Doxercalciferol

Table of Contents > Drugs > Doxercalciferol

	Pronunciation
	U.S. Brand Names
	Synonyms
	Generic Available
	Canadian Brand Names
	Use
	Pregnancy Risk Factor
	Pregnancy Implications
	Lactation
	Contraindications
	Warnings/Precautions
	Adverse Reactions
	Overdosage/Toxicology
	Drug Interactions
	Stability

	Mechanism of Action
	Pharmacodynamics/Kinetics
	Dosage
	Monitoring Parameters
	Reference Range
	Dietary Considerations
	Patient Education
	Dental Health: Effects on Dental Treatment
	Dental Health: Vasoconstrictor/Local Anesthetic Precautions
	Mental Health: Effects on Mental Status
	Mental Health: Effects on Psychiatric Treatment
	Dosage Forms
	References
	International Brand Names

Pronunciation

(doks er kal si fe FEER ole)

U.S. Brand Names

Hectorol®

Synonyms

-Hydroxyergocalciferol

Generic Available

Canadian Brand Names

Hectorol®

Use

Treatment of secondary hyperparathyroidism in patients with chronic kidney disease

Pregnancy Risk Factor

Pregnancy Implications

Reproduction in animals (usual and high dose) do not reveal teratogenic or fetotoxic effects.

Lactation

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to any component of the formulation; history of hypercalcemia or evidence of vitamin D toxicity

Warnings/Precautions

Other forms of vitamin D should be discontinued when doxercalciferol is started. Overdose from vitamin D may lead to progressive hypercalcemia and needs to be avoided. Careful dosage titration and monitoring can minimize risk. Hyperphosphatemia exacerbates secondary hyperparathyroidism, diminishing the effect of doxercalciferol. Hyperphosphatemia should be corrected before initiating therapy. Use with caution in patients with hepatic impairment. Safety and efficacy have not been established in pediatric patients.

Adverse Reactions

Note: As reported in dialysis patients.

>10%:

Cardiovascular: Edema (34%)

Central nervous system: Headache (28%), malaise (28%), dizziness (12%)

Gastrointestinal: Nausea/vomiting (24%)

Respiratory: Dyspnea (12%)

1% to 10%:

Cardiovascular: Bradycardia (7%)

Central nervous system: Sleep disorder (3%)

Dermatologic: Pruritus (8%)

Gastrointestinal: Anorexia (5%), constipation (3%), dyspepsia (5%), weight gain (5%)

Neuromuscular & skeletal: Arthralgia (5%)

Miscellaneous: Abscess (3%)

Overdosage/Toxicology

Doxercalciferol, in excess, can cause hypercalcemia, hypercalciuria, hyperphosphatemia, and oversuppression of PTH secretion. Following withdrawal of the drug and calcium supplements, hypercalcemia treatment consists of a low calcium diet and monitoring. Adjustments of calcium in the dialysis bath can also be made if necessary. When calcium levels normalize, doxercalciferol can be restarted. Reduce each dose by at least 2.5 mcg. Monitor serum calcium levels closely.

Signs and symptoms of early hypercalcemia include: Anorexia, bone pain, constipation, headache, metallic taste, muscle pain, nausea, somnolence, vomiting, weakness, xerostomia

Signs and symptoms of late hypercalcemia include: Albuminuria, anorexia, apathy, AST/ALT increased, BUN increased, cardiac arrhythmias, conjunctivitis (calcific), dehydration, ectopic calcification, growth arrested, hypercholesterolemia, hypertension, hyperthermia, libido decreased, nocturia, pancreatitis, photophobia, polydipsia, polyuria, pruritus, psychosis (rare), rhinorrhea, sensory disturbances, urinary tract infections, weight loss

Drug Interactions

Decreased effect: Cholestyramine, mineral oil (both reduce absorption)

Increased toxicity: Concurrent use of other vitamin D supplements, magnesium-containing antacids and supplements (hypermagnesemia)

Stability

Store at controlled room temperature of 15°C to 30°C (59°F to 86°F); protect injection 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

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 150-300 pg/mL: Maintain the current dose

iPTH level <100 pg/mL: Suspend doxercalciferol for 1 week; resume at a reduced dose (at least 1 mcg lower)

Monitoring Parameters

Dialysis patients: Before initiating, check iPTH, serum calcium and phosphorus. Check weekly thereafter until stable. Serum iPTH, calcium, phosphorus, and alkaline phosphatase should be 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