Drugs Details

Drugs Info of Renagel, Renvela
Drugs Details
  • Drugs Type  : Multum
  • Date : 3rd Apr 2015 12:46 am
  • Brand Name : Renagel, Renvela
  • Generic Name : sevelamer (Pronunciation: se VEL a mer)
Descriptions

The active ingredient in Renvela is sevelamer carbonate, a polymeric amine that binds phosphate and is meant for oral administration. It was developed as a pharmaceutical alternative to sevelamer hydrochloride (Renagel®). Sevelamer carbonate is an anion exchange resin, with the same polymeric structure as sevelamer hydrochloride, in which carbonate replaces chloride as the counterion. While the counterions differ for the two salts, the polymer itself, the active moiety involved in phosphate binding, is the same.

Renvela (sevelamer carbonate) is known chemically as poly(allylamine-co-N,N'-diallyl199 1,3-diamino-2-hydroxypropane) carbonate salt. Sevelamer carbonate is hygroscopic, but insoluble in water. The structure is represented in Figure 1.

Figure 1: Chemical Structure of Sevelamer Carbonate

Chemical Structure of Sevelamer Carbonate - Illustration

 

a, b = number of primary amine groups a + b = 9
c = number of crosslinking groups c = 1
m = large number to indicate extended polymer network

Renvela ® Tablets: Each film-coated tablet of Renvela contains 800 mg of sevelamer carbonate on an anhydrous basis. The inactive ingredients are hypromellose, diacetylated monoglycerides, microcrystalline cellulose, sodium chloride and zinc stearate. The tablet imprint contains iron oxide black ink.

Renvela ® Powder: Each packet of Renvela Powder contains 0.8 g or 2.4 g of sevelamer carbonate on an anhydrous basis. The inactive ingredients are natural and artificial citrus flavor, propylene glycol alginate, sodium chloride, sucralose, and ferric oxide (yellow).

 

What are the possible side effects of sevelamer (Renagel, Renvela)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using sevelamer and call your doctor at once if you have a serious side effect such as:

  • black, bloody, or tarry stools;
  • constipation that gets worse or does not clear up;
  • severe constipation with stomach pain; or
  • fever, chills, body aches, flu symptoms.

Less serious side effects may include:

  • nausea, vomiting, stomach pain, loss of appetite;
  • upset...

Read All Potential Side Effects and See Pictures of Renvela »

What are the precautions when taking sevelamer carbonate (Renvela)?

Before taking sevelamer, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: low blood phosphorus levels, bowel blockage.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: stomach/intestinal problems (e.g., constipation), stomach/intestinal surgeries, swallowing problems (dysphagia).

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits...

Read All Potential Precautions of Renvela »

 

This monograph has been modified to include the generic and brand name in many instances.

Indications

Renvela® (sevelamer carbonate) is indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis.

Dosage Administration

Because of the rapid reaction with the hydrochloric acid in the stomach, the dosing of Renvela powder or tablet is anticipated to be similar to that of the sevelamer hydrochloride salt or tablet.

General Dosing Information

Renvela should be given three times a day with meals.

Patients Not Taking a Phosphate Binder

The recommended starting dose of Renvela is 0.8 to 1.6 g with meals based on serum phosphorus level. Table 1 provides recommended starting doses of Renvela for patients not taking a phosphate binder.

Table 1: Starting Dose for Dialysis Patients Not Taking a Phosphate Binder

SERUM PHOSPHORUS RENVELA® 800 MG TABLET RENVELA POWDER
> 5.5 and < 7.5 mg/dL 1 tablet three times daily with meals 0.8 g three times daily with meals
≥ 7.5 mg/dL 2 tablets three times daily with meals 1.6 g three times daily with meals

 

Switching from Sevelamer Hydrochloride Tablets

For patients switching from sevelamer hydrochloride tablets to sevelamer carbonate tablets or powder, use the same dose in grams. Further titration may be necessary to achieve desired phosphorus levels. The highest daily dose of sevelamer carbonate studied was 14 grams in CKD patients on dialysis.

