PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Vitamin D Supplements

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic vitamin D2 analog; activated by the liver alone; preferred over ergocalciferol in renal failure because of impaired renal conversion of ergocalciferol to its most active form.

    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 pre-dialysis patients with Stage 3 or Stage 4 chronic kidney disease (CrCl 15 to 59 mL/min/1.73m2).
    Oral dosage
    Adults

    Initially, 1 mcg PO once daily. Increase dose by 0.5 mcg every 2 weeks to reach 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. The maximum recommended dose is 3.5 mcg once daily. Serum calcium, phosphorus, and iPTH concentrations should be monitored at least every 2 weeks for 3 months after initiation of therapy or following dosage adjustments, then monthly for 3 months, and every 3 months thereafter once target iPTH concentrations are achieved. IF HYPERCALCEMIA, HYPERPHOSPHATEMIA, OR CALCIUM-PHOSPHOROUS PRODUCT GREATER THAN 55 DEVELOPS: Decrease or suspend doxercalciferol dosage and/or the dose of phosphate binder should be appropriately adjusted. If suspended, the drug should be restarted at a dosage that is at least 0.5 mcg lower. IF iPTH CONCENTRATIONS ARE GREATER THAN 70 pg/mL (stage 3) OR GREATER THAN 110 pg/mL (stage 4): Increase dose by 0.5 mcg PO every 2 weeks as necessary. IF iPTH CONCENTRATIONS ARE 35 to 70 pg/mL (stage 3) OR 70 to 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 for 1 week, then resume at a dose that is at least 0.5 mcg lower than the previous dose once serum iPTH levels have normalized.

    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 are greater than 30 ng/mL and plasma iPTH concentrations are greater than 70 pg/mL (Stage 3) or greater than 110 pg/mL (Stage 4); serum calcium concentrations should be less than 9.5 mg/dL and serum phosphorous concentrations should be less than 4.6 mg/dL.
    Oral dosage
    Adults

    The National Kidney Foundation Guidelines recommend 2.5 mcg PO 3 times per week initially. 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 GREATER 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 PHOSPHOROUS CONCENTRATIONS ARE GREATER THAN 4.6 mg/dL: Hold doxercalciferol. Initiate or increase dose of phosphate binder until the phosphorous concentration is 4.6 mg/dL or less, and resume prior dose of doxercalciferol. IF iPTH CONCENTRATIONS ARE GREATER THAN 70 pg/mL (stage 3) OR GREATER 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 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) for iPTH levels greater than 400 pg/mL. Initially and during dosage titration, serum calcium, phosphorous, and iPTH concentrations should be monitored weekly and periodically thereafter once target iPTH concentrations are achieved (150 to 300 pg/mL). In general, the dosage should be adjusted upward no more frequently than every 8 weeks. The maximum recommended dose is 20 mcg PO administered 3 times a week at dialysis (total 60 mcg/week PO). IF iPTH CONCENTRATIONS DECREASE BY LESS THAN 50% AND ARE MORE THAN 300 pg/mL: Increase dose by 2.5 mcg PO every 8 weeks as necessary. IF iPTH CONCENTRATIONS ARE 150 to 300 pg/mL: Maintain dosage. IF iPTH CONCENTRATIONS ARE 100 to 149 pg/mL: Continue treatment, but at a dose 2.5 mcg PO or 1 mcg IV lower than the previous dose. IF iPTH CONCENTRATIONS ARE LESS THAN 100 pg/mL: Hold doxercalciferol for 1 week, then resume at a dose that is at least 2.5 mcg PO or 1 mcg IV lower than the previous dose. IF CALCIUM-PHOSPHOROUS PRODUCT IS MORE THAN > 55, OR IF HYPERCALEMIA OR HYPERPHOSPHATEMIA DEVELOPS: Decrease the dose or suspend therapy; adjust the dose of phosphate binders. If suspended, the dose should be restarted at least 2.5 mcg PO lower than the previous dosage. 

