Sevelamer

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Sevelamer
Sevelamer.png
Clinical data
Pronunciation( /sɛˈvɛləmər/ or /sɛˈvɛləmɪər/ )
Trade names Renagel, Renvela
AHFS/Drugs.com Monograph
MedlinePlus a601248
License data
Pregnancy
category
  • AU:B3
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 0%
Excretion Feces 100%
Identifiers
  • poly(allylamine-
    co-N,N'-diallyl-1,3-diamino-2-hydroxypropane)
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula [(C3H7N)a+b.(C9H17N2O)c]m
where a+b:c = 9:1
Molar mass variable
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Sevelamer (rINN) is a phosphate binding medication 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 marketed by Sanofi under the brand names Renagel (sevelamer hydrochloride) and Renvela (sevelamer carbonate).

Contents

Chemistry and pharmacology

Sevelamer consists of polyallylamine that is crosslinked with epichlorohydrin. [8] 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.[ citation needed ]

Medical uses

Sevelamer is used in the management of hyperphosphatemia in adult patients with stage 4 and 5 chronic kidney disease (CKD) on hemodialysis. Its efficacy at lowering phosphate levels is similar to that of calcium acetate, but without the accompanying risk of hypercalcemia and arterial calcification. [9] [10] In patients with CKD, it has also been shown to reduce LDL and cholesterol. [11]

Contraindications

Sevelamer therapy is contraindicated in hypophosphatemia or bowel obstruction. [12] In hypophosphatemia, sevelamer could exacerbate the condition by further lowering phosphate levels in the blood, which could be fatal. [13]

Adverse effects

Common adverse drug reactions (ADRs) associated with the use of sevelamer include: nausea and vomiting, constipation, diarrhea, stomach pain, heartburn, gas. [14]

Other effects

Sevelamer can significantly reduce serum uric acid. [15] This reduction has no known detrimental effect and may be helpful in patients with 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. [16]

Related Research Articles

<span class="mw-page-title-main">Hyperparathyroidism</span> Increase in parathyroid hormone levels in the blood

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli. Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium excreted from the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low. With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis.

<span class="mw-page-title-main">Chronic kidney disease</span> Abnormal kidney structure or gradual loss of kidney function

Chronic kidney disease (CKD) is a type of long-term kidney disease, in which either there is a gradual loss of kidney function occurs over a period of months to years, or abnormal kidney structure. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications can relate to hormonal dysfunction of the kidneys and include high blood pressure, bone disease, and anemia. Additionally CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off (lysed) from the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias and in particular when treating non-Hodgkin lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia. This is a potentially fatal complication and patients at increased risk for TLS should be closely monitored while receiving chemotherapy and should receive preventive measures and treatments as necessary. TLS can also occur on its own although this is less common.

<span class="mw-page-title-main">Hyperphosphatemia</span> Excess phosphate in the blood

Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. The disorder is often accompanied by low calcium blood levels, which can result in muscle spasms.

Phosphate binders are medications used to reduce the absorption of dietary phosphate; they are taken along with meals and snacks. They are frequently used in people with chronic kidney failure (CKF), who are less able to excrete phosphate, resulting in an elevated serum phosphate.

Renal osteodystrophy is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.

Lanthanum carbonate, La2(CO3)3, is the salt formed by lanthanum(III) cations and carbonate anions. It is an ore of lanthanum metal (bastnäsite), along with monazite.

<span class="mw-page-title-main">Secondary hyperparathyroidism</span> Medical condition

Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia, with resultant hyperplasia of these glands. This disorder is primarily seen in patients with chronic kidney failure. It is sometimes abbreviated "SHPT" in medical literature.

<span class="mw-page-title-main">Tertiary hyperparathyroidism</span> Medical condition

Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone.

Phosphate nephropathy or nephrocalcinosis is an adverse renal condition that arises with a formation of phosphate crystals within the kidney's tubules. This renal insufficiency is associated with the use of oral sodium phosphate (OSP) such as C.B. Fleet's Phospho soda and Salix's Visocol, for bowel cleansing prior to a colonoscopy.   

<span class="mw-page-title-main">Calciphylaxis</span> Medical condition

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA) or “Grey Scale”, is a rare syndrome characterized by painful skin lesions. The pathogenesis of calciphylaxis is unclear but believed to involve calcification of the small blood vessels located within the fatty tissue and deeper layers of the skin, blood clots, and eventual death of skin cells due to lack of blood flow. It is seen mostly in people with end-stage kidney disease but can occur in the earlier stages of chronic kidney disease and rarely in people with normally functioning kidneys. Calciphylaxis is a rare but serious disease, believed to affect 1-4% of all dialysis patients. It results in chronic non-healing wounds and indicates poor prognosis, with typical life expectancy of less than one year.

<span class="mw-page-title-main">Fibroblast growth factor 23</span> Protein found in humans

Fibroblast growth factor 23 (FGF-23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the FGF23 gene. FGF-23 decreases reabsorption of phosphate in the kidney. Mutations in FGF23 can lead to its increased activity, resulting in autosomal dominant hypophosphatemic rickets.

