Sevelamer Hydrochloride - Renagel
Sevelamer Carbonate - Renvela
NOTE: Referenced from Lexi-Comp - View References below**
Dosing:
Note:The dosing of sevelamer carbonate and sevelamer hydrochloride are similar; when switching from one product to another, the same dose (on a mg per mg basis) should be utilized.
Control of serum phosphorous: Oral:
Patients not taking a phosphate binder: 800-1600 mg 3 times/day with meals; the initial dose may be based on serum phosphorous levels:
>1.78 mmol/L to <2.42 mmol/L: 800 mg 3 times/day
≥2.42 mmol/L to <2.90 mmol/L: 1200-1600 mg 3 times/day
≥2.90 mmol/L: 1600 mg 3 times/day
Maintenance dose adjustment based on serum phosphorous concentration (goal range of 1.13-1.78 mmol/L; maximum dose studied was equivalent to 13 g/day [sevelamer hydrochloride] or 14 g/day [sevelamer carbonate]):
>1.78 mmol/L: Increase by 400-800 mg per meal at 2-week intervals
1.13-1.78 mmol/L: Maintain current dose
<1.13 mmol/L: Decrease by 400-800 mg per meal
Dosage adjustment when switching between phosphate-binder products: 667 mg of calcium acetate is equivalent to ~800 mg sevelamer (carbonate or hydrochloride)
Conversion based on dose per meal:
Calcium acetate 667 mg: Convert to 800 mg Renagel® / Renvela®
Calcium acetate 1334 mg: Convert to 1600 mg Renagel® 800 mg/ Renvela® or 1200 mg Renagel® 400 mg
Calcium acetate 2001 mg: Convert to 2400 mg Renagel® 800 mg / Renvela® or 2000 mg Renagel® 400 mg
Use: Labeled Indications
Reduction or control of serum phosphorous in patients with chronic kidney disease on hemodialysis
Powder for oral suspension: Stir vigorously to suspend mixture just prior to drinking; powder does not dissolve. Drink within 30 minutes of preparing and resuspend just prior to drinking.
Tablets: Swallow whole; do not crush, chew, or break.
Dietary Considerations
Take with meals. Reduced levels of folic acid, and vitamins D, E, and K may occur; most hemodialysis patients in clinical trials received vitamin supplementation.
Storage
Store at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Reconstitution
Powder for oral suspension: Mix powder with water prior to administration. The 0.8 g packet should be mixed with 30 mL of water and the 2.4 g packet should be mixed with 60 mL of water (multiple packets may be mixed together using the appropriate amount of water).
Contraindications
Bowel obstruction
Warnings/Precautions
Disease-related concerns:
• Gastrointestinal disease: Use with caution in patients with gastrointestinal disorders including dysphagia, swallowing disorders, severe gastrointestinal motility disorders (including constipation), or major gastrointestinal surgery.
Concurrent drug therapy issues:
• Gastrointestinal binding: Sevelamer may bind to some drugs in the gastrointestinal tract and decrease their absorption. When changes in absorption of oral medications may have significant clinical consequences (such as antiarrhythmic and antiseizure medications), these medications should be taken at least 1 hour before or 3 hours after a dose of sevelamer.
• Vitamins: May cause reductions in vitamin D, E, K, or folic acid absorption.
Dosage form specific issues:
• Tablets: Should not be taken apart or chewed; broken or crushed tablets will rapidly expand in water/saliva and may be a choking hazard.
Adverse Reactions
>10%: Gastrointestinal: Vomiting (22%), nausea (20%), diarrhea (19%), dyspepsia (16%)
1% to 10%:
Endocrine & metabolic: Hypercalcemia (5% to 7%)
Gastrointestinal: Abdominal pain (9%), flatulence (8%), constipation (8%)
Miscellaneous: Peritonitis (peritoneal dialysis: 8%)
Postmarketing and/or case reports: Fecal impaction, ileus (rare), intestinal obstruction (rare), intestinal perforation (rare), pruritus, rash
Drug Interactions
Calcitriol: Sevelamer may decrease the serum concentration of Calcitriol. Risk C: Monitor therapy
Levothyroxine: Sevelamer may decrease the serum concentration of Levothyroxine. Management: Consider separating administration of sevelamer and levothyroxine by at least several hours whenever possible in order to decrease the risk of a significant interaction. Risk D: Consider therapy modification
Quinolone Antibiotics: Sevelamer may decrease the absorption of Quinolone Antibiotics. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: May cause reductions in vitamin D, E, K, or folic acid absorption. Management: Must be administered with meals. Consider vitamin supplementation.
