Renal Failure (agents)

(2) Consider fluid challenge to rule out pre-renal azotemia if not fluid overloaded.

(3) Lasix: IV bolus 10-200 mg (usually every 2 hours). Doses > 200mg should be infused at 4 to 10 mg/min (usually 4 mg/min) to minimize ototoxicity. IV infusion of 0.25 to 0.4 mg/kg/hour titrated to urine output.

(4) Metolazone (Zaroxylyn ® ) 5-10 mg po qd (max 20 mg/day)

(5) Bumetanide (Bumex ®): IV bolus 0.5 to 4mg over 1-2min prn (usually q2-3 hr). IV infusion: usually 0.5 to 1 mg/hr. T1/2= 1 to 1.5hr Duration of action: 2-4hrs.

(6) Torsemide (Demadex ®): IV bolus: 5 to 100 mg over 1-2 minutes. IV infusion: 5 to 20 mg/hr. [1 mg Bumex] = [10-20 mg Demadex] = [40 mg Lasix]

(7) Mannitol: When instituting treatment with mannitol in patients with marked oliguria, a test dose should be used. Infusion of 0.2 grams/kg over 3 to 5 min should produce a diuresis of at least 30 to 50 ml/hr. A second test dose may be given if no response is seen—if no response with second dose—do not use. To treat oliguria: 12.5 to 25 grams IV every 2 to 4 hours. A 15 to 20% solution may be used. Rate should be adjusted to maintain urinary output at 30-50 ml/hr. (Usual test dose= 12.5 grams over 3 to 5 minutes. )

Ca x PO4 RATIO
When the Ca x PO4 product exceeds 70, there is a possibility of dangerous precipitation of Ca in non-osseous tissues. Use of Ca based PO4 binders may transiently exacerbate the problem. Use of aluminum hydroxide (300 to 600 mg p.o. tid with meals) for periods not to exceed 7-10 days (to avoid Al3+ toxicity) may be necessary. When the Ca x PO4 product falls below this dangerous level, calcium-carbonate or calcium-acetate may be started. RenaGel®, a new polymeric resin that does not contain Ca++ may be used.

Hyperacidity: Oral: 600-1200 mg between meals and at bedtime.

Aluminum antacids may cause constipation, phosphate depletion, and bezoar or fecalith formation. In patients with renal failure, aluminum may accumulate to toxic levels.

Supplied: Suspension, oral: 320 mg/5 mL (473 mL)
AlternaGel®: 600 mg/5 mL (360 mL)

Usual dose: (3 to 4 tablets) 2001-2868 mg with each meal.

[Supplied: 667mg tablet, Gelcap]

INDICATIONS AND USAGE
Predialysis Patients
Calcitriol Capsules are indicated in the management of secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe chronic renal failure (Ccr 15 to 55 mL/min) not yet on dialysis. In children, the creatinine clearance value must be corrected for a surface area of 1.73 square meters. A serum iPTH level of ≥100 pg/mL is strongly suggestive of secondary hyperparathyroidism.

Dialysis Patients
Calcitriol Capsules are indicated in the management of hypocalcemia and the resultant metabolic bone disease in patients undergoing chronic renal dialysis. In these patients, calcitriol administration enhances calcium absorption, reduces serum alkaline phosphatase levels, and may reduce elevated parathyroid hormone levels and the histological manifestations of osteitis fibrosa cystica and defective mineralization.

Hypoparathyroidism Patients
Calcitriol Capsules are also indicated in the management of hypocalcemia and its clinical manifestations in patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypoparathyroidism.

CONTRAINDICATIONS
Calcitriol Capsules should not be given to patients with hypercalcemia or evidence of vitamin D toxicity. Use of Calcitriol Capsules in patients with known hypersensitivity to Calcitriol Capsules (or drugs of the same class) or any of the inactive ingredients is contraindicated.

