- Capsules 0.5 mcg
- Capsules 2.5 mcg
- Injection 2 mcg/mL
Activated by CYP 27 in the liver to metabolically active forms of vitamin D, which controls intestinal absorption of dietary calcium and tubular reabsorption of calcium by the kidney, mobilizes calcium from the skeleton in conjunction with parathyroid hormone (PTH), and suppress PTH synthesis and secretion.
T max for major metabolite is 11 to 12 h (oral) and 8 h (IV).
Activated by CYP 27 in the liver to form 1α-25-(OH) 2 D 2 (major metabolite) and 1α-24-dihydroxyvitamin D 2 (minor metabolite). Activation does not require involvement of kidneys.
The t ½ is approximately 32 to 37 h in healthy volunteers and patients with end-stage renal disease.
Indications and Usage
Treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis (oral or IV); treatment of secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease (oral).
Patients with tendency towards hypercalcemia or evidence of vitamin D toxicity.
Dosage and AdministrationDialysis
IV Initial : 4 mcg 3 times/wk at end of dialysis. Dose titration : Adjust dose as needed to lower blood intact parathyroid hormone (iPTH) into range of 150 to 300 pg/mL. The following dose titrations are suggested: iPTH decreased by less than 50% and above 300 pg/mL – increase by 1 to 2 mcg at 8 wk intervals (max, 6 mcg 3 times/wk); iPTH 150 to 300 pg/mL – maintain dose; iPTH less than 100 pg/mL – suspend for 1 wk, then resume at dose that is at least 1 mcg lower. PO Initial : 10 mcg 3 times/wk at dialysis. Dose titration : Adjust dose as needed to lower blood iPTH into range of 150 to 300 pg/mL. The following dose titrations are suggested: iPTH above 300 pg/mL – increase by 2.5 mcg at 8 wk intervals (max, 20 mcg 3 times/wk); iPTH 150 to 300 pg/mL – maintain dose; iPTH less than 100 pg/mL – suspend for 1 wk, then resume at dose that is at least 2.5 mcg lower.Predialysis: Stage 3
PO Initial : 1 mcg daily if iPTH more than 70 pg/mL. Dose titration : Adjust dose as needed to lower blood iPTH into range of 35 to 70 pg/mL. The following dose titrations are suggested: iPTH above 70 pg/mL – increase by 0.5 mcg every 2 wk (max, 3.5 mcg daily); iPTH 35 to 70 pg/mL – maintain dose; iPTH less than 35 pg/mL – suspend for 1 wk, then resume at dose that is at least 0.5 mcg lower.Predialysis: Stage 4
PO Initial : 1 mcg daily if iPTH more than 110 pg/mL. Dose titration : Adjust dose as needed to lower blood iPTH into range of 70 to 110 pg/mL. The following dose titrations are suggested: iPTH above 110 pg/mL – increase by 0.5 mcg every 2 wk (max, 3.5 mcg daily); iPTH 70 to 110 pg/mL – maintain dose; iPTH less than 70 pg/mL – suspend for 1 wk, then resume at dose that is at least 0.5 mcg lower.
- Ensure that patient has a combined (dietary and calcium-based phosphate binder) daily intake of 1.5 to 2 g.
- For IV bolus administration only. Not for intradermal, subcutaneous, IM, IV infusion, or intraarterial administration.
- Solution should be colorless to faint yellow. Do not administer if solution is discolored, cloudy, or contains particulate matter.
- Discard any unused portion. Do not save for future use.
- Administer without regard to meals. Administer with food if GI upset occurs.
- Administer prescribed dose no more than every other day.
Store capsules at controlled room temperature (68° to 77°F). Store injection at controlled room temperature (59° to 77°F). Protect injection from light.
Intestinal absorption of doxercalciferol may be decreased.CYP-450 inhibitors (eg, erythromycin, ketoconazole)
May inhibit 25-hydroxylation of doxercalciferol, necessitating dosage adjustment.Enzyme inducers (eg, glutethimide, phenobarbital)
May increase 25-hydroxylation, necessitating dosage adjustment.Magnesium-containing antacids
Because risk of hypermagnesemia may be increased, avoid concurrent use.Mineral oil, other substances affecting fat absorption
May alter absorption and availability of doxercalciferol.
Laboratory Test Interactions
None well documented.
Headache, malaise (28%); dizziness (12%); sleep disorder (3%).
Nausea, vomiting (21%); anorexia, dyspepsia (5%); constipation (3%).
Edema (34%); weight increase (5%); hypercalcemia; hyperphosphatemia; oversuppression of iPTH.
Determine serum or plasma iPTH and serum calcium, phosphorous, and alkaline phosphatase periodically.Dialysis
Determine iPTH, serum calcium, and serum phosphorous prior to starting therapy with doxercalciferol, then weekly during the early phase of treatment (first 12 wk), and then periodically thereafter. Reduce dose or suspend doxercalciferol therapy and/or adjust phosphate binder dose if clinically significant hypercalcemia, hyperphosphatemia, or a serum Ca × P product more than 55 mg 2 /dL 2 is noted. If doxercalciferol is suspended, restart at dose that is at least 2.5 mcg lower (oral) or 1 mcg lower (IV).Predialysis
Determine iPTH, serum calcium, and serum phosphorous at least every 2 wk for 3 mo after initiating therapy or following dose adjustments, then monthly for 3 mo, and every 3 mo thereafter.
Category B .
Safety and efficacy not established.
No differences in safety and efficacy observed between patients older than 65 yr of age and younger patients.
May not metabolize doxercalciferol appropriately; use with caution and monitor iPTH, calcium, and phosphorous levels more frequently.
Do not administer to patients with recent history of hypercalcemia or hyperphosphatemia, or evidence of vitamin D toxicity.
Nutritional vitamin D deficiency
Do not use active vitamin D sterols as initial treatment of nutritional vitamin D deficiency. Check and treat patients for nutritional vitamin D deficiency prior to initiating treatment with doxercalciferol.
Incidence of hypercalcemia, hyperphosphatemia, and hypercalciuria has not been fully studied when 25-OH vitamin D levels are at least 30 ng/mL.
Supplemental vitamin D
To avoid hypercalcemia, withhold pharmacologic doses of vitamin D and its derivatives during treatment.
Hypercalcemia, hypercalciuria, hyperphosphatemia, oversuppression of parathyroid hormone secretion.
- Caution patient to take exactly as prescribed, and not to change dose or stop taking unless advised by health care provider.
- Instruct patient to carefully follow the phosphorous-restricted diet and calcium supplementation instructions given to them by health care provider.
- Advise patient to take phosphorous-binding agents exactly as prescribed by health care provider.
- Instruct dialysis patient to avoid using any magnesium-containing products (eg, antacids).
- Instruct patient to immediately notify health care provider if any signs or symptoms of hypercalcemia (eg, appetite loss, constipation, drowsiness, dry mouth, headache, metallic taste, muscle and/or bone pain, nausea, vomiting, weakness) occur.
- Advise patient or caregiver that medication will be prepared and administered by health care provider during hemodialysis session.
- Advise patient or caregiver to read patient information leaflet before starting therapy and to reread and check for new information each time the medication is refilled.
- Advise patient to take prescribed dose without regard to meals, but to take with food if GI upset occurs.
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