    Intravenous dosage
    Adults

    Initially, 4 mcg IV as a bolus injection 3 times weekly at the end of dialysis (approximately every other day) for iPTH levels greater than 400 pg/mL. Initially and during dosage titration, serum calcium, phosphorous, and iPTH concentrations should be monitored weekly and periodically thereafter once target iPTH concentrations are achieved (150 to 300 pg/mL). In general, the dosage should be adjusted upward no more frequently than every 8 weeks. The maximum recommended dose is 6 mcg IV per dose given 3 times weekly (total 18 mcg/week IV). IF iPTH CONCENTRATIONS DECREASE BY LESS THAN 50% AND ARE MORE THAN 300 pg/mL: Increase dose by 1 to 2 mcg IV every 8 weeks as necessary. IF iPTH CONCENTRATIONS DECREASE BY MORE THAN 50% AND ARE MORE THAN 300 pg/mL: Maintain dosage. IfFiPTH CONCENTRATIONS ARE 150 to 300 pg/mL: Maintain dosage. IF iPTH CONCENTRATIONS ARE 100 to 149 pg/mL: Continue treatment, but at a dose 1 mcg IV lower than the previous dose. IF iPTH CONCENTRATIONS ARE LESS THAN 100 pg/mL: Hold doxercalciferol for 1 week, then resume at a dose that is 1 mcg IV lower than the previous dose. IF CALCIUM-PHOSPHOROUS PRODUCT MORE THAN 55, OR IF HYPERCALCEMIA OR HYPERPHOSPHATEMIA DEVELOPS: Hold doxercalciferol until the parameters are appropriately lowered and resume therapy at a dosage that is 1 mcg IV lower.

    For initial dosing and dosage adjustments for patients with Stage 5 chronic kidney disease on dialysis (National Kidney Foundation Guidelines).
    NOTE: Serum phosphorous concentrations should be less than 5.5 mg/dL and the Calcium-Phosphorous 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 1000 pg/mL. In patients with a serum iPTH greater than 1000 pg/mL, the serum calcium concentration should be less than 10 mg/dL.
    Oral or Intravenous dosage
    Adults with a baseline iPTH 300 to 600 pg/mL

     Initially, 5 mcg PO or 2 mcg IV during each hemodialysis session is recommended by the National Kidney Foundation Guidelines. Dosage adjustments should be determined based on serum calcium, phosphorous, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorous 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 phosphorous 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 phosphorous or iPTH concentrations. IF PHOSPHOROUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorous concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHOROUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorous 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 greater 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 greater 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 1000 pg/mL

    Initially, 5 to 10 mcg PO or 2 to 4 mcg IV during each hemodialysis session is recommended by the National Kidney Foundation Guidelines. Dosage adjustments should be determined based on serum calcium, phosphorous, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorous 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 phosphorous 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 phosphorous or iPTH concentrations. IF PHOSPHOROUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorous concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHOROUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorous 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 greater 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 greater 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 greater than 1000 pg/mL

    Initially, 10 to 20 mcg PO or 4 to 8 mcg IV during each hemodialysis session is recommended by the National Kidney Foundation Guidelines. Dosage adjustments should be determined based on serum calcium, phosphorous, and iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorous 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 phosphorous 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 phosphorous or iPTH concentrations. IF PHOSPHOROUS CONCENTRATIONS ARE MORE THAN 6 mg/dL: Hold doxercalciferol until the phosphorous concentration is less than 5.5 mg/dL and reduce doxercalciferol dose by 25% to 50%. Consider increasing phosphate binder dosage. IF PHOSPHOROUS CONCENTRATIONS ARE 5.5 to 6 mg/dL: Increase phosphate binder dosage until phosphorous 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 greater 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 greater 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 for dialysis patients three times per week for a maximum of 60 mcg/week PO or 18 mcg/week IV for dialysis patients; 3.5 mcg/day PO for pre-dialysis patients.

    Elderly

    20 mcg/dose PO or 6 mcg/dose IV for dialysis patients three times per week for a maximum of 60 mcg/week PO or 18 mcg/week IV for dialysis patients; 3.5 mcg/day PO for pre-dialysis patients.

    Adolescents

    Maximum dosage information is not available.

    Children

    Maximum dosage information is not available.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with hepatic dysfunction may not activate doxercalciferol appropriately in the liver. More frequent monitoring of iPTH, calcium, and phosphorus levels should be performed in these patients.

    Renal Impairment

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

    ADMINISTRATION

    Monitoring of the PTH level using an intact PTH (iPTH) assay is recommended.
    The target range of iPTH for chronic renal failure patients receiving doxercalciferol is 150—300 pg/mL.
    The doxercalciferol dose should be individualized based on the iPTH level (see dosage adjustments).
    Serum calcium and phosphorus levels and the calculated calcium—phosphorus product (serum Ca x PO4) should be monitored prior to initiating therapy and weekly during doxercalciferol dose titration.
    After initiating doxercalciferol therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.

