PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Vitamin D Supplements

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic vitamin D2 analog
    Used for treatment of secondary parathyroidism in patients with Stage 3 or 4 CKD and patients with CKD on dialysis
    Activated by liver alone

    COMMON BRAND NAMES

    Hectorol

    HOW SUPPLIED

    Doxercalciferol/Hectorol Intravenous Inj Sol: 1mL, 2mcg
    Doxercalciferol/Hectorol Oral Cap: 0.5mcg, 1mcg, 2.5mcg

    DOSAGE & INDICATIONS

    For the treatment of secondary hyperparathyroidism and resultant bone disease (renal osteodystrophy†).
    For initial dosing and dosage titration in predialysis patients with Stage 3 or 4 chronic kidney disease (CrCl 15 to 59 mL/minute/1.73 m2).
    Oral dosage
    Adults

    Initially, 1 mcg PO once daily. In general, the dosage may be increased by 0.5 mcg every 2 weeks to reach target iPTH concentrations. Prior to increasing the dose, ensure that calcium is within normal limits. The maximum recommended dose is 3.5 mcg once daily. Monitor serum calcium, phosphorus, and iPTH concentrations at least every 2 weeks for 3 months after initiation of therapy or after dosage adjustments, then monthly for 3 months, and every 3 months thereafter once target iPTH concentrations are achieved. Suspend or decrease the dose if iPTH is persistently low or if serum calcium is consistently elevated. If suspended, restart 1 week later at a dose at least 0.5 mcg PO lower than the previous dosage.

    For initial dosing and dosage titration in predialysis patients with Stage 3 or 4 chronic kidney disease (National Kidney Foundation Guidelines)†.
    NOTE: Doxercalciferol is indicated when serum 25-(OH)-vitamin D concentrations are more than 30 ng/mL and plasma iPTH concentrations are more than 70 pg/mL (Stage 3) or more than 110 pg/mL (Stage 4); serum calcium concentrations should be less than 9.5 mg/dL and serum phosphorus concentrations should be less than 4.6 mg/dL.
    Oral dosage
    Adults

    Initially, 2.5 mcg PO 3 times per week. Titrate dose to target iPTH concentrations of 35 to 70 pg/mL for stage 3 chronic kidney disease and 70 to 110 pg/mL for stage 4 chronic kidney disease. Serum calcium, phosphorus, and iPTH concentrations should be monitored monthly for 3 months and every 3 months thereafter once target iPTH concentrations are achieved. IF CALCIUM CONCENTRATIONS ARE MORE THAN 9.5 mg/dL: Hold doxercalciferol until calcium concentration is less than 9.5 mg/dL then resume therapy at 50% of the original dose. IF PHOSPHORUS CONCENTRATIONS ARE MORE THAN 4.6 mg/dL: Hold doxercalciferol. Initiate or increase dose of phosphate binder until the phosphorus concentration is 4.6 mg/dL or less, and resume prior dose of doxercalciferol. IF iPTH CONCENTRATIONS ARE MORE THAN 70 pg/mL (stage 3) OR MORE THAN 110 pg/mL (stage 4): Maintain dosage. IF iPTH CONCENTRATIONS ARE LESS THAN 35 pg/mL (stage 3) OR LESS THAN 70 pg/mL (stage 4): Hold doxercalciferol until iPTH concentrations rise above the target range, then resume doxercalciferol at 50% of the original dose.

    For initial dosing and dosage adjustments for patients with Stage 5 chronic kidney disease on dialysis.
    Oral dosage
    Adults

    Initially, 10 mcg PO 3 times weekly at dialysis (approximately every other day). In general, the dosage may be increased by 2.5 mcg no more frequently than every 8 weeks to target iPTH concentrations in the desired range. Prior to increasing the dose, ensure that calcium is within normal limits. The maximum recommended dose is 20 mcg PO 3 times weekly at dialysis (Max: 60 mcg/week PO). Monitor serum calcium, phosphorus, and iPTH concentrations weekly initially and during dosage titration and periodically thereafter once target iPTH concentrations are achieved.[51248] KDIGO guidelines recommend a treatment target range for iPTH of 2 to 9 times upper limit of normal for patients on dialysis.[38437] Suspend or decrease the dose if iPTH is persistently low or if seum calcium is consistently elevated. If suspended, restart 1 week later at a dose at least 2.5 mcg PO lower than the previous dosage.[51248] KDIGO guidelines emphasize monitoring the individual concentrations of calcium and phosphorus rather than the calcium-phosphorus product.[38437]

