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Doxercalciferol

Pronunciation

(doks er kal si fe FEER ole)

Index Terms

  • 1α-Hydroxyergocalciferol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Hectorol: 0.5 mcg [contains fd&c red #40]

Hectorol: 1 mcg [contains fd&c yellow #6 (sunset yellow)]

Hectorol: 2.5 mcg

Generic: 0.5 mcg, 1 mcg, 2.5 mcg

Solution, Intravenous:

Hectorol: 2 mcg/mL (1 mL); 4 mcg/2 mL (2 mL) [contains alcohol, usp, disodium edta]

Generic: 4 mcg/2 mL (2 mL)

Brand Names: U.S.

  • Hectorol

Pharmacologic Category

  • Vitamin D Analog

Pharmacology

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.

Metabolism

Hepatic via CYP27 to active metabolites, 1α,25-(OH)2D2 (major) and 1α,24-dihydroxyvitamin D2 (minor).

Time to Peak

Major metabolite: 2.1 to 13.9 hours (injection); 11 to 12 hours (oral).

Half-Life Elimination

Major metabolite: ~32 to 37 hours (range: up to 96 hours)

Use: Labeled Indications

Secondary hyperparathyroidism (dialysis): Injection, oral: Treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis

Secondary hyperparathyroidism (predialysis patients): Oral: Treatment of secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease

Contraindications

Hypersensitivity to doxercalciferol or any component of the formulation; tendency toward hypercalcemia or evidence of vitamin D toxicity

Dosing: Adult

Secondary hyperparathyroidism:

Oral:

Dialysis patients:

Initial dose: iPTH >400 pg/mL: 10 mcg 3 times/week at dialysis for 8 weeks

Dose titration:

iPTH level >300 pg/mL (dose should be titrated to lower iPTH to within the range of 150 to 300 pg/mL): Increase to 12.5 mcg 3 times/week at dialysis for 8 more weeks; this titration process can continue at 8-week intervals in 2.5 mcg/dose increments (maximum: 20 mcg 3 times/week).

iPTH level 150 to 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

Hypercalcemia, hyperphosphatemia, or serum calcium times serum 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; decrease each dose (not weekly dose) by at least 2.5 mcg.

Predialysis patients:

Initial dose: iPTH >70 pg/mL with stage 3 disease or >110 pg/mL with stage 4 disease: 1 mcg/day for 2 weeks

Dose titration:

iPTH level >70 pg/mL with stage 3 disease or >110 pg/mL with stage 4 disease (dose should be titrated to lower iPTH to 35 to 70 pg/mL with stage 3 disease or to 70 to 110 pg/mL with stage 4 disease): Increase dose by 0.5 mcg per day every 2 weeks as necessary (maximum dose: 3.5 mcg/day)

iPTH level 35 to 70 pg/mL with stage 3 disease or 70 to 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 per day lower)

Hypercalcemia, hyperphosphatemia, or serum calcium times serum 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 0.5 mcg per day lower).

IV:

Dialysis patients:

Initial dose: iPTH level >400 pg/mL: 4 mcg 3 times/week at the end of dialysis; adjust as needed to lower iPTH into a range of 150 to 300 pg/mL

Dose titration (increase dose at 8-week intervals):

iPTH level decreased by <50% and >300 pg/mL (dose should be titrated to lower iPTH to within a range of 150 to 300 pg/mL): Increase by 1 to 2 mcg at 8-week intervals, as necessary (doses >18 mcg/week have not been studied).

iPTH level decreased by >50% and >300 pg/mL: Maintain current dose

iPTH level 150 to 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 serum 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)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary. The major metabolite, 1α,25-(OH)2D2, is not removed by hemodialysis.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution and consider more frequent monitoring of iPTH, calcium, and phosphorus levels.

Administration

Injection: Administer as an IV bolus.

Dietary Considerations

Based on serum levels, dietary phosphorus may be restricted and/or controlled with phosphorus binders. The daily combined calcium intake (dietary and calcium based phosphate binder) should be 1.5 to 2 g. Additional vitamin D supplements and magnesium-containing antacids should be avoided. Capsules contain coconut oil.

Storage

Capsules: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Injection, single use vial: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light.

Injection, multi-dose use vial: Store intact vial at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). After initial entry, unused portion may be stored at 2°C to 8°C (36°F to 46°F) for up to 3 days. Protect from light.

