Sevelamer

Absorption

Not absorbed following oral administration, however no absorption studies have been performed in patients with renal disease. Sevelamer may bind to dietary phosphates and prevent its gastrointestinal absorption when sevelamer is administered in combination with food.

Toxicity

Sevelamer has been given to normal healthy volunteers in doses of up to 14 grams per day for eight days with no adverse effects. Sevelamer has been given in average doses up to 13 grams per day to hemodialysis patients. There are no reported overdosages of sevelamer in patients. Since sevelamer is not absorbed, the risk of systemic toxicity is low.

The Uses of Sevelamer

Antihyper-phosphatemic.

Indications

For the control of serum phosphorus in patients with Chronic Kidney Disease (CKD) on hemodialysis.

Background

Sevelamer is a phosphate binding drug used to prevent hyperphosphataemia in patients with chronic renal failure. It is marketed by Genzyme under the trade name Renagel.

brand name

Renagel (Genzyme).

Pharmaceutical Applications

In patients on dialysis, Sevelamer or lanthanum salts can be used to maintain normal phosphate blood levels. Sevelamer is a polymer containing amine groups. These protonated amine groups can react with the negatively charged phosphate groups via ionic binding and prevent absorption of phosphate from the gut. Sevelamer is a hydrogel containing cross-linked polyallylamine chains. The negatively charged phosphate can be bound to the positively charged amine groups of the hydrogel in the intestines and removed via the faeces.

Pharmacokinetics

Patients with end-stage renal disease (ESRD) retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification. When the product of serum calcium and phosphorus concentrations (Ca x P) exceeds 55 mg2/dL2, there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency. An increase in parathyroid hormone (PTH) levels is characteristic of patients with chronic renal failure. Increased levels of PTH can lead to osteitis fibrosa, a bone disease. A decrease in serum phosphorus may decrease serum PTH levels. Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Sevelamer taken with meals has been shown to decrease serum phosphorus concentrations in patients with ESRD who are on hemodialysis. In vitro studies have shown that the capsule and tablet formulations bind phosphate to a similar extent. Sevelamer treatment also results in a lowering of low-density lipoprotein (LDL) and total serum cholesterol levels.

Clinical Use

Phosphate-binding agent

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: reduces bioavailability of ciprofloxacin.
Ciclosporin: possibly reduces ciclosporin
concentration.
Calcitriol: absorption may be impaired by sevelamer.
Mycophenolate: may reduce mycophenolate levels.
Tacrolimus: possibly reduces tacrolimus
concentration.
Thyroid hormones: possibly reduces levothyroxine
concentration.

Metabolism

Not Available

Metabolism

Sevelamer is not systemically absorbed.