    Intravenous dosage
    Adults

    Initially, 4 mcg IV 3 times weekly at the end of dialysis (approximately every other day). In general, the dosage may be increased by 1 to 2 mcg no more frequently than every 8 weeks if intact iPTH is not lowered by 50% and fails to reach target range. Prior to increasing the dose, ensure that calcium is within normal limits. The maximum recommended dose is 6 mcg IV 3 times weekly (Max: 18 mcg/week IV). Monitor serum calcium, phosphorus, and iPTH concentrations weekly initially and during dosage titration and periodically thereafter once target iPTH concentrations are achieved. KDIGO guidelines recommend a treatment target range for iPTH of 2 to 9 times upper limit of normal for patients on dialysis. Suspend or decrease the dose if iPTH is persistently low or if serum calcium is consistently elevated. If suspended, restart 1 week later at a dose at least 1 mcg IV lower than the previous dosage. KDIGO guidelines emphasize monitoring the individual concentrations of calcium and phosphorus rather than the calcium-phosphorus product.

    For initial dosing and dosage adjustments for patients with Stage 5 chronic kidney disease on dialysis (National Kidney Foundation Guidelines)†.
    NOTE: Serum phosphorus concentrations should be less than 5.5 mg/dL and the calcium-phosphorus product should be less than 55. Serum calcium concentrations should be less than 9.5 mg/dL in patients with a serum iPTH less than 1,000 pg/mL. In patients with a serum iPTH more than 1,000 pg/mL, the serum calcium concentration should be less than 10 mg/dL.
    Oral dosage
    Adults with a baseline iPTH 300 to 600 pg/mL

    Initially, 5 mcg PO during each hemodialysis session. Dosage adjustments should be determined based on serum calcium, phosphorus, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorus concentrations every 2 weeks for 1 month and then monthly. Serum iPTH concentrations should be monitored monthly for 3 months then every 3 months once target iPTH concentrations are achieved (150 to 300 pg/mL). IF CALCIUM CONCENTRATIONS ARE MORE THAN 10.2 mg/dL: Hold doxercalciferol until calcium concentration is less than 10.2 mg/dL then resume doxercalciferol. Modify dose if necessary depending on phosphorus or iPTH concentrations. Consider reducing dose of calcium-containing phosphate binders if applicable. IF CALCIUM CONCENTRATIONS ARE 9.5 to 10.2 mg/dL: Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify doxercalciferol dose based on phosphorus or iPTH concentrations. IF PHOSPHORUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorus concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHORUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorus is less than 5.5 mg/dL. Reduce doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE MORE THAN 300 pg/mL: Increase doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE 200 to 300 pg/mL: Continue same dosage. IF iPTH CONCENTRATIONS ARE 150 to 200 pg/mL: Decrease doxercalciferol dose by 50% for 2 months. Recheck iPTH. If iPTH is more than 300 pg/mL, increase doxercalciferol dose by 10% to 25%; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, reduce doxercalciferol dose by 25% to 50%; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months. IF iPTH CONCENTRATIONS ARE LESS THAN 150 pg/mL: Hold doxercalciferol for 1 month. Recheck iPTH. If iPTH is more than 300 pg/mL, resume doxercalciferol dose at 75% of initial dose; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, resume doxercalciferol at earlier dose; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months.

    Adults with a baseline iPTH 600 to 1,000 pg/mL

    Initially, 5 to 10 mcg PO or during each hemodialysis session. Dosage adjustments should be determined based on serum calcium, phosphorus, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorus concentrations every 2 weeks for 1 month and then monthly. Serum iPTH concentrations should be monitored monthly for 3 months then every 3 months once target iPTH concentrations are achieved (150 to 300 pg/mL). IF CALCIUM CONCENTRATIONS ARE MORE THAN 10.2 mg/dL: Hold doxercalciferol until calcium concentration is less than 10.2 mg/dL then resume doxercalciferol. Modify dose if necessary depending on phosphorus or iPTH concentrations. Consider reducing dose of calcium-containing phosphate binders if applicable. IF CALCIUM CONCENTRATIONS ARE 9.5 to 10.2 mg/dL: Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify doxercalciferol dose based on phosphorus or iPTH concentrations. IF PHOSPHORUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorus concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHORUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorus is less than 5.5 mg/dL. Reduce doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE MORE THAN 300 pg/mL: Increase doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE 200 to 300 pg/mL: Continue same dosage. IF iPTH CONCENTRATIONS ARE 150 to 200 pg/mL: Decrease doxercalciferol dose by 50% for 2 months. Recheck iPTH. If iPTH is more than 300 pg/mL, increase doxercalciferol dose by 10% to 25%; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, reduce doxercalciferol dose by 25% to 50%; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months. IF iPTH CONCENTRATIONS ARE LESS THAN 150 pg/mL: Hold doxercalciferol for 1 month. Recheck iPTH. If iPTH is more than 300 pg/mL, resume doxercalciferol dose at 75% of initial dose; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, resume doxercalciferol at earlier dose; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months.

