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August 24, 2016
A daily dose of folic acid may slow the decline of renal function in people with chronic kidney disease (CKD) who live in areas without folic acid fortification, the au"...
Overdosage of any form of vitamin D, including Hectorol is dangerous (see OVERDOSAGE). 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 < 55 mg2 /d2L in patients with chronic kidney disease. Radiographic evaluation of suspect anatomical regions may be useful in the early detection of this condition.
Since doxercalciferol is a precursor for 1α,25-(OH)2D2, a potent metabolite of vitamin D2, 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 undergoing dialysis. 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 DOSAGE AND ADMINISTRATION).
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.
Serious hypersensitivity reactions, including fatal outcome, have been reported post marketing in patients on hemodialysis following administration of Hectorol Injection. Hypersensitivity reactions include anaphylaxis with symptoms of angioedema (involving face, lips, tongue and airways), hypotension, unresponsiveness, chest discomfort, shortness of breath, and cardiopulmonary arrest. These reactions may occur separately or together.
Monitor patients receiving Hectorol Injection upon initiation of treatment for hypersensitivity reactions. Should a hypersensitivity reaction occur, discontinue Hectorol, monitor and treat if indicated (see CONTRAINDICATIONS).
The principal adverse effects of treatment with Hectorol Injection are hypercalcemia, hyperphosphatemia, 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. 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 levels within prescribed ranges.
In two open-label, single-arm, multi-centered studies, the incidence of hypercalcemia and hyperphosphatemia increased during therapy with Hectorol Injection (see ADVERSE REACTIONS). The observed increases during Hectorol treatment underscore the importance of regular safety monitoring of serum calcium and phosphorus levels throughout treatment. Patients with higher pretreatment serum levels of calcium ( > 10.5 mg/dL) or phosphorus ( > 6.9 mg/dL) were more likely to experience hypercalcemia or hyperphosphatemia. Therefore, Hectorol should not be given to patients with a recent history of hypercalcemia or hyperphosphatemia, or evidence of vitamin D toxicity.
Table 3: Incidence Rates of Hypercalcemia and
Hyperphosphatemia in Two Phase 3 Studies with Hectorol® Injection
|Study||Hypercalcemia (per 100 patient weeks)||Hyperphosphatemia (per 100 patient weeks)|
|Washout (Off Treatment)||Open-Label (Treatment)||Washout (Off Treatment)||Open-Label (Treatment)|
Serum levels of iPTH, calcium, and phosphorus should be determined prior to initiation of Hectorol treatment. During the early phase of treatment (i.e., first 12 weeks), serum iPTH, calcium, and phosphorus levels should be determined weekly. For dialysis patients in general, serum or plasma iPTH and serum calcium, phosphorus, and alkaline phosphatase should be determined periodically.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate the carcinogenic potential of doxercalciferol have not been conducted. No evidence of genetic toxicity was observed in an in vitro bacterial mutagenicity assay (Ames test) or a mouse lymphoma gene mutation assay. Doxercalciferol caused structural chromatid and chromosome aberrations in an in vitro human lymphocyte clastogenicity assay with metabolic activation. However, doxercalciferol was negative in an in vivo mouse micronucleus clastogenicity assay. Doxercalciferol had no effect on male or female fertility in rats at oral doses up to 2.5 mcg/kg/day (approximately 3 times the maximum recommended human oral dose of 60 mcg/wk based on mcg/m body surface area).
Use In Pregnancy
Pregnancy Category B
Reproduction studies in rats and rabbits, at doses up to 20 mcg/kg/day and 0.1 mcg/kg/day (approximately 25 times and less than the maximum recommended human oral dose of 60 mcg/week based on mcg/m body surface area, respectively) have revealed no teratogenic or fetotoxic effects due to doxercalciferol. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
It is not known whether doxercalciferol is excreted in human milk. Because other vitamin D derivatives are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from doxercalciferol, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and efficacy of Hectorol in pediatric patients have not been established.
Of the 70 patients treated with Hectorol Injection in the two Phase 3 clinical studies, 12 patients were 65 years or over. In these studies, no overall differences in efficacy or safety were observed between patients 65 years or older and younger patients.
Studies examining the influence of hepatic insufficiency on the metabolism of Hectorol were inconclusive. Since patients with hepatic insufficiency may not metabolize doxercalciferol appropriately, the drug should be used with caution in patients with impaired hepatic function. More frequent monitoring of iPTH, calcium, and phosphorus levels should be done in such individuals.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/9/2016
Additional Hectorol Injection Information
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