Renvela

Mineral Binding Agents
Phosphate Absorption Inhibitors

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.[28104] [44734]

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.

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.

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

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

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

RenaGel, Renvela

Rx

Oral phosphate binder
Used for control of serum phosphorus in patients with chronic kidney disease on dialysis
Lowers serum phosphate concentrations without the risk hypercalcemia or aluminum toxicity

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.

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.

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.

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.

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.

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.

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.[44734]

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.

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.

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.

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.

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.

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

No dosage adjustment is needed; the drug is not systemically absorbed. Sevelamer is indicated for patients with chronic kidney disease on dialysis.

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.

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

13 g/day PO of sevelamer hydrochloride; 14 g/day PO of sevelamer carbonate.

13 g/day PO of sevelamer hydrochloride; 14 g/day PO of sevelamer carbonate.

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

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.

Safety and efficacy have not been established.

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

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]