Monitoring Parameters
Serum chemistries, including bicarbonate and chloride
Serum calcium and phosphorus: Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of CKD, and the use of treatments for CKD-mineral and bone disorders (KDIGO, 2009):
CKD stage 3: Every 6-12 months
CKD stage 4: Every 3-6 months
CKD stage 5 and 5D: Every 1-3 months
Periodic 24-hour urinary calcium and phosphorus; magnesium; alkaline phosphatase every 12 months or more frequently in the presence of elevated PTH; creatinine, BUN, albumin; intact parathyroid hormone (iPTH) every 3-12 months depending on CKD severity
Reference Range
Corrected total serum calcium (K/DOQI, 2003): CKD stages 3 and 4: 2.1-2.6 mmol/L; CKD stage 5: 2.1-2.37 mmol/L; KDIGO guidelines recommend maintaining normal ranges for all stages of CKD (3-5D) (KDIGO, 2009)
Phosphorus (K/DOQI, 2003):
CKD stages 3 and 4: 0.87-1.48 mmol/L (adults);
CKD stage 5 (including those treated with dialysis): 1.13-1.78 mmol/L (children >12 years and adults); 1.29-1.94 mmol/L (children 1-12 years)
KDIGO guidelines recommend maintaining normal ranges for CKD stages 3-5 and lowering elevated phosphorus levels toward the normal range for CKD stage 5D (KDIGO, 2009)
Patient Education
Take with meals. Do not break or chew tablets. You may experience headache, dizziness, nausea, vomiting, heartburn, diarrhea, itching, or mild neuromuscular pain or stiffness.
Dosage Forms
Powder for suspension, oral, as carbonate:
Renvela®: 0.8 g/packet (90s); 2.4 g/packet (90s) [contains propylene glycol; citrus-cream flavor]
Tablet, oral, as carbonate:
Renvela®: 800 mg
Tablet, oral, as hydrochloride:
Renagel®: 400 mg, 800 mg
Mechanism of Action
Sevelamer (a polymeric compound) binds phosphate within the intestinal lumen, limiting absorption and decreasing serum phosphate concentrations without altering calcium, aluminum, or bicarbonate concentrations.
Pharmacodynamics/Kinetics
Onset of action: Reduction in serum phosphorus has been demonstrated after 1-2 weeks (Burke, 1997; Chertow, 1997).
Absorption: Not systemically absorbed
Excretion: Feces
Dosing:
Note:The dosing of sevelamer carbonate and sevelamer hydrochloride are similar; when switching from one product to another, the same dose (on a mg per mg basis) should be utilized.
Control of serum phosphorous: Oral:
Patients not taking a phosphate binder: 800-1600 mg 3 times/day with meals; the initial dose may be based on serum phosphorous levels:
>1.78 mmol/L to <2.42 mmol/L: 800 mg 3 times/day
≥2.42 mmol/L to <2.90 mmol/L: 1200-1600 mg 3 times/day
≥2.90 mmol/L: 1600 mg 3 times/day
Maintenance dose adjustment based on serum phosphorous concentration (goal range of 1.13-1.78 mmol/L; maximum dose studied was equivalent to 13 g/day [sevelamer hydrochloride] or 14 g/day [sevelamer carbonate]):
>1.78 mmol/L: Increase by 400-800 mg per meal at 2-week intervals
1.13-1.78 mmol/L: Maintain current dose
<1.13 mmol/L: Decrease by 400-800 mg per meal
Dosage adjustment when switching between phosphate-binder products: 667 mg of calcium acetate is equivalent to ~800 mg sevelamer (carbonate or hydrochloride)
Conversion based on dose per meal:
Calcium acetate 667 mg: Convert to 800 mg Renagel® / Renvela®
Calcium acetate 1334 mg: Convert to 1600 mg Renagel® 800 mg/ Renvela® or 1200 mg Renagel® 400 mg
Calcium acetate 2001 mg: Convert to 2400 mg Renagel® 800 mg / Renvela® or 2000 mg Renagel® 400 mg
Use: Labeled Indications
Reduction or control of serum phosphorous in patients with chronic kidney disease on hemodialysis
Powder for oral suspension: Stir vigorously to suspend mixture just prior to drinking; powder does not dissolve. Drink within 30 minutes of preparing and resuspend just prior to drinking.
Tablets: Swallow whole; do not crush, chew, or break.
