Renvela

Drug overview for RENVELA (sevelamer carbonate):

Generic name: SEVELAMER CARBONATE (seh-VELL-uh-mer)
Drug class: Phosphate Binder Agents
Therapeutic class: Genitourinary Therapy

Sevelamer carbonate and sevelamer hydrochloride are phosphate binders used to reduce the intestinal absorption of phosphates.

No enhanced Uses information available for this drug.

DRUG IMAGES

RENVELA 2.4 GM POWDER PACKET
RENVELA 0.8 GM POWDER PACKET

The following indications for RENVELA (sevelamer carbonate) have been approved by the FDA:

Indications:
Renal osteodystrophy with hyperphosphatemia

Professional Synonyms:
Renal osteodystrophy with hyperphospheremia

The following dosing information is available for RENVELA (sevelamer carbonate):

Dosing
Administration
RENVELA
SEVELAMER CARBONATE

Dosage of sevelamer carbonate should be adjusted according to the patient's serum phosphorus concentrations with the goal of achieving serum phosphorus concentrations within the target range of 3.5-5.5 mg/dL.

Dosage of sevelamer carbonate may be increased or decreased by one 800-mg tablet per meal at 2-week intervals as needed.

In a clinical trial, the average daily dosage of sevelamer carbonate was 6 g; the maximum dosage of the drug studied was 14 g daily.

Dosage of sevelamer hydrochloride should be adjusted according to the patient's serum phosphorus concentrations with the goal of reducing serum phosphorus concentrations to 5.5 mg/dL or less. Dosage of sevelamer hydrochloride may be increased or decreased by 1 tablet per meal at 2-week intervals as needed.

If serum phosphorus concentrations exceed 5.5 mg/dL, sevelamer hydrochloride dosage should be increased by 1 tablet per meal at 2-week intervals. Patients with serum phosphorus concentrations 3.5-5.5

mg/dL should maintain their current dosage of sevelamer hydrochloride. If serum phosphorus concentrations are less than 3.5 mg/dL, sevelamer hydrochloride dosage should be decreased by 1 tablet per meal at 2-week intervals.

In one clinical study, the average daily dosage of sevelamer hydrochloride was 2.4 g (given as three 800-mg tablets) 3 times daily, and the maximum average dosage of the drug studied was 13 g daily.

No enhanced Administration information available for this drug.

Dosing information for RENVELA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
RENVELA 2.4 GM POWDER PACKET	Maintenance	Adults take 1 packet (2.4 gram) mixed with 60 mL of water, stir and drink within 30 minutes, by oral route 3 times per day with meals
RENVELA 0.8 GM POWDER PACKET	Maintenance	Adults take 1 packet (0.8 gram) mixed with 30 mL of water, stir and drink within 30 minutes, by oral route 3 times per day with meals
RENVELA 800 MG TABLET	Maintenance	Adults take 1 tablet (800 mg) by oral route 3 times per day with food

Generic dosing information for SEVELAMER CARBONATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
SEVELAMER 0.8 GM POWDER PACKET	Maintenance	Adults take 1 packet (0.8 gram) mixed with 30 mL of water, stir and drink within 30 minutes, by oral route 3 times per day with meals
SEVELAMER 2.4 GM POWDER PACKET	Maintenance	Adults take 1 packet (2.4 gram) mixed with 60 mL of water, stir and drink within 30 minutes, by oral route 3 times per day with meals
SEVELAMER CARBONATE 800 MG TAB	Maintenance	Adults take 1 tablet (800 mg) by oral route 3 times per day with food

The following drug interaction information is available for RENVELA (sevelamer carbonate):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Phosphate Supplements;Urine pH Modifiers/Phosphate Reducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lanthanum and sevelamer bind to phosphate.(1-2) Tenapanor is a sodium/hydrogen exchanger 3 (NHE3) inhibitor.(3) All three agents are used to lower phosphate absorption in the body.(1-3) CLINICAL EFFECTS: Concurrent use of phosphate supplements or urinary pH modifiers high in phosphate with agents that reduce serum phosphorus may decrease the effectiveness of both agents. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients should normally not receive phosphate supplements or urinary pH modifiers high in phosphate concurrently with agents that reduce serum phosphorus. DISCUSSION: Lanthanum, sevelamer, and tenapanor are indicated to control phosphorus levels. Consider discontinuing or holding phosphate supplements and urinary pH modifiers high in phosphate in patients receiving these agents.	DEXTROSE 5%-ELECTROLYTE #48, GLYCOPHOS, K-PHOS NO.2, K-PHOS ORIGINAL, POTASSIUM PHOSPHATE, POTASSIUM PHOSPHATE-0.9% NACL, POTASSIUM PHOSPHATES, SODIUM PHOSPHATE, SODIUM PHOSPHATE DIBASIC, UROQID-ACID NO.2
Erdafitinib/Serum Phosphate Level-Altering Drugs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1) CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1) DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1)	BALVERSA

