Sevelamer Carbonate (Page 2 of 5)


6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

There are limited clinical trial data on the safety of sevelamer carbonate. However, because it contains the same active ingredient as the hydrochloride salt, the adverse event profiles of the two salts are expected to be similar. In a cross-over study in hemodialysis patients with treatment durations of eight weeks each and no washout, and another cross-over study in hemodialysis patients with treatment durations of four weeks each and no washout between treatment periods, the adverse reactions on sevelamer carbonate powder were similar to those reported for sevelamer hydrochloride.

In a parallel design study of sevelamer hydrochloride with treatment duration of 52 weeks, adverse reactions reported for sevelamer hydrochloride (n = 99) were similar to those reported for the active-comparator group (n = 101). Overall adverse reactions among those treated with sevelamer hydrochloride occurring in > 5% of patients included: vomiting (22%), nausea (20%), diarrhea (19%), dyspepsia (16%), abdominal pain (9%), flatulence (8%), and constipation (8%). A total of 27 patients treated with sevelamer and 10 patients treated with comparator withdrew from the study due to adverse reactions.

Based on studies of 8 to 52 weeks, the most common reason for withdrawal from sevelamer hydrochloride was gastrointestinal adverse reactions (3% to 16%).

In 143 peritoneal dialysis patients studied for 12 weeks using sevelamer hydrochloride, most common adverse reactions were similar to adverse reactions observed in hemodialysis patients. The most frequently occurring treatment emergent serious adverse reaction was peritonitis (8 reactions in 8 patients [8%] in the sevelamer group and 2 reactions in 2 patients [4%] on active control). Thirteen patients (14%) in the sevelamer group and 9 patients (20%) in the active-control group discontinued, mostly for gastrointestinal adverse reactions.

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post-approval use of sevelamer hydrochloride or sevelamer carbonate: hypersensitivity, pruritus, rash, abdominal pain, bleeding gastrointestinal ulcers, colitis, ulceration, necrosis, fecal impaction, and uncommon cases of ileus, intestinal obstruction, and intestinal perforation. Appropriate medical management should be given to patients who develop constipation or have worsening of existing constipation to avoid severe complications.


There are no empirical data on avoiding drug interactions between sevelamer carbonate and most concomitant oral drugs. For oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy (e.g., cyclosporine, tacrolimus, levothyroxine), consider separation of the timing of the administration of the two drugs [see Clinical Pharmacology ( 12.3)] . The duration of separation depends upon the absorption characteristics of the medication concomitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate-release or an extended-release product. Where possible consider monitoring clinical responses and/or blood levels of concomitant drugs that have a narrow therapeutic range.

Table 5: Sevelamer Drug Interactions
Oral drugs for which sevelamer did not alter the pharmacokinetics when administered concomitantly
Oral drugs that have demonstrated interaction with sevelamer and are to be dosed separately from sevelamer carbonate


Mycophenolate mofetil

Dosing Recommendations
Take at least 2 hours before or 6 hours after sevelamer

Take at least 2 hours before sevelamer


8.1 Pregnancy

Risk Summary

Sevelamer carbonate is not absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug.

Clinical Considerations

Sevelamer carbonate may decrease serum levels of fat-soluble vitamins and folic acid in pregnant women [see Clinical Pharmacology ( 12.2)] . Consider supplementation.


Animal data

In pregnant rats given dietary doses of 0.5, 1.5, or 4.5 g/kg/day of sevelamer hydrochloride during organogenesis, reduced or irregular ossification of fetal bones, probably due to a reduced absorption of fat-soluble vitamin D, occurred in mid and high-dose groups (human equivalent doses approximately equal to 3 to 4 times the maximum clinical trial dose of 13 g). In pregnant rabbits given oral doses of 100, 500, or 1,000 mg/kg/day of sevelamer hydrochloride by gavage during organogenesis, an increase of early resorptions occurred in the high-dose group (human equivalent dose twice the maximum clinical trial dose).

8.2 Lactation

Risk Summary

Sevelamer carbonate is not absorbed systemically by the mother following oral administration, and breastfeeding is not expected to result in exposure of the child to sevelamer carbonate.

Clinical Considerations

Sevelamer carbonate may decrease serum levels of fat-soluble vitamins and folic acid in pregnant women [see Clinical Pharmacology ( 12.2)] . Consider supplementation.

8.4 Pediatric Use

The safety and efficacy of sevelamer carbonate in lowering serum phosphorus levels was studied in patients 6 years of age and older with CKD. In this study, sevelamer carbonate was apparently less effective in children with a low baseline serum phosphorus, which described children < 13 years of age and children not on dialysis. Given its mechanism of action, sevelamer carbonate is expected to be effective in lowering serum phosphorus levels in pediatric patients with CKD. Most adverse events that were reported as related, or possibly related, to sevelamer carbonate were gastrointestinal in nature. No new risks or safety signals were identified with the use of sevelamer carbonate in the trial.

Sevelamer carbonate has not been studied in pediatric patients below 6 years of age.

8.5 Geriatric Use

Clinical studies of sevelamer carbonate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.


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.


The active ingredient in sevelamer carbonate for oral suspension is sevelamer carbonate, a polymeric amine that binds phosphate and is meant for oral administration. It was developed as a pharmaceutical alternative to sevelamer hydrochloride. Sevelamer carbonate is an anion exchange resin, with the same polymeric structure as sevelamer hydrochloride, in which carbonate replaces chloride as the counterion. While the counterions differ for the two salts, the polymer itself, the active moiety involved in phosphate-binding, is the same.

Sevelamer carbonate is known chemically as poly(allylamine- co-N,N’-diallyl-1,3­diamino-2-hydroxypropane) carbonate salt. Sevelamer carbonate is hygroscopic, but insoluble in water and other solvents. The structure is represented in Figure 1.

Figure 1: Chemical Structure of Sevelamer Carbonate

Figure 1: Structure of Sevelamer Carbonate
(click image for full-size original)

a, b = number of primary amine groups a + b = 9

c = number of cross-linking groups c = 1

m = large number to indicate extended polymer network

Each packet of sevelamer carbonate powder contains 0.8 g or 2.4 g of sevelamer carbonate on an anhydrous basis. The inactive ingredients are lemon flavor, propylene glycol alginate, silicon dioxide, sodium chloride, and sucralose.

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