Switching between Sevelamer Carbonate Tablets and Powder

Use the same dose in grams. Further titration may be necessary to achieve desired phosphorus levels.

Switching from Calcium Acetate

In a study in 84 CKD patients on hemodialysis, a similar reduction in serum phosphorus was seen with equivalent doses (approximately mg for mg) of sevelamer hydrochloride and calcium acetate. Table 2 gives recommended starting doses of Renvela based on a patient's current calcium acetate dose.

Table 2: Starting Dose for Dialysis Patients Switching From Calcium Acetate to Renvela

CALCIUM ACETATE 667 MG (TABLETS PER MEAL) RENVELA® 800 MG TABLET (TABLETS PER MEAL) RENVELA POWDER
1 tablet 1 tablet 0.8 g
2 tablets 2 tablets 1.6 g
3 tablets 3 tablets 2.4 g

 

Dose Titration for All Patients Taking Renvela

Titrate the Renvela dose by 0.8 g three times per day with meals at two-week intervals as necessary with the goal of controlling serum phosphorus within the target range.

Sevelamer Carbonate Powder Preparation Instructions

The entire contents of each 0.8 or 2.4 g packet should be placed in a cup and mixed thoroughly with the amount of water described in Table 3.

Table 3: Sevelamer Carbonate Powder Preparation Instructions

RENVELA POWDER PACKET STRENGTH MINIMUM AMOUNT OF WATER FOR DOSE PREPARATION (EITHER OUNCES, ML OR TEASPOON/TABLESPOON)
OUNCES ML TSP/TBSP
0.8 g 1 30 6 teaspoons/2 Tablespoons
2.4 g 2 60 4 Tablespoons

 

Multiple packets may be mixed together with the appropriate amount of water. Patients should be instructed to stir the mixture vigorously (it does not dissolve) and drink the entire preparation within 30 minutes and resuspend the preparation right before drinking.

Based on clinical studies, the average prescribed daily dose of sevelamer carbonate is approximately 7.2 g per day.

How Supplied

Dosage Forms And Strengths

Tablets: 800 mg white oval, film-coated, compressed tablets imprinted with “RENVELA 800”

Powder: 0.8 g and 2.4 g pale yellow powder packaged in an opaque, foil lined, heat sealed packet

Storage And Handling

Tablets: Renvela® 800 mg Tablets are supplied as white oval, film-coated, compressed tablets, imprinted with “RENVELA 800”, containing 800 mg of sevelamer carbonate on an anhydrous basis, microcrystalline cellulose, hypromellose, diacetylated monoglycerides, sodium chloride, and zinc stearate.

1 Bottle of 30 ct 800 mg Tablets (NDC 58468-0130-2)
1 Bottle of 270 ct 800 mg Tablets (NDC 58468-0130-1)

Powder: Renvela® for Oral Suspension is supplied as opaque, foil lined, heat sealed, packets containing 0.8 g or 2.4 g of sevelamer carbonate on an anhydrous basis, natural and artificial citrus flavor, propylene glycol alginate, sodium chloride, sucralose, and ferric oxide (yellow).

1 Box (NDC 58468-0131-2) of 90 ct 2.4 g packets (NDC 58468-0131-1)
1 Box (NDC 58468-0132-2) of 90 ct 0.8 g packets (NDC 58468-0132-1)
1 Sample Box (NDC 58468-0131-4) of 90 ct 2.4 g packets (NDC 58468-0131-3)
1 Sample Box (NDC 58468-0131-5) of 15 ct 2.4 g packets (NDC 58468-0131-3)

Storage: Store at 25°C (77°F): excursions permitted to 15-30°C (59-86°F).

[See USP controlled room temperature]

Protect from moisture.

Distributed by: Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 USA. Revised: 05/2011

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Clinical Trials Experience

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.

There are limited data on the safety of Renvela. However, based on the fact that it contains the same active ingredient as the hydrochloride salt, the adverse event profiles of the two salts should be similar. In a cross-over study in hemodialysis patients with treatment durations of eight weeks each and no washout the adverse reactions on sevelamer carbonate tablets were similar to those reported for sevelamer hydrochloride. In another cross-over study in hemodialysis patients, with treatment durations of four weeks each and no washout between treatment periods, the adverse reactions on sevelamer carbonate powder were similar to those reported for sevelamer hydrochloride.