Dietary Considerations
Take with meals. Reduced levels of folic acid, and vitamins D, E, and K may occur; most hemodialysis patients in clinical trials received vitamin supplementation.
Storage
Store at controlled room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Reconstitution
Powder for oral suspension: Mix powder with water prior to administration. The 0.8 g packet should be mixed with 30 mL of water and the 2.4 g packet should be mixed with 60 mL of water (multiple packets may be mixed together using the appropriate amount of water).
Contraindications
Bowel obstruction
Warnings/Precautions
Disease-related concerns:
• Gastrointestinal disease: Use with caution in patients with gastrointestinal disorders including dysphagia, swallowing disorders, severe gastrointestinal motility disorders (including constipation), or major gastrointestinal surgery.
Concurrent drug therapy issues:
• Gastrointestinal binding: Sevelamer may bind to some drugs in the gastrointestinal tract and decrease their absorption. When changes in absorption of oral medications may have significant clinical consequences (such as antiarrhythmic and antiseizure medications), these medications should be taken at least 1 hour before or 3 hours after a dose of sevelamer.
• Vitamins: May cause reductions in vitamin D, E, K, or folic acid absorption.
Dosage form specific issues:
• Tablets: Should not be taken apart or chewed; broken or crushed tablets will rapidly expand in water/saliva and may be a choking hazard.
Adverse Reactions
>10%: Gastrointestinal: Vomiting (22%), nausea (20%), diarrhea (19%), dyspepsia (16%)
1% to 10%:
Endocrine & metabolic: Hypercalcemia (5% to 7%)
Gastrointestinal: Abdominal pain (9%), flatulence (8%), constipation (8%)
Miscellaneous: Peritonitis (peritoneal dialysis: 8%)
Postmarketing and/or case reports: Fecal impaction, ileus (rare), intestinal obstruction (rare), intestinal perforation (rare), pruritus, rash
Drug Interactions
Calcitriol: Sevelamer may decrease the serum concentration of Calcitriol. Risk C: Monitor therapy
Levothyroxine: Sevelamer may decrease the serum concentration of Levothyroxine. Management: Consider separating administration of sevelamer and levothyroxine by at least several hours whenever possible in order to decrease the risk of a significant interaction. Risk D: Consider therapy modification
Quinolone Antibiotics: Sevelamer may decrease the absorption of Quinolone Antibiotics. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: May cause reductions in vitamin D, E, K, or folic acid absorption. Management: Must be administered with meals. Consider vitamin supplementation.
Monitoring Parameters
Serum chemistries, including bicarbonate and chloride
Serum calcium and phosphorus: Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of CKD, and the use of treatments for CKD-mineral and bone disorders (KDIGO, 2009):
CKD stage 3: Every 6-12 months
CKD stage 4: Every 3-6 months
CKD stage 5 and 5D: Every 1-3 months
Periodic 24-hour urinary calcium and phosphorus; magnesium; alkaline phosphatase every 12 months or more frequently in the presence of elevated PTH; creatinine, BUN, albumin; intact parathyroid hormone (iPTH) every 3-12 months depending on CKD severity
Reference Range
Corrected total serum calcium (K/DOQI, 2003): CKD stages 3 and 4: 2.1-2.6 mmol/L; CKD stage 5: 2.1-2.37 mmol/L; KDIGO guidelines recommend maintaining normal ranges for all stages of CKD (3-5D) (KDIGO, 2009)
Phosphorus (K/DOQI, 2003):
CKD stages 3 and 4: 0.87-1.48 mmol/L (adults);
CKD stage 5 (including those treated with dialysis): 1.13-1.78 mmol/L (children >12 years and adults); 1.29-1.94 mmol/L (children 1-12 years)
KDIGO guidelines recommend maintaining normal ranges for CKD stages 3-5 and lowering elevated phosphorus levels toward the normal range for CKD stage 5D (KDIGO, 2009)
Patient Education
Take with meals. Do not break or chew tablets. You may experience headache, dizziness, nausea, vomiting, heartburn, diarrhea, itching, or mild neuromuscular pain or stiffness.
Dosage Forms
Powder for suspension, oral, as carbonate:
Renvela®: 0.8 g/packet (90s); 2.4 g/packet (90s) [contains propylene glycol; citrus-cream flavor]
Tablet, oral, as carbonate:
Renvela®: 800 mg
Tablet, oral, as hydrochloride:
Renagel®: 400 mg, 800 mg
Mechanism of Action
Sevelamer (a polymeric compound) binds phosphate within the intestinal lumen, limiting absorption and decreasing serum phosphate concentrations without altering calcium, aluminum, or bicarbonate concentrations.