    Adults with a baseline iPTH more than 1,000 pg/mL

    Initially, 10 to 20 mcg PO during each hemodialysis session. Dosage adjustments should be determined based on serum calcium, phosphorus, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorus concentrations every 2 weeks for 1 month and then monthly. Serum iPTH concentrations should be monitored monthly for 3 months then every 3 months once target iPTH concentrations are achieved (150 to 300 pg/mL). IF CALCIUM CONCENTRATIONS ARE MORE THAN 10.2 mg/dL: Hold doxercalciferol until calcium concentration is less than 10.2 mg/dL then resume doxercalciferol. Modify dose if necessary depending on phosphorus or iPTH concentrations. Consider reducing dose of calcium-containing phosphate binders if applicable. IF CALCIUM CONCENTRATIONS ARE 9.5 to 10.2 mg/dL: Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify doxercalciferol dose based on phosphorus or iPTH concentrations. IF PHOSPHORUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorus concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHORUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorus is less than 5.5 mg/dL. Reduce doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE MORE THAN 300 pg/mL: Increase doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE 200 to 300 pg/mL: Continue same dosage. IF iPTH CONCENTRATIONS ARE 150 to 200 pg/mL: Decrease doxercalciferol dose by 50% for 2 months. Recheck iPTH. If iPTH is more than 300 pg/mL, increase doxercalciferol dose by 10% to 25%; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, reduce doxercalciferol dose by 25% to 50%; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months. IF iPTH CONCENTRATIONS ARE LESS THAN 150 pg/mL: Hold doxercalciferol for 1 month. Recheck iPTH. If iPTH is more than 300 pg/mL, resume doxercalciferol dose at 75% of initial dose; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, resume doxercalciferol at earlier dose; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months.

    Intravenous dosage
    Adults with a baseline iPTH 300 to 600 pg/mL

    Initially, 2 mcg IV during each hemodialysis session. Dosage adjustments should be determined based on serum calcium, phosphorus, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorus concentrations every 2 weeks for 1 month and then monthly. Serum iPTH concentrations should be monitored monthly for 3 months then every 3 months once target iPTH concentrations are achieved (150 to 300 pg/mL). IF CALCIUM CONCENTRATIONS ARE MORE THAN 10.2 mg/dL: Hold doxercalciferol until calcium concentration is less than 10.2 mg/dL then resume doxercalciferol. Modify dose if necessary depending on phosphorus or iPTH concentrations. Consider reducing dose of calcium-containing phosphate binders if applicable. IF CALCIUM CONCENTRATIONS ARE 9.5 to 10.2 mg/dL: Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify doxercalciferol dose based on phosphorus or iPTH concentrations. IF PHOSPHORUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorus concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHORUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorus is less than 5.5 mg/dL. Reduce doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE MORE THAN 300 pg/mL: Increase doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE 200 to 300 pg/mL: Continue same dosage. IF iPTH CONCENTRATIONS ARE 150 to 200 pg/mL: Decrease doxercalciferol dose by 50% for 2 months. Recheck iPTH. If iPTH is more than 300 pg/mL, increase doxercalciferol dose by 10% to 25%; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, reduce doxercalciferol dose by 25% to 50%; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months. IF iPTH CONCENTRATIONS ARE LESS THAN 150 pg/mL: Hold doxercalciferol for 1 month. Recheck iPTH. If iPTH is more than 300 pg/mL, resume doxercalciferol dose at 75% of initial dose; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, resume doxercalciferol at earlier dose; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months.

    Adults with a baseline iPTH 600 to 1,000 pg/mL

    Initially, 2 to 4 mcg IV during each hemodialysis session. Dosage adjustments should be determined based on serum calcium, phosphorus, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorus concentrations every 2 weeks for 1 month and then monthly. Serum iPTH concentrations should be monitored monthly for 3 months then every 3 months once target iPTH concentrations are achieved (150 to 300 pg/mL). IF CALCIUM CONCENTRATIONS ARE MORE THAN 10.2 mg/dL: Hold doxercalciferol until calcium concentration is less than 10.2 mg/dL then resume doxercalciferol. Modify dose if necessary depending on phosphorus or iPTH concentrations. Consider reducing dose of calcium-containing phosphate binders if applicable. IF CALCIUM CONCENTRATIONS ARE 9.5 to 10.2 mg/dL: Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify doxercalciferol dose based on phosphorus or iPTH concentrations. IF PHOSPHORUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorus concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHORUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorus is less than 5.5 mg/dL. Reduce doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE MORE THAN 300 pg/mL: Increase doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE 200 to 300 pg/mL: Continue same dosage. IF iPTH CONCENTRATIONS ARE 150 to 200 pg/mL: Decrease doxercalciferol dose by 50% for 2 months. Recheck iPTH. If iPTH is more than 300 pg/mL, increase doxercalciferol dose by 10% to 25%; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, reduce doxercalciferol dose by 25% to 50%; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months. IF iPTH CONCENTRATIONS ARE LESS THAN 150 pg/mL: Hold doxercalciferol for 1 month. Recheck iPTH. If iPTH is more than 300 pg/mL, resume doxercalciferol dose at 75% of initial dose; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, resume doxercalciferol at earlier dose; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months.