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-comparator 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 sevelamer hydrochloride was gastrointestinal adverse reactions (3-16%).

In one hundred and forty-three peritoneal dialysis patients studied for 12 weeks using sevelamer hydrochloride, 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 aseptictechnique with the prompt recognition and management of any signs and symptoms associated with peritonitis.

Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post-approval use of sevelamer hydrochloride, which has the same active moiety as sevelamer carbonate: 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.

Read the Renvela (sevelamer carbonate) Side Effects Center for a complete guide to possible side effects

Learn More »
 
 
 

Interactions

Sevelamer carbonate has been studied in human drug-drug interaction studies with warfarin and digoxin. Sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, has been studied in human drug-drug interaction studies with ciprofloxacin, digoxin, warfarin, enalapril, metoprolol and iron.

Ciprofloxacin

In a study of 15 healthy subjects, a co-administered single dose of 2.8 grams of sevelamer hydrochloride decreased the bioavailability of ciprofloxacin by approximately 50%.

Digoxin

In 19 healthy subjects receiving 2.4 grams of sevelamer hydrochloride three times a day with meals for 2 days, sevelamer did not alter the pharmacokinetics of a single dose of digoxin.

In 18 healthy subjects receiving 9.6 grams of sevelamer carbonate once daily with a meal, sevelamer did not alter the pharmacokinetics of a single dose of digoxin.

Warfarin

In 14 healthy subjects receiving 2.4 g of sevelamer hydrochloride three times a day with meals for two days sevelamer did not alter the pharmacokinetics of a single dose of warfarin.

In 14 healthy subjects receiving 9.6 grams of sevelamer carbonate once daily with a meal, sevelamer did not alter the pharmacokinetics of a single dose of warfarin.

Enalapril

In 28 healthy subjects a single 2.4 gram dose of sevelamer hydrochloride did not alter the pharmacokinetics of a single dose of enalapril.

Metoprolol

In 31 healthy subjects a single 2.4 gram dose of sevelamer hydrochloride did not alter the pharmacokinetics of a single dose of metoprolol.

Iron

In 23 healthy subjects, a single 2.8 gram dose of sevelamer hydrochloride did not alter the absorption of a single oral dose of iron as 200 mg exsiccated ferrous sulfate tablet.

Other Concomitant Drug Therapy

There are no empirical data on avoiding drug interactions between Renvela 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. Monitor TSH levels and signs of hypothyroidism 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, there is no information that suggests a dosing regimenthat would be universally appropriate for all drugs. One may, however, administer the drug one hour before or three hours after Renvela, and monitor blood levels of the drug. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control ofseizure disorders were excluded from the clinical trials.

Read the Renvela Drug Interactions Center for a complete guide to possible interactions

Learn More »
 

This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Gastrointestinal Adverse Events

Cases of dysphagia and esophageal tablet retention have been reported in association with use of the tablet formulation of sevelamer, some requiring hospitalization and intervention. Consider using sevelamer suspension in patients with a history of swallowing disorders.

Cases of bowel obstruction and perforation have been reported with sevelamer use.

Patients with dysphagia, swallowing disorders, severe gastrointestinal (GI) motility disorders including severe constipation, or major GI tract surgery were not included in the Renvela clinical studies.

Monitor Serum Chemistries

Bicarbonate and chloride levels should be monitored.