Dosing (Adults):
Renal failure:
Oral: 0.25 mcg/day or every other day (may require 0.5-1 mcg/day).
IV: 0.5 mcg (0.01 mcg/kg) 3 times/week; most doses in the range of 0.5-3 mcg (0.01-0.05 mcg/kg) 3 times/week.

Hypoparathyroidism/pseudohypoparathyroidism: Oral: 0.5-2 mcg/day.
Vitamin D-dependent rickets: Oral: 1 mcg qd.

Supplied: Capsule (Rocaltrol®): 0.25 mcg, 0.5 mcg.
Injection, solution: 1 mcg/mL (1 mL); 2 mcg/mL (2 mL). Calcijex®: 1 mcg/mL (1 mL). Oral soln: (Rocaltrol®): 1 mcg/mL (15 mL).

Mechanism of Action
Calcitriol (1α,25-(OH)2D3) and 1α,25-(OH)2D2 regulate blood calcium at levels required for essential body functions. Specifically, the biologically active vitamin D metabolites control the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidney and, in conjunction with parathyroid hormone (PTH), the mobilization of calcium from the skeleton. They act directly on bone cells (osteoblasts) to stimulate skeletal growth, and on the parathyroid glands to suppress PTH synthesis and secretion. These functions are mediated by the interaction of these biologically active metabolites with specific receptor proteins in the various target tissues. In patients with chronic kidney disease (CKD), deficient production of biologically active vitamin D metabolites (due to lack of or insufficient 25-hydroxyvitamin D-1-alpha-hydroxylase activity) leads to secondary hyperparathyroidism, which contributes to the development of metabolic bone disease

INDICATIONS AND USAGE

Dialysis Patients:
Hectorol is indicated for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

Pre-Dialysis Patients:
Hectorol is indicated for the treatment of secondary hyperparathyroidism in patients with Stage 3 or Stage 4 chronic kidney disease.

CONTRAINDICATIONS
Hectorol should not be given to patients with a tendency towards hypercalcemia or current evidence of vitamin D toxicity.

Dosing (Adults):
Initial dose of doxercalciferol is 10 mcg administered three times weekly at dialysis. The maximum recommended dose of doxercalciferol is 20 mcg administered three times a week at dialysis for a total of 60 mcg/week

Initial U.S. Approval:  2017

Mechanism of Action:
Etelcalcetide is a calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR). Etelcalcetide binds to the CaSR and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion.

INDICATIONS AND USAGE:
PARSABIV is a calcium-sensing receptor agonist indicated for:
Secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis. (1)

Limitations of Use:
PARSABIV has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations.

DOSAGE AND ADMINISTRATION: PDF
Ensure corrected serum calcium is at or above the lower limit of normal prior to initiation, dose increase, or re-initiation. (2.1)

The recommended starting dose is 5 mg administered by intravenous bolus injection three times per week at the end of hemodialysis treatment. (2.1)

The maintenance dose is individualized and determined by titration based on parathyroid hormone (PTH) and corrected serum calcium response. The dose range is 2.5 to 15 mg three times per week. (2.1)

The dose may be increased in 2.5 mg or 5 mg increments no more frequently than every 4 weeks. (2.2)

Measure serum calcium within 1 week after initiation or dose adjustment and every 4 weeks for maintenance. (2.2)
Measure PTH after 4 weeks from initiation or dose adjustment. (2.2)
Decrease or temporarily discontinue PARSABIV in individuals with PTH levels below the target range. (2.2)

Consider decreasing or temporarily discontinuing PARSABIV or use concomitant therapies to increase corrected serum calcium in patients with a corrected serum calcium below the lower limit of normal but at or above 7.5 mg/dL without symptoms of hypocalcemia. (2.2)

Stop PARSABIV and treat hypocalcemia if the corrected serum calcium falls below 7.5 mg/dL or patients report symptoms of hypocalcemia. (2.2)
Do not mix or dilute prior to administration. (2.3)

Administer by intravenous bolus injection into the venous line of the dialysis circuit at the end of the hemodialysis treatment during rinse back or intravenously after rinse back. (2.3)

