Sevelamer is used to control serum phosphorus levels in patients with chronic kidney disease on dialysis. It works by binding to dietary phosphate in the gut and preventing absorption. The starting dose is 2.4-4.8g daily in divided doses with meals, adjusted based on serum phosphate levels. Common side effects include constipation, diarrhea, and GI discomfort. It can interact with various medications by decreasing their absorption and levels when taken together. Monitoring of serum levels of certain vitamins and minerals is recommended during use.

1. Background
Patients with end-stage renal disease (ESRD) retainphosphorus
and can develophyperphosphatemia.Thus can precipitate serum
calcium resulting in ectopic calcificationwhich increasedif the
product of serum calcium and phosphorus concentrations (Cax P)
exceeds 55 mg2/dL2. Hyperphosphatemiaplays a role in the
development of secondary hyperparathyroidism inrenal
insufficiency that is characterizedby increase in parathyroid
hormone (PTH) .Increasedlevels ofPTH can lead to osteitis
fibrosa,a bone disease. Then a decrease in serum phosphorus
(PO4) may decrease serum PTH levels.Strategies to treat
hyperphosphatemiaincludes reduction in dietary intake of
phosphate, inhibition of intestinal phosphate absorptionwith
phosphate binders, and removal ofphosphate with dialysis.
Sevelamer (PO4 binder, bile acid sequestrants & chelating agent)
prevents hyperphosphatemiaby binding to dietary phosphate in
the gut, preventing its absorptionand thus decreasing serum
parathyroidhormone levels. It also results in a lowering oflow-
density lipoprotein(LDL) and total serum cholesterol levels.
Indication&dose
Indicated for the control ofserum phosphorus in patients with
chronic kidney disease (CKD) who are on dialysis initially 2.4-4.8g
daily in 3 divided doses to be taken with meal-adjustedaccording
to serum PO4 concentrationas detailed:
Pt.whodonottakephosphatebinder
× Serum PO4 >9 mg/dL[2.91 mmol/L]:1600 mg PO q8hr
× Serum PO4 7.5-9 mg/dL[2.42-2.91 mmol/L]:1200-1600 mg PO
q8hr
× Serum PO4 5.5-7.5 mg/dL[1.78-2.42 mmol/L]:800mg POq8hr
Pt.whoswitchingfromcalciumacetate

2. × Substitute 800 mg Renagel® or Renvela® for 667 mg of Ca-
acetate
× Substitute 1600 Renvela® or Renagel®for 1334 mg of Ca-acetate
× Substitute 2400 mg Renvela® or Renagel® for 2001 mg Ca-
acetate
Maintenancedose
Target goal is serum PO4 ≤ 5.5 mg/dL
× Serum PO4 >5.5 mg/dL [>1.78 mmol/L]:increase dose by 400-
800 mg/meal
× Serum PO4 3.5-5.5 mg/dL[1.13-1.78 mmol/L]:Maintaincurrent
dose
× Serum PO4 <3.5 mg/dL [1.13 mmol/L] decrease by 400-800 mg
/meal
Dosetitration
Increase by 400-800 mg per meal at 2-week intervals as necessary
to achieve target serum phosphorus levels
Average&maximumdoses
Based on clinical studies, the average prescribedadult daily dose is
~7.2 g/day.It’s been given to normal healthy volunteers in doses of
up to 14 g/day for 8 days & in average doses up to 13-14 g/day to
hemodialysis patients with no adverse effects.Since sevelamer is
not absorbedafter oral administration,the risk ofsystemic toxicity
is low.
AdverseEffects
Common&/verycommon:constipation,diarrhea, GI discomfort,
nausea & vomiting,nasopharyngitis,limbpain, arthralgia,
bronchitis,dyspnea & hypertension
1-10%:abdominal pain, flatulence, peritonitis (during peritoneal
dialysis) & Hypercalcemia
Frequnetlynotknown: skin reactions,pruritus,rash, back pain,
cough, headache, pyrexia, upper RTI,intestinal perforation&
obstruction,fecal impaction

3. PostmarketingReports: hypersensitivity,bleeding gastrointestinal
ulcers,colitis,ulceration,necrosis
Warnings,contraindications&cautions
× Its contraindicatedwith hypersensitivity & bowel obstruction
while used withcaution in dysphagia, GI motility disorders,GI
surgery (Cases ofbowel obstruction,bleeding gastrointestinal
ulcers,colitis,ulceration,necrosis, and GI perforationreported;
inflammatory disorders may resolve upondiscontinuation;
reevaluate treatment in patients who developsevere
gastrointestinal symptoms)
× Tablets should not be crushed,broken, or chewed (tablets rapidly
expand and become a choking hazard). Dysphagiaand esophageal
tablet retention reported,in some cases requiring hospitalization
and intervention;consider sevelamer oral suspensionin patients
with history ofswallowing disorders.
× Monitor serum bicarbonate and chloride level, fat soluble vitamin
and folic acid levels,especially in pregnancy.
Pregnancy &lactation
It is expected to result in fetal exposure to the drug, may decrease
serum levels of fat-soluble vitamins and folic acid in pregnant
women; consider supplementation. Manufacturer advice avoidance
or use when potential benefits outweighs risk.
× In breastfeeding,it is not absorbed systemically by mother
following oral administration;so is not expected to result in
exposure of child to drug
Interactions
Contraindicated:potassium phosphates & sodium phosphates IV, It
decreases effects of bothagents, IV by cationbinding in GI tract.
Contraindicated.Sevelamer decreases serum phosphate
concentrationby binding dietary phosphate.

4. Serious-UseAlternative:with erdafitinib, avoid co-administration
with erdafitinib during initial dosing adjustment period (ie, first 21
days). Increases inserum phosphate levels are a pharmacodynamic
effect of FGFR inhibition. Serum phosphate binders may obscure
decisions regarding initial dosage increase.
MonitorClosely: it may decrease GI absorption,increase elimination
& thus decrease level of these drugs. They should be taken1 hr
before or 3 hr after sevelamer dose; as ex
× Antibiotic:ciprofloxacin
× Acetazolamide diuretic
× Adenosie
× Antiarrhythmic:amiodarone, lidocaine, procainamide &
verapamil
× Antiepileptic: carbamazepine,gabapentin, lamotrigine,
levetiracetam,phenobarbital,phenytoin, topiramate & valproic
acid
× benzodiazepines: diazepam, clonazepam & lorazepam
× Beta blockers:acebutolol,esomolol,sotalol & propranolol
× Inotropic:digoxin
Dichlorphenamide&sevelamer.Either increases toxicity ofthe other by
pharmacodynamic synergism.Modify Therapy/Monitor Closely.Both
drugs can cause metabolic acidosis.
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References
Medscape website, Drugs & Diseases:sevelamer
BritishNational Formulary
Drug Bank website: sevelamer
Katzung basic & clinical pharmacology 14th Edition