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  • CLASSES

    Mineral Binding Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Oral phosphate binder
    Used for control of serum phosphorus in patients with chronic kidney disease on dialysis
    Lowers serum phosphate without the risk of increasing serum calcium concentrations

    COMMON BRAND NAMES

    RenaGel, Renvela

    HOW SUPPLIED

    RenaGel/Renvela/Sevelamer Carbonate/Sevelamer Hydrochloride Oral Tab: 400mg, 800mg
    Renvela/Sevelamer Carbonate Oral Pwd F/Recon: 0.8g, 2.4g

    DOSAGE & INDICATIONS

    For the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis.
    Oral dosage (sevelamer hydrochloride tablets, i.e., Renagel)
    Adults not receiving phosphate binders with serum phosphorus of 5.6 to 7.4 mg/dL

    800 mg PO 3 times daily, initially. Adjust dose by 800 mg 3 times daily every 2 weeks based on serum phosphorus concentration with a goal serum phosphorus of 3.5 to 5.5 mg/dL or less. The average dose of sevelamer hydrochloride in clinical trials was 2,400 mg PO 3 times daily. The maximum average daily dose of sevelamer hydrochloride was 13 g/day.

    Adults not receiving phosphate binders with serum phosphorus of 7.5 mg/dL or more

    1,600 mg PO 3 times daily, initially. Adjust dose by 800 mg 3 times daily every 2 weeks based on serum phosphorus concentration with a goal serum phosphorus of 3.5 to 5.5 mg/dL or less. The average dose of sevelamer hydrochloride in clinical trials was 2,400 mg PO 3 times daily. The maximum average daily dose of sevelamer hydrochloride was 13 g/day.

    Adults being switched from calcium acetate to sevelamer hydrochloride

    800 mg/meal sevelamer hydrochloride for 667 mg/meal calcium acetate; 1,600 mg/meal sevelamer hydrochloride for 1,334 mg/meal calcium acetate; or 2,400 mg/meal sevelamer hydrochloride for 2,001 mg/meal calcium acetate. Adjust dose by 800 mg 3 times daily every 2 weeks based on serum phosphorus concentration with a goal serum phosphorus of 3.5 to 5.5 mg/dL or less. The average dose of sevelamer hydrochloride in clinical trials was 2,400 mg PO 3 times daily. The maximum average daily dose of sevelamer hydrochloride was 13 g/day.

    Oral dosage (sevelamer carbonate tablets and oral suspension packets, i.e., Renvela)

    NOTE: Patients may be switched from sevelamer hydrochloride (Renagel) to sevelamer carbonate (Renvela) using the same dose in g/meal PO. Adust dose based on serum phosphorus concentration.

    Adults not receiving phosphate binders with serum phosphorus of 5.6 to 7.4 mg/dL

    800 mg PO 3 times daily, initially. Adjust dose by 800 mg 3 times daily every 2 weeks based on serum phosphorus concentration to achieve target serum phosphorus concentration. The average dose of sevelamer carbonate in clinical trials was 2,400 mg PO 3 times daily. The maximum daily dose of sevelamer carbonate was 14 g/day.[44734]

    Adults not receiving phosphate binders with serum phosphorus of 7.5 mg/dL or more

    1,600 mg PO 3 times daily, initially. Adjust dose by 800 mg 3 times daily every 2 weeks based on serum phosphorus concentration to achieve target serum phosphorus concentration. The average dose of sevelamer carbonate in clinical trials was 2,400 mg PO 3 times daily. The maximum daily dose of sevelamer carbonate was 14 g/day.

    Adults being switched from calcium acetate to sevelamer carbonate

    800 mg/meal sevelamer carbonate for 667 mg/meal calcium acetate; 1,600 mg/meal sevelamer carbonate for 1,334 mg/meal calcium acetate; or 2,400 mg/meal sevelamer carbonate for 2,001 mg/meal calcium acetate. Adjust dose by 800 mg 3 times daily every 2 weeks based on serum phosphorus concentration to achieve target serum phosphorus concentration. The average dose of sevelamer carbonate in clinical trials was 2,400 mg PO 3 times daily. The maximum average daily dose of sevelamer carbonate was 14 g/day..

    Children and Adolescents 6 to 17 years with BSA of 1.2 m2 or more

    1,600 mg/meal or snack PO, initially. Adjust dose by 800 mg/dose every 2 weeks based on serum phosphorus concentration to achieve target serum phosphorus concentration.

    Children and Adolescents 6 to 17 years with BSA of 0.75 to 1.1 m2

    800 mg/meal or snack PO, initially. Adjust dose by 400 mg/dose every 2 weeks based on serum phosphorus concentration to achieve target serum phosphorus concentration.

    MAXIMUM DOSAGE

    Adults

    13 g/day PO of sevelamer hydrochloride (Renagel); 14 g/day PO of sevelamer carbonate (Renvela).

    Geriatric

    13 g/day PO of sevelamer hydrochloride (Renagel); 14 g/day PO of sevelamer carbonate (Renvela).

    Adolescents

    14 g/day PO of sevelamer carbonate (Renvela); safety and efficacy have not been established for sevelamer hydrochloride (Renagel).