Drug Interaction

Drug Names

Phosphate Supplements;Urine pH Modifiers/Phosphate Reducers

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Lanthanum and sevelamer bind to phosphate.(1-2) Tenapanor is a sodium/hydrogen exchanger 3 (NHE3) inhibitor.(3) All three agents are used to lower phosphate absorption in the body.(1-3)

CLINICAL EFFECTS: Concurrent use of phosphate supplements or urinary pH modifiers high in phosphate with agents that reduce serum phosphorus may decrease the effectiveness of both agents.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should normally not receive phosphate supplements or urinary pH modifiers high in phosphate concurrently with agents that reduce serum phosphorus.

DISCUSSION: Lanthanum, sevelamer, and tenapanor are indicated to control phosphorus levels. Consider discontinuing or holding phosphate supplements and urinary pH modifiers high in phosphate in patients receiving these agents.

DEXTROSE 5%-ELECTROLYTE #48, GLYCOPHOS, K-PHOS NO.2, K-PHOS ORIGINAL, POTASSIUM PHOSPHATE, POTASSIUM PHOSPHATE-0.9% NACL, POTASSIUM PHOSPHATES, SODIUM PHOSPHATE, SODIUM PHOSPHATE DIBASIC, UROQID-ACID NO.2

Erdafitinib/Serum Phosphate Level-Altering Drugs

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1)

CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1)

DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1)

