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Drug overview for HECTOROL (doxercalciferol):
Generic name: DOXERCALCIFEROL (DOX-er-kal-SIF-er-ol)
Drug class: Vitamin D
Therapeutic class: Metabolic Modifiers
Doxercalciferol (1-alpha-hydroxyvitamin D2, 1-hydroxyvitamin D2), the 1-hydroxylated form of ergocalciferol, is a synthetic vitamin D analog.
No enhanced Uses information available for this drug.
Generic name: DOXERCALCIFEROL (DOX-er-kal-SIF-er-ol)
Drug class: Vitamin D
Therapeutic class: Metabolic Modifiers
Doxercalciferol (1-alpha-hydroxyvitamin D2, 1-hydroxyvitamin D2), the 1-hydroxylated form of ergocalciferol, is a synthetic vitamin D analog.
No enhanced Uses information available for this drug.
DRUG IMAGES
HECTOROL 4 MCG/2 ML VIAL
The following indications for HECTOROL (doxercalciferol) have been approved by the FDA:
Indications:
Hyperparathyroidism secondary to chronic renal failure with dialysis
Professional Synonyms:
Hyperparathyroidism associated with dialysis dependent renal failure
Indications:
Hyperparathyroidism secondary to chronic renal failure with dialysis
Professional Synonyms:
Hyperparathyroidism associated with dialysis dependent renal failure
The following dosing information is available for HECTOROL (doxercalciferol):
Doxercalciferol dosage must be individualized carefully according to serum or plasma intact parathyroid hormone (iPTH) concentrations, with close monitoring of serum calcium and phosphorus concentrations. Serum calcium, phosphorus, and alkaline phosphatase, in addition to serum or plasma iPTH concentrations should be determined periodically; frequent monitoring may be necessary during doxercalciferol dosage adjustments. In patients undergoing dialysis, serum or plasma iPTH, serum calcium, and serum phosphorus concentrations should be determined prior to initiation of therapy with doxercalciferol and weekly during the early phase of therapy (i.e., the first 12 weeks).
In predialysis patients, serum calcium, serum phosphorus, and plasma iPTH concentrations should be monitored at least every 2 weeks for 3 months after initiation of therapy or after subsequent dosage changes, then monthly for 3 months (once dosage is stabilized), and every 3 months thereafter.
The manufacturer recommends that dosage of doxercalciferol be titrated to reduce iPTH concentrations to within a target range; specific target ranges are recommended based on the degree of renal impairment. The manufacturer states that the iPTH target range for those with chronic kidney disease (CKD) stage 3 (glomerular filtration rate (GFR) 30-59 mL/minute per 1.73 m2), stage 4 (GFR 15-29 mL/minute per 1.73 m2), or stage 5 (GFR less than 15 mL/minute per 1.73 m2 or on dialysis) is 35-70, 70-110, or 150-300 pg/mL, respectively.
However, the target ranges recommended by the manufacturer are based on the National Kidney Foundation's 2003 Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Nephrology experts currently state that the optimal iPTH concentration for patients with stage 3a (estimated GFR 45-59 mL/minute per 1.73 m2) to stage 5 CKD who are not undergoing dialysis is unknown, but modest increases in iPTH concentration may represent an appropriate adaptive response to declining renal function. For patients with stage 5 CKD undergoing dialysis, some experts suggest that iPTH concentrations may be maintained within a range of approximately 2-9 times the assay's upper limit of normal (ULN) (which may correspond to a range of approximately 130-600 pg/mL for commercially available assays ).
Although some clinicians suggest that this range is too broad, available assays for PTH exhibit substantial variability; the previously recommended range of 150-300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer commercially available. Oversuppression of PTH may increase the risk of adynamic bone disease and should be avoided. (See Uses: Mineral and Bone Disorder Secondary to Chronic Renal Disease, in the Vitamin D Analogs General Statement 88:16.) Nephrology experts currently recommend that the individual values for serum calcium and phosphorus (evaluated together) be used instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.