Pharmacodynamics/Kinetics
Onset of action: Reduction in serum phosphorus has been demonstrated after 1-2 weeks (Burke, 1997; Chertow, 1997).
Absorption: Not systemically absorbed
Excretion: Feces
References
Burke SK, Slatopolsky EA, and Goldberg DI, "RenaGel, a Novel Calcium- and Aluminium-Free Phosphate Binder, Inhibits Phosphate Absorption in Normal Volunteers,"Nephrol Dial Transplant, 1997, 12(8):1640-4.[PubMed 9269642]
Chertow GM, Burke SK, Lazarus JM, et al, "Poly[allylamine Hydrochloride] (RenaGel): A Noncalcemic Phosphate Binder for the Treatment of Hyperphosphatemia in Chronic Renal Failure," Am J Kidney Dis, 1997, 29(1):66-71.[PubMed 9002531]
Delmez J, Block G, Robertson J, et al, “A Randomized, Double-Blind, Crossover Design Study of Sevelamer Hydrochloride and Sevelamer Carbonate in Patients on Hemodialysis,” Clin Nephrol, 2007, 68(6):386-91.[PubMed 18184521]
"K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease, Guideline 13. Treatment of Bone Disease in Chronic Kidney Disease." Available at http://www.kidney.org/professionals/KDOQI/guidelines_bone/index.htm
"K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease," 2002. Available at http://www.kidney.org/professionals/KDOQI/guidelines_ckd/toc.htm
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group, "KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)," Kidney Int Suppl, 2009, 76(S113):1-130.[PubMed 19644521]
Mahdavi H, Kuizon BD, Gales B, et al, “Sevelamer Hydrochloride: An Effective Phosphate Binder in Dialyzed Children,” Pediatr Nephrol, 2003, 18(12):1260-4.[PubMed 14586677]
Pieper AK, Haffner D, Hoppe B, et al, “A Randomized Crossover Trial Comparing Sevelamer With Calcium Acetate in Children With CKD,” Am J Kid Dis, 2006, 47(4):625-35.[PubMed 16564940]
Storms LE, Chicella MF, and Dice JE, “Sevelamer Therapy for Pediatric End-Stage Renal Disease,” Pharmacotherapy, 2006, 26(3):410-13.[PubMed 16503722]
Burke SK, Slatopolsky EA, and Goldberg DI, "RenaGel, a Novel Calcium- and Aluminium-Free Phosphate Binder, Inhibits Phosphate Absorption in Normal Volunteers,"Nephrol Dial Transplant, 1997, 12(8):1640-4.[PubMed 9269642]
Chertow GM, Burke SK, Lazarus JM, et al, "Poly[allylamine Hydrochloride] (RenaGel): A Noncalcemic Phosphate Binder for the Treatment of Hyperphosphatemia in Chronic Renal Failure," Am J Kidney Dis, 1997, 29(1):66-71.[PubMed 9002531]
Delmez J, Block G, Robertson J, et al, “A Randomized, Double-Blind, Crossover Design Study of Sevelamer Hydrochloride and Sevelamer Carbonate in Patients on Hemodialysis,” Clin Nephrol, 2007, 68(6):386-91.[PubMed 18184521]
"K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease, Guideline 13. Treatment of Bone Disease in Chronic Kidney Disease." Available at http://www.kidney.org/professionals/KDOQI/guidelines_bone/index.htm
"K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease," 2002. Available at http://www.kidney.org/professionals/KDOQI/guidelines_ckd/toc.htm
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group, "KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)," Kidney Int Suppl, 2009, 76(S113):1-130.[PubMed 19644521]
Mahdavi H, Kuizon BD, Gales B, et al, “Sevelamer Hydrochloride: An Effective Phosphate Binder in Dialyzed Children,” Pediatr Nephrol, 2003, 18(12):1260-4.[PubMed 14586677]
Pieper AK, Haffner D, Hoppe B, et al, “A Randomized Crossover Trial Comparing Sevelamer With Calcium Acetate in Children With CKD,” Am J Kid Dis, 2006, 47(4):625-35.[PubMed 16564940]
Storms LE, Chicella MF, and Dice JE, “Sevelamer Therapy for Pediatric End-Stage Renal Disease,” Pharmacotherapy, 2006, 26(3):410-13.[PubMed 16503722]