Version May 2024
Dosage guidance:
Clinical considerations: Phosphate binding capacity: Sevelamer hydrochloride 400 mg binds ~32 mg of phosphate; 800 mg binds ~64 mg of phosphate (Ref).
Hyperphosphatemia:
Sevelamer carbonate (Renvela): Children ≥6 years and Adolescents:
Patients not taking a phosphate binder (Ref):
Initial dose:
BSA ≥0.75 to <1.2 m2: Oral: 800 mg 3 times daily with meals; titrate as needed by 400 mg per dose at 2-week intervals.
BSA ≥1.2 m2: Oral: 1,600 mg 3 times daily with meals; titrate as needed by 800 mg per dose at 2-week intervals.
Dosage adjustment when switching from calcium acetate to sevelamer carbonate: 667 mg of calcium acetate is equivalent to ~800 mg of sevelamer; conversion based on dose per meal:
Calcium acetate 667 mg: Convert to 800 mg sevelamer carbonate.
Calcium acetate 1,334 mg: Convert to 1,600 mg sevelamer carbonate.
Calcium acetate 2,001 mg: Convert to 2,400 mg sevelamer carbonate.
Sevelamer hydrochloride (Renagel):
Infants ≥10 months and Children <2 years: Very limited data: Oral: Mean final dose of 140 ± 86 mg/kg/day (5.38 ± 3.24 g/day) was reported in a small trial (n=18; age range: 10 months to 18 years) to achieve the targeted serum phosphorus level. Initial dosing was based upon prior phosphate binder dose and serum phosphorus concentrations (Ref). In a case report of a 19-month-old, an initial dose of 100 mg/kg/day divided every 8 hours with titration up to 130 mg/kg/day was reported to effectively lower serum phosphorus levels (Ref).
Children ≥2 years and Adolescents: Limited data available: Oral: Initial dose: 400 or 800 mg 3 times daily administered with meals; titrate at monthly intervals in 1,200 mg/day increments (ie, 400 mg at each meal) to target phosphorus level; final mean range: 140 to 163 mg/kg/day (5.38 to 6.7 g/day); dosing based on experience in 46 patients; prior or final comparative calcium salt phosphate-binder dose: 4 ± 3 g/day (Ref).
Dosage adjustment when switching from calcium acetate to sevelamer hydrochloride: 667 mg of calcium acetate is equivalent to ~800 mg of sevelamer; conversion based on dose per meal.
Renal failure; pretreatment of oral and enteral nutrition formula, expressed breast milk, or cow's milk to decrease phosphate load: Limited data available: Infants and Children:
Expressed breast milk, infant/enteral formula, or cow's milk: Sevelamer hydrochloride or sevelamer carbonate: Add 800 mg (tablets or powder) to up to 400 mL of breast milk or 100 mL of infant formula, tube feeding, and cow's milk; after the addition of sevelamer, allow to sit for 10 minutes, then decant liquid for feed and leave the precipitate at the bottom. Reported experience has shown a decrease in phosphate of >85% in breast milk, 42% in cow's milk, 48% in tube feeding, and 68% in infant formula (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, adjustment is unnecessary as sevelamer is indicated for use in chronic kidney disease.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Sevelamer: Drug information")
Dosage guidance:
Dosing: Sevelamer carbonate and sevelamer hydrochloride are dosed the same on a milligram-to-milligram basis; when switching between products, use the same dose.
Hyperphosphatemia in chronic kidney disease, treatment:
Note: Use in combination with dietary phosphate restriction (KDIGO 2017). Sevelamer carbonate is preferred in patients with nondialysis-dependent chronic kidney disease or metabolic acidosis due to risk of metabolic acidosis with sevelamer hydrochloride (Quarles 2022).
Oral: Initial: Based on serum phosphorous levels:
>5.5 to <7.5 mg/dL: 800 mg 3 times daily with meals.
7.5 to <9 mg/dL: 1,200 to 1,600 mg 3 times daily with meals.
≥9 mg/dL: 1,600 mg 3 times daily with meals.
Dosage adjustment: Increase or decrease dose by 400 to 800 mg per meal at 2-week intervals as needed to obtain targeted serum phosphorus concentrations; usual dosage range: 800 to 2,400 mg 3 times daily (Quarles 2022; manufacturer’s labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (not systemically absorbed) (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed: No supplemental dose or dosage adjustment necessary (not systemically absorbed) (Ref).
Peritoneal dialysis: Unlikely to be dialyzed: No dosage adjustment necessary (not systemically absorbed) (Ref).