Drug Interactions

Aluminum Hydroxide: Vitamin D Analogs may increase the serum concentration of Aluminum Hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Avoid combination

Bile Acid Sequestrants: May decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification

Calcium Salts: May enhance the adverse/toxic effect of Vitamin D Analogs. Monitor therapy

Cardiac Glycosides: Vitamin D Analogs may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy

Danazol: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Magnesium Salts: Doxercalciferol may enhance the hypermagnesemic effect of Magnesium Salts. Management: Consider using a non-magnesium-containing antacid or phosphate-binding product in patients also receiving doxercalciferol. If magnesium-containing products must be used with doxercalciferol, serum magnesium concentrations should be monitored closely. Consider therapy modification

Mineral Oil: May decrease the serum concentration of Vitamin D Analogs. More specifically, mineral oil may interfere with the absorption of Vitamin D Analogs. Management: Avoid concomitant, oral administration of mineral oil and vitamin D analogs. Consider separating the administration of these agents by several hours to minimize the risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination

Orlistat: May decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Consider therapy modification

Sucralfate: Vitamin D Analogs may increase the serum concentration of Sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Vitamin D Analogs: May enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combination

Adverse Reactions

Adverse events as reported in dialysis patients.

>10%:

Cardiovascular: Edema (34%)

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

Gastrointestinal: Nausea and vomiting (21%)

Respiratory: Dyspnea (12%)

1% to 10%:

Cardiovascular: Bradycardia (7%)

Central nervous system: Sleep disorder (3%)

Dermatologic: Pruritus (8%)

Endocrine & metabolic: Weight gain (5%), hyperphosphatemia (intravenous: 2% to 4%), hypercalcemia (intravenous: 1%)

Gastrointestinal: Anorexia (5%), dyspepsia (5%)

Infection: Abscess (3%)

Neuromuscular & skeletal: Arthralgia (5%)

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, including the heart and arteries. Phosphate and vitamin D (and its derivatives) should be withheld during therapy to avoid hypercalcemia. Avoid use in patients with a recent history of hypercalcemia. Patients with high calcium levels (>10.5 mg/dL) prior to treatment are more likely to develop hypercalcemia.

• Hypersensitivity: Serious hypersensitivity reactions (some fatal), including anaphylaxis with angioedema, dyspnea, hypotension, chest discomfort, cardiopulmonary arrest, and unresponsiveness, have been reported with IV doxercalciferol. Monitor for hypersensitivity when initiating IV treatment; discontinue if such reaction occurs.

Disease-related concerns:

• Hepatic impairment: Patients with hepatic insufficiency may not appropriately metabolize doxercalciferol. Use with caution in patients with hepatic impairment; may require more frequent iPTH, calcium, and phosphorous monitoring.

• Hyperphosphatemia: Avoid use in patients with a recent history of hyperphosphatemia. Patients with high phosphorous levels (>6.9 mg/dL) prior to treatment are more likely to develop hyperphosphatemia. Correct before initiating therapy; exacerbates secondary hyperparathyroidism, diminishing the effect of doxercalciferol.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Doxercalciferol is not for initial treatment of nutritional vitamin D deficiency. Other forms of vitamin D should be discontinued when doxercalciferol is started. Do not administer doxercalciferol to patients with a recent history of hypercalcemia or hyperphosphatemia, or evidence of vitamin D toxicity (may have increased risk of hypercalcemia or hyperphosphatemia).

Monitoring Parameters

Serum calcium and phosphorus: Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of CKD, and the use of treatments for CKD-mineral and bone disorders (KDIGO, 2009):

CKD stage 3: Every 6 to 12 months

CKD stage 4: Every 3 to 6 months

CKD stage 5 and 5D: Every 1 to 3 months

In dialysis patients, iPTH, serum calcium and phosphorus should be determined prior to initiation of therapy and weekly thereafter for the first 12 weeks. For predialysis patients, serum calcium and phosphorus and plasma levels of iPTH should be monitored at least every two weeks for 3 months after initiation of therapy or following dose adjustments, then monthly for 3 months, and every 3 months thereafter.

Periodic 24-hour urinary calcium and phosphorus; magnesium; alkaline phosphatase every 12 months or more frequently in the presence of elevated PTH; creatinine, BUN, albumin; intact parathyroid hormone (iPTH) every 3 to 12 months depending on CKD severity; signs/symptoms of hypersensitivity reactions (upon IV initiation)

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience joint pain or weight gain. Have patient report immediately to prescriber signs of high calcium (weakness, confusion, fatigue, headache, nausea and vomiting, constipation, or bone pain), severe dizziness, passing out, dry mouth, increased thirst, polyuria, abnormal heartbeat, angina, shortness of breath, lack of appetite, change in taste, muscle pain, seizures, bradycardia, or edema (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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