Indications for use
control of hyperphosphatemia in adult patients on hemodialysis or peritoneal dialysis
control of hyperphosphatemia in chronic kidney disease in adult patients not on dialysis with a phosphorus concentration ≥ 1.78 mmol / l
in the context of a multiple therapeutic approach that may include calcium supplements, 1,25-dihydroxy vitamin D3 or one of its analogs to control the development of renal osteodystrophy.

List of information required before use
Contraindications

• hypersensitivity to the active substance or any of the excipients of the drug
• hypophosphatemia
• individuals with hereditary galactose intolerance, Lapp enzyme deficiency (LAPD)-lactase, glucose-galactose malabsorption
• intestinal obstruction
• concomitant use with ciprofloxacin
• children under 6 years of age

Necessary precautions for use
The safety and efficacy of sevelamer have not been established in adult patients with chronic kidney disease not on dialysis with serum phosphorus concentrations <1.78 mmol/l. Therefore, the drug is not recommended for use in such patients.
Other conditions
Sevelamer efficacy and safety studies have not been conducted in patients with the following conditions:
· Dysphagia
· Swallowing disorders
· Severe gastrointestinal motility disorders, including untreated or severe gastroparesis, gastric retention, and abnormal or irregular bowel movements
· Acute inflammatory bowel disease
· Major gastrointestinal surgery
Treatment of these patients with SEVELAMER should be initiated only after careful benefit/risk assessment. If therapy is initiated, patients with these disorders should be monitored. Treatment with SEVELAMER should be reconsidered in patients who develop severe constipation or other severe gastrointestinal symptoms.
Intestinal obstruction (complete and partial)
In very rare cases, intestinal obstruction (complete or partial) has been observed in patients during therapy with sevelamer hydrochloride (capsules/tablets), which contains the same active ingredient as sevelamer carbonate. Constipation may be a precursor symptom. In case of constipation during treatment with SEVELAMER, the patient should be closely monitored. In patients who develop severe constipation or other severe gastrointestinal disorders, therapy should be reconsidered.
Fat-soluble vitamins and folate deficiency
Depending on the diet and the severity of the disease, patients with chronic kidney disease may have decreased levels of fat-soluble vitamins A, D, E and K. It is possible that sevelamer is able to bind fat-soluble vitamins contained in the food they eat. In patients receiving sevelamer but not taking vitamin supplements, vitamin A, D, E, and K levels should be regularly assessed. Vitamin supplements should be given if needed. In patients with chronic kidney disease who are not receiving dialysis and who are taking vitamin D supplements (approximately 400 IU of native vitamin D daily), which may be included in a multivitamin preparation, it is recommended to separate the administration of sevelamer carbonate and vitamin D. In patients receiving peritoneal dialysis, it is recommended that fat-soluble vitamins and folate levels be additionally monitored, since vitamin A, D, E, and K levels were not measured in these patients in clinical studies.
Folate deficiency
There are currently insufficient data to exclude the possibility of folate deficiency during long-term sevelamer therapy. In patients who are not taking additional folate but are taking sevelamer, folate levels should be regularly assessed.
Hypocalcemia/hypercalcemia
Patients with chronic kidney disease may develop hypocalcemia or hypercalcemia. SEVELAMER does not contain calcium. Therefore, serum calcium levels should be monitored regularly and elemental calcium supplementation should be considered if necessary.
Metabolic acidosis
Patients with chronic kidney disease are predisposed to developing metabolic acidosis. Therefore, monitoring serum bicarbonate levels is recommended as part of good clinical practice.
Peritonitis
Patients undergoing dialysis treatment are at risk for dialysis-specific infections. Peritonitis is a known complication in patients undergoing peritoneal dialysis and in clinical studies in patients treated with sevelamer hydrochloride, the incidence of peritonitis was higher in the sevelamer group than in the control group. Patients undergoing peritoneal dialysis should be closely monitored to ensure proper aseptic technique is used and to promptly identify any signs or symptoms of peritonitis.
Difficulty Swallowing and Breathing
There have been rare reports of difficulty swallowing with sevelamer tablets. Many of these cases involved patients with underlying medical conditions, including swallowing disorders or esophageal problems. Swallowing ability should be closely monitored in patients with underlying medical conditions. Sevelamer carbonate powder should be considered for patients with a history of difficulty swallowing.
Hypothyroidism
Close monitoring of patients with hypothyroidism is recommended when sevelamer carbonate and levothyroxine are co-administered.
Hyperparathyroidism
Sevelamer is not indicated for the control of hyperparathyroidism. In patients with secondary hyperparathyroidism, sevelamer should be used as part of a combination therapy that may include calcium supplements, 1,25-dihydroxyvitamin D3 or one of its analogues to reduce intact parathyroid hormone (iPTH) levels.
