Hectorol Information
Hectorol () Description
Doxercalciferol, the active ingredient in Hectorol () , is a synthetic vitamin D analog that undergoes metabolic activation to form 1α,25-dihydroxyvitamin D (1α,25-(OH)D), a naturally occurring, biologically active form of vitamin D. Hectorol () is available as soft gelatin capsules containing 0.5 mcg, 1 mcg or 2.5 mcg doxercalciferol. Each capsule also contains fractionated triglyceride of coconut oil, ethanol, and butylated hydroxyanisole (BHA). The capsule shells contain gelatin, glycerin and titanium dioxide. In addition, the 0.5 mcg capsule shells contain yellow iron oxide and FD&C Red No. 40, the 1 mcg capsule shells contain FD&C Yellow No. 6, and the 2.5 mcg capsule shells contain yellow iron oxide.
Doxercalciferol is a colorless crystalline compound with a calculated molecular weight of 412.66 and a molecular formula of CHO. It is soluble in oils and organic solvents, but is relatively insoluble in water. Chemically, doxercalciferol is (1α,3β,5Z,7E,22E)-9,10-secoergosta-5,7,10(19),22-tetraene-1,3-diol. The structural formula is presented in below:
Other names frequently used for doxercalciferol are 1α-hydroxyvitamin D, 1α-OH-D, and 1α-hydroxyergocalciferol.
Hectorol () Clinical Pharmacology
Vitamin D levels in humans depend on two sources: (1) exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D (cholecalciferol) and (2) dietary intake of either vitamin D (ergocalciferol) or vitamin D. Vitamin D and vitamin D must be metabolically activated in the liver and the kidney before becoming fully active on target tissues. The initial step in the activation process is the introduction of a hydroxyl group in the side chain at C-25 by the hepatic enzyme, CYP 27 (a vitamin D-25-hydroxylase). The products of this reaction are 25-(OH)D and 25-(OH)D, respectively. Further hydroxylation of these metabolites occurs in the mitochondria of kidney tissue, catalyzed by renal 25-hydroxyvitamin D-1-α-hydroxylase to produce 1α,25-(OH)D, the primary biologically active form of vitamin D, and 1α,25-(OH)D (calcitriol), the biologically active form of vitamin D.
Doxercalciferol is absorbed from the gastrointestinal tract and activated by CYP 27 in the liver to form 1α,25-(OH)D (major metabolite) and 1α,24-dihydroxyvitamin D (minor metabolite). Activation of doxercalciferol does not require the involvement of the kidneys.
In healthy volunteers, peak blood levels of 1α,25-(OH)D, the major metabolite of doxercalciferol, are attained at 11-12 hours after repeated oral doses of 5 to 15 mcg of Hectorol () and the mean elimination half-life of 1α,25-(OH)D is approximately 32 to 37 hours with a range of up to 96 hours. The mean elimination half-life in patients with end-stage renal disease (ESRD) on dialysis appears to be similar. Hemodialysis causes a temporary increase in 1α,25-(OH)D mean concentrations, presumably due to volume contraction. 1α,25-(OH)D is not removed from blood during hemodialysis.
Hectorol () Contraindications
Hectorol () should not be given to patients with a tendency towards hypercalcemia or current evidence of vitamin D toxicity.
Hectorol () Warnings
Overdosage of any form of vitamin D, including Hectorol () , is dangerous (see ). Progressive hypercalcemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention. Acute hypercalcemia may exacerbate tendencies for cardiac arrhythmias and seizures and may potentiate the action of digitalis drugs. Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. The serum calcium times serum phosphorus (Ca X P) product should be maintained at
Since doxercalciferol is a precursor for 1α,25-(OH)D, a potent metabolite of vitamin D, pharmacologic doses of vitamin D and its derivatives should be withheld during Hectorol () treatment to avoid possible additive effects and hypercalcemia.
Oral calcium-based or other non-aluminum-containing phosphate binders and a low phosphate diet should be used to control serum phosphorus levels in patients with chronic kidney disease. Uncontrolled serum phosphorus exacerbates secondary hyperparathyroidism and can lessen the effectiveness of Hectorol () in reducing blood PTH levels. If hypercalcemia occurs after initiating Hectorol () therapy, the dose of Hectorol () and/or calcium-containing phosphate binders should be decreased. If hyperphosphatemia occurs after initiating Hectorol () , the dose of Hectorol () should be decreased and/or the dose of phosphate binders increased. (See dosing recommendations for Hectorol () under section.)
Magnesium-containing antacids and Hectorol () should not be used concomitantly in patients on chronic renal dialysis because such use may lead to the development of hypermagnesemia.
Hectorol () Precautions
Active vitamin D sterols should not be used as initial treatment of nutritional vitamin D deficiency (as defined by low 25-hydroxy vitamin D). Patients should be checked and treated for nutritional vitamin D deficiency prior to initiating treatment with Hectorol () .
The principal adverse effects of treatment with Hectorol () are hypercalcemia, hyperphosphatemia, hypercalciuria, and oversuppression of PTH (iPTH less than 150 pg/mL). Prolonged hypercalcemia can lead to calcification of soft tissues, including the heart and arteries, and hyperphosphatemia can exacerbate hyperparathyroidism. Hypercalciuria can accelerate the onset of renal failure through nephrocalcinosis. Oversuppression of PTH may lead to adynamic bone syndrome. All of these potential adverse effects should be managed by regular patient monitoring and appropriate dosage adjustments. During treatment with Hectorol () , patients usually require dose titration, as well as adjustment in co-therapy (i.e., dietary phosphate binders) in order to maximize PTH suppression while maintaining serum calcium and phosphorus within prescribed ranges.