    Adults with a baseline iPTH more than 1,000 pg/mL

    Initially, 4 to 8 mcg IV during each hemodialysis session. Dosage adjustments should be determined based on serum calcium, phosphorus, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorus concentrations every 2 weeks for 1 month and then monthly. Serum iPTH concentrations should be monitored monthly for 3 months then every 3 months once target iPTH concentrations are achieved (150 to 300 pg/mL). IF CALCIUM CONCENTRATIONS ARE MORE THAN 10.2 mg/dL: Hold doxercalciferol until calcium concentration is less than 10.2 mg/dL then resume doxercalciferol. Modify dose if necessary depending on phosphorus or iPTH concentrations. Consider reducing dose of calcium-containing phosphate binders if applicable. IF CALCIUM CONCENTRATIONS ARE 9.5 to 10.2 mg/dL: Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify doxercalciferol dose based on phosphorus or iPTH concentrations. IF PHOSPHORUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorus concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHORUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorus is less than 5.5 mg/dL. Reduce doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE MORE THAN 300 pg/mL: Increase doxercalciferol dose by 25% to 50%. IF iPTH CONCENTRATIONS ARE 200 to 300 pg/mL: Continue same dosage. IF iPTH CONCENTRATIONS ARE 150 to 200 pg/mL: Decrease doxercalciferol dose by 50% for 2 months. Recheck iPTH. If iPTH is more than 300 pg/mL, increase doxercalciferol dose by 10% to 25%; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, reduce doxercalciferol dose by 25% to 50%; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months. IF iPTH CONCENTRATIONS ARE LESS THAN 150 pg/mL: Hold doxercalciferol for 1 month. Recheck iPTH. If iPTH is more than 300 pg/mL, resume doxercalciferol dose at 75% of initial dose; if iPTH is 200 to 300 pg/mL, continue same dose; if iPTH is 150 to 200 pg/mL, resume doxercalciferol at earlier dose; if iPTH is less than 150 pg/mL, hold doxercalciferol for 3 months.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    20 mcg/dose PO or 6 mcg/dose IV 3 times weekly for a maximum of 60 mcg/week PO or 18 mcg/week IV for dialysis patients are FDA-approved maximum dosages; however, guidelines recommend up to 8 mcg/dose IV for a maximum of 24 mcg/week IV; 3.5 mcg/day PO for pre-dialysis patients.

    Geriatric

    20 mcg/dose PO or 6 mcg/dose IV 3 times weekly for a maximum of 60 mcg/week PO or 18 mcg/week IV for dialysis patients are FDA-approved maximum dosages; however, guidelines recommend up to 8 mcg/dose IV for a maximum of 24 mcg/week IV; 3.5 mcg/day PO for predialysis patients.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with hepatic dysfunction may not activate doxercalciferol appropriately in the liver. Monitor iPTH, calcium, and phosphorus concentrations more frequently in these patients.

    Renal Impairment

    Doxercalciferol is indicated for patients with chronic renal failure; therefore, the recommended doses are appropriate.

    ADMINISTRATION

    Oral Administration

    Doxercalciferol may be administered with or without food.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Doxercalciferol is administered as an intravenous bolus injection at the end of dialysis session.
     
    Intravenous injection
    No further dilution needed.
    Storage: For single-dose vials, discard any unused portion. For multidose vials, unused contents remain stable under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for 3 days. Discard any unused portion after 3 days.

    STORAGE

    Hectorol:
    - Discard unused product 3 days after opening
    - Protect from light
    - Store in original container
    - Store opened container in refrigerator (36 to 46 degrees F)
    - Store unopened product at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Doxercalciferol is contraindicated in patients with a previous hypersensitivity to doxercalciferol or any of its ingredients. All patients receiving doxercalciferol injection should be monitored closely upon treatment initiation for hypersensitivity reactions. Serious reactions including anaphylaxis, angioedema, hypotension, unresponsiveness, chest discomfort, shortness of breath, and cardiopulmonary arrest may occur separately or together. If symptoms of hypersensitivity occur, discontinue doxercalciferol and monitor and/or treat the patient as clinically appropriate.