    Children

    6 years and older: 14 g/day PO of sevelamer carbonate (Renvela); safety and efficacy have not been established for sevelamer hydrochloride (Renagel).
    Less than 6 years: Use not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed; the drug is not systemically absorbed.

    Renal Impairment

    No dosage adjustment is needed. Sevelamer is indicated in patients with renal impairment.
     
    Intermittent hemodialysis
    No dosage adjustment is needed; the drug is not systemically absorbed.

    ADMINISTRATION

    Oral Administration

    Available as sevelamer hydrochloride tablets (Renagel), sevelamer carbonate tablets (Renvela), and sevelamer carbonate powder for oral suspension (Renvela).
    Administer orally with meals.
    For a concomitant oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of sevelamer. The duration of separation depends upon the absorption characteristics of the medication concomitantly administered. Where possible, consider monitoring clinical responses and/or blood concentrations of concomitant drugs that have a narrow therapeutic range.[28104] [44734]

    Oral Liquid Formulations

    Preparation of sevelamer carbonate powder for oral suspension (0.8 or 2.4 g packets): Empty entire contents of packet into a cup and mix thoroughly with water. For the 0.8 g packet, suspend with 30 mL of water; for the 2.4 g packet, suspend with 60 mL of water. Stir the mixture vigorously; it does not dissolve. Administer suspension within 30 minutes of preparation; resuspend, if necessary, before administration. As an alternative to water, pre-mix the entire contents of the sachet into a small amount of food or beverage. Consume immediately (within 30 minutes) as part of the meal. Do not heat sevelamer carbonate powder or add to heated food or liquids.[44734]

    STORAGE

    RenaGel:
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Renvela:
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Sevelamer is contraindicated in patients with known hypersensitivity to sevelamer or to any of the excipients.

    Constipation, dysphagia, GI obstruction, surgery

    Sevelamer is contraindicated in patients with GI obstruction. Patients with dysphagia, swallowing disorders, severe GI motility disorders (including severe constipation), or major GI surgery were not included in sevelamer clinical trials. Cases of dysphagia and esophageal tablet retention have been reported in association with use of the tablet formulation of sevelamer, some requiring hospitalization and intervention. Consider using sevelamer suspension in patients with a history of swallowing disorders.[28104] [44734]

    Pregnancy

    The effect of sevelamer on the absorption of vitamins and other nutrients has not been studied in human pregnancy. Sevelamer is not absorbed systemically after oral administration, and maternal use is not expected to result in fetal exposure to the drug. Sevelamer may decrease serum concentrations of fat-soluble vitamins and folic acid in pregnant women; consider supplementation. In pregnant rats, sevelamer administration during organogenesis (adjusted exposure of less than 13 g) was associated with reduced or irregular ossification of fetal bones probably due to reduced absorption of vitamin D. In pregnant rabbits, sevelamer administration during organogenesis (adjusted exposure of 2 times the maximum daily dose of 13 g) was associated with an increased incidence of early resorption.[28104] [44734]

    Breast-feeding

    Sevelamer is not absorbed systemically by the mother after oral administration, and breast-feeding is not expected to result in exposure of the child to sevelamer. Sevelamer may decrease serum concentrations of fat-soluble vitamins and folic acid in breast-feeding women; consider supplementation.[28104] [44734]

    ADVERSE REACTIONS

    Severe

    GI bleeding / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    bowel necrosis / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    hyperkalemia / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 8.0-8.0
    colitis / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known
    vitamin K deficiency / Delayed / Incidence not known
    vitamin D deficiency / Delayed / Incidence not known
    folate deficiency / Delayed / Incidence not known

    Mild

    vomiting / Early / 22.0-22.0
    nausea / Early / 20.0-20.0
    diarrhea / Early / 19.0-19.0
    dyspepsia / Early / 16.0-16.0
    abdominal pain / Early / 9.0-9.0
    flatulence / Early / 8.0-8.0
    infection / Delayed / 8.0-8.0
    pruritus / Rapid / Incidence not known
    rash / Early / Incidence not known