HOW SUPPLIED:
Injection: 2.5 mg/0.5 mL solution in a single-dose vial
Injection: 5 mg/mL solution in a single-dose vial
Injection: 10 mg/2 mL solution in a single-dose vial

Dosing (Adults):
The recommended dosage of ferric sodium gluconate for the repletion treatment of iron deficiency in hemodialysis patients is 10 ml of ferric sodium gluconate (125 mg of elemental iron) diluted in 100 ml of 0.9% sodium chloride solution administered intravenously over 1 hour. Most patients will require a minimum cumulative dose of 1 gram of elemental iron, administered over eight sessions at sequential dialysis treatments to achieve favorable hemoglobin or hematocrit response.

Mechanism of Action
Paricalcitol is a synthetic, biologically active vitamin D analog of calcitriol with modifications to the side chain (D2) and the A (19-nor) ring. Preclinical and in vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion.

INDICATIONS AND USAGE
Zemplar is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease Stage 5.

CONTRAINDICATIONS
Zemplar should not be given to patients with evidence of vitamin D toxicity, hypercalcemia, or hypersensitivity to any ingredient in this product (see WARNINGS).

WARNINGS
Acute overdose of Zemplar may cause hypercalcemia, and require emergency attention. During dose adjustment, serum calcium and phosphorus levels should be monitored closely (e.g., twice weekly). If clinically significant hypercalcemia develops, the dose should be reduced or interrupted. Chronic administration of Zemplar may place patients at risk of hypercalcemia, elevated Ca × P product, and metastatic calcification.

Treatment of patients with clinically significant hypercalcemia consists of immediate dose reduction or interruption of Zemplar therapy and includes a low calcium diet, withdrawal of calcium supplements, patient mobilization, attention to fluid and electrolyte imbalances, assessment of electrocardiographic abnormalities (critical in patients receiving digitalis), hemodialysis or peritoneal dialysis against a calcium-free dialysate, as warranted. Serum calcium levels should be monitored frequently until normocalcemia ensues.

Phosphate or vitamin D-related compounds should not be taken concomitantly with Zemplar.

Dosing: 0.04 to 0.1 mcg/kg (2.8 to 7.0 mcg) IV 3 times/week at dialysis. Max dose 0.24 mcg/kg (16.8 mcg).

DOSAGE AND ADMINISTRATION
Starting dose is 10 mL with each meal.
Titrate the dose every 2 to 3 weeks until an acceptable serum phosphorus level is reached. Most patients require 15 to 20 mL with each meal.

HOW SUPPLIED
Oral Solution: 667 mg calcium acetate per 5 mL.

HOW SUPPLIED/ STORAGE AND HANDLING

PHOSLYRA for oral administration is a clear solution containing 667 mg calcium acetate per 5 mL. PHOSLYRA is supplied in amber-colored, multiple-dose bottles, packaged with a marked dosing cup in the following size:

473 mL (16 fl. oz) bottle (NDC 49230-643-31)

Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Sevelamer carbonate taken with meals has been shown to control serum phosphorus concentrations in patients with CKD who are on dialysis.

Mechanism of Action
Renvela contains sevelamer carbonate, a non-absorbed phosphate binding crosslinked polymer, free of metal and calcium. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the gastrointestinal tract and decreasing absorption, sevelamer carbonate lowers the phosphate concentration in the serum (serum phosphorus).

INDICATIONS AND USAGE
Renvela® (sevelamer carbonate) is indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis.

DOSAGE AND ADMINISTRATION
Because of the rapid reaction with the hydrochloric acid in the stomach, the dosing of Renvela powder or tablet is anticipated to be similar to that of the sevelamer hydrochloride salt or tablet.

General Dosing Information
Renvela should be given three times a day with meals.

Patients Not Taking a Phosphate Binder. The recommended starting dose of Renvela is 0.8 to 1.6 g with meals based on serum phosphorus level. Table1 provides recommended starting doses of Renvela for patients not taking a phosphate binder.