    Hypercalcemia, hyperphosphatemia

    Doxercalciferol is contraindicated in patients with hypercalcemia. Acute hypercalcemia may increase the risk of cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart. Chronic hypercalcemia may lead to generalized vascular calcification and other soft-tissue calcification. Severe hypercalcemia may require emergency treatment. Monitor calcium and phosphorus concentrations weekly in patients with CKD on dialysis or every 2 weeks for patients with Stage 3 or 4 CKD when initiating doxercalciferol or during dose adjustments. Once a maintenance dose has been established, monitor serum calcium monthly for 3 months and then every 3 months. If hypercalcemia occurs, reduce the doxercalciferol dose or discontinue doxercalciferol until serum calcium is normal. Patients with high pretreatment concentrations of calcium or phosphorus are more likely to develop hypercalcemia or hyperphosphatemia during doxercalciferol therapy. Hypercalcemia may be worsened by concomitant administration of high doses of calcium-containing preparations, thiazide diuretics, or other vitamin D compounds. Additionally, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. Monitor serum calcium frequently in these situations; dose adjustments of doxercalciferol may be necessary. Advise patients of the symptoms of elevated calcium, such as feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst and urination, and weight loss, and to report new or worsening symptoms should they occur.[51248]

    Hypervitaminosis D

    Since doxercalciferol is a vitamin D analog, it is contraindicated in patients with signs and symptoms of hypervitaminosis D (vitamin D toxicity). Symptoms of vitamin D toxicity include hypercalcemia, hypercalciuria, and hyperphosphatemia.[51248]

    Hepatic disease

    Patients with impaired liver function may not metabolize doxercalciferol appropriately. Therefore, use doxercalciferol with caution in patients with hepatic disease. Monitor intact parathyroid hormone (iPTH), calcium, and phosphorus concentrations more frequently in these patients.[51248]

    Pregnancy

    Limited data with doxercalciferol in human pregnancy are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed when rats and rabbits were administered doxercalciferol during organogenesis at up to 25 times the maximum recommended human dose based on body surface area. Chronic kidney disease in pregnancy increases the risk for maternal hypertension and preeclampsia, miscarriage, preterm delivery polyhydramnios, stillbirth, and low birth weight infants.[51248]

    Breast-feeding

    There is no information regarding the presence of doxercalciferol in human milk, the effects of doxercalciferol on the breast-fed infant, or the effects of doxercalciferol on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for doxercalciferol and any potential adverse effects on the breast-fed child from doxercalciferol or the underlying maternal condition. Monitor infants exposed to doxercalciferol through breast milk for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation, and weight loss. Consider serum calcium monitoring in the infant.

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 7.0-7.0
    angioedema / Rapid / Incidence not known
    respiratory arrest / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known
    bone fractures / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    hypervitaminosis D / Delayed / Incidence not known
    coma / Early / Incidence not known

    Moderate

    edema / Delayed / 7.0-34.0
    constipation / Delayed / 26.0-26.0
    dyspnea / Early / 12.0-19.0
    anemia / Delayed / 19.0-19.0
    hypertonia / Delayed / 11.0-11.0
    angina / Early / 8.0-8.0
    dehydration / Delayed / 7.0-7.0
    chest pain (unspecified) / Early / 7.0-7.0
    depression / Delayed / 7.0-7.0
    leukopenia / Delayed / 7.0-7.0
    hypercalcemia / Delayed / Incidence not known
    hyperphosphatemia / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    hypercalciuria / Delayed / Incidence not known
    bone pain / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    confusion / Early / Incidence not known
    hypertension / Early / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    hyperthermia / Delayed / Incidence not known
    psychosis / Early / Incidence not known

