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Pronunciation
(doks er kal si fe FEER ole)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of secondary hyperparathyroidism in patients with chronic kidney disease
Pregnancy Risk Factor
B
Pregnancy Considerations
Reproduction in animals (usual and high dose) do not reveal teratogenic or fetotoxic effects.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Excretion in breast milk is unknown. Other vitamin D derivatives are excreted in breast milk; there is a potential for adverse effects. Therefore, the manufacturer recommends that breast-feeding be discontinued or doxercalciferol discontinued, depending upon importance of the drug to the mother.
Contraindications
History of hypercalcemia or evidence of vitamin D toxicity
Warnings/Precautions
Concerns related to adverse effects:
• Excessive vitamin D: Excessive vitamin D administration may lead to over suppression of PTH, progressive or acute hypercalcemia, hypercalciuria, hyperphosphatemia and adynamic bone disease.
• Hypercalcemia: Progressive and/or acute hypercalcemia may increase risk of cardiac arrhythmias and seizures; chronic hypercalcemia may lead to generalized vascular and other soft-tissue calcification. Phosphate and vitamin D (and its derivatives) should be withheld during therapy to avoid hypercalcemia.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Hyperphosphatemia: Should be corrected before initiating therapy; exacerbates secondary hyperparathyroidism, diminishing the effect of doxercalciferol.
Concurrent drug therapy issues:
• Cardiac glycosides: Use with caution in patients taking cardiac glycosides; digitalis toxicity is potentiated by hypercalcemia.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues:
• Injection: Intended for I.V. use only.
Other warnings/precautions:
• Appropriate use: Other forms of vitamin D should be discontinued when doxercalciferol is started.
Adverse Reactions
Note: As reported in dialysis patients.
>10%:
Cardiovascular: Edema (34%)
Central nervous system: Headache (28%), malaise (28%), dizziness (12%)
Gastrointestinal: Nausea/vomiting (21%)
Respiratory: Dyspnea (12%)
1% to 10%:
Cardiovascular: Bradycardia (7%)
Central nervous system: Sleep disorder (3%)
Dermatologic: Pruritus (8%)
Endocrine & metabolic: Hypercalcemia (I.V. ~1%), hyperphosphatemia (I.V. 2% to 4%)
Gastrointestinal: Anorexia (5%), dyspepsia (5%), weight gain (5%)
Neuromuscular & skeletal: Arthralgia (5%)
Miscellaneous: Abscess (3%)
Drug Interactions
There are no known significant interactions.
Storage
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). The injection should be protected from light.
Mechanism of Action
Doxercalciferol is metabolized to the active form of vitamin D. The active form of vitamin D controls the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidneys, and in conjunction with PTH, the mobilization of calcium from the skeleton.
Pharmacodynamics/Kinetics
Metabolism: Hepatic via CYP27 to active metabolites
Half-life elimination: Active metabolite: 32-37 hours; up to 96 hours
Dosage
Oral:
Dialysis patients: Dose should be titrated to lower iPTH to 150-300 pg/mL; dose is adjusted at 8-week intervals (maximum dose: 20 mcg 3 times/week)
Initial dose: iPTH >400 pg/mL: 10 mcg 3 times/week at dialysis
Dose titration:
iPTH level decreased by 50% and >300 pg/mL: Dose can be increased to 12.5 mcg 3 times/week for 8 more weeks; this titration process can continue at 8-week intervals; each increase should be by 2.5 mcg/dose
iPTH level 150-300 pg/mL: Maintain current dose
iPTH level <100 pg/mL: Suspend doxercalciferol for 1 week; resume at a reduced dose; decrease each dose (not weekly dose) by at least 2.5 mcg
Predialysis patients: Dose should be titrated to lower iPTH to 35-70 pg/mL with stage 3 disease or to 70-110 pg/mL with stage 4 disease: Dose may be adjusted at 2-week intervals (maximum dose: 3.5 mcg/day)
Initial dose: 1 mcg/day
Dose titration:
iPTH level >70 pg/mL with stage 3 disease or >110 pg/mL with stage 4 disease: Increase dose by 0.5 mcg every 2 weeks as necessary
iPTH level 35-70 pg/mL with stage 3 disease or 70-110 pg/mL with stage 4 disease: Maintain current dose