Long-term treatment of chronic kidney disease
Clinical studies of one year duration have shown no cases of sevelamer accumulation. However, absorption or accumulation of sevelamer during long-term treatment (> 1 year) of chronic kidney disease cannot be absolutely excluded.
Inflammatory gastrointestinal disorders
Cases of serious inflammatory disorders of various parts of the gastrointestinal tract (including serious complications such as bleeding, perforation, ulceration, necrosis, colitis, colonic/cecal masses) associated with the presence of sevelamer crystals have been reported. Inflammatory disorders may resolve after discontinuation of sevelamer. Sevelamer treatment should be reconsidered in patients who develop symptoms of serious gastrointestinal disorders.
Lactose
SEVELAMER contains lactose. This drug is not recommended for use in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Interactions with other medicinal products
Interaction studies have not been performed
Dialysis
Interaction studies with other medicinal products have not been performed in patients receiving dialysis. Types of interactions with medicinal products that may affect the effect of the medicinal product
Ciprofloxacin
In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same active ingredient as sevelamer carbonate, was shown to reduce the bioavailability of ciprofloxacin by approximately 50% when co-administered with a single dose of sevelamer hydrochloride. Therefore, SEVELAMER should not be co-administered with ciprofloxacin.
Cyclosporin, mycophenolate mofetil and tacrolimus in transplant patients
In transplant patients, co-administration of sevelamer hydrochloride was found to reduce the levels of cyclosporin, mycophenolate mofetil and tacrolimus without any clinical consequences (e.g., graft rejection). The possibility of interaction cannot be excluded, therefore, careful monitoring of cyclosporine, mycophenolate mofetil and tacrolimus blood concentrations is necessary during the use of this combination and after stopping treatment.
Levothyroxine
Very rare cases of hypothyroidism have been reported in patients receiving sevelamer hydrochloride, which contains the same active substance as sevelamer carbonate, and levothyroxine. Therefore, careful monitoring of TSH levels is recommended in patients receiving SEVELAMER concomitantly with levothyroxine.
Antiarrhythmic and antiepileptic agents
Patients taking antiarrhythmic agents for the control of arrhythmia and antiepileptic agents for the control of epilepsy were excluded from clinical studies. Therefore, a possible reduction in absorption cannot be excluded. The antiarrhythmic drug should be taken at least one hour before or three hours after SEVELAMER, and blood monitoring may be considered.
Digoxin, warfarin, enalapril, or metoprolol
In a drug interaction study in healthy volunteers, sevelamer hydrochloride, which contains the same active substance as sevelamer carbonate, had no effect on the bioavailability of digoxin, warfarin, enalapril, or metoprolol.
Proton pump inhibitors
In postmarketing experience, patients taking proton pump inhibitors have been shown to have a higher risk of developing digoxin, warfarin, enalapril, or metoprolol pump with sevelamer carbonate, elevated phosphate levels have been observed in very rare cases. Caution should be exercised when prescribing PPIs to patients concomitantly taking SEVELAMER. Serum phosphate levels should be monitored and the SEVELAMER dosage adjusted accordingly.
Bioavailability
Sevelamer carbonate is not absorbed from the gastrointestinal tract and may affect the bioavailability of other medicinal products. When taking any medicinal product for which decreased bioavailability may have clinical significance for efficacy and safety, it should be taken one hour before or three hours after SEVELAMER, or the physician should consider monitoring its blood levels.
Special warnings
Pediatric use
The safety and efficacy of SEVELAMER in children under 6 years of age and in children with a body surface area of less than 0.75 m2 have not been established. No data are available.
The safety and efficacy of SEVELAMER in children over 6 years of age or in children with a body surface area > 0.75 m2 have been established.
For pediatric patients, the oral suspension is prescribed, since tablets are not suitable for this group of patients.
During pregnancy or lactation
There are no or insufficient data on the use of sevelamer in pregnant women.
SEVELAMER should be prescribed to pregnant women only if clearly needed and only after careful assessment of the risk/benefit ratio for both the mother and the fetus.
There are no data on the excretion of sevelamer/metabolites in breast milk. Since sevelamer is a non-absorbable substance, this indicates a low probability of its excretion in breast milk. A decision on whether to discontinue/continue breastfeeding or to discontinue/continue SEVELAMER therapy should be made taking into account the benefit of breastfeeding for the child and the benefit of SEVELAMER therapy for the mother.
Fertility
There is no data on the effect of sevelamer on human reproductive function.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
SEVELAMER has no or little effect on the ability to drive vehicles and potentially dangerous mechanisms.

