Drug Description
Each sachet contains 2.4 g sevelamer carbonate.
Presentation
Powder for oral suspension.Pale yellow powder.
Indications
Renvela is indicated for the control of hyperphosphataemia in adult patients receiving haemodialysis or peritoneal dialysis.Renvela is also indicated for the control of hyperphosphataemia in adult patients with chronic kidney disease not on dialysis with serum phosphorus > 1.78 mmol/l.Renvela should be used within the context of a multiple therapeutic approach, which could include calcium supplement, 1,25-dihydroxy Vitamin D3 or one of its analogues to control the development of renal bone disease.
Adult Dosage
Posology:Starting doseThe recommended starting dose of sevelamer carbonate is 2.4 g or 4.8 g per day based on clinical needs and serum phosphorus level. Renvela powder for oral suspension must be taken three times per day with meals.Serum phosphorus level in patientsTotal daily dose of sevelamer carbonate to be taken over 3 meals per day1.78 – 2.42 mmol/l (5.5 – (7.5 mg/dl)2.4 g*> 2.42 mmol/l (> 7.5 mg/dl)4.8 g**Plus subsequent titrating as per instructionsFor patients previously on phosphate binders (sevelamer hydrochloride or calcium based), Renvela should be given on a gram for gram basis with monitoring of serum phosphorus levels to ensure optimal daily doses.Titration and maintenanceSerum phosphorus levels must be monitored and the dose of sevelamer carbonate titrated every 24 weeks until an acceptable serum phosphorus level is reached, with regular monitoring thereafter.Patients taking Renvela should adhere to their prescribed diets.In clinical practice, treatment will be continuous based on the need to control serum phosphorus levels and the daily dose is expected to be an average of approximately 6 g per day.Paediatric populationThe safety and efficacy of Renvela has not been established in children below the age of 18 years. Renvela is not recommended in children below the age of 18 years.Method of administrationThe powder should be dispersed in 60 ml of water per sachet prior to administration. The suspension should be ingested within 30 minutes after being prepared.
Contra Indications
• Hypersensitivity to the active substance or to any of the excipients.• Hypophosphataemia• Bowel obstruction.
Special Precautions
Efficacy and safety of Renvela has not been studied in children below the age of 18 years.The safety and efficacy of Renvela have not been established in adult patients with chronic kidney disease not on dialysis with serum phosphorus < 1.78 mmol/l. Therefore Renvela is currently not recommended for use in these patients.Experience in nondialysis patients with serum phosphorus 1.78 mmol/l is limited. Regular monitoring every 2-3 months when starting treatment with Renvela is recommended.The safety and efficacy of Renvela have not been established in patients with the following disorders:• dysphagia• swallowing disorders• severe gastrointestinal motility disorders including untreated or severe gastroparesis, retention of gastric contents and abnormal or irregular bowel motion• active inflammatory bowel disease• major gastrointestinal tract surgeryTherefore caution should be exercised when Renvela is used in these patients.Intestinal obstruction and ileus/subileusIn very rare cases, intestinal obstruction and ileus/subileus have been observed in patients during treatment with sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate. Constipation may be a preceding symptom. Patients who are constipated should be monitored carefully while being treated with Renvela. Renvela treatment should be reeva luated in patients who develop severe constipation or other severe gastrointestinal symptoms.Fatsoluble vitaminsPatients with CKD may develop low levels of fat-soluble vitamins A, D, E and K, depending on dietary intake and the severity of their disease. It cannot be excluded that Renvela can bind fatsoluble vitamins contained in ingested food. In patients not taking supplemental vitamins but on sevelamer, serum vitamin A, D, E and K status should be assessed regularly. It is recommended that vitamin supplements be given if necessary. It is recommended that CKD patients not on dialysis are given vitamin D supplements (approximately 400 IU of native vitamin D daily) which can be part of a multivitamin preparation to be taken apart from their dose of Renvela. In patients undergoing peritoneal dialysis additional monitoring of fat-soluble vitamins and folic acid is recommended, since vitamin A, D, E and K levels were not measured in a clinical study in these patients.Folate deficiencyThere is at present insufficient data to exclude the possibility of folate deficiency during long term Renvela treatment.Hypocalcaemia/hypercalcaemiaPatients with CKD may develop hypocalcaemia or hypercalcaemia. Renvela does not contain any calcium. Serum calcium levels should therefore be monitored at regular intervals and elemental calcium should be given as a supplement if required.Metabolic acidosisPatients with chronic kidney disease are predisposed to developing metabolic acidosis. As part of good clinical practice, monitoring