Drug Interactions
There have been no adequate, well-controlled studies regarding drug-herb interactions.
There have been no adequate, well-controlled studies regarding drug-lifestyle interactions.
There have been no adequate, well-controlled studies regarding the effect of a variety of foods on the intestinal phosphorus binding of RENAGEL.
RENAGEL (sevelamer hydrochloride) was studied in human drug-drug interaction studies with digoxin, warfarin, enalapril, metoprolol and iron. RENAGEL had no effect on the bioavailability of these medications. However, in a study of 15 healthy subjects, a co-administered single dose of 7 RENAGEL Capsules (approximately 2.8 g) decreased the bioavailability of ciprofloxacin by approximately 50%. Consequently, RENAGEL should not be taken simultaneously with ciprofloxacin.
During post-marketing experience, very rare cases of increased TSH levels have been reported in patients co-administered RENAGEL and levothyroxine. Closer monitoring of TSH levels is therefore recommended for patients receiving both medications.
When administering any other medication where a reduction in the bioavailability of that medication would have a clinically significant effect on safety or efficacy, the physician should consider monitoring blood levels or dosing that medicine apart from RENAGEL (at least one hour before or three hours after RENAGEL). 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.
There have been no adequate, well-controlled studies regarding drug-laboratory interactions.
Information for the Patient
Renagel
Special Handling Instructions
None.
Dosage and Administration
The tablets should not be bitten, chewed or broken apart prior to dosing.
RENAGEL (sevelamer hydrochloride) should be taken immediately prior to or with meals, since its action is to bind ingested phosphate (see Action and Clinical Pharmacology, Mechanism of Action).
When administering any other medication where a reduction in the bioavailability of that medication would have a clinically significant effect on safety or efficacy, the physician should consider monitoring blood levels or dosing that medicine apart from RENAGEL (at least one hour before or three hours after RENAGEL).
When switching from calcium-based phosphate binders to RENAGEL, an equivalent starting dose on a mg/weight basis of RENAGEL should be prescribed.
Dosage adjustments, when necessary should be recommended every 1 to 3 weeks by increasing one tablet per meal (3 per day) until the target serum phosphorus levels are met.
The total daily dose should be divided according to meal portions during the day.
If a dose is forgotten, it should be skipped. Double dosing is not advisable.
Dosage should be adjusted based upon the target serum phosphorus levels. The dose may be increased or decreased by one tablet per meal at two week intervals as necessary. The average final dose in the chronic phase of a 52 week Phase 3 clinical trial designed to lower serum phosphorous to 1.6 mmol/L or less was approximately 7.1 grams, (approximately nine 800 mg tablets per day equivalent to three 800 mg tablets per meal). The maximum average daily RENAGEL dose studied was 13 g.
Adverse Reactions
During post-marketing experience with RENAGEL, the following have been reported without attribution to causality: pruritus, rash, abdominal pain and in very rare cases, intestinal obstruction, ileus and intestinal perforation.
The most frequently occurring serious adverse event with RENAGEL use was peritonitis at 8.2%, compared to 4.3 % with calcium. Patients receiving dialysis are subject to certain risks for infection specific to the dialysis modality. Peritonitis is a known complication in patients receiving peritoneal dialysis (PD). Therefore, patients on PD 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 events have been observed with RENAGEL use with an incidence of <10%, but greater than calcium and without attribution to causality, including: abdominal distension, constipation, diarrhea, nausea, chest pain, fatigue, pyrexia, catheter site infection, anorexia, headache, cough and pruritus.
Some patients experienced adverse events related to hypercalcemia in the calcium group but not in the RENAGEL group.
Indications and Clinical Use
RENAGEL (sevelamer hydrochloride) is indicated for:
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the control of hyperphosphatemia in patients with ESRD (End Stage Renal Disease) undergoing dialysis.
Overdosage
For management of a suspected drug overdose, CPhA recommends that you contact your regional Poison Control Centre. See the eCPS Directories section for a list of Poison Control Centres.
Since RENAGEL (sevelamer hydrochloride) is not absorbed, the risk of systemic toxicity is minimal. RENAGEL has been given to healthy volunteers at doses up to 14 grams per day for 8 days with no adverse effects. The maximum average daily dose of RENAGEL that has been given to hemodialysis patients is 13 grams.
Dosage Forms, Composition and Packaging
Each oval, film-coated tablet, imprinted with “RENAGEL 800”, on the crown, single side, contains: sevelamer HCl 800 mg. Nonmedicinal ingredients: colloidal silicon dioxide and stearic acid; coating: diacetylated monoglyceride and hypromellose; printing ink: hypromellose (hydroxypropyl methylcellulose), iron oxide black (E172), isopropyl alcohol and propylene glycol. Bottles of 180.
Warnings and Precautions
No special considerations are needed for elderly patients.
The safety and efficacy of RENAGEL in patients with dysphagia, swallowing disorders, severe gastrointestinal (GI) motility disorders including severe constipation, or major GI tract surgery have not been established. Caution should be exercised when RENAGEL is used in patients with these GI disorders.
RENAGEL (sevelamer hydrochloride) tablets should be swallowed intact and should not be crushed, chewed, or broken into pieces.
Patients with renal insufficiency may develop hypocalcemia. As RENAGEL does not contain calcium, serum calcium levels should be monitored and elemental calcium should be supplemented whenever considered necessary. In cases of hypocalcemia, patients should be given an evening calcium supplement. Approximately 1000 mg elemental calcium is recommended.
Caution should be exercised to avoid hypophosphatemia, a serum phosphorus of <0.8 mmol/L (see Dosage and Administration).
The safety and efficacy of RENAGEL in patients with renal disease who are not undergoing dialysis has not been studied.
The safety and efficacy of RENAGEL has not been established in pediatric patients. The minimum age of patients treated with RENAGEL in clinical trials was 18 years old.
The safety of RENAGEL has not been established in pregnant women. In preclinical studies, there was no evidence that RENAGEL induced embryolethality, fetotoxicity or teratogenicity at the doses tested (up to 1 g/kg/day in rabbits; up to 4.5 g/kg/day in rats). RENAGEL should only be given to pregnant women if the benefits outweigh the risks.
There have been no adequate, well-controlled studies in lactating, or nursing women.
Serum phosphorus and serum calcium should be monitored every 1 to 3 weeks until the target phosphorus level is reached. The dose of RENAGEL should be adjusted based on serum phosphorus concentration and titrated to a target serum phosphorus of ≤1.8 mmol/L.
RENAGEL does not contain calcium or alkali supplementation; serum calcium, bicarbonate, and chloride levels should be monitored.
Storage and Stability
Store at controlled room temperature 15 to 30°C. Protect from moisture.
Action and Clinical Pharmacology
RENAGEL (sevelamer hydrochloride) is a nonabsorbed polymer phosphate binder. When taken with meals RENAGEL inhibits intestinal absorption of ingested phosphate.
RENAGEL binds bile acids and therefore lowers LDL serum cholesterol. Since RENAGEL does not contain aluminum or other metals, it does not cause aluminum or other metal intoxication.
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.
Contraindications
RENAGEL (sevelamer hydrochloride) is contraindicated in the following situations:
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patients with hypophosphatemia
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patients with bowel obstruction
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patients hypersensitive to sevelamer hydrochloride or one of the other ingredients in the product (colloidal silicon dioxide, stearic acid).
