Sevelamer is an oral phosphate binder indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis. Sevelamer hydrochloride and sevelamer carbonate are both anion exchange resins with the same polymeric structure but differing counterions (hydrochloride vs. carbonate). Unlike the hydrochloride formulation, sevelamer carbonate is a buffered formulation that does not cause metabolic acidosis as a side effect. The phosphate lowering effects of sevelamer are comparable to calcium acetate or aluminum phosphate binders. Since it does not contain aluminum or calcium, sevelamer does not cause hypercalcemia or aluminum intoxication. In addition, sevelamer has beneficial cholesterol-lowering effects, which may be beneficial in patients with cardiovascular comorbidities.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer orally with meals.
-Consider separating the administration time of sevelamer and other medications where reduction in bioavailability has a clinically significant effect on its safety or efficacy (e.g., levothyroxine, tacrolimus). The duration of separation depends on the absorption characteristics of the medication concomitantly administered. Consider monitoring clinical responses and/or blood concentrations of concomitant drugs that have a narrow therapeutic range.
Oral Liquid Formulations
Sevelamer Carbonate Powder for Oral Suspension
-Place the powder in a cup and suspend in the appropriate amount of water:-For 0.4 g (half of a 0.8 g packet), use a minimum of 30 mL.
-For 0.8 g packet, use a minimum of 30 mL.
-For 2.4 g packet, use a minimum of 60 mL.
-Stir the mixture vigorously; it does not dissolve.
-Administer within 30 minutes of initial preparation. May mix again before administration if needed.
-As an alternative to water, the powder may be mixed into a small amount of food or beverage. Consume within 30 minutes as part of the meal. Do not heat the powder or add to heated food or liquids.
Other Administration Route(s)
Extemporaneous Compounding-Other
Pretreatment of Infant or Enteral Formula, Expressed Breast Milk, or Cow's Milk
NOTE: The addition of sevelamer to formula, breast milk, or cow's milk is not an FDA-approved method of administration. Published data are limited and full clinical implications are unknown.
-Add sevelamer 800 mg (tablet or powder) to up to 400 mL breast milk or up to 100 mL formula or cow's milk.
-Firmly stir or shake until visibly suspended. It may take 5 to 10 minutes for whole tablets to dissolve completely.
-Allow the resulting suspension sit for 10 minutes to allow for phosphate precipitation.
-Using a large syringe, carefully decant the liquid from the top of the container without disturbing the sevelamer hydrogel resin on the bottom of the container. The particulate contains the viscous hydrogel and bound phosphorous. Discard any liquid and particulate remaining in the container.
Gastrointestinal side effects are common with sevelamer use. Nausea (20%), vomiting (22%), dyspepsia (16%), diarrhea (19%), flatulence (8%), abdominal pain (9%), and constipation (8%) were reported in adult patients receiving sevelamer during clinical trials. Appropriately manage patients who develop or have worsening constipation to avoid severe complications. GI bleeding, GI ulceration, colitis, bowel necrosis, fecal impaction, GI obstruction, ileus, and GI perforation have been reported with sevelamer use. Inflammatory disorders may resolve upon drug discontinuation. Re-evaluate treatment in patients who develop severe GI symptoms. Dysphagia and esophageal tablet retention have been reported in association with use of sevelamer tablets, some requiring hospitalization and intervention. Consider using the liquid formulation in patients with a history of swallowing disorders.
In patients receiving peritoneal dialysis, peritonitis (infection) occurred in 8% of patients in the sevelamer group compared to 4% of patients in the control group. Use appropriate aseptic technique in this population. Monitor patients closely for prompt recognition and management of signs and symptoms associated with peritonitis.
Hypersensitivity reactions including rash and pruritus have been reported during postmarketing surveillance with sevelamer.