Monitor for Reduced Vitamins D, E, K (clotting factors) and Folic Acid Levels

In preclinical studies in rats and dogs, sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, reduced vitamins D, E, and K (coagulation parameters) and folic acid levels at doses of 6-10 times the recommended human dose. In short-term clinical trials, there was no evidence of reduction in serum levels of vitamins. However, in a one-year clinical trial, 25-hydroxyvitamin D (normal range 10 to 55 ng/mL) fell from 39 ± 22 ng/mL to 34 ± 22 ng/mL (p < 0.01) with sevelamer hydrochloride treatment. Most (approximately 75%) patients in sevelamer hydrochloride clinical trials received vitamin supplements, which is typical of patients ondialysis.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Standard lifetime carcinogenicity bioassays were conducted in mice and rats. Rats were given sevelamer hydrochloride by diet at 0.3, 1, or 3 g/kg/day. There was an increased incidence of urinary bladder transitional cell papilloma in male rats of the high dose group (human equivalent dose twice the maximum clinical trial dose of 13 g). Mice received dietary administration of sevelamer hydrochloride at doses of up to 9 g/kg/day (human equivalent dose 3 times the maximum clinical trial dose). There was no increased incidence of tumors observed in mice.

In an in vitro mammalian cytogenetic test with metabolic activation, sevelamer hydrochloride caused a statistically significant increase in the number of structural chromosome aberrations. Sevelamer hydrochloride was not mutagenic in the Ames bacterial mutation assay.

Sevelamer hydrochloride did not impair the fertility of male or female rats in a dietary administration study in which the females were treated from 14 days prior to mating through gestation and the males were treated for 28 days prior to mating. The highest dose in this study was 4.5 g/kg/day (human equivalent dose 3 times the maximum clinical trial dose of 13 g).

Developmental Toxicity

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 and 3-4 times the maximum clinical trial dose of 13 g). 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).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Sevelamer products should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The effect of sevelamer hydrochloride on the absorption of vitamins and other nutrients has not been studied in pregnant women. Requirements for vitamins and other nutrients are increased in pregnancy. In pregnant rats given doses of sevelamer hydrochloride during organogenesis, reduced or irregular ossification of fetal bones, probably due to a reduced absorption of fat-soluble vitamin D, occurred at a dose approximately equal to the maximum clinical trial dose of 13 g on a body surface area basis. In pregnant rabbits given oral doses of sevelamer hydrochloride by gavage during organogenesis, an increase of early resorptions occurred at dose approximately twice the maximum clinical trial dose on a body surface area basis [see Nonclinical Toxicology].

Labor and Delivery

No sevelamer hydrochloride treatment-related effects on labor and delivery were seen in animal studies [see Nonclinical Toxicology]. The effects of sevelamer carbonate on labor and delivery in humans is unknown.

Pediatric Use

The safety and efficacy of Renvela has not been established in pediatric patients.

Geriatric Use

Clinical studies of Renvela did not include sufficient numbers of subjects aged 65 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.

This monograph has been modified to include the generic and brand name in many instances.

OverDose

Sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, has been given to normal healthy volunteers in doses of up to 14 grams per day for eight days with no adverse effects. In CKD patients on dialysis, the maximum dose studied was 14 grams of sevelamer carbonate and 13 grams of sevelamer hydrochloride. There are no reports of overdosage with sevelamer carbonate or sevelamer hydrochloride in patients. Since sevelamer is not absorbed, the risk of systemic toxicity is low.

 
 

ContrainDications

Renvela is contraindicated in patients with bowel obstruction.

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Patients with chronic kidney disease (CKD) retain phosphorus and can develop hyperphosphatemia. 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.

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 carbonate taken with meals has been shown to control serum phosphorus concentrations in patients with CKD who are on dialysis.

Mechanism of Action

Renvela contains sevelamer carbonate, a non-absorbed phosphate binding crosslinked polymer, free of metal and calcium. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in thegastrointestinal tract and decreasing absorption, sevelamer carbonate lowers the phosphate concentration in the serum (serum phosphorus).

Pharmacodynamics

In addition to effects on serum phosphorus levels, sevelamer hydrochloride has been shown to bind bile acids in vitro and in vivo in experimental animal models. Bile acid binding by ion exchange resins is a well-established method of lowering blood cholesterol. Because sevelamer binds bile acids, it may interfere with normal fat absorption and thus may reduce absorption of fat soluble vitamins such as A, D and K. In clinical trials of sevelamer hydrochloride, both the mean total and LDL cholesterol declined by 15-31%. This effect is observed after 2 weeks. Triglycerides, HDL cholesterol andalbumin did not change.

