Sefos

Sevelamer carbonate.

Each film-coated tablet contains: Sevelamer Carbonate 800 mg.
Sefos contains Sevelamer, a non-absorbed phosphate binding cross linked polymer, free of metal and calcium. Sevelamer carbonate was developed as a pharmaceutical alternative to Sevelamer hydrochloride in which carbonate replaces chloride as the counterion. While the counterions differ from the two salts the polymer itself, the active moiety in phosphate binding, is the same.

Pharmacology: Pharmacodynamics: Patients with chronic kidney disease retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcifications. 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. An increase in parathyroid hormone (PTH) level is characteristics of patients with chronic kidney disease. Increased level of PTH can lead to osteitis fibrosa. A decrease in serum phosphorus may decrease serum PTH levels.
Treatment of hyperphosphatemia includes reduction of 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 decrease serum phosphorus concentration in patients with chronic kidney disease who are on hemodialysis. In vitro studies have shown that the capsule and tablet formulations bind phosphate to a similar extent.
Sevelamer Carbonate treatment also results in a lowering of low-density lipoprotein (LDL) and total serum cholesterol levels.
Mode of Action/Pharmacodynamic Characteristics Mechanism of action: Sevelamer Carbonate contains Sevelamer hydrochloride, a non-absorbed phosphate binding poly (allylamine hydrochloride) polymer, free of metal and calcium. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a partially protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the dietary tract, Sevelamer hydrochloride lowers the phosphate concentration in the serum. In clinical trials, Sevelamer hydrochloride has been shown to be effective in reducing serum phosphorus in patients receiving hemodialysis or peritoneal dialysis.
Sevelamer hydrochloride decreases the incidence of hypercalcemic episodes as compared to patients using calcium based phosphate binders alone. The effects on phosphate and calcium were proven to be maintained throughout a study with one year follow-up.
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. In clinical trials, both the mean total and LDL cholesterol is declined by 15 - 31%. This effect is observed after 2 weeks and is maintained with long-term treatment. Triglycerides, HDL cholesterol and albumin did not change.
In the clinical studies in hemodialysis patients, Sevelamer hydrochloride alone did not have a consistent and clinically significant effect on serum intact parathyroid hormone (iPTH). In patients with secondary hyperparathyroidism, Sevelamer Carbonate should be used within the context of a multiple therapeutic approach, which could include calcium supplements, and 1, 25-dihydroxyvitamin D3 or one of its analogues to lower the intact parathyroid hormone (iPTH) levels.

Sevelamer carbonate is indicated for the control of serum phosphorus in patient with chronic kidney disease (CKD) on dialysis. It is also indicated for the control of hyperphosphatemia in adult patients receiving hemodialysis or peritoneal dialysis. It is also approved for adult CKD patients not on dialysis with serum phosphorus > 1.78 mmol/L (5.5 mg/dL).

General: Adults and Elderly (>65 years): Patient Not Taking a Phosphorus Binder: The recommended starting dose for patients not taking a phosphate binder is 800 to 1600 mg, which can be administered as one to two Sevelamer carbonate 800 mg tablets with each meal based on serum phosphorus level. (See Table 1.)

Click on icon to see table/diagram/image

Patients Switching From a Calcium Based Binder: When patients are converting from a calcium based phosphate binder, Sevelamer hydrochloride should be given in equivalent doses on a mg for mg weight basis compared to the patient's previous calcium based phosphate binder. Table 2 gives recommended starting doses of Sevelamer Carbonate based on a patient's current calcium acetate dose. (See Table 2.)

Click on icon to see table/diagram/image

Dose Titration for All Patients Taking Sevelamer Carbonate: Serum phosphorous levels should be closely monitored and the dose of Sevelamer Carbonate accordingly with the goal of lowering serum phosphorus to 1.78 mmol/L (5.5 mg/dL) or less. Serum phosphorus should be tested every 2 to 3 weeks until a stable phosphorus level is reached, and on a regular basis thereafter.
Special Populations: Pediatric patients: The safety and efficacy of Sevelamer Carbonate has not been established in patients below the age of 18 years.
Elderly Patients: Same as adults.
Administration: Route of administration is oral.
Sevelamer Carbonate 800 mg tablets can be taken three times per day with meals at a dosage based on individual patient requirements to control phosphate levels.
Tablets should be swallowed intact and should not be crushed, chewed, or broken into pieces prior to administration.

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.

