Renagel Information
Renagel () Indications And Usage
Renagel () (sevelamer hydrochloride) is indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis. The safety and efficacy of Renagel () in CKD patients who are not on dialysis have not been studied.
Renagel () Dosage Forms And Strengths
800 mg and 400 mg Tablets.
Renagel () Contraindications
Renagel () is contraindicated in patients with bowel obstruction.
Renagel () Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug can not be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In a parallel design study of sevelamer hydrochloride with treatment duration of 52 weeks, adverse reactions reported for sevelamer hydrochloride (n=99) were similar to those reported for the active-control group (n=101). Overall adverse reactions among those treated with sevelamer hydrochloride occurring in > 5% of patients included: vomiting (22%), nausea (20%), diarrhea (19%), dyspepsia (16%), abdominal pain (9%), flatulence (8%) and constipation (8%). A total of 27 patients treated with sevelamer and 10 patients treated with comparator withdrew from the study due to adverse reactions.
Based on studies of 8-52 weeks, the most common reason for withdrawal from Renagel () was gastrointestinal adverse reactions (3-16%).
In one hundred and forty-three peritoneal dialysis patients studied for 12 weeks most adverse reactions were similar to adverse reactions observed in hemodialysis patients. The most frequently occurring treatment emergent serious adverse reaction was peritonitis (8 reactions in 8 patients [8%] in the sevelamer group and 2 reactions in 2 patients [4%] on active-control). Thirteen patients (14%) in the sevelamer group and 9 patients (20%) in the active-control group discontinued, mostly for gastrointestinal adverse reactions. Patients on peritoneal dialysis should be closely monitored to ensure the reliable use of appropriate aseptic technique with the prompt recognition and management of any signs and symptoms associated with peritonitis.
The following adverse reactions have been identified during post-approval use of sevelamer hydrochloride (Renagel () ): pruritus, rash, abdominal pain, fecal impaction and uncommon cases of ileus, intestinal obstruction, and intestinal perforation. Appropriate medical management should be given to patients who develop constipation or have worsening of existing constipation to avoid severe complications.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.
Renagel () Drug Interactions
Renagel () has been studied in human drug-drug interaction studies with ciprofloxacin, digoxin, warfarin, enalapril, metoprolol and iron.
There are no empirical data on avoiding drug interactions between Renagel () and most concomitant drugs. During postmarketing experience, very rare cases of increased thyroid stimulating hormone (TSH) levels have been reported in patients co-administered sevelamer hydrochloride and levothyroxine. Closer monitoring of TSH levels is therefore recommended in patients receiving both medications.
When administering an oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, the drug should be administered 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 medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials. Special precautions should be taken when prescribing Renagel () to patients also taking these medications.
Renagel () Overdosage
Renagel () has been given to normal healthy volunteers in doses of up to 14 grams per day for eight days with no adverse effects. Renagel () has been given in average doses up to 13 grams per day to hemodialysis patients. There are no reports of overdosage with Renagel () in patients. Since Renagel () is not absorbed, the risk of systemic toxicity is low.
Renagel () Description
The active ingredient in Renagel () Tablets is sevelamer hydrochloride, a polymeric amine that binds phosphate and is meant for oral administration. Sevelamer hydrochloride is poly(allylamine hydrochloride) crosslinked with epichlorohydrin in which forty percent of the amines are protonated. It is known chemically as poly(allylamine--N,N’-diallyl-1,3-diamino-2-hydroxypropane) hydrochloride. Sevelamer hydrochloride is hydrophilic, but insoluble in water. The structure is represented in .
a, b = number of primary amine groups a + b = 9
c = number of crosslinking groups c = 1
n = fraction of protonated amines n = 0.4
m = large number to indicate extended polymer network
The primary amine groups shown in the structure are derived directly from poly(allylamine hydrochloride). The crosslinking groups consist of two secondary amine groups derived from poly(allylamine hydrochloride) and one molecule of epichlorohydrin.
Renagel () Clinical Pharmacology
Patients with chronic kidney disease (CKD) on dialysis 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/dL, there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency.
Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Renagel () taken with meals has been shown to decrease serum phosphorus concentrations in patients with CKD who are on dialysis.
Renagel () Clinical Studies
The ability of Renagel () to lower serum phosphorus in CKD patients on dialysis was demonstrated in six clinical trials: one double-blind placebo controlled 2-week study (Renagel () N=24); two open-label uncontrolled 8-week studies (Renagel () N=220) and three active-controlled open-label studies with treatment durations of 8 to 52 weeks (Renagel () N=256). Three of the active-controlled studies are described here. One is a crossover study with two 8-week periods comparing Renagel () to an active-control. The second is a 52-week parallel study comparing Renagel () with active-control. The third is a 12-week parallel study comparing Renagel () and active-control in peritoneal dialysis patients.
Eighty-four CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus > 6.0 mg/dL) following a two-week phosphate binder washout period received Renagel () and active-control for eight weeks each in random order. Treatment periods were separated by a two-week phosphate binder washout period. Patients started on treatment three times per day with meals. Over each eight-week treatment period, at three separate time points the dose of Renagel () could be titrated up 1 capsule or tablet per meal (3 per day) to control serum phosphorus, the dose of active-control could also be altered to attain phosphate control. Both treatments significantly decreased mean serum phosphorus by about 2 mg/dL ().
The distribution of responses is shown in . The distributions are similar for sevelamer hydrochloride and active control. The median response is a reduction of about 2 mg/dL in both groups. About 50% of subjects have reductions between 1 and 3 mg/dL.
Average daily Renagel () dose at the end of treatment was 4.9 g (range of 0.0 to 12.6 g).
Two hundred CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a two-week phosphate binder washout period were randomized to receive Renagel () 800 mg tablets (N=99) or an active-control (N=101). The two treatments produced similar decreases in serum phosphorus. At week 52, using last-observation-carried-forward, Renagel () and active-control both significantly decreased mean serum phosphorus ().
Sixty-one percent of Renagel () patients and 73% of the control patients completed the full 52 weeks of treatment.
Figure 3
Average daily Renagel () dose at the end of treatment was 6.5 g (range of 0.8 to 13 g).
Renagel () How Supplied/storage And Handling
Renagel () 800 mg Tablets are supplied as oval, film-coated, compressed tablets, imprinted with “Renagel () 800” containing 800 mg of sevelamer hydrochloride on an anhydrous basis, hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid. Renagel () 800 mg Tablets are packaged in bottles of 180 tablets.
Renagel () 400 mg Tablets are supplied as oval, film-coated, compressed tablets, imprinted with “Renagel () 400” containing 400 mg of sevelamer hydrochloride on an anhydrous basis, hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid. Renagel () 400 mg Tablets are packaged in bottles of 360 tablets.
1 Bottle of 30 ct 800 mg Tablets (NDC 58468-0021-3)
1 Bottle of 180 ct 800 mg Tablets (NDC 58468-0021-1)
1 Bottle of 360 ct 400 mg Tablets (NDC 58468-0020-1)
Do not use Renagel () after the expiration date on the bottle.
[See USP controlled room temperature]
Protect from moisture.
Renagel () Patient Counseling Information
Renagel () may cause constipation that if left untreated, may lead to severe complications. Patients should be cautioned to report new onset or worsening of existing constipation promptly to their physician.
Distributed by:
Genzyme Corporation
500 Kendall Street
Cambridge, MA 02142 USA
Renagel ()