    Mild

    infection / Delayed / 30.0-30.0
    malaise / Early / 28.0-28.0
    headache / Early / 28.0-28.0
    rhinitis / Early / 22.0-22.0
    nausea / Early / 21.0-21.0
    vomiting / Early / 21.0-21.0
    cough / Delayed / 19.0-19.0
    asthenia / Delayed / 15.0-15.0
    insomnia / Early / 15.0-15.0
    paresthesias / Delayed / 15.0-15.0
    dizziness / Early / 12.0-12.0
    pruritus / Rapid / 7.0-8.0
    dyspepsia / Early / 5.0-7.0
    sinusitis / Delayed / 7.0-7.0
    anorexia / Delayed / 5.0-5.0
    weight gain / Delayed / 5.0-5.0
    arthralgia / Delayed / 5.0-5.0
    polydipsia / Early / Incidence not known
    metallic taste / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    rhinorrhea / Early / Incidence not known
    drowsiness / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    polyuria / Early / Incidence not known
    xerostomia / Early / Incidence not known
    nocturia / Early / Incidence not known
    weakness / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Diphenhydramine: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Acetaminophen; Propoxyphene: (Moderate) Cytochrome P450 enzyme inhibitors, such as propoxyphene, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Aluminum Hydroxide: (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, concomitant use should be avoided, if possible, in patients with chronic renal failure. (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, concomitant use should be avoided, if possible, in patients with chronic renal failure. (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Amiodarone: (Moderate) Amiodarone inhibits CYP450 and may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if amiodarone is coadministered with doxercalciferol.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Amobarbital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) CYP450 enzyme inhibitors, like clarithromycin, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol. (Moderate) Cytochrome P450 enzyme inhibitors, such as omeprazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Aprepitant, Fosaprepitant: (Moderate) Aprepitant/fosaprepitant inhibits CYP450 and may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if aprepitant/fosaprepitant is coadministered.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Aspirin, ASA; Omeprazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as omeprazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Atenolol; Chlorthalidone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Azilsartan; Chlorthalidone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Barbiturates: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Bendroflumethiazide; Nadolol: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Cytochrome P450 enzyme inhibitors, such as metronidazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Cytochrome P450 enzyme inhibitors, such as metronidazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Bosentan: (Moderate) Hepatic enzyme inducers such as bosentan, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Bupropion: (Moderate) CYP450 enzyme inhibitors, like bupropion, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if cytochrome P450 inhibitors are coadministered with doxercalciferol.
    Bupropion; Naltrexone: (Moderate) CYP450 enzyme inhibitors, like bupropion, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if cytochrome P450 inhibitors are coadministered with doxercalciferol.
    Burosumab: (Contraindicated) Vitamin D analogs are contraindicated in patients receiving burosumab; discontinue vitamin D analogs 1 week prior to initiation of burosumab.
    Butabarbital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Butalbital; Acetaminophen: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Calcifediol: (Major) Withhold calcifediol treatment when using other vitamin D analogs, like doxercalciferol, due to the risk of additive toxicity including hypercalcemia, hypercalciuria, and hyperphosphatemia.
    Calcitonin: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, vitamin D preparations should be avoided. Vitamin D analogs can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of vitamin D is necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
    Calcitriol: (Major) The use of doxercalciferol with calcitriol is not recommended because of the increased potential for additive effects and toxicity. Due to the possibility of systemic absorption after topical administration of calcitriol, caution may be warranted in patients receiving high doses of doxercalciferol.
    Calcium Acetate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Carbonate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Carbonate; Risedronate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Carbonate; Simethicone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Chloride: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Gluconate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium; Vitamin D: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Carbamazepine: (Moderate) Hepatic enzyme inducers such as carbamazepine, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Chlorothiazide: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Chlorthalidone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Chlorthalidone; Clonidine: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Cholestyramine: (Moderate) Administer doxercalciferol at least 1 hour before or 4 to 6 hours after taking cholestyramine. Cholestyramine can decrease the intestinal absorption of fat or fat soluble vitamins including vitamin D analogs, such as oral doxercalciferol.
    Chromium: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Cimetidine: (Moderate) CYP450 enzyme inhibitors, like cimetidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Cinacalcet: (Moderate) CYP450 enzyme inhibitors, like cinacalcet, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Clarithromycin: (Moderate) CYP450 enzyme inhibitors, like clarithromycin, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Clopidogrel: (Moderate) Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors including clopidogrel may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if clopidogrel is coadministered with doxercalciferol.
    Colestipol: (Moderate) Separate administration of doxercalciferol by 1 hour before or 4 hours after a colestipol dose to limit effects on oral absorption. Because it sequesters bile acids, colestipol may interfere with normal fat absorption and thus may reduce absorption of fat-soluble vitamins like doxercalciferol.
    Cyclosporine: (Moderate) CYP450 enzyme inhibitors, like cyclosporine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Danazol: (Moderate) CYP450 enzyme inhibitors, like danazol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Delavirdine: (Moderate) CYP450 enzyme inhibitors, like delavirdine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Desogestrel; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Dextromethorphan; Quinidine: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Digoxin: (Moderate) Doxercalciferol should be administered with caution to patients receiving digoxin. Vitamin D analogs may cause hypercalemia which increases the risk of digitalis toxicity. In patients receiving doxercalciferol and digoxin concurrently, monitor serum calcium frequently and monitor the patient for signs of digitalis toxicity. More frequent monitoring is necessary when initiating or adjusting the dose of doxercalciferol.
    Dihydrotachysterol: (Major) The use of dihydrotachysterol with doxercalciferol is not recommended because of the increased potential for additive effects and toxicity.
    Diltiazem: (Moderate) CYP450 enzyme inhibitors, like diltiazem, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Diphenhydramine: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Diphenhydramine; Ibuprofen: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Diphenhydramine; Naproxen: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Diphenhydramine; Phenylephrine: (Moderate) Doxercalciferol is converted in the liver to its active metabolites. Although not specifically studied, cytochrome P450 enzyme inhibitors including diphenhydramine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if products containing diphenhydramine are coadministered with doxercalciferol.
    Disulfiram: (Moderate) CYP450 enzyme inhibitors, like disulfiram, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Drospirenone; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Duloxetine: (Moderate) Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors including duloxetine may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if duloxetine is coadministered with doxercalciferol.
    Efavirenz: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers such as efavirenz may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers such as efavirenz may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers such as efavirenz may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Erythromycin: (Moderate) CYP450 enzyme inhibitors, like erythromycin, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Erythromycin; Sulfisoxazole: (Moderate) CYP450 enzyme inhibitors, like erythromycin, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Ethinyl Estradiol; Norelgestromin: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Ethinyl Estradiol; Norgestrel: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Etonogestrel; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Fluconazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as fluconazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Gemfibrozil: (Moderate) CYP450 enzyme inhibitors, like gemfibrozil, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Grapefruit juice: (Moderate) Although not specifically studied, cytochrome P450 enzyme inhibitors, such as grapefruit juice, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy.