iPTH level is <35 pg/mL with stage 3 disease or <70 pg/mL with stage 4 disease: Suspend doxercalciferol for 1 week, then resume at a reduced dose (at least 0.5 mcg lower)
I.V.:
Dialysis patients: Dose should be titrated to lower iPTH to 150-300 pg/mL; dose is adjusted at 8-week intervals (maximum dose: 18 mcg/week)
Initial dose: iPTH level >400 pg/mL: 4 mcg 3 times/week after dialysis, administered as a bolus dose
Dose titration:
iPTH level decreased by <50% and >300 pg/mL: Dose can be increased by 1-2 mcg at 8-week intervals, as necessary
iPTH level decreased by >50% and >300 pg/mL: Maintain current dose
iPTH level 150-300 pg/mL: Maintain current dose
iPTH level <100 pg/mL: Suspend doxercalciferol for 1 week; resume at a reduced dose (at least 1 mcg lower)
Hypercalcemia, hyperphosphatemia, or serum calcium times phosphorus product >55 mg2/dL2: Decrease or suspend dose and/or adjust dose of phosphate binders; if dose is suspended, resume at a reduced dose (at least 1 mcg lower)
Dosage adjustment in hepatic impairment: Use with caution; no guidelines for dosage adjustment
Monitoring Parameters
Dialysis patients: Before initiating, check iPTH, serum calcium, and phosphorus. Check weekly for first 12 weeks of therapy. Thereafter, serum iPTH, calcium, phosphorus, and alkaline phosphatase should be periodically monitored.
Predialysis patients: iPTH, serum calcium and phosphorus every 2 weeks for 3 months following initiation and dose adjustments, then monthly for 3 months, then every 3 months
Reference Range
Serum calcium times phosphorus product should be <55 mg2/dL2 with chronic kidney disease
Target range by stage of chronic kidney disease:
Stage 3:
GFR 30-59 mL/minute: iPTH 35-70 pg/mL
Serum phosphorus: 2.7-4.6 mg/dL
Stage 4:
GFR 15-29 mL/minute: iPTH 70-110 pg/mL
Serum phosphorus: 2.7-4.6 mg/dL
Stage 5:
GFR <15 mL/minute or dialysis: iPTH 150-300 pg/mL
Serum phosphorus: 3.5-5.5 mg/dL
Dietary Considerations
Based on serum levels, dietary phosphorus may be restricted and/or controlled with calcium-based phosphorus binders. The daily combined calcium intake (dietary and calcium based phosphate binder) should be 1.5-2 g. Additional vitamin D supplements and magnesium-containing antacids should be avoided. Capsules contain coconut oil.
Patient Education
Be clear on dose and directions for taking. Stop other vitamin D products. Do not miss doses. Avoid magnesium-containing antacids and supplements. Report headache, dizziness, weakness, sleepiness, severe nausea, vomiting, dry mouth, loss of appetite, constipation, metallic taste, muscle and/or bone pain, significant fluid retention, malaise, shortness of breath, and difficulty thinking or concentrating to your prescriber. Do not take over-the-counter medicines or supplements without first consulting your prescriber. Follow diet and calcium supplements as directed by your prescriber.
Geriatric Considerations
No special changes in dose are required. Caution should be used in the elderly using magnesium products (MOM, magnesium containing antacids, etc). These should be stopped if possible before initiating doxercalciferol.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness and malaise are common; may cause confusion or sleep disorders
Mental Health: Effects on Psychiatric Treatment
Nausea and vomiting are common; use caution with SSRIs
Nursing: Physical Assessment/Monitoring
Monitor therapeutic effectiveness (laboratory results), adverse reactions. Monitor for fluid retention. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse reactions to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, softgel:
Hectorol®: 0.5 mcg, 2.5 mcg [contains coconut oil]
Injection, solution:
Hectorol®: 2 mcg/mL (2 mL) [contains disodium edetate]
Pricing: U.S. (www.drugstore.com)
Capsules (Hectorol)
0.5 mcg (50): $268.85
2.5 mcg (50): $937.28
References
Eknoyan G, Levin A, and Levin NW, “Bone Metabolism and Disease in Chronic Kidney Disease,” Am J Kidney Dis, 2003, 42(4 Suppl 3):1-201.
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 6. Serum Calcium and Calcium-Phosphorus Product,” Am J Kidney Dis, 2003, 42(4 Suppl 3):77-84.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2009
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