BALVERSA

There are 6 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Thyroid Preps/Bile Acid Sequestrants; Lanthanum; Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bile acid sequestrants, lanthanum and sevelamer may decrease the gastrointestinal absorption of thyroid drugs.(1) CLINICAL EFFECTS: Simultaneous administration of a bile acid sequestrant, lanthanum or sevelamer may result in decreased absorption and effectiveness of thyroid drugs.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: For maximal bioavailability, thyroid preparations should be taken on an empty stomach at least 4 hours apart from bile acid sequestrants and sevelamer.(1-3) Thyroid preparations should be taken at least 2 hours apart from lanthanum.(4) DISCUSSION: The effect of cholestyramine on the absorption of thyroid drugs appears to be clinically significant, resulting in approximately a 50% decrease in thyroid absorption. Cholestyramine has been used to treat thyroid overdoses. When administered with colesevelam (3.75 g), the area-under-curve (AUC) and maximum concentration (Cmax) of levothyroxine (600 mcg) decreased by 22% and by 33%, respectively. When administered 1 hour prior to colesevelam, the AUC of levothyroxine increased by 6% and the Cmax of levothyroxine decreased by 2%, respectively. When administered 4 hours prior to colesevelam, the AUC and Cmax of levothyroxine increased by 1% and 8%, respectively. Although used for hyperphosphatemia, sevelamer is linked to this monograph due to its structural and pharmacologic similarities to colesevelam. Both agents are non-absorbed cross linked polymers with a high affinity for bile acids.(2,3) An in vivo study in healthy subjects evaluated the bioavailability of levothyroxine 1 mg when given with or without sevelamer 800 mg. Concomitant administration of sevelamer decreased levothyroxine AUC by 46%.(13) One case report described a newly diagnosed hypothyroid patient with a TSH of 297 mU/L (reference 0.03 - 4.20 mU/L). She took her daily levothyroxine with her morning blood pressure medications, acetaminophen, B-vitamins and sevelamer 3200 mg. Over 3 months of treatment her levothyroxine dose was increased to 150 mcg daily but the TSH remained high at 196 mU/L. Her levothyroxine dose was changed to an evening dose taken at least 4 hours after medications. Three weeks later she was symptomatically improved and TSH had decreased to 19 mU/L. She was inadvertently rechallenged on the morning levothyroxine and sevelamer regimen due to a hospitalization. After the hospital stay her TSH risen to 76 mU/L; on return to her evening regimen her TSH again normalized.(14)	ADTHYZA, ARMOUR THYROID, CYTOMEL, ERMEZA, EUTHYROX, LEVO-T, LEVOTHYROXINE SODIUM, LEVOTHYROXINE SODIUM DILUTION, LEVOXYL, LIOTHYRONINE SODIUM, NIVA THYROID, NP THYROID, PCCA T3 SODIUM DILUTION, PCCA T4 SODIUM DILUTION, RENTHYROID, SYNTHROID, THYQUIDITY, THYROID, TIROSINT, TIROSINT-SOL, UNITHROID
Mycophenolate/Aluminum & Magnesium Antacids; Lanthanum; Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum or magnesium antacids and non-calcium containing phosphate binders such as lanthanum and sevelamer decrease the absorption of mycophenolate.(1-3) CLINICAL EFFECTS: The simultaneous administration of mycophenolate with aluminum or magnesium antacids and non-calcium containing phosphate binders such as lanthanum and sevelamer may decrease the levels of mycophenolate and its clinical effects. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of mycophenolate mofetil states that calcium free phosphate binders, such as sevelamer, should not be administered simultaneously with mycophenolate mofetil. Administer sevelamer at least 2 hours after administration of mycophenolate mofetil to decrease the extent of the interaction.(1) The US manufacturer of mycophenolate sodium states that mycophenolate sodium should not be administered simultaneously with antacids. Administer aluminum or magnesium containing antacids at least 2 hours after mycophenolate.(2) Close monitoring of mycophenolic acid levels may be warranted in patients on mycophenolate mofetil therapy that are initiating or discontinuing concurrent therapy with these agents. Patients on concurrent therapies may also require higher doses of mycophenolate mofetil in order to achieve desired blood levels. DISCUSSION: In a study in 10 rheumatoid arthritis patients, the simultaneous administration of mycophenolate and Maalox TC (an antacid containing magnesium and aluminum hydroxide) resulted in decreases in the maximum concentration (Cmax) and area-under-curve (AUC) of mycophenolate by 33% and 17%, respectively.(1,2) In a study of 3 adult patients and 6 pediatric patients with stable renal graft function receiving mycophenolate mofetil, sevelamer (3-4 capsules of 403 mg twice daily) decreased the AUC and Cmax of mycophenolic acid by 26% and 36%, respectively.(1,3) In a study in 12 stable renal transplant patients, administration of magnesium-aluminum-containing antacids (30 ml) increased the Cmax and AUC of a single dose of mycophenolate sodium by 25% and 37%, respectively.(2)	CELLCEPT, MYCOPHENOLATE MOFETIL, MYCOPHENOLIC ACID, MYFORTIC, MYHIBBIN
Oral Fluoroquinolones/Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sevelamer may bind to oral fluoroquinolones, preventing its absorption.(1) CLINICAL EFFECTS: Simultaneous administration of sevelamer may result in decreased levels and clinical effectiveness of oral fluoroquinolones.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If concurrent therapy is warranted, the oral fluoroquinolone should be administered at least two hours before or six hours after sevelamer.(2) DISCUSSION: In a study in 15 subjects, simultaneous administration of ciprofloxacin (750 mg) and sevelamer (seven 403 mg capsules) decreased the bioavailability of ciprofloxacin by 48%.(1,2) Oral fluoroquinolones linked to this monograph are: balofloxacin, cinoxacin, ciprofloxacin, delafloxacin, enoxacin, fleroxacin, flumequine, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nadifloxacin, nalidixic acid, nitroxoline, norfloxacin, ofloxacin, pefloxacin, pipemidic acid, prulifloxacin, rosoxacin, sparfloxacin, temafloxacin, tosufloxacin, and trovafloxacin.	BAXDELA, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, GATIFLOXACIN SESQUIHYDRATE, LEVOFLOXACIN, LEVOFLOXACIN HEMIHYDRATE, MOXIFLOXACIN HCL, NALIDIXIC ACID, OFLOXACIN
Lomitapide/Bile Acid Sequestrants; Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bile acid sequestrants and sevelamer may decrease the gastrointestinal absorption of lomitapide. CLINICAL EFFECTS: Simultaneous administration of a bile acid sequestrant or sevelamer may result in decreased absorption and effectiveness of lomitapide.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: For maximal bioavailability, the manufacturer of lomitapide states lomitapide and bile acid sequestrant administration should be separated by at least 4 hours.(1) Although used for hyperphosphatemia, sevelamer is linked to this monograph due to its structural and pharmacologic similarities to colesevelam. Both agents are non-absorbed cross linked polymers with a high affinity for bile acids.(2) DISCUSSION: Lomitapide maximal systemic concentrations occur approximately 6 hours after administration. Although an interaction study has not been performed, the manufacturer of lomitapide recommends separating bile acid sequestrant administration for a minimum of 4 hours before or after lomitapide dose.(1)	JUXTAPID
Obeticholic acid/Bile Acid Sequestrants; Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bile acid sequestrants and sevelamer may decrease the gastrointestinal absorption of obeticholic acid. CLINICAL EFFECTS: Simultaneous administration of a bile acid sequestrant or sevelamer may result in decreased absorption and effectiveness of obeticholic acid.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: For maximal bioavailability, the manufacturer of obeticholic acid states obeticholic acid should be administered at least 4 hours before or after a bile acid sequestrant or sevelamer.(1) Although used for hyperphosphatemia, sevelamer is linked to this monograph due to its structural and pharmacologic similarities to colesevelam. Both agents are non-absorbed cross linked polymers with a high affinity for bile acids.(2) DISCUSSION: Bile acid sequestrants may be needed to treat pruritis due to primary biliary cholangitis and/or obeticholic acid therapy.(1,3) In a clinical trial of patients receiving obeticholic acid and bile acid sequestrants, obeticholic acid trough concentrations were slightly lower compared with patients who did not receive bile acid sequestrants. This resulted in a modest attenuation of efficacy in obeticholic acid 5mg, but did not appear to affect efficacy in patients receiving obeticholic acid 10 mg.(3)	OCALIVA
Vadadustat/Polyvalent Cations and Phosphate Binders SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Vadadustat may form a chelate with iron supplements, phosphate binders, and other medicinal products whose primary component consists of polyvalent cations such as aluminum, calcium, magnesium, selenium, and zinc.(1) CLINICAL EFFECTS: Simultaneous administration of vadadustat and polyvalent cations and phosphate binders decreases the exposure and effectiveness of vadadustat.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of vadadustat states that it should be administered at least 1 hour before or 2 hours after any medications or products whose primary component consists of iron, phosphate binders and polyvalent cations.(1) DISCUSSION: Two studies evaluating the pharmacokinetics, safety, and tolerability of a single oral dose of vadadustat coadministered with a phosphate binder or iron supplement were conducted in healthy adult participants. Vadadustat exposure was reduced by coadministration with sevelamer carbonate, calcium acetate, ferric citrate, and ferrous sulfate. Geometric least squares mean ratios for area under the concentration-time curve (AUC) were reduced 37% to 55% by phosphate binders and 46% by ferrous sulfate. However, when vadadustat was administered 1 hour before phosphate binders, 90% confidence intervals for vadadustat exposure were within the no-effect boundaries of +50% to -33%, indicating that drug-drug interactions can be reduced by administering vadadustat 1 hour before phosphate binders.(2)	VAFSEO