Pharmacokinetics

A mass balance study using 14C-sevelamer hydrochloride, in 16 healthy male and female volunteers showed that sevelamer hydrochloride is not systemically absorbed. No absorption studies have been performed in patients with renal disease.

Clinical Studies

The ability of sevelamer to control serum phosphorus in CKD patients on dialysis was predominantly determined from the effects of the hydrochloride salt to bind phosphate. Six clinical trials used sevelamer hydrochloride and three clinical trials used sevelamer carbonate. The sevelamer hydrochloride studies include one double-blind, placebo controlled 2-week study (sevelamer N=24); two open-label, uncontrolled, 8-week studies (sevelamer N=220) and three active-controlled open-label studies with treatment durations of 8 to 52 weeks (sevelamer N=256). The sevelamer carbonate studies include one double-blind, active-controlled, cross-over study with two 8-week treatment periods using sevelamer carbonate tablets (N=79), one open-label, active-controlled, cross-over study with two 4-week treatment periods using sevelamer carbonate powder (N=31) and one randomized, parallel, open-label study using sevelamer carbonate powder (N=144) dosed once daily or sevelamer hydrochloride tablets (N=73) dosed three times daily for 24 weeks. Six of the active-controlled studies are described here (three sevelamer carbonate and three sevelamer hydrochloride studies).

Cross-Over Study of Sevelamer Carbonate (Renvela®) 800 mg Tablets and Sevelamer Hydrochloride (Renagel®) 800 mg Tablets

Stage 5 CKD patients on hemodialysis were entered into a five-week sevelamer hydrochloride run-in period and 79 patients received, in randomorder, sevelamer carbonate 800 mg tablets and sevelamer hydrochloride 800 mg tablets for eight weeks each, with no intervening washout. Study dose during the cross-over period was determined based on the sevelamer hydrochloride dose during the run-in period on a gram per gram basis. The phosphorus levels at the end of each of the two cross-over periods were similar. Average actual daily dose was 6 g/day divided among meals for both treatments. Thirty-nine of those completing the cross-over portion of the study were entered into a two-week washout period during which patients were instructed not to take any phosphate binders; this confirmed the activity of sevelamer in this study.

Cross-Over Study of Sevelamer Carbonate (Renvela®) Powder and Sevelamer Hydrochloride (Renagel®) Tablets

Stage 5 CKD patients on hemodialysis were entered into a four-week sevelamer hydrochloride run-in period and 31 patients received, in random order, sevelamer carbonate powder and sevelamer hydrochloride tablets for four weeks each with no intervening washout. Study dose during the cross-over period was determined based on the sevelamer hydrochloride dose during the run-in period on a gram per gram basis. The phosphorus levels at the end of each of the two cross-over periods were similar. Average actual daily dose was 6.0 g/day divided among meals for sevelamer carbonate powder and 6.4 g/day divided among meals for sevelamer hydrochloride tablets.

Sevelamer Hydrochloride Versus Active-Control, Cross-Over Study in Hemodialysis Patients

Eighty-four CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus > 6.0 mg/dL) following a two-week phosphate binder washout period were randomized in a cross-over design to receive in random order sevelamer hydrochloride and active-control for eight weeks each. 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 sevelamer hydrochloride could be titrated up to control serum phosphorus, the dose of active-control could also be altered to attain phosphorus control. Both treatments significantly decreased mean serum phosphorus by about 2 mg/dL (Table 4).

Table 4: Mean Serum Phosphorus (mg/dL) at Baseline and Endpoint

  SEVELAMER HYDROCHLORIDE
(N=81)
ACTIVE CONTROL
(N=83)
Baseline at End of Washout 8.4 8.0
Endpoint 6.4 5.9
Change from Baseline at Endpoint (95% Confidence Interval) -2.0* (-2.5, -1.5) -2.1* (-2.6, -1.7)
*p < 0.0001, within treatment group comparison

 

The distribution of responses is shown in Figure 2. 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.Figure 2. Percentage of patients (Y-axis) attaining a phosphorus reduction from baseline (mg/dL) at least as great as the value of the X-axis.