The manufacturer states that the initial oral dosage of doxercalciferol for the treatment of secondary hyperparathyroidism in adult patients with CKD undergoing dialysis who have a baseline iPTH concentration exceeding 400 pg/mL is 10 mcg 3 times weekly at dialysis (approximately every other day). The manufacturer states that the initial dosage is then titrated as needed to reduce serum iPTH concentrations to within the range of 150-300 pg/mL. If the response is inadequate (i.e., iPTH is not reduced by 50% and fails to reach the target range), the dosage may be increased at 8-week intervals by 2.5
mcg per dose. The maximum recommended dosage is 20 mcg 3 times weekly (60 mcg weekly). If serum or plasma iPTH concentrations decline to less than 100 pg/mL, doxercalciferol therapy should be withheld for 1 week and then therapy should be reinitiated at a dose at least 2.5
mcg lower than the last dose. The manufacturer states that if hypercalcemia, hyperphosphatemia, or a serum calcium (in mg/dL) times serum phosphorus (in mg/dL) product exceeds 55 mg2/dL2, the dosage of doxercalciferol should be reduced or therapy withheld and/or the dosage of concomitantly administered phosphate binders be adjusted. If the serum calcium concentration is more than 1 mg/dL above the ULN, doxercalciferol should be discontinued immediately, a low-calcium diet should be instituted and calcium supplements withdrawn, and serum calcium concentrations should be measured at least weekly; therapy can be reinstituted when normocalcemia ensues (generally in 2-7 days).
If therapy with doxercalciferol has been temporarily interrupted, doxercalciferol should be reinitiated at a dose that is at least 2.5 mcg lower than the last dose.
The manufacturer states that the initial IV dosage of doxercalciferol for the treatment of secondary hyperparathyroidism in adult patients with CKD undergoing dialysis who have a baseline iPTH concentration exceeding 400 pg/mL is 4 mcg 3 times weekly at the end of dialysis (approximately every other day). The manufacturer states that the initial dosage is then titrated as needed to reduce serum iPTH concentrations to within the range of 150-300 pg/mL. If the response is inadequate (i.e., iPTH is not reduced by 50% and fails to reach the target range), the dose given 3 times weekly may be increased by 1-2 mcg at 8-week intervals.
IV dosages exceeding 18 mcg weekly have not been studied. If serum or plasma iPTH concentrations decline to less than 100 pg/mL, doxercalciferol therapy should be withheld for 1 week and then therapy should be reinitiated at a dose at least 1 mcg lower than the last dose. The manufacturer states that if hypercalcemia, hyperphosphatemia, or a serum calcium times serum phosphorus product exceeds 55 mg2/dL2, the dosage of doxercalciferol should be reduced or therapy withheld and/or the dosage of concomitantly administered phosphate binders should be adjusted.
If the serum calcium concentration is more than 1 mg/dL above the ULN, doxercalciferol should be discontinued immediately, a low-calcium diet should be instituted and calcium supplements withdrawn, and serum calcium concentrations should be measured at least weekly; therapy can be reinstituted when normocalcemia ensues (generally in 2-7 days). If therapy with doxercalciferol has been temporarily interrupted, doxercalciferol should be reinitiated at a dose that is at least 1 mcg lower than the last dose.
The manufacturer states that the initial oral dosage of doxercalciferol for the treatment of secondary hyperparathyroidism in adult patients with CKD who do not yet require maintenance dialysis (predialysis patients) and who have a baseline iPTH concentration of more than 70 pg/mL (stage 3 CKD) or 110 pg/mL (stage 4 CKD) is 1 mcg daily. The manufacturer states that the initial dosage is then titrated as needed to reduce serum iPTH concentrations to within the range of 35-70 pg/mL for those with stage 3 CKD or 70-110 pg/mL for those with stage 4 CKD. If the response is inadequate (i.e., iPTH fails to reach the target range), the dosage may be increased at 2-week intervals by 0.5
mcg per dose. The maximum recommended dosage is 3.5 mcg daily.
If serum or plasma iPTH concentrations decline to less than 35 or 70 pg/mL in those with stage 3 or stage 4 CKD, respectively, doxercalciferol therapy should be withheld for 1 week and then therapy should be reinitiated at a dose at least 0.5 mcg lower than the last dose. The manufacturer states that if hypercalcemia, hyperphosphatemia, or a serum calcium times serum phosphorus product exceeds 55 mg2/dL2, the dosage of doxercalciferol should be reduced or therapy withheld and/or the dosage of concomitantly administered phosphate binders should be adjusted.
