Sevelamer

Sevelamer
Clinical data
Trade names Renagel, Renvela
AHFS/Drugs.com Monograph
MedlinePlus a601248
License data
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
    Routes of
    administration    		 oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 0%
    Excretion faecal 100%
    Identifiers
    CAS Number
    PubChem CID
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    ECHA InfoCard 100.207.865 Edit this at Wikidata
    Chemical and physical data
    Formula [(C3H7N)a+b.(C9H17N2O)c]m
    where a+b:c = 9:1
    Molar mass variable
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    Sevelamer (rINN) (/sɛˈvɛləmər/ or /sɛˈvɛləmɪər/) is a phosphate binding drug used to treat hyperphosphatemia in patients with chronic kidney disease. When taken with meals, it binds to dietary phosphate and prevents its absorption. Sevelamer was invented and developed by GelTex Pharmaceuticals. Sevelamer is currently marketed by Sanofi under the trade names Renagel (sevelamer hydrochloride) and Renvela (sevelamer carbonate).

    Chemistry and pharmacology

    Sevelamer consists of polyallylamine that is crosslinked with epichlorohydrin.[1] The marketed form sevelamer hydrochloride is a partial hydrochloride salt being present as approximately 40% amine hydrochloride and 60% sevelamer base. The amine groups of sevelamer become partially protonated in the intestine and interact with phosphate ions through ionic and hydrogen bonding.

    Medical uses

    Sevelamer is used in the management of hyperphosphatemia in adult patients with stage 4 and 5 chronic kidney disease on hemodialysis. Its efficacy at lowering phosphate levels is similar to that of calcium acetate, but without the accompanying risk of hypercalcemia.

    Contraindications

    Sevelamer therapy is contraindicated in hypophosphatemia or bowel obstruction. In hypophosphatemia, sevelamer could exacerbate the condition by further lowering phosphate levels in the blood, which could be fatal.

    Adverse effects

    Common adverse drug reactions (ADRs) associated with the use of sevelamer include: hypotension, hypertension, nausea and vomiting, dyspepsia, diarrhea, flatulence, and/or constipation.

    Other effects

    Sevelamer can significantly reduce serum uric acid.[2] This reduction has no known detrimental effect and several beneficial effects, including reducing hyperuricemia, uric acid nephrolithiasis, and gout.

    Sevelamer is able to sequester advanced glycation end products (AGEs) in the gut, preventing their absorption into the blood. AGEs contribute to oxidative stress, which can damage cells (like beta cells, which produce insulin in the pancreas). As Vlassara and Uribarri explain in a 2014 review on AGEs, this may explain why sevelamer, but not calcium carbonate (a phosphate binder that does not sequester AGEs), has been shown to lower AGEs in the blood, as well as oxidative stress and inflammatory markers.[3]

    References

    1. ↑ (1) Rosenbaum, D. P.; Mandeville, W. H.; Pitruzzello, M.; Goldberg, D. I. Nephrology Dialysis Transplantation Effect of RenaGel A, a Non-Absorbable, Cross-Linked, Polymeric Phosphate Binder, on Urinary Phosphorus Excretion in Rats. 1997, 961–964.
    2. ↑ Garg JP, Chasan-Taber S, Blair A, et al. (January 2005). "Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial". Arthritis and Rheumatism. 52 (1): 290–5. doi:10.1002/art.20781. PMID 15641045.
    3. ↑ Vlassara H, Uribarri J. "Advanced Glycation End Products (AGE) and Diabetes: Cause, Effect, or Both?". J. Curr Diab Rep. 14 (453). doi:10.1007/s11892-013-0453-1. PMC 3903318.
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