 

Distribution of responses - Illustration

 

Average daily sevelamer hydrochloride dose at the end of treatment was 4.9 g (range of 0.0 to 12.6 g).

Sevelamer Hydrochloride Versus Active-Control in Hemodialysis Patients

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 sevelamer hydrochloride 800 mg tablets (N=99) or an active control (N=101). At week 52, using last-observation-carried-forward, sevelamer and active-control both significantly decreased mean serum phosphorus (Table 5).

Table 5: Mean Serum Phosphorus (mg/dL) and Ion Product at Baseline and Change from Baseline to End of Treatment

  SEVELAMER HCL
(N=94)
ACTIVE-CONTROL
(N=98)
Phosphorus Baseline 7.5 7.3
Change from Baseline at Endpoint -2.1 -1.8
Ca x Phosphorus Ion Product Baseline 70.5 68.4
Change from Baseline at Endpoint -19.4 -14.2

 

Sixty-one percent of sevelamer hydrochloride patients and 73% of the control patients completed the full 52 weeks of treatment.

Figure 3, a plot of the phosphorus change from baseline for the completers, illustrates the durability of response for patients who are able to remain on treatment.

Figure 3: Mean Phosphorus Change from Baseline for Patients who Completed 52 Weeks of Treatment

View Enlarged Table

 

Average daily sevelamer hydrochloride dose at the end of treatment was 6.5 g (range of 0.8 to 13 g).

Sevelamer Hydrochloride Versus Active-Control in Peritoneal Dialysis Patients

One hundred and forty-three patients on peritoneal dialysis who were hyperphosphatemic (serum phosphorus > 5.5 mg/dL) following a two-week phosphate binder washout period were randomized to receive sevelamer hydrochloride (N=97) or active-control (N=46) open label for 12 weeks. Average daily sevelamer hydrochloride dose at the end of treatment was 5.9 g (range 0.8 to 14.3 g). Thirteen patients (14%) in the sevelamer group and 9 patients (20%) in the active-control group discontinued, mostly forgastrointestinal adverse reactions. There were statistically significant changes in serum phosphorus (p < 0.001) for sevelamer hydrochloride (-1.6 mg/dL from baseline of 7.5 mg/dL), similar to the active-control.

Once a Day Versus Three Times a Day Dosing

Stage 5 CKD patients on hemodialysis with a serum phosphate level of > 5.5 mg/dl after washout from baseline therapies were randomized in a 2:1 ratio to receive either sevelamer carbonate powder once-daily (N=144) or sevelamer hydrochloride as a tablet with the dose divided three times per day (N=73) for 24 weeks. The initial dose for the two groups was 4.8 g/day. At the end of the study, the total daily dose was 6.2 g/day of sevelamer carbonate powder once daily and 6.7 g/day of sevelamer hydrochloride tablets three times per day. A greater percentage of subjects on the once daily dose than three times per day regimen discontinued therapy prematurely, 35% versus 15%. The reasons for discontinuation were largely driven by adverse events and withdrawal of consent in the once daily dosing regimen. Serum phosphate levels and calcium-phosphate product were better controlled on the three times per day regimen than on the once daily regimen. Mean serum phosphorus decreased 2.0 mg/dL for sevelamer carbonate powder once dailyand 2.9 mg/dL for sevelamer hydrochloride tablets three times per day.

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Dosing

Inform patients to take Renvela as directed with meals and adhere to their prescribed diets.

For patients using an oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, advise the patient to take the oral medication at least one hour before or three hours after Renvela. Blood levels of the oral medication should be monitored, if applicable, to determine if there is a significant interaction between the oral medication and Renvela.

For Renvela powder, brief the patient on preparation of the powder in water.

Sevelamer Carbonate Powder Preparation Instructions

The entire contents of each 0.8 or 2.4 g packet should be placed in a cup and mixed thoroughly with the amount of water described in Table 6.

