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Hectorol Injection

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Hectorol Injection

Hectorol Injection

WARNINGS

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/dL2in 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-(0H)2D2, a potent metabolite of vitamin D2, pharmacologic doses of vitamin D and its derivatives should be withheld during Hectorol (doxercalciferol injection) 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 (doxercalciferol injection) in reducing blood PTH levels. If hypercalcemia occurs after initiating Hectorol (doxercalciferol injection) therapy, the dose of Hectorol (doxercalciferol injection) and/or calcium-con-taining phosphate binders should be decreased. If hyperphosphatemia occurs after initiating Hectorol (doxercalciferol injection) , the dose of Hectorol (doxercalciferol injection) should be decreased and/or the dose of phosphate binders increased. (See dosing recommendations for Hectorol under DOSAGE AND ADMINISTRATION section.)

Magnesium-containing antacids and Hectorol (doxercalciferol injection) should not be used concomitantly in patients on chronic renal dialysis because such use may lead to the development of hypermagnesemia.

PRECAUTIONS

General

The principal adverse effects of treatment with Hectorol (doxercalciferol injection) 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 (doxercalciferol injection) , 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 section). The observed increases during Hectorol (doxercalciferol injection) treatment underscore the importance of regular safety monitoring of serum calcium and phosphorus levels throughout treatment. Patients with higher pre-treatment serum levels of calcium (> 10.5 mg/dL) or phosphorus (> 6.9 mg/dL) were more likely to experience hypercalcemia or hyperphosphatemia. Therefore, Hectorol (doxercalciferol injection) 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 (doxercalciferol injection) '9 Injection

Study Hypercalcemia (per 100 patient weeks) Hyperphosphatemia (per 100 patient weeks)
Washout (Off Treatment) Open-Label (Treatment) Washout (Off Treatment) Open-Label (Treatment)
Study C 0.9 0.9 0.9 2.4
Study D 0.3 1.0 1.2 3.7

Laboratory Tests

Serum levels of IPTH, calcium, and phosphorus should be determined prior to Initiation of Hectorol (doxercalciferol injection) 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 doxercalclferol 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. Doxercalclferol caused structural chromatid and chromosome aberrations In an in vitro human lymphocyte clastogenlclty assay with metabolic activation. However, doxercalclferol was negative In an in vivo mouse micronucleus clastogenlclty assay. Doxercalclferol 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 meg/week based on mcg/m2 body surface area, respectively) have revealed no teratogenic or fetotoxic effects due to doxercalclferol. 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.

Nursing Mothers

It is not known whether doxercalclferol 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 doxercalclferol, 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.

Pediatric Use

Safety and efficacy of Hectorol (doxercalciferol injection) in pediatric patients have not been established.

Geriatric Use

Of the 70 patients treated with Hectorol (doxercalciferol injection) 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.

Hepatic Insufficiency

Studies examining the influence of hepatic insufficiency on the metabolism of Hectorol (doxercalciferol injection) were inconclusive. Since patients with hepatic insufficiency may not metabolize doxercalclferol 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.

Last reviewed on RxList: 1/24/2011
This monograph has been modified to include the generic and brand name in many instances.

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