The patient, spouse, or guardian should be informed about compliance with dosage instructions, adherence to instructions about diet, calcium supplementation, and avoidance of the use of nonprescription drugs without prior approval from their physician. Patients should also be carefully informed about the symptoms of hypercalcemia (see section).
Patients' total combined elemental calcium intake (dietary and phosphate binder) should not exceed 2 g daily.
Hectorol () Adverse Reactions
Hectorol () has been evaluated for safety in clinical studies in 55 patients (27 active and 28 placebo) with chronic kidney disease, Stages 3 or 4. In two placebo-controlled, double-blind, multicenter studies, discontinuation of therapy due to any adverse event occurred in one (3.7%) of 27 patients treated with Hectorol () for 24 weeks (dosage titrated to achieve target iPTH levels, see ) and in three (10.7%) of 28 patients treated with placebo for 24 weeks. Adverse events occurring in the Hectorol () group at a frequency of 5% or greater and more frequently than in the placebo group are as follows: – Infection, Chest Pain; – Constipation, Dyspepsia; – Anemia; – Dehydration; – Depression, Hypertonia, Insomnia, Paresthesia; – Cough increased, Dyspnea, Rhinitis.
Potential adverse effects of Hectorol () are, in general, similar to those encountered with excessive vitamin D intake. The early and late signs and symptoms of vitamin D intoxication associated with hypercalcemia include:
Hectorol () Overdosage
Administration of Hectorol () to patients in excess doses can cause hypercalcemia, hypercalciuria, hyperphosphatemia, and oversuppression of PTH secretion leading in certain cases to adynamic bone disease. High intake of calcium and phosphate concomitant with Hectorol () may lead to similar abnormalities. High levels of calcium in the dialysate bath may contribute to hypercalcemia.
Hectorol () Dosage And Administration
The recommended initial dose of Hectorol () is 10 mcg administered three times weekly at dialysis (approximately every other day). The initial dose should be adjusted, as needed, in order to lower blood iPTH into the range of 150 to 300 pg/mL. The dose may be increased at 8-week intervals by 2.5 mcg if iPTH is not lowered by 50% and fails to reach the target range. The maximum recommended dose of Hectorol () is 20 mcg administered three times a week at dialysis for a total of 60 mcg per week. Drug administration should be suspended if iPTH falls below 100 pg/mL and restarted one week later at a dose that is at least 2.5 mcg lower than the last administered dose. During titration, iPTH, serum calcium, and serum phosphorus levels should be obtained weekly. If hypercalcemia, hyperphosphatemia, or a serum calcium times serum phosphorus product greater than 55 mg/dL is noted, the dose of Hectorol () should be decreased or suspended and/or the dose of phosphate binders should be appropriately adjusted. If suspended, the drug should be restarted at a dose that is at least 2.5 mcg lower.
Dosing must be individualized and based on iPTH levels with monitoring of serum calcium and serum phosphorus levels. The following is a suggested approach in dose titration:
The recommended initial dose of Hectorol () is 1 mcg administered once daily. The initial dose should be adjusted, as needed, in order to lower blood iPTH to within target ranges (see table below). The dose may be increased at 2-week intervals by 0.5 mcg to achieve the target range of iPTH. The maximum recommended dose of Hectorol () is 3.5 mcg administered once per day.
Serum levels of calcium and phosphorus and plasma levels of iPTH should be monitored at least every two weeks for 3 months after initiation of Hectorol () therapy or following dose adjustments in Hectorol () therapy, then monthly for 3 months, and every 3 months thereafter. If hypercalcemia, hyperphosphatemia, or a serum calcium times phosphorus product greater than 55 mg/dL is noted, the dose of Hectorol () should be decreased or suspended and/or the dose of phosphate binders should be appropriately adjusted. If suspended, the drug should be restarted at a dose that is at least 0.5 mcg lower.
Dosing must be individualized and based on iPTH levels with monitoring of serum calcium and serum phosphorus levels. presents a suggested approach in dose titration:
Hectorol () How Supplied
NDC 58468-0120-1 0.5 mcg doxercalciferol in soft gelatin, salmon, oval capsules, imprinted ; foil induction sealed bottles of 50.
NDC 58468-0124-1
1 mcg doxercalciferol in soft gelatin, peach, oval capsules, imprinted ; foil induction sealed bottles of 50.
NDC 58468-0121-1
2.5 mcg doxercalciferol in soft gelatin, butter yellow, oval capsules, imprinted ; foil induction sealed bottles of 50.
Manufactured by Catalent Pharma Solutions forGenzyme Corporation, 500 Kendall Street, Cambridge, MA 02142 800-847-0069 Hectorol () and GENZYME are registered trademarks of Genzyme Corporation.
Hectorol () Package Carton - Principal Display Panel - . Mcg Capsules
NDC 58468-0120-1
Hectorol ()
(doxercalciferol capsules)
0.5 mcg
50 Capsules
Rx only
Hectorol () Package Carton - Principal Display Panel - Mcg Capsules
NDC 58468-0124-1
Hectorol ()
(doxercalciferol capsules)
1 mcg
50 Capsules
Rx only
Hectorol () Package Carton - Principal Display Panel - . Mcg Capsules
NDC 58468-0121-1
Hectorol ()
(doxercalciferol capsules)
2.5 mcg
50 Capsules
Rx only