Table 6: Sevelamer Carbonate Powder Preparation Instructions

RENVELA POWDER PACKET STRENGTH MINIMUM AMOUNT OF WATER FOR DOSE PREPARATION (EITHER OUNCES, ML OR TEASPOON/TABLESPOON)
OUNCES ML TSP/TBSP
0.8 g 1 30 6 teaspoons/2 Tablespoons
2.4 g 2 60 4 Tablespoons

 

Multiple packets may be mixed together with the appropriate amount of water. Patients should be instructed that the powder does not dissolve and therefore it should be stirred vigorously just before drinking. The entire preparation should be consumed within 30 minutes.

Adverse Reactions

Renvela 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.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

SEVELAMER - ORAL

 

(seh-VELL-uh-mer)

 

COMMON BRAND NAME(S): Renagel, Renvela

 

USES: Sevelamer is used to lower high blood phosphorus (phosphate) levels in patients who are on dialysis due to severe kidney disease. Dialysis removes some phosphate from your blood, but it is difficult to remove enough to keep your phosphate levels balanced. Decreasing blood phosphate levels can help keep your bones strong, prevent unsafe buildup of minerals in your body, and possibly decrease the risk of heart disease and strokes that can result from high phosphate levels. Sevelamer works by holding onto phosphate from the diet so that it can pass out of your body.

 

HOW TO USE: Take this medication by mouth, usually 3 times daily with meals or as directed by your doctor. Swallow the tablet whole. Do not crush, chew, or split the tablet. Dosage is based on your medical condition, any other medications you take to lower your phosphate levels, and your response to therapy.

If you are taking the powder form of this medication, check the manufacturer package directions for the proper amount of water to use for your specific dose. Stir the mixture well and drink the mixture within 30 minutes. If the powder settles to the bottom of the glass, then stir again right before drinking.

Use this medication regularly in order to get the most benefit from it. Remember to take it after each meal every day, or on the schedule given to you by your doctor.

Do not take other medications by mouth for 1 hour before you take this medication or for 3 hours afterward. Taking other medications during that time could decrease the effectiveness of the other drugs. Consult your pharmacist for more information.

Consumer Overview Side Effect

SIDE EFFECTS: Headache, diarrhea, stomach upset, nausea, vomiting, cough, gas, or constipation may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if these unlikely but serious side effects occur: problems with your dialysis access site, severe constipation/inability to have a bowel movement, stomach/abdominal pain or swelling.

Seek immediate medical attention if any of these rare but very serious side effects occur: trouble breathing, chest pain, pain/redness/swelling in the lower legs.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Renvela (sevelamer carbonate) Side Effects Center for a complete guide to possible side effects

Learn More »
 

PRECAUTIONS: Before taking sevelamer, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: low blood phosphorus levels, bowel blockage.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: stomach/intestinal problems (e.g., constipation), stomach/intestinal surgeries, swallowing problems (dysphagia).

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially: mycophenolate.

Sevelamer may interfere with the effectiveness of many drugs by making it more difficult for them to be absorbed by the stomach. Consult your pharmacist about the best times to take your medication(s).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Your doctor may direct you to follow a special diet to help lower your blood phosphate levels. Follow the diet closely.

Do not share this medication with others.

Laboratory and/or medical tests (such as blood phosphate, calcium, bicarbonate and chloride levels) should be performed regularly to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, skip the missed dose unless you have just eaten. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised December 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Renagel, Renvela

Generic Name: sevelamer (Pronunciation: se VEL a mer)

  • What is sevelamer (Renvela)?
  • What are the possible side effects of sevelamer (Renvela)?
  • What is the most important information I should know about sevelamer (Renvela)?
  • What should I discuss with my healthcare provider before taking sevelamer (Renvela)?
  • How should I take sevelamer (Renvela)?
  • What happens if I miss a dose (Renvela)?
  • What happens if I overdose (Renvela)?
  • What should I avoid while taking sevelamer (Renvela)?
  • What other drugs will affect sevelamer (Renvela)?
  • Where can I get more information?

What is sevelamer (Renvela)?

 

Sevelamer is a phosphate binder. Sevelamer helps prevent hypocalcemia (low levels of calcium in the body) caused by elevated phosphorus.

Sevelamer is used to control phosphorus levels in people with chronic kidney disease who are on dialysis.

