Sevelamer Carbonate

Registered South African indications:

• Control of hyperphosphataemia in patients receiving haemodialysis or peritoneal dialysis and adult chronic kidney disease (CKD) patients not on dialysis with serum phosphorus >1,78 mmol/l 

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypophosphataemia
• Bowel obstruction

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Patients with chronic kidney disease not on dialysis with serum phosphorus <1.78 mmol/l
• 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 surgery
• Constipation
• Pre-existing folate deficiency
• Peritoneal dialysis
• Fat-soluble vitamin deficiency
• Dysphagia/ Difficulty swallowing
  - Swallowing disorders
  - Oesophageal abnormalities
• Hyperparathyroidism
• Hypothyroidism
• Long-term chronic treatment (>1 year) 
• Pre-existing inflammatory gastrointestinal disorders 
• Galactose intolerance 
• Total lactase deficiency 
• Glucose-galactose malabsorption 

Forms avail. in SA and covered in this monograph: tab

Control of hyperphosphataemia in patients receiving haemodialysis or peritoneal dialysis
Control of hyperphosphataemia in patients with chronic kidney disease not on dialysis with serum phosphorus ≥1.78 mmol/l

• Oral (tab): Initial: 2.4-4.8g, dly, in 3 divided doses with meals, based on clinical needs and serum phosphorus level (see table below):

*Plus subsequent titrating as per instructions, see Additional Prescribing Points (Titration and Maintenance)

Sevelamer should be used within the context of a multiple therapeutic approach, which could include calcium supplement, 1,25-dihydroxy Vitamin Dor one of its analogues to control the development of renal bone disease

For patients previously on phosphate binders (sevelamer hydrochloride or calcium based), sevelamer should be given on a gram for gram basis with monitoring of serum phosphorus levels to ensure optimal daily doses 

Tablets should be swallowed intact and should not be crushed, chewed, or broken into pieces prior to administration 

Not established for use in children below 18 years 

Pregnancy

• Caution; not recommended
• There are no or limited amount of data from the use of sevelamer in pregnant women. Animal studies have shown some reproductive toxicity when sevelamer was administered to rats at high doses
• Sevelamer has also been shown to reduce the absorption of several vitamins including folic acid
• The potential risk to humans is unknown. Sevelamer 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

Breastfeeding

• Caution; not recommended
• 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 breastfeeding or to continue/ discontinue therapy with sevelamer should be made taking into account the benefit of breastfeeding to the child and the benefit of sevelamer therapy to the woman

Fertility

• There are no data from the effect of sevelamer on fertility in humans
• Studies in animals have shown that sevelamer did not impair fertility in male or female rats at exposures at a human equivalent dose 2 times the maximum clinical trial dose of 13g/day, based on a comparison of relative body surface area 

Renal Impairment

• Caution; no information available 

Hepatic Impairment

• Caution; no information available 

Elderly

• No dose adjustment recommended 

Porphyria Information

• Not porphyrinogenic (NP) 

Drugs in Sport

• Permitted - No warnings 

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Abdominal pain
  - Upper abdominal pain
• Diarrhoea
• Dyspepsia
• Flatulence
• Intestinal obstruction 
• Ileus/ subileus 
• Intestinal perforation 
• Gastrointestinal bleeding
• Ulceration
• Gastrointestinal necrosis
• Colitis

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity

• Ciprofloxacin
• Ciclosporin
• Mycophenolate mofetil
• Tacrolimus
• Levothyroxine
• Anti-arrhythmic agents
• Anti-seizure agents
• Proton pump inhibitors

• Serum electrolytes
• Parathyroid hormone levels
  - Intact parathyroid hormone
• Urinary electrolytes
• alkaline phosphatase
• Creatinine level
• Blood urea nitrogen
• Albumin

Specific cases may require

• Fat-soluble vitamin levels
• Folic acid

Additional observations

• Constipation

Titration and maintenance

• Serum phosphorus levels must be monitored and the dose of sevelamer carbonate titrated by 0.8g, three times per day (2.4 g/day) increments every 2-4 weeks until an acceptable serum phosphorus level is reached, with regular monitoring thereafter
• Patients taking sevelamer 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 6g per day

Coadministration with other medicinal products

• Sevelamer carbonate is not absorbed 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 sevelamer carbonate, or the physician should consider monitoring blood levels

Sevelamer carbonate is 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. In two randomised, cross over clinical studies, sevelamer carbonate, when administered three times per day has been shown to be therapeutically equivalent to sevelamer hydrochloride and therefore effective in controlling serum phosphorus in CKD patients on haemodialysis. 

Tablet 800mg

• Renvela (Sanofi Aventis) originator