If the serum calcium concentration exceeds 10.7 mg/dL, doxercalciferol should be discontinued immediately, a low-calcium diet should be instituted and calcium supplements withdrawn, and serum calcium concentrations should be measured at least weekly; therapy can be reinstituted when normocalcemia ensues (generally in 2-7 days). If therapy with doxercalciferol has been temporarily interrupted, doxercalciferol should be reinitiated at a dose that is at least 0.5 mcg lower than the last dose.
In predialysis patients, serum calcium, serum phosphorus, and plasma iPTH concentrations should be monitored at least every 2 weeks for 3 months after initiation of therapy or after subsequent dosage changes, then monthly for 3 months (once dosage is stabilized), and every 3 months thereafter.
The manufacturer recommends that dosage of doxercalciferol be titrated to reduce iPTH concentrations to within a target range; specific target ranges are recommended based on the degree of renal impairment. The manufacturer states that the iPTH target range for those with chronic kidney disease (CKD) stage 3 (glomerular filtration rate (GFR) 30-59 mL/minute per 1.73 m2), stage 4 (GFR 15-29 mL/minute per 1.73 m2), or stage 5 (GFR less than 15 mL/minute per 1.73 m2 or on dialysis) is 35-70, 70-110, or 150-300 pg/mL, respectively.
However, the target ranges recommended by the manufacturer are based on the National Kidney Foundation's 2003 Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Nephrology experts currently state that the optimal iPTH concentration for patients with stage 3a (estimated GFR 45-59 mL/minute per 1.73 m2) to stage 5 CKD who are not undergoing dialysis is unknown, but modest increases in iPTH concentration may represent an appropriate adaptive response to declining renal function. For patients with stage 5 CKD undergoing dialysis, some experts suggest that iPTH concentrations may be maintained within a range of approximately 2-9 times the assay's upper limit of normal (ULN) (which may correspond to a range of approximately 130-600 pg/mL for commercially available assays ).
Although some clinicians suggest that this range is too broad, available assays for PTH exhibit substantial variability; the previously recommended range of 150-300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer commercially available. Oversuppression of PTH may increase the risk of adynamic bone disease and should be avoided. (See Uses: Mineral and Bone Disorder Secondary to Chronic Renal Disease, in the Vitamin D Analogs General Statement 88:16.) Nephrology experts currently recommend that the individual values for serum calcium and phosphorus (evaluated together) be used instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.
The manufacturer states that the initial oral dosage of doxercalciferol for the treatment of secondary hyperparathyroidism in adult patients with CKD undergoing dialysis who have a baseline iPTH concentration exceeding 400 pg/mL is 10 mcg 3 times weekly at dialysis (approximately every other day). The manufacturer states that the initial dosage is then titrated as needed to reduce serum iPTH concentrations to within the range of 150-300 pg/mL. If the response is inadequate (i.e., iPTH is not reduced by 50% and fails to reach the target range), the dosage may be increased at 8-week intervals by 2.5
mcg per dose. The maximum recommended dosage is 20 mcg 3 times weekly (60 mcg weekly). If serum or plasma iPTH concentrations decline to less than 100 pg/mL, doxercalciferol therapy should be withheld for 1 week and then therapy should be reinitiated at a dose at least 2.5
mcg lower than the last dose. The manufacturer states that if hypercalcemia, hyperphosphatemia, or a serum calcium (in mg/dL) times serum phosphorus (in mg/dL) product exceeds 55 mg2/dL2, the dosage of doxercalciferol should be reduced or therapy withheld and/or the dosage of concomitantly administered phosphate binders be adjusted. If the serum calcium concentration is more than 1 mg/dL above the ULN, doxercalciferol should be discontinued immediately, a low-calcium diet should be instituted and calcium supplements withdrawn, and serum calcium concentrations should be measured at least weekly; therapy can be reinstituted when normocalcemia ensues (generally in 2-7 days).
If therapy with doxercalciferol has been temporarily interrupted, doxercalciferol should be reinitiated at a dose that is at least 2.5 mcg lower than the last dose.
The manufacturer states that the initial IV dosage of doxercalciferol for the treatment of secondary hyperparathyroidism in adult patients with CKD undergoing dialysis who have a baseline iPTH concentration exceeding 400 pg/mL is 4 mcg 3 times weekly at the end of dialysis (approximately every other day). The manufacturer states that the initial dosage is then titrated as needed to reduce serum iPTH concentrations to within the range of 150-300 pg/mL. If the response is inadequate (i.e., iPTH is not reduced by 50% and fails to reach the target range), the dose given 3 times weekly may be increased by 1-2 mcg at 8-week intervals.