Sevelamer may also be used for purposes not listed in this medication guide.

Renagel 800 mg

oval, white, imprinted with RENAGEL 800

What are the possible side effects of sevelamer (Renvela)?

 

Get emergency medical help if you have any of thesesigns of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using sevelamer and call your doctor at once if you have a serious side effect such as:

  • black, bloody, or tarry stools;
  • constipation that gets worse or does not clear up;
  • severe constipation with stomach pain; or
  • fever, chills, body aches, flu symptoms.

Less serious side effects may include:

  • nausea, vomiting, stomach pain, loss of appetite;
  • upset stomach, gas, bloating;
  • diarrhea, mild constipation;
  • tired feeling;
  • itching; or
  • joint pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Renvela (sevelamer carbonate) Side Effects Center for a complete guide to possible side effects

Learn More »
 

What is the most important information I should know about sevelamer (Renvela)?

 

You should not take this medication if you are allergic to sevelamer, or if you have a bowel obstruction.

Before taking sevelamer, tell your doctor if you have severe constipation, a blockage in your intestines, a stomach or intestinal disorder, trouble swallowing, or if you have recently had stomach or intestinal surgery.

Avoid taking any other medicines within 1 hour before or 3 hours after you take sevelamer. Sevelamer can bind to other medications and make them less effective.

Before taking sevelamer, tell your doctor if you are taking ciprofloxacin (Cipro), a heart rhythm medication, or a seizure medication.

Do not take calcium or other mineral supplements without your doctor's advice. Use only the specific type of calcium or mineral supplement your doctor recommends.

Side Effects Centers
  • Renagel
  • Renvela

Patient Detailed How Take

What should I discuss with my healthcare provider before taking sevelamer (Renvela)?

 

You should not take this medication if you are allergic to sevelamer, or if you have a bowel obstruction.

To make sure you can safely take sevelamer, tell your doctor if you have any of these other conditions:

  • trouble swallowing;
  • severe constipation;
  • a blockage in your intestines;
  • a stomach or intestinal disorder; or
  • if you have recently had stomach or intestinal surgery.

FDA pregnancy category C. It is not known whether sevelamer will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether sevelamer passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take sevelamer (Renvela)?

 

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Take sevelamer with meals.

Do not crush, chew, or break the sevelamer tablet. Swallow the pill whole. Sevelamer tablets expand when they are wet, and breaking or crushing the pill may make it harder to swallow.

Sevelamer powder must be dissolved in water before you take it. The 0.8-gram packet should be mixed with at least 1 ounce (2 tablespoons) of water. The 2.4-gram packet should be mixed with at least 2 ounces (4 tablespoons) of water.

Stir the powder in water until it is completely dissolved. Drink all of this mixture right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

To be sure this medication is helping your condition and not causing harmful effects, your blood may need to be tested on a regular basis. Do not miss any scheduled appointments.

Sevelamer may be only part of a complete program of treatment that also includes a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you must eat or avoid to help control your condition.

Store at room temperature away from moisture and heat.

Side Effects Centers
  • Renagel
  • Renvela

Patient Detailed Avoid Taking

What happens if I miss a dose (Renvela)?

 

Take the missed dose as soon as you remember. Be sure to take the missed dose with food. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Renvela)?

 

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking sevelamer (Renvela)?

 

Avoid taking any other medicines within 1 hour before or 3 hours after you take sevelamer. Sevelamer can bind to other medications and make them less effective.

Do not take calcium or other mineral supplements without your doctor's advice. Use only the specific type of calcium or mineral supplement your doctor recommends.

What other drugs will affect sevelamer (Renvela)?

 

Tell your doctor about all other medicines you use, especially:

  • ciprofloxacin (Cipro);
  • levothyroxine (Synthroid, Levothroid, Levoxyl);
  • a heart rhythm medication; or
  • a seizure medication.

This list is not complete and other drugs may interact with sevelamer. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

 

Your pharmacist can provide more information about sevelamer.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 9.02. Revision date: 7/27/2012.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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Side Effects Centers
  • Renagel
  • Renvela

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