    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 sessions.
     
    Intravenous injection:
    No further dilution needed.
    Withdraw appropriate dose from ampule using a filter needle.
    Change needles before injecting as an IV bolus.
    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
    - Opened vials may be refrigerated (36 to 46 degress F)
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 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

    Doxercalciferol is contraindicated in patients with hypercalcemia or a recent history of hypercalcemia. Use caution when administering doxercalciferol to patients with hyperphosphatemia. Patients with high pre-treatment levels of calcium or phosphorus are more likely to develop hypercalcemia or hyperphosphatemia during doxercalciferol therapy. Monitor calcium and phosphorus levels closely during doxercalciferol dosage adjustments. If clinically significant hypercalcemia or hyperphosphatemia develops or the calculated calcium-phosphorus product (i.e., serum Ca x PO4) is > 55, the doxercalciferol dose should be held and decreased. Chronic doxercalciferol dosing may place the patient at risk for hypercalcemia, elevated calcium-phosphorus product, and metastatic calcification. Uncontrolled serum phosphate levels can exacerbate secondary hyperparathyroidism and can lessen the effectiveness of doxercalciferol therapy. After initiating doxercalciferol therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia (10.6—11.2 mg/dL for 3 consecutive levels) or increased to correct persistent mild hyperphosphatemia (7—8 mg/dL for 3 consecutive levels).

    Children

    The safety and efficacy of doxercalciferol in children have not been determined.

    Hypervitaminosis D

    Since doxercalciferol is a vitamin D analog, it is contraindicated in patients with signs and symptoms of hypervitaminosis D (vitamin D toxicity). Patients should be instructed not to take vitamin D-related compounds with doxercalciferol. Symptoms of vitamin D toxicity include hypercalcemia, hypercalciuria, and hyperphosphatemia.

    Hepatic disease

    Patients with impaired liver function may not metabolize doxercalciferol appropriately. Therefore, doxercalciferol should be used with caution in patients with hepatic disease. More frequent monitoring of intact parathyroid hormone (iPTH), calcium, and phosphorus levels should be done in these patients.

    Pregnancy

    Doxercalciferol is a FDA pregnancy risk category B drug. There are no adequate and well-controlled studies of doxercalciferol in pregnant women; however, animal studies have not revealed teratogenic or fetotoxic effects due to doxercalciferol. Doxercalciferol should only be used during pregnancy if the potential benefit justifies the potential risks to the fetus.

    Breast-feeding

    According to the manufacturer, caution should be exercised when administering doxercalciferol to women who are breast-feeding their infants. It is not known if doxercalciferol is excreted into breast milk; however, vitamin D is excreted in limited amounts. In one lactating woman given large doses of vitamin D, the infant developed hypercalcemia. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 6.6-6.6
    pancreatitis / Delayed / Incidence not known
    hypervitaminosis D / Delayed / Incidence not known
    coma / Early / Incidence not known
    respiratory arrest / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known

    Moderate

    edema / Delayed / 34.4-34.4
    dyspnea / Early / 11.5-11.5
    constipation / Delayed / 3.3-3.3
    hyperphosphatemia / Delayed / Incidence not known
    hypercalcemia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hypercalciuria / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    bone pain / Delayed / Incidence not known
    dehydration / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hyperthermia / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    hypotension / Rapid / Incidence not known