CRRT: No dosage adjustment necessary (not systemically absorbed) (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (not systemically absorbed) (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely due to low systemic absorption.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Metabolic acidosis (children: 34% [Pieper 2006]; adults: Frequency not defined)
Gastrointestinal: Diarrhea (19%), dyspepsia (16%), nausea (20%), vomiting (22%)
1% to 10%: Gastrointestinal: Abdominal pain (9%), constipation (8%), flatulence (8%), peritonitis (peritoneal dialysis: 8%)
Postmarketing:
Dermatologic: Pruritus, skin rash
Gastrointestinal: Colitis, dysphagia, fecal impaction, gastric ulcer with hemorrhage, gastrointestinal necrosis, gastrointestinal ulcer, intestinal obstruction, intestinal perforation
Hypersensitivity: Hypersensitivity reaction
Hypersensitivity to sevelamer or any component of the formulation; bowel obstruction
Canadian labeling: Additional contraindications (not in US labeling): Hypophosphatemia; active mucosal injury (eg, necrosis, perforation, ulcerative colitis, GI bleeding)
Concerns related to adverse effects:
• GI effects: Bowel obstruction, bleeding GI ulcers, colitis, ulceration, necrosis, and perforation have been reported; consider discontinuation of therapy in patients who develop severe symptoms. Dysphagia and esophageal tablet retention have also been reported with the tablet formulation; consider change to suspension formulation in patients with a history of swallowing disorders.
Disease-related concerns:
• Gastrointestinal disease: Use with caution in patients with gastrointestinal disorders including dysphagia, swallowing disorders, severe gastrointestinal motility disorders (including severe constipation), or major gastrointestinal surgery.
Concurrent drug therapy issues:
• 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.
In a trial conducted in pediatric patients (n=18; age range: 10 months to 18 years), an increase in metabolic acidosis was noted in patients receiving sevelamer hydrochloride (incidence: 34.4%) (Pieper 2006); in another pediatric trial (n=17; age range: 2 to 18 years), no untoward effects were reported (Mahdavi 2003). Patients should be closely monitored.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Packet, Oral, as carbonate:
Renvela: 0.8 g (1 ea, 90 ea); 2.4 g (1 ea, 90 ea) [citrus flavor]
Generic: 0.8 g (1 ea, 90 ea); 2.4 g (1 ea, 90 ea)
Tablet, Oral, as carbonate:
Renvela: 800 mg
Generic: 800 mg
Tablet, Oral, as hydrochloride:
Renagel: 800 mg [DSC]
Generic: 400 mg, 800 mg
Yes
Pack (Renvela Oral)
0.8 g (per each): $21.42
2.4 g (per each): $21.42
Pack (Sevelamer Carbonate Oral)
0.8 g (per each): $11.35 - $19.25
2.4 g (per each): $11.35 - $19.25
Tablets (Renvela Oral)
800 mg (per each): $7.14
Tablets (Sevelamer Carbonate Oral)
800 mg (per each): $0.22 - $6.10
Tablets (Sevelamer HCl Oral)
400 mg (per each): $4.02
800 mg (per each): $7.20 - $8.04
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral, as carbonate:
Renvela: 0.8 g (90 ea); 2.4 g (90 ea)
Tablet, Oral, as carbonate:
Renvela: 800 mg
Generic: 800 mg
Tablet, Oral, as hydrochloride:
Renagel: 800 mg
Note: An oral suspension product is commercially available. Sevelamer carbonate is commercially available as powder for oral suspension packets; however, it is a different salt form than described below:
50 mg/mL Sevelamer Hydrochloride Oral Suspension
A 50 mg/mL oral suspension may be made with tablets, distilled water, and simple syrup. Place fifteen 800 mg sevelamer hydrochloride tablets in a beaker with 120 mL of distilled water. Allow tablets to soak and disintegrate; stir occasionally. Add ~60 mL of simple syrup to the beaker and mix until a uniform suspension is achieved. Pour mixture into a calibrated cylinder and add quantity of simple syrup sufficient to make 240 mL. Pour mixture back into beaker and stir until thoroughly mixed. Transfer to amber bottle. Stable for 14 days under refrigeration. Label "shake well."
Oral: Administer with meals. Consider separating administration of oral medications from sevelamer when reduced bioavailability would significantly affect the concomitant medication's safety or efficacy (eg, cyclosporine, tacrolimus, levothyroxine); duration of separation varies based on absorption characteristics and whether it is an immediate-release or extended-release product; monitor clinical response and/or blood concentrations of concomitant medications.
Tablets: Swallow tablets whole; do not break, chew, or crush; contents will expand with water.
