Brands, Medical Use, Clinical Data
- Capsules and film-coated tablets (800 mg or 400 mg)
Brands / Synonyms
For the control of serum phosphorus in patients with Chronic Kidney Disease (CKD) on hemodialysis.
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.
Mechanism of Action
Sevelamer prevents hyperphosphatemia by binding to dietary phosphate in the gut, preventing its absorption and thus decreasing serum parathyroid hormone levels.
Not absorbed following oral administration, however no absorption studies have been performed in patients with renal disease.
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.
Biotrnasformation / Drug Metabolism
Renagel is contraindicated in patients with hypophosphatemia or bowel obstruction. Renagel is
contraindicated in patients known to be hypersensitive to sevelamer hydrochloride or any of its constituents.
Renagel Capsules were studied in human drug-drug interaction studies with digoxin, warfarin,
enalapril metoprolol and iron.
Digoxin: In 19 healthy subjects receiving 6 Renagel capsules three times a day with meals for
2days, Renagel did not alter the pharmaco-kinetics of a single dose of digoxin.
Warfarin: In 14 healthy subjects receiving 6 Renagel capsules three times a day with meals for
2days, Renagel did not alter the pharmaco-kinetics of a single dose of warfarin.
Enalapril: In 28 healthy subjects a single dose of 6 Renagel capsules did not alter the
pharmacokinetics of a single dose of enalapril.
Metoprolol: In 31 healthy subjects a single dose of 6 Renagel capsules did not alter the
pharmacokinetics of a single dose of metoprolol.
Iron: In 23 healthy subjects, a single dose of 7 Renagel capsules did not alter the absorption
of a single oral dose of iron as 200 mg exsiccated ferrous sulfate tablet.
However, when administering any other oral medication where a reduction in the bioavailability ofthat
medication would have a clinically significant effect on safety or efficacy, the drug should beadministered at least
one hour before or three hours after Renagel, or the physician should consider monitoring blood levels of the drug.
Patients taking anti-arrhythmic and anti-seizure medications were excluded from the clinical trials. Special
precautions should be taken when prescribing Renagel to patients also taking these medications.