Sevelamer Carbonate is contraindicated in patients with hypophosphatemia or bowel obstruction.
Sevelamer Carbonate is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

The safety and efficacy of Sevelamer Carbonate in patients with dysphagia, swallowing disorders, severe gastrointestinal motility disorders including severe constipation or major gastrointestinal tract surgery have not been established. Consequently, caution should be exercised when Sevelamer Carbonate is used in patients with these disorders. Sevelamer Carbonate treatment should be reevaluated in patients who develop severe constipation or other severe gastrointestinal symptoms.
Uncommon case reports of difficulty swallowing the tablet have been report. Many of these cases involved patients with contributing co-morbid conditions affecting the ability to swallow including disorders of oroesophageal abnormalities. Caution should be exercised when the tablets are used in these patients. Consider using powder for oral suspension in patients with a history of difficulty swallowing.
Patients with CKD may develop low vitamin A, D, E and K levels, depending on dietary intake and the severity of their disease. Treatment with Sevelamer in preclinical studies, approximately at the equivalent of 6-10 times the maximum clinical trial dose, has been shown to reduce the absorption of vitamins D, E and K folic acid. Therefore, in patients not taking supplemental vitamins but on Sevelamer, serum vitamin A, D, and E levels and vitamin K status should be assessed regularly.

Pregnancy: The safety of Sevelamer Carbonate has not been established in pregnant or lactating women. Sevelamer Carbonate should only be given to pregnant or lactating women if clearly needed and after careful risk/benefit analysis has been conducted for both the mother and fetus or infant.
There have been no adequate well controlled studies in women undergoing labor and delivery.
Lactation: There have been not studies of the excretion of Sevelamer in human milk, but since Sevelamer is not absorbed, excretion in breast milk is not expected.

The most frequently occurring adverse reactions for the Sevelamer Carbonate tablets in a short term (8-week cross-over) study were: nausea (3%) and vomiting (3%). Most frequently occurring treatment related adverse events for Sevelamer Carbonate powder in a short term (4-week cross-over) study were: nausea (7%), constipation (3%) and vomiting (3%). In long-term studies with Sevelamer hydrochloride, which contains the same active moiety as Sevelamer Carbonate, the most common adverse events included: vomiting (22%), nausea (20%), diarrhea (19%), dyspepsia (16%), abdominal pain (9%), flatulence (8%) and constipation (8%).
Adverse events possibly related to Sevelamer hydrochloride included dyspepsia (12.4%), diarrhea (5.2%), nausea (5.2%), constipation (4.1%), pruritus (4.1%), abdominal distension (3.1%), vomiting (3.1%), fatigue (3.1 %), and anorexia (3.1 %).
In a double-blind, placebo-controlled dose titration with a treatment duration of 8 weeks, the adverse events experienced by the patients in the Sevelamer Carbonate and placebo groups were similar. The most frequently reported treatment-related events were gastrointestinal dis-orders. Adverse reactions among those treated with Sevelamer Carbonate Included: constipation (7.4%), abdominal distension (4.4 %), and abdominal discomfort (3.0%).
During post-marketing experience, the following adverse events have been reported in patients receiving Sevelamer Carbonate although no direct relationship to Sevelamer Carbonate could be established: hypersensitivity, pruritus, rash, abdominal pain and uncommon cases of ileus, intestinal obstruction and intestinal perforation.
Sevelamer Carbonate has also been studied in patients with CKD not on dialysis.
Adverse reactions among those treated with Sevelamer Carbonate Included: constipation (7.4.%), abdominal distension (4.4 %), and abdominal discomfort (3.0%).
During post-marketing experience, the following adverse events have been reported in patients receiving Sevelamer Carbonate although no direct relationship to Sevelamer Carbonate could be established: hypersensitivity, pruritus, rash, abdominal pain and uncommon cases of ileus, intestinal obstruction and intestinal perforation.
Sevelamer Carbonate has also been studied in patients with CKD not on dialysis.

Drug/Drug: Interaction studies have not been conducted in patients on dialysis.
Sevelamer Carbonate had no effect on the bioavailability of a single-dose of digoxin, warfarin, enalapril, metoprolol or iron. However, the bioavailability of ciprofloxacin was decreased by approximately 50% when co-administered with Sevelamer Carbonate in a single dose study. Consequently, Sevelamer Carbonate should not be taken simultaneously with ciprofloxacin.
During postmarketing experience, reduced concentrations of cyclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant patients when co-administered with Sevelamer hydrochloride without any clinical consequences for example, graft rejection. The possibility of an interaction cannot be excluded and close monitoring of blood concentrations of cyclosporin, mycophenolate mofetil and tacrolimus should be considered during the use of any of these agents in combination with Sevelamer and after its withdrawal. During post-marketing experience, very rare cases of increased TSH levels have been reported in patients co-administered Sevelamer Carbonate and levothyroxine. Closer monitoring of TSH levels is therefore recommended in patients receiving both medications.
During postmarketing experience, very rare cases of increased phosphate levels have been reported in patients taking proton pump inhibitors co-administered with Sevelamer hydrochloride.
Food: In all clinical studies patients were instructed to take Sevelamer with meals.

Store at temperatures not exceeding 30°C.
Keep away from direct heat and sunlight exposure.

Antidotes & Detoxifying Agents

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

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