Sevelamer Hydrochloride

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Sevelamer Hydrochloride Prescribing Information

Patients Not Taking a Phosphate Binder

. The recommended starting dose of sevelamer hydrochloride tablets is 800 to 1600 mg, which can be administered as one or two 800 mg sevelamer hydrochloridetablets or two to four 400 mg sevelamer hydrochloridetablets, with meals based on serum phosphorus level. Table 1 provides recommended starting doses of sevelamer hydrochloride for patients not taking a phosphate binder.

Table 1: Starting Dose for Dialysis Patients Not Taking a Phosphate Binder
Serum Phosphorus	Sevelamer Hydrochloride Tablets 800 mg	Sevelamer Hydrochloride Tablets 400 mg
> 5.5 and < 7.5mg/dL	1 tablet three times daily with meals	2 tablets three times daily with meals
≥ 7.5 and < 9.0 mg/dL	2 tablets three times daily with meals	3 tablets three times daily with meals
≥ 9.0 mg/dL	2 tablets three times daily with meals	4 tablets three times daily with meals

Patients Switching from Calcium Acetate

. In a study in 84 CKD patients on hemodialysis, a similar reduction in serum phosphorus was seen with equivalent doses (approximately mg for mg) of sevelamer hydrochloride tablets and calcium acetate. Table 2 gives recommended starting doses of sevelamer hydrochloride tablets based on a patient's current calcium acetate dose.

Table 2: Starting Dose for Dialysis Patients Switching From Calcium Acetate to Sevelamer Hydrochloride Tablets
Calcium Acetate 667 mg (Tablets per meal)	Sevelamer Hydrochloride Tablets 800 mg (Tablets per meal)	SevelamerHydrochloride Tablets 400 mg (Tablets per meal)
1 tablet	1 tablet	2 tablets
2 tablets	2 tablets	3 tablets
3 tablets	3 tablets	5 tablets

Dose Titration for All Patients Taking Sevelamer Hydrochloride Tablets

. Adjust dosage based on the serum phosphorus concentration with a goal of lowering serum phosphorus to 5.5 mg/dL or less. Increase or decrease by one tablet per meal at two-week intervals as necessary. Table 3 gives a dose titration guideline. The average dose in a Phase 3 trial designed to lower serum phosphorus to 5.0 mg/dL or less was approximately three sevelamer hydrochloride 800 mg tablets per meal. The maximum average daily sevelamer hydrochloride dose studied was 13 g.

Table 3: Dose Titration Guideline
Serum Phosphorus	Sevelamer Hydrochloride Tablets Dose
>5.5 mg/dL	Increase 1 tablet per meal at 2-week intervals
3.5 to 5.5 mg/dL	Maintain current dose
<3.5 mg/dL	Decrease 1 tablet per meal

Risk Summary

Sevelamer hydrochloride is not absorbed systemically following oral administration and maternal use is not expected to result in fetal exposure to the drug.

Clinical Considerations

Sevelamer hydrochloride may decrease serum levels of fat soluble vitamins and folic acid in pregnant women

[See Clinical Pharmacology (

12.2 Pharmacodynamics

In addition to effects on serum phosphate levels, sevelamer hydrochloride has been shown to bind bile acids

in vitro

and

in vivo

in experimental animal models. Bile acid binding by ion exchange resins is a well-established method of lowering blood cholesterol. Because sevelamer binds bile acids, it may interfere with normal fat absorption and thus may reduce absorption of fat-soluble vitamins such as A, D, and K. In clinical trials of sevelamer hydrochloride, both the mean total and LDL cholesterol declined by 15% to 31%. This effect is observed after 2 weeks. Triglycerides, HDL cholesterol, and albumin did not change.

)]

. Consider supplementing with these vitamins.

Data

Animal data:

In pregnant rats given dietary doses of 0.5, 1.5, or 4.5 g/kg/day of sevelamer hydrochloride during organogenesis, reduced or irregular ossification of fetal bones, probably due to a reduced absorption of fat-soluble vitamin D, occurred at 7 to 21 times the maximum human equivalent dose of 13 g based on 60 kg body weight. In pregnant rabbits given oral doses of 100, 500, or 1000 mg/kg/day of sevelamer hydrochloride by gavage during organogenesis, an increase of early resorptions occurred in the high-dose group (human equivalent dose approximately 5 times the maximum clinical trial dose based on 60 kg body weight).

Serious cases of dysphagia, bowel obstruction, bleeding gastrointestinal ulcers, colitis, ulceration, necrosis, and perforation have been associated with sevelamer use, some requiring hospitalization and surgery. (
5.1 Gastrointestinal Adverse Events
Patients with dysphagia, swallowing disorders, severe gastrointestinal (GI) motility disorders, including severe constipation, or major GI tract surgery were not included in the sevelamer hydrochloride clinical studies.
Dysphagia and esophageal tablet retention have been reported in association with use of sevelamer tablets, some requiring hospitalization and intervention. Consider using sevelamer suspension in patients with a history of swallowing disorders.
Cases of bowel obstruction, bleeding gastrointestinal ulcers, colitis, ulceration, necrosis, and perforation have also been reported with sevelamer use.
[see Adverse Reactions ].
Inflammatory disorders may resolve upon sevelamer hydrochloride discontinuation. Treatment with sevelamer hydrochloride should be re-evaluated in patients who develop severe gastrointestinal symptoms.
)

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Sevelamer Hydrochloride

Sevelamer Hydrochloride Prescribing Information

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