Sevelamer hydrochloride has been associated with a worsening in metabolic acidosis, as indicated by a decrease in serum bicarbonate. With an average dose of 4.6 g/day of sevelamer hydrochloride, serum bicarbonate concentrations changed from a baseline of 20.2 mEq/L to 17.9 mEq/L at 24 months (p = 0.002); no significant changes were seen in patients taking calcium carbonate or aluminum hydroxide. In another study, both serum bicarbonate concentrations and pH decreased significantly after 2 years of sevelamer hydrochloride administration in a dose-dependent fashion; serum bicarbonate concentrations changed from 19.05 mEq/L to 17.61 mEq/L and pH changed from 7.326 to 7.298. Changes in serum bicarbonate and pH were not noted in the group of patients taking calcium carbonate. Monitor serum bicarbonate and chloride concentrations. Increases in serum potassium concentrations (hyperkalemia) have been noted in adult studies. The exact mechanism of this effect is unknown, but theories include acid loading with the binding of bicarbonate in the gut by sevelamer hydrochloride.
Monitor patients receiving sevelamer for vitamin D deficiency, vitamin E deficiency, vitamin K deficiency, and folate deficiency. In preclinical animal studies, sevelamer hydrochloride reduced vitamins D, E, and K (coagulation parameters) and folic acid concentrations at doses of 6 to 10 times the recommended human dose. In short-term clinical trials, reduction in serum vitamin levels did not occur. However, 25-hydroxyvitamin D (normal range: 10 to 55 ng/mL) decreased from 39 ng/mL to 34 ng/mL in a one-year clinical trial of sevelamer hydrochloride treatment. Approximately 75% patients in clinical trials received vitamin supplements, which is typical of patients on dialysis.
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, some requiring hospitalization and intervention, have been reported with the use of the tablet formulation. Consider using the sevelamer suspension in patients with a history of swallowing disorders.
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.
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.
For the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis:
Oral dosage (sevelamer hydrochloride):
Adults with a serum phosphorus of 5.6 to 7.4 mg/dL not taking a phosphate binder: 800 mg PO 3 times daily with meals, initially. Titrate by 800 mg/dose every 2 weeks as needed to achieve a target serum phosphorus concentration of 3.5 to 5.5 mg/dL. The average dose in clinical trials was 2,400 mg PO 3 times daily. Max: 13 g/day.
Adults with a serum phosphorus of 7.5 mg/dL or more not taking a phosphate binder: 1,600 mg PO 3 times daily with meals, initially. Titrate by 800 mg/dose every 2 weeks as needed to achieve a target serum phosphorus concentration of 3.5 to 5.5 mg/dL. The average dose in clinical trials was 2,400 mg PO 3 times daily. Max: 13 g/day.
Adults being switched from calcium acetate to sevelamer hydrochloride: 800 mg PO 3 times daily with meals for those previously taking calcium acetate 667 mg/meal; 1,600 mg PO 3 times daily for those taking calcium acetate 1,334 mg/meal; or 2,400 mg PO 3 times daily for those taking calcium acetate 2,001 mg/meal. Titrate by 800 mg/dose every 2 weeks as needed to achieve a target serum phosphorus concentration of 3.5 to 5.5 mg/dL. The average dose in clinical trials was 2,400 mg PO 3 times daily. Max: 13 g/day.
Children* and Adolescents*: Limited data available. An initial dose of 400 to 800 mg PO 3 times daily with meals, titrated every 2 to 4 weeks as needed to achieve target serum phosphorus concentrations has been used. An initial dose of 800 mg PO 3 times daily, which was equivalent to a mean dose of 121 mg/kg/day (4.5 g/day), was used in a pilot study in patients (n = 17; age: 2 to 17 years) with serum phosphorus concentrations less than 7.5 mg/dL at study initiation. The dose was titrated by 1,200 mg/day (400 mg/dose 3 times daily) every month as needed to achieve target serum concentrations. Final mean dose was 163 mg/kg/day (6.7 g/day). Prior to the trial's 2-week washout period, patients were on a stable calcium-containing phosphate binder dose of 4 g/day. In an open-label crossover study (n = 18; mean age: 12.4 years, range: 0.9 to 17 years), sevelamer was administered as 400 mg tablets in a dose equivalent to the patient's previous phosphate binder dose and titrated every 2 weeks to achieve target serum concentrations. Final mean sevelamer dose was 140 mg/kg/day (5.38 g/day). Comparatively, calcium acetate at a mean final dose of 4.28 g/day provided similar serum phosphorus concentrations.
Oral dosage (sevelamer carbonate):
NOTE: Patients may be switched from sevelamer hydrochloride to sevelamer carbonate using the same dose in g/meal PO. Adust dose based on serum phosphorus concentration.