    Haloperidol: (Moderate) Cytochrome P450 enzyme inhibitors, such as haloperidol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts. (Moderate) Magnesium-containing drug products should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of vitamin D analogs and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Hydantoins: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers such as phenytoin and fosphenytoin may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol. Phenytoin can decrease the activity of vitamin D by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Ibritumomab Tiuxetan: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Imatinib: (Moderate) Cytochrome P450 enzyme inhibitors, such as imatinib, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Isoniazid, INH: (Moderate) Cytochrome P450 enzyme inhibitors, such as isoniazid, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as rifampin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol. (Moderate) Cytochrome P450 enzyme inhibitors, such as isoniazid, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Isoniazid, INH; Rifampin: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as rifampin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol. (Moderate) Cytochrome P450 enzyme inhibitors, such as isoniazid, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Itraconazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as itraconazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Ketoconazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as ketoconazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) CYP450 enzyme inhibitors, like clarithromycin, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Leflunomide: (Moderate) Cytochrome P450 enzyme inhibitors, such as leflunomide, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Magnesium Citrate: (Moderate) Magnesium-containing drug products, such as magnesium citrate, should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of vitamin D analogs and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Magnesium Hydroxide: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, concomitant use should be avoided, if possible, in patients with chronic renal failure.
    Magnesium Salts: (Moderate) Magnesium-containing drug products should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of vitamin D analogs and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Magnesium: (Moderate) Magnesium-containing drug products should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of vitamin D analogs and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Mephobarbital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Methohexital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Methyclothiazide: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Metolazone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Metronidazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as metronidazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Mifepristone: (Moderate) Cytochrome P450 enzyme inhibitors, such as mifepristone, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Mineral Oil: (Moderate) Separate administration of oral vitamin D analogs by 1 hour before or 4 to 6 hours after mineral oil to limit effects on absorption and availability of the vitamin D analog. Absorption of fat-soluble vitamins may be decreased with concomitant administration of mineral oil. The bioavailability of orally administered vitamin D analogs may also be decreased.
    Modafinil: (Moderate) Cytochrome P450 enzyme inhibitors, such as modafinil, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Nevirapine: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as nevirapine, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Norethindrone; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Norgestimate; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Omeprazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as omeprazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as rifabutin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol. (Moderate) Cytochrome P450 enzyme inhibitors, such as omeprazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Omeprazole; Sodium Bicarbonate: (Moderate) Cytochrome P450 enzyme inhibitors, such as omeprazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Orlistat: (Moderate) Orlistat reduced the absorption of fat-soluble vitamins absorption during clinical trials. The bioavailability of orally administered vitamin D analogs may also be decreased. In patients receiving orally-administered vitamin D analogs along with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamin analogs be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
    Paricalcitol: (Major) The use of doxercalciferol with paricalcitol is not recommended because of the increased potential for additive effects and toxicity.
    Pentobarbital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Phenicol Derivatives: (Moderate) CYP450 enzyme inhibitors, like chloramphenicol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Phenobarbital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Phosphorated Carbohydrate Solution: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Phosphorus: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Polycarbophil: (Moderate) The concurrent use of vitamin D analogs, like doxercalciferol with calcium polycarbophil may contribute to vitamin D-induced hypercalcemia. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
    Potassium Phosphate: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Potassium Phosphate; Sodium Phosphate: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Primidone: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Propafenone: (Moderate) Cytochrome P450 enzyme inhibitors, such as propafenone, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Propoxyphene: (Moderate) Cytochrome P450 enzyme inhibitors, such as propoxyphene, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Protease inhibitors: (Moderate) Protease inhibitors may decrease efficacy of doxercalciferol. Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors, including protease inhibitors, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if these drugs are administered together.
    Pyridoxine, Vitamin B6: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Quinidine: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Quinine: (Moderate) Cytochrome P450 enzyme inhibitors, such as quinine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Ranolazine: (Moderate) Cytochrome P450 enzyme inhibitors, including ranolazine, may inhibit the conversion of doxercalciferol to its active metabolite and result in decreased efficacy of doxercalciferol.
    Rifabutin: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as rifabutin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Rifampin: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as rifampin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Secobarbital: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) CYP450 enzyme inhibitors, like ethinyl estradiol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
    Selective serotonin reuptake inhibitors: (Moderate) Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors, including selective serotonin reuptake inhibitors (SSRIs), may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if SSRIs are coadministered with doxercalciferol.
    Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Magnesium-containing drug products should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of vitamin D analogs and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    St. John's Wort, Hypericum perforatum: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as St. John's Wort, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as sulfamethoxazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Tacrine: (Moderate) Cytochrome P450 enzyme inhibitors, such as tacrine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Terbinafine: (Moderate) Cytochrome P450 enzyme inhibitors, such as terbinafine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Thiazide diuretics: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Thiopental: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as barbiturates, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    Thioridazine: (Moderate) Cytochrome P450 enzyme inhibitors, such as thioridazine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Ticlopidine: (Moderate) Cytochrome P450 enzyme inhibitors, such as ticlopidine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Trandolapril; Verapamil: (Moderate) Cytochrome P450 enzyme inhibitors, such as verapamil, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
    Verapamil: (Moderate) Cytochrome P450 enzyme inhibitors, such as verapamil, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Voriconazole: (Moderate) Cytochrome P450 enzyme inhibitors, such as voriconazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Zafirlukast: (Moderate) Cytochrome P450 enzyme inhibitors, such as zafirlukast, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Zileuton: (Moderate) Cytochrome P450 enzyme inhibitors, such as zileuton, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.