    Mild

    headache / Early / 27.9-27.9
    malaise / Early / 27.9-27.9
    nausea / Early / 21.3-21.3
    vomiting / Early / 21.3-21.3
    dizziness / Early / 11.5-11.5
    pruritus / Rapid / 8.2-8.2
    dyspepsia / Early / 4.9-4.9
    anorexia / Delayed / 4.9-4.9
    arthralgia / Delayed / 4.9-4.9
    weight gain / Delayed / 4.9-4.9
    infection / Delayed / 3.3-3.3
    xerostomia / Early / Incidence not known
    metallic taste / Early / Incidence not known
    polydipsia / Early / Incidence not known
    drowsiness / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    nocturia / Early / Incidence not known
    fatigue / Early / Incidence not known
    rhinorrhea / Early / Incidence not known
    polyuria / Early / Incidence not known
    weakness / Early / Incidence not known
    weight loss / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; 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.
    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: (Major) 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: (Major) 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: (Major) 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; Hydrochlorothiazide, HCTZ; Olmesartan: (Major) 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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Major) 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; Lansoprazole: (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.
    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: (Major) 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.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    Azilsartan; Chlorthalidone: (Major) 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: (Major) 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: (Major) 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: (Major) 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.
    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.
    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 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; 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. (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.
    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 Salts: (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: (Major) 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: (Major) 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: (Major) 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: (Major) 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: (Major) 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) Cholestyramine can decrease the intestinal absorption of fat or fat soluble vitamins including vitamin D analogs, such as oral doxercalciferol. If a patient must receive treatment with both drugs, separate the administration time as far apart as possible.
    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.
    Collagenase: (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.
    Cyanocobalamin, Vitamin B12: (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. (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.
    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.
    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.
    Enalapril; Hydrochlorothiazide, HCTZ: (Major) 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: (Major) 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; Desogestrel: (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; Ethynodiol Diacetate: (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; Etonogestrel: (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: (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; Norethindrone Acetate; 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.
    Ethinyl Estradiol; Norethindrone: (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; 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.
    Ethinyl Estradiol; Norgestimate: (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.
    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: (Major) 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.
    Gefitinib: (Moderate) CYP450 enzyme inhibitors, like gefitinib, 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.
    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.
    Griseofulvin: (Moderate) Although these interactions have not been specifically studied, hepatic enzyme inducers, such as griseofulvin, may affect the 25-hydroxylation of doxercalciferol and may necessitate dosage adjustments of doxercalciferol.
    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: (Major) 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: (Major) 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; Irbesartan: (Major) 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; Lisinopril: (Major) 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; Losartan: (Major) 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: (Major) 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; Metoprolol: (Major) 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: (Major) 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; Olmesartan: (Major) 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; Propranolol: (Major) 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; Quinapril: (Major) 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; Spironolactone: (Major) 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; Telmisartan: (Major) 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; Triamterene: (Major) 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; Valsartan: (Major) 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.
    Iron Salts: (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.
    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.
    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.
    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: (Major) 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: (Major) 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, RU-486: (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) Absorption of fat-soluble vitamins is reported to be decreased with prolonged oral administration of mineral oil. The bioavailability of orally administered vitamin D analogs may also be decreased. However, despite warnings in various texts, there is little direct evidence that the interaction is of practical/clinical importance with limited use as directed. It may be prudent for those taking Vitamin D analogs to separate administration by 1 hour before or 4 hours after a mineral oil oral dosage to help limit absorption interactions. Theoretically, the effect on fat-soluble vitamin absorption may more likely occur with prolonged or chronic administration of mineral oil.
    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.
    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; 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.
    Pantothenic Acid, Vitamin B5: (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.
    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.
    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 Salts: (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; 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.
    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.
    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.
    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.
    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.
    Streptogramins: (Moderate) CYP450 enzyme inhibitors, like dalfopristin;quinupristin, 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.
    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.
    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: (Major) 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.
    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.
    Zinc Salts: (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.

    PREGNANCY AND LACTATION

    Pregnancy

    Doxercalciferol is a FDA pregnancy risk category B drug. There are no adequate and well-controlled studies of doxercalciferol in pregnant women; however, animal studies have not revealed teratogenic or fetotoxic effects due to doxercalciferol. Doxercalciferol should only be used during pregnancy if the potential benefit justifies the potential risks to the fetus.

    According to the manufacturer, caution should be exercised when administering doxercalciferol to women who are breast-feeding their infants. It is not known if doxercalciferol is excreted into breast milk; however, vitamin D is excreted in limited amounts. In one lactating woman given large doses of vitamin D, the infant developed hypercalcemia. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    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, 24-dihydroxyvitamin D2 (minor metabolite). The elimination half-life is 32—37 hours in healthy volunteers and patients with end-stage renal failure.

    Oral Route

    Doxercalciferol is absorbed from the GI tract and activated in the liver. In healthy volunteers, peak blood levels of the major metabolite are reached 11—12 hours after repeated oral doses of doxercalciferol 5—15 mcg.

    Intravenous Route

    Peak blood levels are reached in about 8 hours after a single intravenous dose of 5 mcg of doxercalciferol.