Adults with a serum phosphorus of 5.6 to 7.4 mg/dL not taking a phosphate binder: 800 mg PO 3 times daily with meals, initially. Titrate by 800 mg/dose every 2 weeks as needed to achieve target phosphorus concentrations. The average dose in clinical trials was 2,400 mg PO 3 times daily. Max: 14 g/day.
Adults with a serum phosphorus of 7.5 mg/dL or more not taking a phosphate binder: 1,600 mg PO 3 times daily with meals, initially. Titrate by 800 mg/dose every 2 weeks as needed to achieve target serum phosphorus concentrations. The average dose in clinical trials was 2,400 mg PO 3 times daily. Max: 14 g/day.
Adults being switched from calcium acetate to sevelamer carbonate: 800 mg PO 3 times daily with meals for those previously taking calcium acetate 667 mg/meal; 1,600 mg PO 3 times daily for those taking calcium acetate 1,334 mg/meal; or 2,400 mg PO 3 times daily for those taking calcium acetate 2,001 mg/meal. Titrate by 800 mg/dose every 2 weeks as needed to achieve target serum phosphorus concentrations. The average dose in clinical trials was 2,400 mg PO 3 times daily. Max: 14 g/day.
Children and Adolescents 6 to 17 years with BSA of 1.2 m2 or more not taking a phosphate binder: 1,600 mg PO 3 times daily with meals, initially. Titrate by 800 mg/dose every 2 weeks as needed to achieve target serum phosphorus concentrations. Max: 14 g/day.
Children and Adolescents 6 to 17 years with BSA of 0.75 to 1.1 m2 not taking a phosphate binder: 800 mg PO 3 times daily with meals, initially. Titrate by 400 mg/dose every 2 weeks as needed to achieve target serum phosphorus concentrations. Max: 14 g/day.
Children and Adolescents 6 to 17 years being switched from calcium acetate to sevelamer carbonate: 800 mg PO 3 times daily with meals for those previously taking calcium acetate 667 mg/meal; 1,600 mg PO 3 times daily for those taking calcium acetate 1,334 mg/meal; or 2,400 mg PO 3 times daily for those taking calcium acetate 2,001 mg/meal. Titrate by 800 mg/dose every 2 weeks as needed to achieve target serum phosphorus concentrations. Max: 14 g/day.
-for the reduction of bioavailable phosphorus content in infant or enteral formula, expressed breast milk, or cow's milk*:
Extracorporeal dosage (pretreatment of infant or enteral formula, expressed breast milk, or cow's milk)*:
Neonates, Infants, and Children: Limited data available. Add 800 mg (tablet or powder) to up to 400 mL breast milk or up to 100 mL infant or enteral formula or cow's milk. Allow the suspension to sit for 10 minutes. Decant the liquid for feeding, leaving the precipitate at the bottom. Do not consume the precipitate; it contains the bound phosphorus. Using the aforementioned technique, phosphate concentrations decreased 42% in semi-skimmed cow's milk, 48% in enteral formula, 68% in infant formula, and more than 85% in breast milk.
Maximum Dosage Limits:
-Adults
13 g/day PO of sevelamer hydrochloride; 14 g/day PO of sevelamer carbonate.
-Geriatric
13 g/day PO of sevelamer hydrochloride; 14 g/day PO of sevelamer carbonate.
-Adolescents
14 g/day PO of sevelamer carbonate; safety and efficacy have not been established for sevelamer hydrochloride.
-Children
6 to 12 years: 14 g/day PO of sevelamer carbonate; safety and efficacy have not been established for sevelamer hydrochloride.
1 to 5 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed; the drug is not systemically absorbed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed; the drug is not systemically absorbed. Sevelamer is indicated for patients with chronic kidney disease on dialysis.
*non-FDA-approved indication
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.
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.
Sevelamer binds dietary phosphate within the gastrointestinal tract. Amine groups in the sevelamer molecule interact with phosphate molecules in the gut through ionic and hydrogen bonding. This decreases phosphate absorption, thereby lowering phosphate concentrations in the serum.
Sevelamer is administered orally. It is not systemically absorbed.
Affected cytochrome P450 isoenzymes and drug transporters: none