of serum bicarbonate levels is therefore recommended.PeritonitisPatients receiving dialysis are subject to certain risks for infection specific to dialysis modality. Peritonitis is a known complication in patients receiving peritoneal dialysis and in a clinical study with sevelamer hydrochloride, a greater number of peritonitis cases were reported in the sevelamer group than in the control group. Patients on peritoneal dialysis should be closely monitored to ensure the correct use of appropriate aseptic technique with the prompt recognition and management of any signs and symptoms associated with peritonitis.Antiarrhythmic and antiseizure medicinal productsCaution should be exercised when prescribing Renvela to patients also taking arrhythmias and anti-seizure medicinal products.HypothyroidismCloser monitoring of patients with hypothyroidism co-administered with sevelamer carbonate and levothryroxine is recommended.Longterm chronic treatmentIn a clinical trial of one year, no evidence of accumulation of sevelamer was seen. However the potential absorption and accumulation of sevelamer during longterm chronic treatment (> one year) cannot be totally excluded.HyperparathyroidismRenvela is not indicated for the control of hyperparathyroidism. In patients with secondary hyperparathyroidism Renvela should be used within the context of a multiple therapeutic approach, which could include calcium as supplements, 1,25 - dihydroxy Vitamin D3 or one of its analogues to lower the intact parathyroid hormone (iPTH) levels.
Interactions
Interaction studies have not been conducted in patients on dialysis.In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same active moiety as Renvela, decreased the bioavailability of ciprofloxacin by approximately 50% when co-administered with sevelamer hydrochloride in a single dose study. Consequently, Renvela should not be taken simultaneously with ciprofloxacin.Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant patients when co-administered with sevelamer hydrochloride without any clinical consequences (i.e graft rejection). The possibility of an interaction cannot be excluded and a close monitoring of blood concentrations of ciclosporin, mycophenolate mofetil and tacrolimus should be considered during the use of combination and after its withdrawal.Very rare cases of hypothyroidism have been reported in patients co-administered sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, and levothyroxine. Closer monitoring of thyroid stimulating hormone (TSH) levels is therefore recommended in patients receiving sevelamer carbonate and levothyroxine.Patients taking anti-arrhythmic medicinal products for the control of arrhythmias and anti-seizure medicinal products for the control of seizure disorders were excluded from clinical trials. Caution should be exercised when prescribing Renvela to patients also taking these medicinal products.In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same active moiety as Renvela, had no effect on the bioavailability of digoxin, warfarin, enalapril or metoprolol.Renvela is not absorbed compound and may affect the bioavailability of other medicinal products. When administering any medicinal product where a reduction in the bioavailability could have a clinically significant effect on safety or efficacy, the medicinal product should be administered at least one hour before or three hours after Renvela, or the physician should consider monitoring blood levels.
Adverse Reactions
The safety of sevelamer (as either carbonate and hydrochloride salts) has been investigated in numerous clinical trials involving a total of 969 haemodialysis patients with treatment duration of 4 to 50 weeks (724 patients treated with sevelamer hydrochloride and 245 with sevelamer carbonate), 97 peritoneal dialysis patients with treatment duration of 12 weeks (all treated with sevelamer hydrochloride) and 128 patients with CKD not on dialysis with treatment duration of 8 to 12 weeks (79 patients treatment with sevelamer hydrochloride and 49 with sevelamer carbonate).The most frequently occurring ( 5% of patients) undesirable effects possibly or probably related to sevelamer were all in the gastrointestinal disorders system organ class. Most of these adverse reactions were mild to moderate in intensity. Data possibly or probably related to sevelamer from these studies are listed by frequency in the table below. The reporting rate is classified as very common (1/10), common (1/100, <1/10), uncommon (1/1,000, <1/100), rare (1/10,000, <1/1,000), very rare (<1/10,000), including isolated.Gastrointestinal disordersVery common (1/10): Nausea, vomiting, upper abdominal pain, constipationCommon (1/100 to <1/10): Diarrhoea, dyspepsia, flatulence, abdominal painPost-marketing experience: In very rare cases (estimated post-marketing frequency of < 1/10,000), intestinal obstruction and ileus/subileus have been observed in patients during treatment with sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate.
Manufacturer
Genzyme Therapeutics
Drug Availability
POM – Prescription Only Medicine
Updated
08 March 2010