IV dosages exceeding 18 mcg weekly have not been studied. If serum or plasma iPTH concentrations decline to less than 100 pg/mL, doxercalciferol therapy should be withheld for 1 week and then therapy should be reinitiated at a dose at least 1 mcg lower than the last dose. The manufacturer states that if hypercalcemia, hyperphosphatemia, or a serum calcium times serum phosphorus product exceeds 55 mg2/dL2, the dosage of doxercalciferol should be reduced or therapy withheld and/or the dosage of concomitantly administered phosphate binders should be adjusted.
If the serum calcium concentration is more than 1 mg/dL above the ULN, doxercalciferol should be discontinued immediately, a low-calcium diet should be instituted and calcium supplements withdrawn, and serum calcium concentrations should be measured at least weekly; therapy can be reinstituted when normocalcemia ensues (generally in 2-7 days). If therapy with doxercalciferol has been temporarily interrupted, doxercalciferol should be reinitiated at a dose that is at least 1 mcg lower than the last dose.
The manufacturer states that the initial oral dosage of doxercalciferol for the treatment of secondary hyperparathyroidism in adult patients with CKD who do not yet require maintenance dialysis (predialysis patients) and who have a baseline iPTH concentration of more than 70 pg/mL (stage 3 CKD) or 110 pg/mL (stage 4 CKD) is 1 mcg daily. The manufacturer states that the initial dosage is then titrated as needed to reduce serum iPTH concentrations to within the range of 35-70 pg/mL for those with stage 3 CKD or 70-110 pg/mL for those with stage 4 CKD. If the response is inadequate (i.e., iPTH fails to reach the target range), the dosage may be increased at 2-week intervals by 0.5
mcg per dose. The maximum recommended dosage is 3.5 mcg daily.
If serum or plasma iPTH concentrations decline to less than 35 or 70 pg/mL in those with stage 3 or stage 4 CKD, respectively, doxercalciferol therapy should be withheld for 1 week and then therapy should be reinitiated at a dose at least 0.5 mcg lower than the last dose. The manufacturer states that if hypercalcemia, hyperphosphatemia, or a serum calcium times serum phosphorus product exceeds 55 mg2/dL2, the dosage of doxercalciferol should be reduced or therapy withheld and/or the dosage of concomitantly administered phosphate binders should be adjusted.
If the serum calcium concentration exceeds 10.7 mg/dL, doxercalciferol should be discontinued immediately, a low-calcium diet should be instituted and calcium supplements withdrawn, and serum calcium concentrations should be measured at least weekly; therapy can be reinstituted when normocalcemia ensues (generally in 2-7 days). If therapy with doxercalciferol has been temporarily interrupted, doxercalciferol should be reinitiated at a dose that is at least 0.5 mcg lower than the last dose.
Doxercalciferol is administered orally without regard to meals. The drug also is administered by direct IV injection.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| HECTOROL 4 MCG/2 ML VIAL | Maintenance | Adults infuse 2 milliliters (4 mcg) by intravenous route 3 times per week at the end of dialysis |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| DOXERCALCIFEROL 4 MCG/2 ML VL | Maintenance | Adults infuse 2 milliliters (4 mcg) by intravenous route 3 times per week atthe end of dialysis |
The following drug interaction information is available for HECTOROL (doxercalciferol):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Burosumab/Oral Phosphates; Active Vitamin D Analogs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Both burosumab and phosphates or vitamin D may increase serum phosphate levels. This combination may lead to greater increases in serum phosphate than anticipated. CLINICAL EFFECTS: The combination of burosumab with oral phosphates or active vitamin D analogs may result in hyperphosphatemia and may increase the risk of nephrocalcinosis.(1) PREDISPOSING FACTORS: Patients with renal impairment have alterations in mineral metabolism that may increase the risk of hyperphosphatemia.(1) PATIENT MANAGEMENT: The concomitant use of burosumab with oral phosphates or active vitamin D analogs is contraindicated. Discontinue oral phosphate and/or active vitamin D analogs one week before starting burosumab.(1) DISCUSSION: Burosumab restores dysfunctional renal phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D to treat X-linked hypophosphatemia. Additional oral phosphates and/or active vitamin D analogs may raise serum phosphate higher than anticipated. |
CRYSVITA |
There are 0 severe interactions.
