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Pronunciation
(se VEL a mer)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Reduction or control of serum phosphorous in patients with chronic kidney disease on hemodialysis
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal studies have shown reduced or irregular ossification of fetal bones. Because sevelamer may cause a reduction in the absorption of some vitamins, it should be used with caution in pregnant women.
Lactation
Excretion in breast milk unknown/use caution (not absorbed systemically but may alter maternal nutrition)
Breast-Feeding Considerations
It is not known whether sevelamer is excreted in human milk. Because sevelamer may cause a reduction in the absorption of some vitamins, it should be used with caution in nursing women.
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
Metabolism/Transport Effects
None known.
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
Mycophenolate: Sevelamer may decrease the serum concentration of Mycophenolate. 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.
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.
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
Absorption: Not systemically absorbed
Excretion: Feces
Dosage
Oral: 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.
Children (unlabeled use): In a pilot study of 17 pediatric patients aged 11.8 ± 3.7 years on hemodialysis (n=3) or peritoneal dialysis (n=14), initial doses of 121 ± 50 mg/kg/day (4.5 ± 5 g/day) were used. Doses were adjusted based on the serum phosphorus with final doses of 163 ± 46 mg/kg (6.7 ± 2.4 g/day) without any adverse effects (Mahdavi, 2003). In a study of 18 patients aged 0.9-18 years with chronic kidney disease, a mean dose of 140 ± 86 mg/kg/day (5.38 ± 3.24 g/day) resulted in good phosphorus control with minimal adverse effects. Initial doses were based on prior phosphate-binder dose and were adjusted based on the serum phosphorus (Pieper, 2006).
Adults: Patients not taking a phosphate binder: 800-1600 mg 3 times/day with meals; the initial dose may be based on serum phosphorous levels:
>5.5 mg/dL to <7.5 mg/dL: 800 mg 3 times/day
≥7.5 mg/dL to <9.0 mg/dL: 1200-1600 mg 3 times/day
≥9.0 mg/dL: 1600 mg 3 times/day
Maintenance dose adjustment based on serum phosphorous concentration (goal range of 3.5-5.5 mg/dL; maximum dose studied was equivalent to 13 g/day [sevelamer hydrochloride] or 14 g/day [sevelamer carbonate]):
>5.5 mg/dL: Increase by 400-800 mg per meal at 2-week intervals
3.5-5.5 mg/dL: Maintain current dose
<3.5 mg/dL: 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
Administration: Oral
Must be administered with meals.
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). 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
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: 8.4-10.2 mg/dL (2.1-2.6 mmol/L); CKD stage 5: 8.4-9.5 mg/dL (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: 2.7-4.6 mg/dL (0.87-1.48 mmol/L) (adults); maintain within age-appropriate limits (children)
CKD stage 5 (including those treated with dialysis): 3.5-5.5 mg/dL (1.13-1.78 mmol/L) (children >12 years and adults); 4-6 mg/dL (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)
Serum calcium-phosphorus product (K/DOQI, 2003): CKD stage 3-5: <55 mg2/dL2 (children >12 years and adults); <65 mg2/dL2 (children ≤12 years)
PTH: Whole molecule, immunochemiluminometric assay (ICMA): 1.0-5.2 pmol/L; whole molecule, radioimmunoassay (RIA): 10.0-65.0 pg/mL; whole molecule, immunoradiometric, double antibody (IRMA): 1.0-6.0 pmol/L
Target ranges by stage of chronic kidney disease (KDIGO, 2009): CKD stage 3-5: Optimal iPTH is unknown; maintain normal range (assay-dependent); CKD stage 5D: Maintain iPTH within 2-9 times the upper limit of normal for the assay used
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.
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.
Geriatric Considerations
No specific dose changes needed for the elderly. Since electrolyte changes (ie, phosphorus, calcium) can have dramatic effects in the elderly, monitor closely.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Monitor blood pressure; calcium (phosphate) product.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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
Pricing: U.S. (www.drugstore.com)
Tablets (Renagel)
400 mg (180): $308.88
800 mg (30): $101.99
Tablets (Renvela)
800 mg (30): $80.99
References
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.
"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.
Mahdavi H, Kuizon BD, Gales B, et al, “Sevelamer Hydrochloride: An Effective Phosphate Binder in Dialyzed Children,” Pediatr Nephrol, 2003, 18(12):1260-4.
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.
Storms LE, Chicella MF, and Dice JE, “Sevelamer Therapy for Pediatric End-Stage Renal Disease,” Pharmacotherapy, 2006, 26(3):410-13.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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