Sevelamer

Sevelamer is marketed by Genzyme Corporation as Renvela (sevelamer carbonate) and Renagel (sevelamer hydrochloride). The Food and Drug Administration approved the use of sevelamer in October 30, 1998. Sevelamer is used to reduce the amount of phosphorus in the blood of patients with chronic kidney disease who are on dialysis. It is well-tolerated, but it may reduce the absorption of some other drugs.

Uses/Indications

Sevelamer is used in adult patients with end-stage (stage 4 or 5) kidney disease who are on dialysis.

How Sevelamer Is Taken

Sevelamer is taken orally in capsule or tablet form. It is available in doses of 400 mg or 800 mg. The daily dose is dependent on levels of phosphorus in the blood. Typically, doses of 800-1600 mg taken three times a day are needed. Sevelamer works best when taken with food, and the capsules should not be broken or chewed.

How Sevelamer Works

A large proportion of phosphorus, in a form called phosphate, is excreted from the body in urine. In kidney failure, this phosphorus is not excreted and accumulates in the body. Phosphorus accumulation can cause many problems. Sevelamer is a large crosslinked polymer that contains multiple amines. The amines carry a positive charge in the intestine and interact with negatively-charged phosphate molecules through ionic and hydrogen bonding. This binding in the intestines prevents phosphorus from being absorbed into the bloodstream. The phosphate is eliminated in the feces. Sevelamer does not influence the absorption of calcium, aluminum, or bicarbonate. Sevelamer is not itself absorbed, and therefore cannot accumulate in the body.

How the Body Affects Sevelamer

Sevelamer is not absorbed or metabolized in the body. It is excreted unchanged in the feces along with the bound phosphorus.

Side Effects

Some common side effects of sevelamer include the following:

• Diarrhea
• Infection
• Pain
• Vomiting
• Indigestion
• Low blood pressure
• Headache
• Blood clot formation
• Decreased absorption of vitamins D, E, K, and folic acid
• Bowel Obstruction

Some serious side effects that require medical attention include severe abdominal pain, new or worsening constipation, or other severe intestinal symptoms.

Risks and Precautions

Sevelamer is not used in patients with low levels of phosphate in the blood (hypophosphatemia), or in patients with an obstructed bowel. Some complications can occur in patients with a history of digestive tract surgery or chronic constipation.

Sevelamer may bind to other drugs and prevent their absorption (see “Drug Interactions”). To avoid this, sevelamer is given one hour before or three hours after taking these drugs.

Drug Interactions

A change in gastric pH, or the acidity of the stomach, can influence the effectiveness of sevelamer. In one case report, blood concentrations of phosphate became elevated when a 30-year-old woman being treated with sevelamer increased her dose of omeprazole (Prilosec, Zegerid).^[1] Omeprazole had reduced the acidity of her stomach, which hindered the ability of sevelamer to bind phosphorus.

Sevelamer has the potential to reduce the absorption of several drugs. It reduced the blood concentrations of the antibiotic ciprofloxacin (Ciprodex) by approximately 50% in healthy volunteers.^[2] The authors of the study suggest that this interaction could reduce the effectiveness of ciprofloxacin. ^[2]

Sevelamer may also reduce the absorption of mycophenolate mofetil (CellCept) in kidney transplant patients.^[3] In a study of 18 patients, 4 days of sevelamer reduced blood concentrations of mycophenolate mofetil by 30% and reduced peak blood levels by 25%.

The effects of sevelamer on the absorption of cyclosporine (Neoral) are controversial. Sevelamer had no effect on the absorption of cyclosporine in a study of 18 kidney transplant patients.^[3] some researchers have pointed out problems with this study, which showed negative findings. ^[4] These researchers suggest that sevelamer does indeed limit absorption of cyclosporine. This interaction needs to be examined in a well-controlled clinical trial before any conclusions can be made.

Clinical Trials

The effectiveness of sevelamer was investigated in healthy volunteers for 18 days.^[5] The highest dose of sevelamer reduced the daily excretion of phosphorus in the urine by 40% compared to treatment with the placebo. The amount of phosphorous excreted in the feces per day had almost doubled at the highest dose of sevelamer. These changes indicated that less phosphorus was being absorbed into the body. In a study of patients with kidney failure and receiving dialysis, sevelamer reduced the levels of phosphate in the blood by 20%, whereas treatment with a placebo had no effect. ^[6]

References

1. ↑ Capitanini A, Lupi A, Osteri F, et al. Gastric pH, sevelamer hydrochloride and omeprazole. Clin Nephrol. 2005 Oct;64(4):320-2. Abstract
2. ↑ ^{2.0 2.1} Kays MB, Overholser BR, Mueller BA, Moe SM, Sowinski KM. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis. 2003 Dec;42(6):125. Abstract
3. ↑ ^{3.0 3.1} Pieper AK, Buhle F, et al. The effect of sevelamer on the pharmacokinetics of cyclosporin A and mycophenolate mofetil after renal transplantation. Nephrol Dial Transplant. 2004 Oct;19(10):2630-3. Abstract
4. ↑ Uehlinger D, Marti HP, Jadoul M, Wauters JP. Sevelamer and pharmacokinetics of cyclosporin A after kidney transplantation. Nephrol Dial Transplant. 2005 Mar;20(3):661. Abstract
5. ↑ Burke SK, Slatopolsky EA, Goldberg DI. RenaGel, a novel calcium- and aluminum-free phosphate binder, inhibits phosphate absorption in normal volunteers. Nephrol Dial Transplant. 1997 Aug;12(8):1640-4. Abstract
6. ↑ Hertow GM, Burke SK, Lazarus JM, et al. Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis. 1997 Jan;29(1):66-71. Abstract

External Links

American Association of Kidney Patients

Genzyme Corporation