    DRUG INTERACTIONS

    Ciprofloxacin: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after sevelamer. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. In a study of 15 healthy subjects, the bioavailability of ciprofloxacin was decreased by approximately 50% when coadministered with sevelamer.
    Clonazepam: (Major) When sevelamer is coadministered with oral drugs considered to have narrow therapeutic ranges (e.g., anticonvulsants), the potential for reduced drug absorption could result in clinical significance, with the potential for loss of efficacy. To minimize this interaction, patients should be advised to separate the administration of anticonvulsants by at least 1 hour before or 3 hours after sevelamer. In addition, patients should be monitored for changes in efficacy of the anticonvulsant when these drugs are coadministered.
    Cyclosporine: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of cyclosporine from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because cyclosporine has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after sevelamer. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and sevelamer together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Erdafitinib: (Major) Avoid coadministration of sevelamer with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sevelamer decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by sevelamer may interfere with the determination of this initial dose increase.
    Ethosuximide: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of ethosuximide from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because ethosuximide has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Gemifloxacin: (Major) Administer sevelamer at least 3 hours before or 2 hours after gemifloxacin. Gemifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
    Ibritumomab Tiuxetan: (Contraindicated) Pharmacologically, sevelamer decreases serum phosphate concentrations. Therefore, phosphate salts would be expected to counteract the pharmacological benefits of sevelamer. It would be illogical to administer phosphate or phosphorus salts to patients who require sevelamer.
    Levofloxacin: (Major) Administer sevelamer at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones.
    Levothyroxine: (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by 4 hours. Sevelamer appears to decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by 4 hours. Sevelamer appears to decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by 4 hours. Sevelamer appears to decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
    Liothyronine: (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by 4 hours. Sevelamer appears to decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
    Lithium: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of lithium from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because lithium has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after sevelamer. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
    Mycophenolate: (Major) Do not administer sevelamer simultaneously with mycophenolate mofetil. The mean mycophenolic acid Cmax was decreased by 36%, and the mean mycophenolic acid AUC(0-12h) was decreased by 26% when sevelamer and mycophenolate mofetil were coadministered in adult and pediatric patients. If sevelamer and mycophenolate are needed, administer sevelamer 2 hours after mycophenolate mofetil intake in order to minimize the impact on the absorption of mycophenolic acid.
    Norfloxacin: (Major) Administer sevelamer at least 2 hours before or 2 hours after norfloxacin. Norfloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
    Ofloxacin: (Major) Administer sevelamer at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations.
    Phenytoin: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of phenytoin from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because phenytoin has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Phosphorated Carbohydrate Solution: (Contraindicated) Pharmacologically, sevelamer decreases serum phosphate concentrations. Therefore, phosphate salts would be expected to counteract the pharmacological benefits of sevelamer. It would be illogical to administer phosphate or phosphorus salts to patients who require sevelamer.
    Phosphorus: (Contraindicated) Pharmacologically, sevelamer decreases serum phosphate concentrations. Therefore, phosphate salts would be expected to counteract the pharmacological benefits of sevelamer. It would be illogical to administer phosphate or phosphorus salts to patients who require sevelamer.
    Potassium Phosphate: (Contraindicated) Pharmacologically, sevelamer decreases serum phosphate concentrations. Therefore, phosphate salts would be expected to counteract the pharmacological benefits of sevelamer. It would be illogical to administer phosphate or phosphorus salts to patients who require sevelamer.
    Potassium Phosphate; Sodium Phosphate: (Contraindicated) Pharmacologically, sevelamer decreases serum phosphate concentrations. Therefore, phosphate salts would be expected to counteract the pharmacological benefits of sevelamer. It would be illogical to administer phosphate or phosphorus salts to patients who require sevelamer.
    Procainamide: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of procainamide from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because procainamide has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Tacrolimus: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of tacrolimus from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because tacrolimus has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Theophylline, Aminophylline: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of oral theophylline from sevelamer. According to the manufacturer of sevelamer, clinicians should consider separating the timing of administration of sevelamer and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. The duration of separation should be based on the absorption characteristics of the coadministered drug. Because theophylline; aminophylline has a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of sevelamer.
    Thyroid hormones: (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by 4 hours. Sevelamer appears to decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.

    PREGNANCY AND LACTATION

    Pregnancy

    The effect of sevelamer on the absorption of vitamins and other nutrients has not been studied in human pregnancy. Sevelamer is not absorbed systemically after oral administration, and maternal use is not expected to result in fetal exposure to the drug. Sevelamer may decrease serum concentrations of fat-soluble vitamins and folic acid in pregnant women; consider supplementation. In pregnant rats, sevelamer administration during organogenesis (adjusted exposure of less than 13 g) was associated with reduced or irregular ossification of fetal bones probably due to reduced absorption of vitamin D. In pregnant rabbits, sevelamer administration during organogenesis (adjusted exposure of 2 times the maximum daily dose of 13 g) was associated with an increased incidence of early resorption.[28104] [44734]

    Sevelamer is not absorbed systemically by the mother after oral administration, and breast-feeding is not expected to result in exposure of the child to sevelamer. Sevelamer may decrease serum concentrations of fat-soluble vitamins and folic acid in breast-feeding women; consider supplementation.[28104] [44734]

    MECHANISM OF ACTION

    Sevelamer binds dietary phosphate within the gastrointestinal tract. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the gastrointestinal tract and decreasing absorption, sevelamer carbonate lowers the phosphate concentration in the serum. When taken with meals, sevelamer lowers both serum phosphate and parathyroid hormone, but does not increase serum calcium. Sevelamer also lowers serum total and LDL cholesterol levels with no effect on HDL cholesterol or triglyceride levels in healthy volunteers and end-stage renal disease patients. During clinical trials, sevelamer hydrochloride decreased total and LDL cholesterol by 15% to 31%, with the effects evident approximately 2 weeks after sevelamer initiation.

    PHARMACOKINETICS

    Sevelamer is administered orally. A mass balance study using 14C-sevelamer hydrochloride in healthy volunteers showed that sevelamer is not absorbed systemically.