    PREGNANCY AND LACTATION

    Pregnancy

    Limited data with doxercalciferol in human pregnancy are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed when rats and rabbits were administered doxercalciferol during organogenesis at up to 25 times the maximum recommended human dose based on body surface area. Chronic kidney disease in pregnancy increases the risk for maternal hypertension and preeclampsia, miscarriage, preterm delivery polyhydramnios, stillbirth, and low birth weight infants.[51248]

    There is no information regarding the presence of doxercalciferol in human milk, the effects of doxercalciferol on the breast-fed infant, or the effects of doxercalciferol on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for doxercalciferol and any potential adverse effects on the breast-fed child from doxercalciferol or the underlying maternal condition. Monitor infants exposed to doxercalciferol through breast milk for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation, and weight loss. Consider serum calcium monitoring in the infant.

    MECHANISM OF ACTION

    Doxercalciferol is metabolized in the liver to the activated form of vitamin D2, 1,25-dihydroxyergocalciferol. Unlike natural vitamin D2, doxercalciferol does not require activation by the kidneys. Since doxercalciferol is not active when it is absorbed, it does not affect the absorption of calcium by the gut. Once activated, doxercalciferol is slowly released from the liver, and has the same functions as natural activated vitamin D2. Specifically, activated vitamin D controls the absorption of dietary calcium, the tubular reabsorption of calcium by the kidney, and, with parathyroid hormone (PTH), regulates the mobilization of calcium from bone. Vitamin D acts directly on osteoblasts to stimulate skeletal growth and on the parathyroid gland to suppress PTH synthesis and secretion. In uremic patients, decreased production of vitamin D metabolites leads to secondary hyperparathyroidism, which contributes to metabolic bone disease in patients with renal failure.

    PHARMACOKINETICS

    Doxercalciferol is given orally or intravenously. Doxercalciferol undergoes activation by the hepatic enzyme cytochrome P450 (CYP) 27 (a vitamin D-25-hydroxylase) to form 1,25-dihydroxyergocalciferol, the major metabolite, and 1alpha, 25-dihydroxyvitamin D2 (minor metabolite). The mean elimination half-life is 32 to 37 hours, with a range of up to 96 hours.[51248]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP 27
    Doxercalciferol is activated by CYP 27 in the liver. Cytochrome P450 inducers or inhibitors may alter the 25-hydroxylation of doxercalciferol resulting in decreased or increased formation of active doxercalciferol.[51248]

    Oral Route

    Doxercalciferol is absorbed from the GI tract and activated in the liver. In healthy volunteers, peak blood concentrations of the major metabolite are reached 11 to 12 hours after repeated oral doses of doxercalciferol.

    Intravenous Route

    Peak blood concentrations are reached approximately 8 hours after a single intravenous dose of doxercalciferol.[51248]