OR028.
- ↑ Senatore F et al .: In: Nephrol Dial Transplant. 2012; 27 (Suppl 2), Abstract SAO057.
- ↑ Dell Anna F et al .: 4th Annual Meeting of the German Society of Nephrology 2012, Hamburg, Poste.
- ↑ Senatore F et al .: 41st European Dialysis and Transplant Nurses Association / European Renal Care Association (EDTNA / ERCA) International Conference 2012, Strasbourg, poster.
- ↑ Colestilan: KBV - Colestilan , access date: October 1, 2014.
- ^ Resolution "Drugs Directive / Annex XII: Colestilan" of the GBA of October 1, 2013.
- ↑ A13-15 Colestilan - Benefit assessment according to Section 35a SGB V (dossier assessment); Accessed March 27, 2020.
- ↑ Benefit assessment procedure for the active ingredient colestilan (hyperphosphataemia); Accessed March 27, 2020.