RENAGEL- sevelamer hydrochloride tablet
Carilion Materials Management
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.
Patients Not Taking a Phosphate Binder. The recommended starting dose of Renagel is 800 to 1600 mg, which can be administered as one or two 800 mg Renagel® Tablets, or two to four 400 mg Renagel® Tablets, with meals based on serum phosphorus level. Table 1 provides recommended starting doses of Renagel for patients not taking a phosphate binder.
|Serum Phosphorus||Renagel® 800 mg||Renagel® 400 mg|
|>5.5 and <7.5 mg/dL||1 tablet three times daily with meals||2 tablets three times daily with meals|
|≥7.5 and <9.0 mg/dL||2 tablets three times daily with meals||3 tablets three times daily with meals|
|≥9.0 mg/dL||2 tablets three times daily with meals||4 tablets three times daily with meals|
Patients 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 Renagel and calcium acetate. Table 2 gives recommended starting doses of Renagel based on a patient’s current calcium acetate dose.
|Calcium Acetate 667 mg |
(Tablets per meal)
|Renagel® 800 mg |
(Tablets per meal)
|Renagel® 400 mg |
(Tablets per meal)
|1 tablet||1 tablet||2 tablets|
|2 tablets||2 tablets||3 tablets|
|3 tablets||3 tablets||5 tablets|
Dose Titration for All Patients Taking Renagel. Dosage should be adjusted based on the serum phosphorus concentration with a goal of lowering serum phosphorus to 5.5 mg/dL or less. The dose may be increased or decreased by one tablet per meal at two-week intervals as necessary. Table 3 gives a dose titration guideline. The average dose in a Phase 3 trial designed to lower serum phosphorus to 5.0 mg/dL or less was approximately three Renagel 800 mg tablets per meal. The maximum average daily Renagel dose studied was 13 grams.
|Serum Phosphorus||Renagel® Dose|
|>5.5 mg/dL||Increase 1 tablet per meal at 2 week intervals|
|3.5–5.5 mg/dL||Maintain current dose|
|<3.5 mg/dL||Decrease 1 tablet per meal|
800 mg and 400 mg tablets.
Renagel is contraindicated in patients with bowel obstruction.
Renagel is contraindicated in patients with known hypersensitivity to sevelamer hydrochloride or to any of the excipients.
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 also 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 Renagel clinical studies.
Bicarbonate and chloride levels should be monitored.
In preclinical studies in rats and dogs, sevelamer hydrochloride reduced vitamins D, E, and K (coagulation parameters) and folic acid levels at doses of 6 to 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 on dialysis.
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 to 52 weeks, the most common reason for withdrawal from Renagel was gastrointestinal adverse reactions (3%–16%).
In 143peritoneal 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 postapproval use of sevelamer hydrochloride (Renagel®): hypersensitivity, 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.
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