Cavsamir

Sevelamer carbonate.

Each film coated tablet contains: Sevelamer carbonate 800 mg.
Excipients/Inactive Ingredients: Mannitol, Crospovidone Type B (XL-10), Hydroxypropyl Cellulose (Klucel LF), Colloidal Silicon Dioxide, Zinc Stearate, Opadry AMB Translucent (OY-B-29000), Purified water, Opacode Black S-1-17823 & Isopropyl alcohol.

Pharmacology: Pharmacodynamics: Sevelamer carbonate contains sevelamer, a non-absorbed phosphate binding crosslinked polymer, free of metal and calcium. Sevelamer contains multiple amines separated by one carbon from the polymer backbone which become protonated in the stomach. These protonated amines bind negatively charged ions such as dietary phosphate in the intestine. By binding phosphate in the gastrointestinal tract and decreasing absorption, sevelamer lowers the phosphorus concentration in the serum. Regular monitoring of serum phosphorus levels is always necessary during phosphate binder administration.
Pharmacokinetics: Pharmacokinetic studies have not been carried out with sevelamer carbonate. Sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, is not absorbed from the gastrointestinal tract, as confirmed by an absorption study in healthy volunteers.

CAVSAMIR is indicated for the control of hyperphosphataemia in adult patients receiving haemodialysis or peritoneal dialysis.
CAVSAMIR 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.
CAVSAMIR 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.

Starting Dose: One or two 800-mg tab 3 times daily with meals.
Because of the rapid disintegration of the carbonate salt tablet and its rapid reaction with the hydrochloric acid in the stomach, the dosing of sevelamer is anticipated to be similar to that of the hydrochloride salt.
Patients Not Taking a Phosphate Binder: Recommended Starting Dose: 800-1600 mg, which can be administered as 1 or 2 sevelamer 800-mg tablets, with meals based on serum phosphorus level. The table as follows provides the recommended starting doses of sevelamer for patients not taking a phosphate binder. (See Table 1.)

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Patients Switching From Sevelamer Hydrochloride: For patients switching from sevelamer hydrochloride, sevelamer carbonate should be prescribed on a gram per gram basis. Further titration to the desired phosphate levels may be necessary. The highest daily dose of sevelamer carbonate studied was 14 g in chronic kidney disease (CKD) patients on dialysis.
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 sevelamer hydrochloride and calcium acetate. Table 2 gives recommended starting doses of CAVSAMIR based on a patient's current calcium acetate dose. (See Table 2.)

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Dose Titration for All Patients Taking sevelamer: The dose should be increased or decreased by 1 tab/meal at 2-week intervals, as necessary, with the goal of controlling serum phosphorus within the target range of 1.13-1.78 mmol/L.
Patients taking Sevelamer should adhere to their prescribed diets.
Paediatric population: The safety and efficacy of sevelamer carbonate has not been established in pediatric patients. Sevelamer is not recommended for use in children below 18 years.
For paediatric patients the oral suspension should be administered, as tablet formulations are not appropriate for this population.
Route of administration: For oral use.
Tablets should be swallowed intact and should not be crushed, chewed, or broken into pieces prior to administration.

In CKD patients on dialysis, the maximum average daily dose was 14 grams of sevelamer carbonate in a single daily dose. 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.

Hypersensitivity to the active substance or to any of the excipients.
Hypophosphataemia.
Bowel obstruction.

Sevelamer is currently not recommended for use in adult patients with chronic kidney disease not on dialysis with serum phosphorus < 1.78 mmol/l.
Caution should be exercised when Sevelamer is used in patients with the following disorders: Dysphagia; swallowing disorders; Severe gastrointestinal motility disorders including untreated or severe constipation or major gastrointestinal tract surgery. Use with caution in patients with these gastrointestinal disorders.
Monitor serum chemistries: Bicarbonate and chloride levels should be monitored.
Reductions in Vitamins A, D, E, K (clotting factors) and Folic Acid Levels: Patients 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 Sevelamer can bind fat-soluble 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 Sevelamer. In patients undergoing peritoneal dialysis additional monitoring of fat-soluble vitamins and folic acid is recommended.
Effects on Ability to Drive and Use Machines: Sevelamer has no or negligible influence on the ability to drive and use machines.

Pregnancy: There are no or limited amount of data from the use of sevelamer in pregnant women. Sevelamer has been shown to reduce the absorption of several vitamins including folic acid. The potential risk to humans is unknown. Sevelamer carbonate should only be given to pregnant women if clearly needed and after a careful risk/benefit analysis has been conducted for both the mother and the foetus.
Breast-feeding: It is unknown whether sevelamer/metabolites are excreted in human milk. The non-absorbed nature of sevelamer indicates that excretion of sevelamer in breast milk is unlikely. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with sevelamer carbonate should be made taking into account the benefit of breast-feeding to the child and the benefit of sevelamer carbonate therapy to the woman.
Fertility: There are no data from the effect of sevelamer on fertility in humans. It has been shown that sevelamer did not impair fertility in male or female rats at exposures at a human equivalent dose 2 times the maximum dose of 13 g/day, based on a comparison of relative BSA.

Summary of the safety profile: The most frequently occurring adverse reactions were all in the gastrointestinal disorders system organ class. Most of these adverse reactions were mild to moderate in intensity.
Tabulated list of adverse reactions: Adverse reactions that occurred are listed by frequency in the table as follows. The reporting rate is classified as very common, common, uncommon, rare, very rare, not known. (See Table 3.)

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Paediatric population: In general, the safety profile for children and adolescents (6 to 18 years of age) is similar to the safety profile for adults.

There are no empirical data on avoiding drug interactions between sevelamer and most concomitant oral drugs. For oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy (e.g., cyclosporine, tacrolimus, levothyroxine), consider separation of the timing of the administration of the two drugs. The duration of separation depends upon the absorption characteristics of the medication concomitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate release or an extended release product. Where possible consider monitoring clinical responses and/or blood levels of concomitant drugs that have a narrow therapeutic range.
Sevelamer carbonate did not alter the pharmacokinetics when administered concomitantly in the following drugs digoxin, enalapril, iron, metoprolol and warfarin.
The anti-arrhythmic and anti-seizure medical product should be taken at least one hour before or three hours after sevelamer, and blood monitoring can be considered.
Very rare cases of increased phosphate levels have been reported in patients taking proton pump inhibitors co-administered with sevelamer carbonate. Caution should be exercised when prescribing PPI (omeprazole, pantoprazole, or lansoprazole) to patients concomitantly treated with sevelamer. The phosphate serum level should be monitored and the sevelamer carbonate dosage adjusted consequently.
Oral drugs that have demonstrated interaction with sevelamer and are to be dosed separately from sevelamer: Ciprofloxacin: Dosing Recommendations - Take at least 2 hours before or 6 hours after sevelamer.
Mycophenolate mofetil: Dosing Recommendations - Take at least 2 hours before sevelamer.

Store below 30°C. Dispense in a tight container. Protect from moisture.
Shelf Life: 24 months.

Antidotes & Detoxifying Agents

V03AE02 - sevelamer ; Belongs to the class of drugs used in the treatment of hyperkalemia and hyperphosphatemia.

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