There are 0 moderate interactions.
The following contraindication information is available for HECTOROL (doxercalciferol):
Drug contraindication overview.
Tendency toward hypercalcemia. Evidence of vitamin D toxicity. Doxercalciferol injection is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation. (See Hypersensitivity Reactions under Warnings/Precautions: Sensitivity Reactions, in Cautions.)
Tendency toward hypercalcemia. Evidence of vitamin D toxicity. Doxercalciferol injection is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation. (See Hypersensitivity Reactions under Warnings/Precautions: Sensitivity Reactions, in Cautions.)
There are 2 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Hypercalcemia |
| Hypervitaminosis D |
There are 1 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Hyperphosphatemia |
There are 2 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Disease of liver |
| Hypoparathyroidism |
The following adverse reaction information is available for HECTOROL (doxercalciferol):
Adverse reaction overview.
In studies that evaluated use of oral doxercalciferol in patients with CKD requiring dialysis, adverse effects occurring in more than 2% of patients and more frequently than placebo include edema, headache, malaise, nausea/vomiting, dizziness, dyspnea, pruritus, bradycardia, anorexia, abscess, arthralgia, weight increase, constipation, and sleep disorder. In studies that evaluated oral doxercalciferol in predialysis patients with stage 3 or 4 CKD, adverse effects occurring in more than 5% of patients and more frequently than placebo include infection, chest pain, constipation, dyspepsia, anemia, dehydration, depression, hypertonia, insomnia, paresthesia, increased cough, dyspnea, and rhinitis. Potential adverse effects of doxercalciferol generally are similar to those of excessive vitamin D intake, with early manifestations of such toxicity (in association with hypercalcemia) including weakness, headache, somnolence, nausea, dry mouth, constipation, muscle or bone pain, and metallic taste and late manifestations including polyuria, polydipsia, anorexia, weight loss, nocturia, calcific conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated serum AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias, and rarely overt psychosis.
In studies that evaluated use of oral doxercalciferol in patients with CKD requiring dialysis, adverse effects occurring in more than 2% of patients and more frequently than placebo include edema, headache, malaise, nausea/vomiting, dizziness, dyspnea, pruritus, bradycardia, anorexia, abscess, arthralgia, weight increase, constipation, and sleep disorder. In studies that evaluated oral doxercalciferol in predialysis patients with stage 3 or 4 CKD, adverse effects occurring in more than 5% of patients and more frequently than placebo include infection, chest pain, constipation, dyspepsia, anemia, dehydration, depression, hypertonia, insomnia, paresthesia, increased cough, dyspnea, and rhinitis. Potential adverse effects of doxercalciferol generally are similar to those of excessive vitamin D intake, with early manifestations of such toxicity (in association with hypercalcemia) including weakness, headache, somnolence, nausea, dry mouth, constipation, muscle or bone pain, and metallic taste and late manifestations including polyuria, polydipsia, anorexia, weight loss, nocturia, calcific conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated serum AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias, and rarely overt psychosis.
There are 8 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Dyspnea |
Abscess Arthralgia Bradycardia Infection |
| Rare/Very Rare |
|---|
|
Anaphylaxis Angioedema Hypotension |
There are 22 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Chest pain Dizziness Edema Headache disorder Malaise Pruritus of skin Vomiting |
Anorexia Cough Depression Dyspepsia Hyperphosphatemia Hypertonia Paresthesia Rhinitis Sleep disorder Weight gain |
| Rare/Very Rare |
|---|
|
Chest discomfort Constipation Hypercalcemia Nausea Stinging of skin |
The following precautions are available for HECTOROL (doxercalciferol):
Safety and efficacy not established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Category B. (See Users Guide.)
It is not known if doxercalciferol is distributed in milk; discontinue nursing or drug because of potential risk (e.g., hypercalcemia) in nursing infants.
No substantial differences in safety and efficacy relative to younger adults.
The following prioritized warning is available for HECTOROL (doxercalciferol):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for HECTOROL (doxercalciferol)'s list of indications:
| Hyperparathyroidism secondary to CRF with dialysis | |
| N18.6 | End stage renal disease |
| N25.81 | Secondary hyperparathyroidism of renal origin |
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