<span class="mw-page-title-main">Nephrocalcinosis</span> Medical condition caused by the deposition of calcium salts in the kidneys

Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe the deposition of poorly soluble calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined by progressive kidney dysfunction. These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on x-ray, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with medullary sponge kidney on an abdominal x-ray. It may be severe enough to cause renal tubular acidosis or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium salts.

Calcium acetate/magnesium carbonate is a fixed-dose combination drug that contains 110 mg calcium and 60 mg magnesium ions and is indicated as a phosphate binder for dialysis patients with hyperphosphataemia. It is registered by Fresenius Medical Care under the trade names Renepho (Belgium) and OsvaRen.

<span class="mw-page-title-main">Tenapanor</span> Medication

Tenapanor, sold under the brand name Ibsrela among others, is a medication used for the treatment of adults with a disease of the gut called irritable bowel syndrome with constipation commonly referred to as IBS-C. It is used in form of tenapanor hydrochloride. It is also used in the treatment of chronic kidney disease. Tenapanor is a sodium hydrogen exchanger 3 (NHE3) inhibitor.

Sucroferric oxyhydroxide, sold under the brand name Velphoro, is a non-calcium, iron-based phosphate binder used for the control of serum phosphorus levels in adults with chronic kidney disease (CKD) on haemodialysis (HD) or peritoneal dialysis (PD). It is used in form of chewable tablets.

<span class="mw-page-title-main">Etelcalcetide</span> Chemical compound

Etelcalcetide, sold under the brand name Parsabiv, is a calcimimetic medication for the treatment of secondary hyperparathyroidism in people undergoing hemodialysis. It is administered intravenously at the end of each dialysis session. Etelcalcetide functions by binding to and activating the calcium-sensing receptor in the parathyroid gland. Parsabiv is currently owned by Amgen and Ono Pharmaceuticals in Japan.

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:

<span class="mw-page-title-main">Vadadustat</span> Chemical compound

Vadadustat, sold under the brand name Vafseo, is a medication used for the treatment of symptomatic anemia associated with chronic kidney disease. Vadadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor.

A renal diet is a diet aimed at keeping levels of fluids, electrolytes, and minerals balanced in the body in individuals with chronic kidney disease or who are on dialysis. Dietary changes may include the restriction of fluid intake, protein, and electrolytes including sodium, phosphorus, and potassium. Calories may also be supplemented if the individual is losing weight undesirably.

References

  1. "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. "Kidney disease". Health Canada . 9 May 2018. Retrieved 13 April 2024.
  3. "Renvela EPAR". European Medicines Agency. 10 June 2009. Retrieved 29 June 2024.
  4. "Renvela PI". Union Register of medicinal products. 12 June 2009. Retrieved 29 June 2024.
  5. "Sevelamer carbonate Winthrop (previously Sevelamer carbonate Zentiva) EPAR". European Medicines Agency. 15 January 2015. Retrieved 29 June 2024.
  6. "Sevelamer carbonate PI". Union Register of medicinal products. 19 January 2015. Retrieved 29 June 2024.
  7. "Renagel EPAR". European Medicines Agency (EMA). 28 January 2000. Retrieved 5 September 2024.
  8. Ramsdell R (June 1999). "Renagel: a new and different phosphate binder". review. ANNA Journal. 26 (3): 346–7. PMID   10633608.
  9. Burke SK (September 2000). "Renagel: reducing serum phosphorus in haemodialysis patients". review. Hospital Medicine. 61 (9): 622–7. doi:10.12968/hosp.2000.61.9.1419. PMID   11048603.
  10. Habbous S, Przech S, Acedillo R, Sarma S, Garg AX, Martin J (January 2017). "The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis". review. Nephrology, Dialysis, Transplantation. 32 (1): 111–125. doi: 10.1093/ndt/gfw312 . PMID   27651467.
  11. Patel L, Bernard LM, Elder GJ (February 2016). "Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials". review. Clinical Journal of the American Society of Nephrology. 11 (2): 232–44. doi:10.2215/CJN.06800615. PMC   4741042 . PMID   26668024.
  12. Yuste C (2017). "Gastrointestinal complications induced by sevelamer crystals". Clinical Kidney Journal. 10 (4): 539–544. doi:10.1093/ckj/sfx013. PMC   5570024 . PMID   28852493.
  13. Emmett M (September 2004). "A comparison of clinically useful phosphorus binders for patients with chronic kidney failure". review. Kidney International Supplements. 66 (90): S25–32. doi: 10.1111/j.1523-1755.2004.09005.x . PMID   15296504.
  14. "Sevelamer". MedlinePlus.
  15. Locatelli F, Del Vecchio L (May 2015). "Cardiovascular mortality in chronic kidney disease patients: potential mechanisms and possibilities of inhibition by resin-based phosphate binders". review. Expert Review of Cardiovascular Therapy. 13 (5): 489–99. doi:10.1586/14779072.2015.1029456. PMID   25804298. S2CID   32586527.
  16. Vlassara H, Uribarri J (January 2014). "Advanced glycation end products (AGE) and diabetes: cause, effect, or both?". review. Current Diabetes Reports. 14 (1): 453. doi:10.1007/s11892-013-0453-1. PMC   3903318 . PMID   24292971.