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The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of tolvaptan (Jinarc, Otuska) to slow progression of cyst developmen"...
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug can not be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
There are limited data on the safety of Renvela. However, based on the fact that it contains the same active ingredient as the hydrochloride salt, the adverse event profiles of the two salts should be similar. In a cross-over study in hemodialysis patients with treatment durations of eight weeks each and no washout the adverse reactions on sevelamer carbonate tablets were similar to those reported for sevelamer hydrochloride. In 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 8-52 weeks, the most common reason for withdrawal from sevelamer hydrochloride was gastrointestinal adverse reactions (3-16%).
In one hundred and forty-three peritoneal dialysis patients studied for 12 weeks using sevelamer hydrochloride, most 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. Patients on peritoneal dialysis should be closely monitored to ensure the reliable use of appropriate aseptic technique with the prompt recognition and management of any signs and symptoms associated with peritonitis.
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, which has the same active moiety as sevelamer carbonate: pruritus, rash, abdominal pain, 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.
Read the Renvela (sevelamer carbonate) Side Effects Center for a complete guide to possible side effects
Sevelamer carbonate has been studied in human drug-drug interaction studies with warfarin and digoxin. Sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, has been studied in human drug-drug interaction studies with ciprofloxacin, digoxin, warfarin, enalapril, metoprolol and iron.
In a study of 15 healthy subjects, a co-administered single dose of 2.8 grams of sevelamer hydrochloride decreased the bioavailability of ciprofloxacin by approximately 50%.
In 19 healthy subjects receiving 2.4 grams of sevelamer hydrochloride three times a day with meals for 2 days, sevelamer did not alter the pharmacokinetics of a single dose of digoxin.
In 18 healthy subjects receiving 9.6 grams of sevelamer carbonate once daily with a meal, sevelamer did not alter the pharmacokinetics of a single dose of digoxin.
In 14 healthy subjects receiving 2.4 g of sevelamer hydrochloride three times a day with meals for two days sevelamer did not alter the pharmacokinetics of a single dose of warfarin.
In 14 healthy subjects receiving 9.6 grams of sevelamer carbonate once daily with a meal, sevelamer did not alter the pharmacokinetics of a single dose of warfarin.
In 28 healthy subjects a single 2.4 gram dose of sevelamer hydrochloride did not alter the pharmacokinetics of a single dose of enalapril.
In 31 healthy subjects a single 2.4 gram dose of sevelamer hydrochloride did not alter the pharmacokinetics of a single dose of metoprolol.
In 23 healthy subjects, a single 2.8 gram dose of sevelamer hydrochloride did not alter the absorption of a single oral dose of iron as 200 mg exsiccated ferrous sulfate tablet.
Other Concomitant Drug Therapy
There are no empirical data on avoiding drug interactions between Renvela and most concomitant drugs. During postmarketing experience, very rare cases of increased thyroid stimulating hormone (TSH) levels have been reported in patients co-administered sevelamer hydrochloride and levothyroxine. Monitor TSH levels and signs of hypothyroidism in patients receiving both medications.
When administering an oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, there is no information that suggests a dosing regimen that would be universally appropriate for all drugs. One may, however, administer the drug one hour before or three hours after Renvela, and monitor blood levels of the drug. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials.
Read the Renvela Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 8/3/2011
This monograph has been modified to include the generic and brand name in many instances.
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