Switching from Sevelamer Hydrochloride Tablets. For patients switching from sevelamer hydrochloride tablets to sevelamer carbonate tablets or powder, use the same dose in grams. Further titration may be necessary to achieve desired phosphorus levels. The highest daily dose of sevelamer carbonate studied was 14 grams in CKD patients on dialysis.

Switching between Sevelamer Carbonate Tablets and Powder. Use the same dose in grams. Further titration may be necessary to achieve desired phosphorus levels.

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 and calcium acetate. Table 2 gives recommended starting doses of Renvela based on a patient’s current calcium acetate dose

Dose Titration for All Patients Taking Renvela. Titrate the Renvela dose by 0.8 g TID with meals at two-week intervals as necessary with the goal of controlling serum phosphorus within the target range.

2.2 Sevelamer Carbonate Powder Preparation Instructions
The entire contents of each 0.8 or 2.4 g packet should be placed in a cup and mixed thoroughly with the amount of water described in Table 3.

Table 3. Sevelamer Carbonate Powder Preparation Instructions

Multiple packets may be mixed together with the appropriate amount of water. Patients should be instructed to stir the mixture vigorously (it does not dissolve) and drink the entire preparation within 30 minutes or resuspend the preparation right before drinking.

Based on clinical studies, the average prescribed daily dose of sevelamer carbonate is approximately 7.2 g per day.

DOSAGE FORMS AND STRENGTHS
Tablets: 800 mg white oval, film-coated, compressed tablets imprinted with “RENVELA 800”

Powder: 0.8 g and 2.4 g pale yellow powder packaged in an opaque, foil lined, heat sealed packet

Sevelamer HCL:
---------------------------------------------
ESRD (hyperphosphatemia): 2 to 4 (800-1600 mg) caps orally three times daily with meals.

Note: the dose may be based on serum phosphorous.
Initial phosphate level:
>6.0 mg/dl and <7.5 mg/dl: 800 mg 3 times/day
>7.5 mg/dl and <9.0 mg/dl: 1200-1600 mg 3 times/day
>9.0 mg/dl: 1600 mg 3 times/day

Adjustment: Dosage should be adjusted based on serum phosphorous concentration, with a goal of lowering to <6.0 mg/dl.

Supplied: 400 mg, 800 mg tablet

Initial U.S. Approval:  2013

Mechanism of Action: In the aqueous environment of the GI tract, phosphate binding takes place by ligand exchange between hydroxyl groups and/or water in sucroferric oxyhydroxide and the phosphate in the diet. The bound phosphate is eliminated with feces.Both serum phosphorus levels and calcium-phosphorus product levels are reduced as a consequence of the reduced dietary phosphate absorption.

INDICATIONS AND USAGE:  Velphoro is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.
osphorus levels in patients with chronic kidney disease on dialysis.
DOSAGE AND ADMINISTRATION
Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, the tablets may be crushed.

Starting Dose
The recommended starting dose of Velphoro is 3 tablets (1,500 mg) per day, administered as 1 tablet (500 mg) 3 times daily with meals.

Titration and Maintenance
Monitor serum phosphorus levels and titrate the dose of Velphoro in decrements or increments of 500 mg (1 tablet) per day as needed until an acceptable serum phosphorus level is reached, with regular monitoring afterwards. Titrate as often as weekly.

Based on clinical studies, on average patients required 3 to 4 tablets (1,500 mg to 2,000 mg) a day to control serum phosphorus levels.
The highest daily dose studied in a Phase 3 clinical trial in ESRD patients was 6 tablets (3,000 mg) per day.

Administration
Velphoro must be administered with meals. To maximize the dietary phosphate binding, distribute the total daily dose among meals. No additional fluid above the amount usually taken by the patient is required.
If one or more doses of Velphoro are missed, the medication should be resumed with the next meal. Do not attempt to replace a missed dose.

HOW SUPPLIED: Velphoro (sucroferric oxyhydroxide) chewable tablet 500 mg