Version May 2024
Secondary hyperparathyroidism:
Chronic kidney disease (CKD) patients on dialysis :
Note: KDIGO guidelines recommend maintaining intact parathyroid hormone (PTH) levels in the range of ~2 to 9 times the upper normal limit for the assay. Caution is advised to avoid hypercalcemia or elevated phosphate levels (KDIGO 2017).
Initial:
Oral: 10 mcg 3 times/week at dialysis (no more frequently than every other day).
IV: 4 mcg 3 times/week at the end of dialysis (no more frequently than every other day).
Dose titration: Ensure serum calcium is within normal limits prior to increasing the dose.
Oral: Titrate the dose by 2.5 mcg/dose at 8-week intervals to achieve target plasma PTH level. Maximum: 20 mcg 3 times/week at dialysis (60 mcg weekly). Hold therapy or decrease dose if PTH is persistently and abnormally low or if corrected serum calcium is consistently above normal range; if doxercalciferol is held, may restart 1 week later at a dose that is at least 2.5 mcg lower than the previous dose.
IV: Titrate the dose by 1 to 2 mcg/dose at 8-week intervals if plasma PTH is not lowered by 50% and to achieve target plasma PTH level. Maximum: 18 mcg weekly. Hold therapy or decrease dose if PTH is persistently and abnormally low or if corrected serum calcium is consistently above normal range; if doxercalciferol is held, may restart 1 week later at a dose that is at least 1 mcg lower than the previous dose.
CKD patients not on dialysis (CKD stage ≥G3):
Note: KDIGO guidelines do not recommend routine use of vitamin D analogs (eg, doxercalciferol) in patients not on dialysis with CKD stages G3 to G5; it may be reasonable to reserve use for patients with CKD stages G4 or G5 and with severe and progressive hyperparathyroidism. Caution is advised to avoid hypercalcemia or elevated phosphate levels (KDIGO 2017).
Initial: Oral: 1 mcg once daily.
Dose titration: Oral: Titrate the dose by 0.5 mcg/dose at 2-week intervals to achieve target plasma PTH level. Maximum: 3.5 mcg once daily. Ensure serum calcium is within normal limits prior to increasing the dose. Hold therapy or decrease dose if PTH is persistently and abnormally low or if corrected serum calcium is consistently above normal range; if doxercalciferol is held, may restart 1 week later at a dose that is at least 0.5 mcg lower than the previous dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary. The major metabolite, 1α,25-(OH)2D2, is not removed by hemodialysis.
There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution and consider more frequent monitoring of iPTH, calcium, and phosphate levels.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Edema (7% to 34%)
Central nervous system: Headache (28%), malaise (28%), insomnia (15%), paresthesia (15%), dizziness (12%), hypertonia (11%)
Gastrointestinal: Constipation (26%), nausea and vomiting (21%)
Hematologic & oncologic: Anemia (19%)
Infection: Infection (30%)
Neuromuscular & skeletal: Asthenia (15%)
Respiratory: Rhinitis (22%), cough (19%), dyspnea (12% to 19%)
1% to 10%:
Cardiovascular: Angina pectoris (8%), bradycardia (7%), chest pain (7%)
Central nervous system: Depression (7%), sleep disorder (3%)
Dermatologic: Pruritus (7% to 8%)
Endocrine & metabolic: Dehydration (7%), weight gain (5%)
Gastrointestinal: Dyspepsia (5% to 7%), anorexia (5%)
Genitourinary: Urinary tract infection (7%)
Hematologic & oncologic: Leukopenia (7%)
Infection: Abscess (3%)
Neuromuscular & skeletal: Arthralgia (5%)
Respiratory: Sinusitis (7%)
Frequency not defined:
Endocrine & metabolic: Hypercalcemia, hyperphosphatemia
<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, burning sensation of skin, chest discomfort, hypersensitivity reaction, hypotension, unresponsive to stimuli
Hypersensitivity to doxercalciferol or any component of the formulation; hypercalcemia; vitamin D toxicity
Concerns related to adverse effects:
• Excessive vitamin D: Excessive vitamin D administration may lead to over suppression of parathyroid hormone (PTH), progressive or acute hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease.
• Hypercalcemia: Monitor calcium levels closely; patients with chronic renal failure are at an increased risk for hypercalcemia. Avoid use in patients with a recent history of hypercalcemia. Risk of hypercalcemia may be increased by concomitant use of calcium-containing supplements and/or medications that increase serum calcium (eg, thiazide diuretics). Patients with high calcium levels (>10.5 mg/dL) prior to treatment are more likely to develop 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, exacerbate nephrolithiasis, and has been associated with increased mortality in adults with chronic kidney disease (CKD). Reduce dose or discontinue therapy if hypercalcemia occurs.
• 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 phosphate monitoring.
• Hyperphosphatemia: Patients with high phosphate 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.
