Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Renvela is not indicated in children below the age of 18 years.

The safety and efficacy of sevelamer carbonate have not been established in adult patients with chronic kidney disease not on dialysis with serum phosphorus < 1.78 mmol/l. Therefore it is currently not recommended for use in these patients.

The safety and efficacy of sevelamer carbonate 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 surgery
Treatment of these patients with Renvela should only be initiated after careful benefit/risk assessment. If the therapy is initiated, patients suffering from these disorders should be monitored.
Renvela treatment should be reevaluated in patients who develop severe constipation or other severe gastrointestinal symptoms.


Intestinal obstruction and ileus/subileus
In very rare cases, intestinal obstruction and ileus/subileus have been observed in patients during treatment with sevelamer hydrochloride (capsules/tablets), 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. The treatment should be re-evaluated in patients who develop severe constipation or other severe gastrointestinal symptoms.

Fat-soluble vitamins and folate deficiency
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 carbonate 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 carbonate. 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.
There is at present insufficient data to exclude the possibility of folate deficiency during long term sevelamer carbonate treatment. In patients not taking supplemental folic acid but on sevelamer, folate level should be assessed regularly.


Hypocalcaemia/hypercalcaemia
Patients with CKD may develop hypocalcaemia or hypercalcaemia. Sevelamer carbonate 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 acidosis
Patients with chronic kidney disease are predisposed to developing metabolic acidosis. As part of good clinical practice, monitoring of serum bicarbonate levels is therefore recommended.

Peritonitis
Patients 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 trial 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.

Swallowing and choking difficulties
Uncommon reports of difficulty swallowing the Renvela tablet have been reported. Many of these cases involved patients with co-morbid conditions including swallowing disorders or oesophageal abnormalities. Proper swallowing ability should be carefully monitored in patients with co-morbid conditions. The use of sevelamer carbonate powder in patients with a history of difficulty swallowing should be considered.

Hypothyroidism
Closer monitoring of patients with hypothyroidism co-administered with sevelamer carbonate and levothyroxine is recommended (see section 4.5).

Hyperparathyroidism
Sevelamer carbonate is not indicated for the control of hyperparathyroidism. In patients with secondary hyperparathyroidism sevelamer carbonate 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.

Inflammatory gastrointestinal disorders
Cases of serious inflammatory disorders of different parts of the gastrointestinal tract (including serious complications such as haemorrhage, perforation, ulceration, necrosis, colitis and colonic/caecal mass) associated with the presence of sevelamer crystals have been reported (see section 4.8). Inflammatory disorders may resolve upon sevelamer discontinuation. Sevelamer carbonate treatment should be re-evaluated in patients who develop severe gastrointestinal symptoms.

Excipients
This medicine contains less than 1 mmol sodium (23 mg) per tablet that is to say essentially ‘sodium- free’.

Effects on Driving

4.7   Effects on ability to drive and use machines

Sevelamer has no or negligible influence on the ability to drive and use machines.