Recommended use
Dosage regimen
Starter dose
The recommended starting dose of SEVELAMER is 2.4 g or 4.8 g per day, depending on the clinical need and the level of phosphorus in the blood serum. SEVELAMER should be taken 3 times a day with meals.

1.78 - 2.42 mmol/L (5.5 - 7.5 mg/dL)
2.4 g* (1 tablet 3 times daily)
> 2.42 mmol/L (> 7.5 mg/dL)
4.8 g* (2 tablets 3 times daily)
* plus further titration, see Titration and maintenance dose section
For patients previously treated with phosphate binders (sevelamer hydrochloride or calcium-based preparations), SEVELAMER should be administered on a gram-for-gram basis with monitoring of serum phosphorus levels to ensure optimal daily doses.
Titration and maintenance dose
Serum phosphorus levels should be monitored. The dose of SEVELAMER titrated to 0.8 g three times daily (2.4 g daily) should be increased every 2-4 weeks until an acceptable serum phosphorus level is achieved, with regular monitoring thereafter. The dose is adjusted based on the serum phosphorus concentration.
Patients taking SEVELAMER should adhere to their prescribed diet.
Special patient groups
Children
The safety and efficacy of SEVELAMER has been established in children over 6 years of age or in children with a body surface area > 0.75 m2.
For pediatric patients, the oral suspension is prescribed since tablets are not suitable for this patient group.
Elderly patients
No dose adjustment is required for this patient group.
Patients with hepatic impairment
No studies have been conducted in this patient group.
Method and route of administration
For oral use.
Tablets should be swallowed whole and should not be crushed, chewed or broken into pieces before administration. SEVELAMER should be taken with food and should not be taken on an empty stomach.
Duration of treatment
Treatment should be continuous, based on the need to monitor serum phosphorus levels.
The daily dose is expected to be approximately 6 g per day on average.
Measures to be taken in case of overdose
Sevelamer hydrochloride, which contains the same active ingredient as sevelamer carbonate, has been administered to healthy volunteers at a dose of 14 g per day for 8 days without adverse effects. In patients with chronic kidney disease, a maximum average daily dose of 14.4 g of sevelamer carbonate in a single daily dose has been studied.
Symptoms observed in case of overdose are similar to the adverse reactions listed in the Description of adverse reactions section, including mainly constipation and other known gastrointestinal disorders.
Appropriate symptomatic treatment should be given.
Recommendations for seeking advice from a health care professional to clarify the method of using the drug
If you have questions about the use of the drug, consult your doctor.

Description of adverse reactions that occur with standard use of the drug and measures to be taken in this case
Like all drugs, the drug can cause adverse reactions, but not everyone gets them. The frequency of adverse events is determined according to the following criteria: very common (≥ 1/10), common (≥1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), unknown (cannot be estimated from the available data).

Very common

• nausea, vomiting, upper abdominal pain, constipation

Common

• diarrhea, dyspepsia, flatulence, abdominal pain

Very rare

• hypersensitivity

Unknown

• pruritus
• rash
• intestinal obstruction, complete/partial intestinal obstruction, intestinal perforation, gastrointestinal bleeding, gastrointestinal ulcers, gastrointestinal necrosis, colitis, intestinal masses
• crystallizing intestine.

Children

• Generally, the safety profile for children and adolescents (6-18 years) is identical to that for adults.

If adverse drug reactions occur, contact your health care provider, pharmacist, or directly to the Adverse Drug Reactions (Actions) Information Database, including reports of drug ineffectiveness
Republican State enterprise on the Right of Economic Management National Center for Expertise of Medicines and Medical Devices of the Committee for Medical and Pharmaceutical Control of the Ministry of Healthcare of the Republic of Kazakhstan
http://www.ndda.kz

Additional information
Composition of the medicinal product
One film-coated tablet contains
active substance - sevelamer carbonate 800 mg;
excipients: lactose monohydrate, colloidal silicon dioxide anhydrous, zinc stearate, purified water.
Shell: hypromellose (15 mPas), hypromellose (5 mPas), diacetylated monoglycerides.
Description of appearance, smell, taste
Oval-shaped tablets, film-coated from white to almost white, with the marking “SVL” on one side.

Dosage form and packaging
180 tablets in a HDPE jar with a screw cap with first-opening control. A label is glued to the jar.
1 jar together with instructions for use in Kazakh and Russian are placed in a cardboard pack.

Shelf life
3 years
Do not use after the expiration date.

Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children!