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 0.5 mcg, 1 mcg, 2.5 mcg
Solution, Intravenous:
Hectorol: 2 mcg/mL (1 mL [DSC]); 4 mcg/2 mL (2 mL) [contains alcohol, usp, disodium edta]
Generic: 4 mcg/2 mL (2 mL)
Yes
Capsules (Doxercalciferol Oral)
0.5 mcg (per each): $12.00
1 mcg (per each): $20.40
2.5 mcg (per each): $23.88
Solution (Doxercalciferol Intravenous)
4 mcg/2 mL (per mL): $1.80 - $2.70
Solution (Hectorol Intravenous)
4 mcg/2 mL (per mL): $4.17
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Injection: Administer as an IV bolus.
Secondary hyperparathyroidism (patients on dialysis): Injection, oral: Treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis
Secondary hyperparathyroidism (patients not on dialysis): Oral: Treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Management: Consider avoiding chronic use of aluminum and aluminum-containing products in patients who are also taking active vitamin D analogs. If coadministered, monitor aluminum status and for signs and symptoms of aluminum-related toxicities. Risk D: Consider therapy modification
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 (eg, cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Risk D: Consider therapy modification
Burosumab: Vitamin D Analogs may enhance the adverse/toxic effect of Burosumab. Risk X: Avoid combination
Calcium Salts: May enhance the adverse/toxic effect of Vitamin D Analogs. Risk C: Monitor therapy
Cardiac Glycosides: Vitamin D Analogs may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
Danazol: May enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy
Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Risk D: Consider therapy modification
Erythromycin (Systemic): May increase the serum concentration of Doxercalciferol. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification
Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Vitamin D Analogs. Risk X: Avoid combination
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Vitamin D Analogs. Risk X: Avoid combination
Orlistat: May decrease the absorption of Vitamins (Fat Soluble). Management: Administer oral fat soluble vitamins at least 2 hours before or 2 hours after the administration of orlistat. Avoid concomitant administration due to the risk of impaired vitamin absorption. Risk D: 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. Management: Consider avoiding chronic use of aluminum and aluminum-containing products, such as sucralfate, in patients who are also taking active vitamin D analogs. If combined, monitor for signs and symptoms of aluminum-related toxicities. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy
Vitamin D Analogs: May enhance the adverse/toxic effect of other Vitamin D Analogs. Risk X: Avoid combination
Adverse events have not been observed in animal reproduction studies
It is not known if doxercalciferol is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother; monitor the breastfed infant for signs and symptoms of hypercalcemia
Based on serum levels, dietary phosphate may be restricted and/or controlled with phosphate-lowering agents. The daily combined elemental calcium intake (dietary and calcium based phosphate-lowering agents) should not exceed 2 g. Additional vitamin D supplements and magnesium-containing antacids should be avoided. Capsules contain coconut oil.
Serum calcium, phosphate, and parathyroid hormone (PTH): Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of chronic kidney disease (CKD), and the use of treatments for chronic kidney disease-mineral and bone disorder (CKD-MBD) (KDIGO 2017):
CKD stage G3a to G3b: Serum calcium and phosphate: Every 6 to 12 months; PTH: Frequency based on baseline level and progression of CKD
CKD stage G4: Serum calcium and phosphate: Every 3 to 6 months; PTH: Every 6 to 12 months
CKD stage G5 and G5D: Serum calcium and phosphate: Every 1 to 3 months; PTH: Every 3 to 6 months
In dialysis patients, iPTH, serum calcium and phosphate should be determined prior to initiation of therapy and weekly thereafter for the first 12 weeks. For predialysis patients, serum calcium and phosphate 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 phosphate; 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)
Note: Due to the complexity and interdependency of the laboratory parameters used for therapeutic decisions in chronic kidney disease-mineral and bone disorder (CKD-MBD) patients, serial assessments of phosphate, calcium, and parathyroid hormone (PTH) levels should be considered together (KDIGO 2017).
Calcium (total): Adults: Normal range: 8.5 to 10.5 mg/dL (2.12 to 2.62 mmol/L) (IOM 2011). Avoid hypercalcemia for chronic kidney disease (CKD) stages G3a to G5D (KDIGO 2017).
Phosphorus: 2.5 to 4.5 mg/dL (0.81 to 1.45 mmol/L). Lower elevated phosphorus levels toward the normal range for CKD stages G3a to G5D (KDIGO 2017).
PTH:
CKD stage G3a to G5: Optimal PTH level is unknown; evaluate patients with progressively elevated intact PTH levels or if levels are consistently above the normal range (assay-dependent) (KDIGO 2017).
Dialysis patients: Maintain intact parathyroid hormone (iPTH) within 2 to 9 times the upper limit of normal for the assay used (KDIGO 2017).
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).
Half-life elimination: Major metabolite: ~32 to 37 hours (range: up to 96 hours)
Time to peak: Major metabolite: 8 hours (injection); 11 to 12 hours (oral).
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