The following contraindication information is available for RENVELA (sevelamer carbonate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Hypophosphatemia or bowel obstruction.

There are 1 contraindications. Absolute contraindication.

Contraindication List
Gastrointestinal obstruction

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Severe constipation

There are 4 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Dysphagia
Gastrointestinal hypomotility
Gastrointestinal tract surgery
Vitamin D deficiency

The following adverse reaction information is available for RENVELA (sevelamer carbonate):

Overview
Severe
Less Severe

Adverse reaction overview.

There are limited data on safety of sevelamer carbonate. The manufacturer states that since the active ingredient (sevelamer) is the same for sevelamer carbonate and sevelamer hydrochloride, the adverse event profiles of the 2 salts should be similar. Adverse effects occurring in 5% or more of patients receiving sevelamer hydrochloride include abdominal pain, diarrhea, constipation, dyspepsia, flatulence, nausea, peritonitis (in patients on peritoneal dialysis), and vomiting.

There are 10 severe adverse reactions.

More Frequent	Less Frequent
Peritonitis	None.

Rare/Very Rare
Acute gastrointestinal ulcer with hemorrhage Colitis Fecal impaction Gastrointestinal obstruction Gastrointestinal perforation Hypersensitivity drug reaction Ileus Intestinal ischemic necrosis Intestinal perforation

There are 13 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Constipation Diarrhea Dyspepsia Flatulence Nausea Vomiting	Abdominal distension Anorexia Arthralgia Pruritus of skin

Rare/Very Rare
Dysphagia Skin rash

The following precautions are available for RENVELA (sevelamer carbonate):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy not established in children younger than 18 years of age.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Category C. (See Users Guide.) It should be considered that vitamin and other nutrient requirements are increased during pregnancy and the effect of sevelamer hydrochloride on absorption of vitamins and other nutrients has not been studied in pregnant women.

Caution is advised if the drug is administered in nursing women.

Experience in those 65 years of age and older is insufficient to determine whether they respond differently from younger adults. Dosage generally should be selected cautiously, usually initiating therapy at the low end of the dosage range.

Renal osteodystrophy with hyperphosphatemia
N25.0	Renal osteodystrophy