doxercalciferol (Rx)

Frequency Not Defined

Edema

Palpitation

Chills

Dizziness

Headache

Malaise

Nausea

Vomiting

Hypercalcemia

Hypercalciuria

Anorexia

Constipation

Dyspepsia

Arthralgia

Edema

Weight increase

Sleep disorder

Dyspnea Pruritus

Postmarketing Reports

Hypersensitivity reactions (patients on hemodialysis)

Contraindications

Hypersensitivity

Hypercalcemia, hyperphosphatemia, hypervitaminosis D

Cautions

Monitor serum calcium and phosphorus frequently; reduce dose or stop the drug if Ca x P product >75 mg²/dL²

Acute hypercalcemia may exacerbate tendencies for cardiac arrhythmias and seizures and may potentiate action of digitalis drugs; chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification; in chronic kidney disease maintain Ca x P product at <55 mg²/dL²

Use with caution in patients receiving digitalis; digitalis toxicity is potentiated by hypercalcemia

Decrease dose if hypercalcemia or hyperphosphatemia occurs

Serious hypersensitivity reactions, including fatal outcome, in patients on hemodialysis, reported post marketing; hypersensitivity reactions include anaphylaxis with symptoms of angioedema (involving face, lips, tongue and airways), hypotension, unresponsiveness, chest discomfort, shortness of breath, and cardiopulmonary arrest; reactions may occur separately or together

Use oral calcium-based or other non-aluminum-containing phosphate binders and a low phosphate diet to control serum phosphorus levels in patients undergoing dialysis

Pregnancy

Limited available data in pregnant women are insufficient to identify drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes; there are risks to mother and fetus associated with chronic kidney disease in pregnancy as it increases risk for maternal hypertension and preeclampsia, miscarriage, preterm delivery polyhydramnios, stillbirth, and low-birth-weight infants

Animal data

• In reproduction studies in rats and rabbits treated during organogenesis at up to 20 mcg/kg/day and 0.1 mcg/kg/day, respectively (approximately 25 times (rats) and less than (rabbits) maximum recommended human oral dose of 60 mcg/week based on mcg/m2 body surface area), no adverse developmental effects observed

Lactation

There is no information available on presence of doxercalciferol in human milk, effects of drug on breastfed infant, or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Infants exposed to drug through breast milk should be monitored for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation and weight loss; consider monitoring of serum calcium in infant

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Doxercalciferol is metabolized to the active form of vitamin D, which in turn controls the reabsorption of calcium by the kidneys, controls the intestinal absorption of dietary calcium, and along with parathyroid hormone controls the mobilization of calcium from the skeleton.

Absorption

Onset: IV: 10-12 wk, PO: 3-4 months

Peak Plasma Time: 8-12 hr

Metabolism

Metabolism: in liver to hepatic vitamin D 25-hydroxylases to 1,25-dihydroxyvitamin D2 (active)

Metabolites: 1,25-dihydroxyvitamin D2 (active), responsible for most of metabolic effects of doxercalciferol and 1,24-dihydroxyvitamin D2 (minor metabolite)

Elimination

Half-Life: 32-37 hr (active metabolite 1,25-dihydroxyvitamin D2)

Dialyzable: No (HD)

IV Administration

Administer by IV bolus at end of dialysis session

Storage

Capsule: 15-30ºC (59-86ºF)

Unopened vial: 15-30ºC (59-86ºF)

Opened multiple-dose vial: May store up to 3 days at 2-8ºC (36-46ºF); discard unused portion in vial after 3 days