FOSEAL

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.

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 mg 2 /dL 2, 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.

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.

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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.

Sevelamer carbonate tablets are contraindicated in patients with bowel obstruction.

Sevelamer carbonate tablets are contraindicated in patients with known hypersensitivity to sevelamer carbonate, sevelamer hydrochloride, or to any of the excipients.

Bowel obstruction.

Known hypersensitivity to sevelamer carbonate,sevelamer hydrochloride, or to any of the excipients.

Starting dose of sevelamer carbonate tablet is 0.8 or 1.6 grams administered orally three times per day with meals based on serum phosphorus levels for adult patients and based on body surface area (BSA) category for pediatric patients Titrate by 0.8 grams per meal in two week intervals for adult patients as needed to obtain serum phosphorus target.

Titrate based on

BSA category for pediatric patients in two week intervals for 6 weeks and then every 4 weeks as needed to obtain serum phosphorus target. 2.1 General Dosing Information Starting Dose for Adult Patients Not Taking a Phosphate Binder.

The recommended starting dose of sevelamer carbonate tablets are 0.8 to 1.6 grams taken orally with meals based on serum phosphorus level.

Table 1 provides recommended starting doses of sevelamer carbonate tablets for adult patients not taking a phosphate binder.

Table 1.

Starting Dose for Adult Dialysis Patients Not Taking a Phosphate Binder Serum Phosphorus Sevelamer Carbonate > 5.5 and < 7.5 mg/dL 0.8 grams three times daily with meals ≥ 7.5 mg/dL 1.6 grams three times daily with meals Dose Titration for Adult Patients Taking Sevelamer Carbonate Tablets.

Titrate the sevelamer carbonate tablets dose by 0.8 grams three times per day with meals at two-week intervals as necessary to achieve target serum phosphorus levels.

Based on clinical studies, the average prescribed adult daily dose of sevelamer carbonate is approximately 7.2 grams per day. The highest daily adult dose of sevelamer carbonate studied was 14 grams in CKD patients on dialysis.

Starting Dose for Pediatric Patients Not Taking a Phosphate Binder.

The recommended starting dose for pediatric patients 6 years of age and older is 0.8 to 1.6 grams taken three times per day with meals based on the patient’s body surface area (BSA) category; see Table 2.

Table 2: Recommended Starting Dosage and Titration Increment Based on Pediatric Patient’s Body Surface Area (m 2 ) BSA (m 2 ) Starting Dose Per Meal/Snack Titration Increases/ Decreases Per Dose ≥0.75 to <1.2 0.8 grams Titrate by 0.4 grams ≥1.2 1.6 grams Titrate by 0.8 grams Dose Titration for Pediatric Patients Taking Sevelamer Carbonate Tablets.

Titrate the sevelamer caronate dose as needed to achieve target levels at two-week intervals based on BSA category, as shown in Table 2.

For adult patients switching from sevelamer hydrochloride tablets to sevelamer carbonate tablets or powder, use the same dose in grams.

Switching between Sevelamer Carbonate Tablets and

Use the same dose in grams.

Table 3 gives recommended starting doses of sevelamer carbonate tablets based on a patient’s current calcium acetate dose.

Table 3.

Starting Dose for Dialysis Patients Switching from Calcium Acetate to Sevelamer carbonate Tablets Calcium Acetate 667 mg (Tablets per meal) Sevelamer Carbonate 1 tablet 0.8 grams 2 tablets 1.6 grams 3 tablets 2.4 grams.

Sevelamer carbonate

Tablets 800 mg are supplied as white to off-white, oval, film-coated tablets plain on one side and imprinted ‘R789’ on other side, containing 800 mg of sevelamer carbonate on an anhydrous basis, ammonium hydroxide, colloidal silicon dioxide, crospovidone, hydroxypropyl cellulose, lecithin, mannitol, polyvinyl alcohol, propylene glycol, shellac, talc, xanthan gum and zinc stearate.

The tablet imprint contains iron oxide black ink.

Bottles of 30 NDC 55111-789-30 Bottles of 90 NDC 55111-789-90 Bottles of 270 NDC 55111-789-27 Unit dose package of 100 (25 x 4) NDC 55111-789-11 Storage: Store at 20°-25°C (68°-77°F); Protect from moisture.

Sevelamer carbonate is not absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug.

Sevelamer carbonate may decrease serum levels of fat soluble vitamins and folic acid in pregnant women.

Consider supplementation.

Data Animal data

In pregnant rats given dietary doses of 0.5, 1.5, or 4.5 g/kg/day of sevelamer hydrochloride during organogenesis, reduced or irregular ossification of fetal bones, probably due to a reduced absorption of fat-soluble vitamin D, occurred in mid and high-dose groups (human equivalent doses approximately equal to to 4 times the maximum clinical trial dose of 13 grams).

In pregnant rabbits given oral doses of 100, 500 or 1000 mg/kg/day of sevelamer hydrochloride by gavage during organogenesis, an increase of early resorptions occurred in the high-dose group (human equivalent dose twice the maximum clinical trial dose).

The safety and efficacy of sevelamer carbonate in lowering serum phosphorus levels was studied in patients 6 years of age and older with CKD.

In this study, sevelamer carbonate was apparently less effective in children with a low baseline serum phosphorus, which described children <13 years of age and children not on dialysis.

Given its mechanism of action, sevelamer carbonate is expected to be effective in lowering serum phosphorus levels in pediatric patients with CKD.

Most adverse events that were reported as related, or possibly related, to sevelamer carbonate were gastrointestinal in nature.

No new risks or safety signals were identified with the use of sevelamer carbonate in the trial.

Sevelamer carbonate tablets have not been studied in pediatric patients below 6 years of age.

Clinical studies of sevelamer carbonate did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.