Sevelamer

Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant patients when co-administered with sevelamer hydrochloride without any clinical consequences (e.g. graft rejection). The possibility of an interaction cannot be excluded and a close monitoring of blood concentrations of ciclosporin, mycophenolate mofetil and tacrolimus should be considered during the use of combination and after its withdrawal.

During post-marketing experience, 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 to patients concomitantly treated with sevelamer. The phosphate serum level should be monitored and the sevelamer dosage adjusted consequently.

Patients taking anti-arrhythmic medicinal products for the control of arrhythmias and anti-seizure medicinal products for the control of seizure disorders were excluded from clinical trials. Therefore, possible reduction in absorption cannot be excluded. The anti-arrhythmic medical product should be taken at least one hour before or three hours after sevelamer, and blood monitoring can be considered.

In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, decreased the bioavailability of ciprofloxacin by approximately 50% when co-administered with sevelamer hydrochloride in a single dose study. Consequently, sevelamer carbonate should not be taken simultaneously with ciprofloxacin.

Very rare cases of hypothyroidism have been reported in patients co-administered with sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, and levothyroxine. Closer monitoring of thyroid stimulating hormone (TSH) levels is therefore recommended in patients receiving sevelamer carbonate and levothyroxine.

The safety and efficacy of sevelamer carbonate have not been established in patients with severe gastrointestinal motility disorders including untreated or severe gastroparesis, retention of gastric contents and abnormal or irregular bowel motion.

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

The safety and efficacy of sevelamer carbonate have not been established in patients with active inflammatory bowel disease. Treatment of these patients with sevelamer should only be initiated after careful benefit/risk assessment. If the therapy is initiated, patients suffering from these disorders should be monitored.

The safety and efficacy of sevelamer carbonate have not been established in patients with major gastrointestinal tract surgery. Treatment of these patients with sevelamer should only be initiated after careful benefit/risk assessment. If the therapy is initiated, patients suffering from these disorders should be monitored.

The safety and efficacy of sevelamer carbonate have not been established in patients with swallowing disorders. Treatment of these patients with sevelamer should only be initiated after careful benefit/risk assessment. If the therapy is initiated, patients suffering from these disorders should be monitored.

The safety and efficacy of sevelamer carbonate have not been established in patients with dysphagia. Treatment of these patients with sevelamer should only be initiated after careful benefit/risk assessment. If the therapy is initiated, patients suffering from these disorders should be monitored.

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 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.

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. 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 13 g/day, based on a comparison of relative BSA.

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

Summary of the safety profile

The most frequently occurring (≥5% of patients) 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

The safety of sevelamer (as either carbonate and hydrochloride salts) has been investigated in numerous clinical trials involving a total of 969 haemodialysis patients with treatment duration of 4 to 50 weeks (724 patients treated with sevelamer hydrochloride and 245 with sevelamer carbonate), 97 peritoneal dialysis patients with treatment duration of 12 weeks (all treated with sevelamer hydrochloride) and 128 patients with CKD not on dialysis with treatment duration of 8 to 12 weeks (79 patients treatment with sevelamer hydrochloride and 49 with sevelamer carbonate).

Adverse reactions that occurred during clinical trials or that were spontaneously reported from post-marketing experience are listed by frequency in the table below. The reporting rate is classified as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

^* post-marketing experience

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.