Powder for oral suspension (sevelamer carbonate): Administer reconstituted oral suspension immediately or within 30 minutes; oral suspension may need to be resuspended immediately before drinking. Alternatively, the powder contents of the packet may be premixed with a small amount of food or beverage and consumed immediately (or within 30 minutes) as part of a meal. Do not heat or add to heated food or liquid.
Administer with meals.
Powder for oral suspension: May prepare an oral suspension in water using the directed amount of water appropriate for the packet size or may premix the entire content of the packet with a small amount of food or beverage (do not heat or add to heated foods or liquids).
Preparations should be consumed immediately or within 30 minutes. Oral suspension in water may need to be resuspended immediately before drinking.
Tablets: Swallow whole; do not crush, chew, or break.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Reduction of serum phosphorus in patients with chronic kidney disease on dialysis (Sevelamer carbonate [eg, Renvela]: FDA approved in patients ≥6 years and adults; Sevelamer hydrochloride [eg, Renagel]: FDA approved in adults).
Renagel may be confused with Reglan, Regonol, Renvela
Renvela may be confused with Reglan, Regonol, Renagel
Sevelamer may be confused with Savella
Renagel [US, Canada, and multiple international markets] may be confused with Remegel brand name for aluminium hydroxide and magnesium carbonate [Netherlands] and for calcium carbonate [Hungary, Great Britain and Ireland] and with Remegel Wind Relief brand name for calcium carbonate and simethicone [Great Britain]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Calcitriol (Systemic): Sevelamer may decrease the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy
Cholic Acid: Sevelamer may decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 hour before or 4 to 6 hours after administration of any bile acid-binding products, such as sevelamer, to minimize the potential for a significant interaction. Risk D: Consider therapy modification
Ciprofloxacin (Systemic): Sevelamer may decrease the serum concentration of Ciprofloxacin (Systemic). Management: Administer ciprofloxacin at least 2 hours before or 6 hours after sevelamer administration. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Sevelamer may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Levothyroxine: Sevelamer may decrease the serum concentration of Levothyroxine. Management: Separate administration of sevelamer and levothyroxine by at least 4 hours to decrease the risk of a significant interaction. Monitor clinical and laboratory response to levothyroxine closely when used together with sevelamer. Risk D: Consider therapy modification
Mycophenolate: Sevelamer may decrease the serum concentration of Mycophenolate. Management: Administer mycophenolate at least 2 hours prior to sevelamer administration. Risk D: Consider therapy modification
Roxadustat: Sevelamer may decrease the serum concentration of Roxadustat. Management: Administer roxadustat at least 1 hour after the administration of sevelamer. Risk D: Consider therapy modification
Tacrolimus (Systemic): Sevelamer may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
May cause reductions in vitamin D, E, K, or folic acid absorption. Management: Must be administered with meals. Consider vitamin supplementation.
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.
Sevelamer is not absorbed systemically; however, it may reduce maternal absorption of fat soluble vitamins and folic acid; supplementation may be needed.
General recommendations: Serum chemistries (eg, bicarbonate, chloride, magnesium), creatinine, BUN, and albumin.
KDIGO 2017 guidelines: Note: Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of chronic kidney disease (CKD), and the use of treatments for CKD-mineral and bone disorders.
Children and Adolescents:
|
CKD |
Calcium |
Phosphorous |
Alkaline Phosphatase |
PTH |
|---|---|---|---|---|
|
G2 to G3b |
Every 6 to 12 months |
Every 6 to 12 months |
Based on clinical condition |
Based on baseline and progression of disease |
|
G4 |
Every 3 to 6 months |
Every 3 to 6 months |
Every 12 months (more often in presence of elevated PTH) |
Every 6 to 12 months |
|
G5 and G5d |
Every 1 to 3 months |
Every 1 to 3 months |
Every 12 months (more often in presence of elevated PTH) |
Every 3 to 6 months |
Corrected total serum calcium (KDIGO 2017):
CKD stages 3a to 5D: Maintain in age-appropriate normal ranges.
Phosphorus (KDIGO 2017):
CKD G3a to G5D: Lower elevated phosphorus levels toward the normal range.
Sevelamer (a polymeric compound) binds phosphate within the intestinal lumen, limiting absorption and decreasing serum phosphate concentrations without altering calcium, aluminum, or bicarbonate concentrations.
Onset of action: Reduction in serum phosphorus has been demonstrated after 1-2 weeks (Burke 1997; Chertow 1997).
Absorption: Not systemically absorbed
Excretion: Feces
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