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  • CLASSES

    Vitamin D Supplements

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic calcitriol analog
    Used for secondary hyperparathyroidism associated with CKD
    Decreases PTH with lower incidence of hypercalcemia and hyperphosphatemia vs. calcitriol

    COMMON BRAND NAMES

    Zemplar

    HOW SUPPLIED

    Paricalcitol/Zemplar Intravenous Inj Sol: 1mL, 2mcg, 5mcg
    Paricalcitol/Zemplar Oral Cap: 1mcg, 2mcg, 4mcg

    DOSAGE & INDICATIONS

    For the prevention and treatment of secondary hyperparathyroidism and resultant metabolic bone disease (renal osteodystrophy†).
    NOTE: Dosage adjustments should be determined based on serum calcium, serum phosphorous, and serum or plasma iPTH concentrations. Initially and following a dosage adjustment, serum calcium, serum phosphorous, and serum or plasma iPTH concentrations should be monitored at least every 2 weeks for 3 months, monthly for 3 months, and then every 3 months thereafter.
    For initial dosing and dosage titration in pre-dialysis patients with Stage 3 or 4 chronic kidney disease.
    NOTE: In general, the dose should be adjusted no more frequently than every 2 to 4 weeks in adults and every 4 weeks in pediatric patients. In clinical trials of paricalcitol in adults, the average weekly dose was 9.6 mcg in patients taking once daily and 9.5 mcg in patients taking 3 times per week.
    Oral dosage
    Adults with iPTH concentration of 500 pg/mL or less (Initial dosing)

    Initially, 1 mcg PO once daily or 2 mcg PO 3 times per week. If the dose is administered 3 times per week, it should be administered no more frequently than every other day. Subsequent dosing should be individualized based on iPTH, serum calcium, and serum phosphorus concentrations to maintain an iPTH level within the target range.

    Adults with iPTH concentration more than 500 pg/mL (Initial dosing)

    Initially, 2 mcg PO once daily or 4 mcg PO 3 times per week. If the dose is administered 3 times per week, it should be administered no more frequently than every other day. Subsequent dosing should be individualized based on iPTH, serum calcium, and serum phosphorus concentrations to maintain an iPTH level within the target range.

    Adults with iPTH concentration less than 60 pg/mL or more than 60% decrease (Dose titration)

    Decrease the paricalcitol dose by 1 mcg/dose for the once daily dosage or 2 mcg/dose for the 3 times per week dosage. If the patient is taking the lowest dose on the daily regimen and a further reduction in dosage is needed, the dose can be decreased to 1 mcg PO 3 times per week. If a further dose reduction is required, the drug should be withheld and restarted at a lower dose.

    Adults with iPTH concentration decreased by 30% to 60% (Dose titration)

    Maintain the same dose.

    Adults with iPTH concentration decreased by less than 30%, the same, or increasing (Dose titration)

    Increase the dose by 1 mcg/dose for the once daily dosage or 2 mcg/dose for the 3 times per week dosage.

    Children and Adolescents 10 to 17 years (Initial dosing)

    Initially, 1 mcg PO 3 times per week, administered no more frequently than every other day. Subsequent dosing should be individualized based on iPTH, serum calcium, and serum phosphorus concentrations to maintain an iPTH level within the target range.

    Children and Adolescents 10 to 17 years (Dose titration)

    Every 4 weeks, may increase each dose by 1 mcg increments, maintaining the 3 times per week regimen (e.g., increase 1 mcg PO 3 times per week to 2 mcg PO 3 times per week) based on iPTH, serum calcium, and serum phosphorus concentrations to maintain an iPTH level within the target range. At any time, each dose may be decreased by 1 mcg. Paricalcitol may be stopped if the patient requires reduction while receiving 1 mcg 3 times per week, resuming when appropriate.

    If calcium concentration is elevated in any patient

    Decrease or hold the paricalcitol dose until parameters normalize.

    For initial dosing and dosage titration in patients with Stage 5 chronic kidney disease on dialysis.
    Oral dosage
    Adults (Initial dosing)

    The recommended initial dose can be calculated as follows: dose (mcg) = baseline iPTH concentration (pg/mL) / 80. To minimize the risk of hypercalcemia, patients should not be treated until their baseline serum calcium has been adjusted to 9.5 mg/dL or less. The calculated dose is administered 3 times per week, no more frequently than every other day. Subsequent dosing should be individualized based on iPTH, serum calcium, and serum phosphorus concentrations to maintain an iPTH level within the target range.

    Adults (Dose titration)

    Titrate dose based on formula: dose (mcg) = most recent iPTH concentration (pg/dL) / 80. If serum calcium is elevated, decrease the paricalcitol dose by 2 to 4 mcg lower than that calculated by the most recent iPTH/80. As iPTH concentrations approach the target range, small individualized dose adjustments may be necessary to achieve a stable iPTH. In situations where monitoring of iPTH, calcium, or phosphorus concentrations are monitored less frequently than once per week, a more modest initial and dose titration ratio (i.e., iPTH divided by 100) may be necessary.

    Children and Adolescents 10 to 17 years (Initial dosing)

    The recommended initial dose can be calculated as follows: dose (mcg) = baseline iPTH concentration (pg/mL) / 120. The calculated dose, rounded down to the nearest whole number, is administered 3 times per week, no more frequently than every other day. Subsequent dosing should be individualized based on iPTH, serum calcium, and serum phosphorus concentrations to maintain an iPTH level within the target range.

    Children and Adolescents 10 to 17 years (Dose titration)

    Every 4 weeks, may increase each dose by 1 mcg increments, maintaining the 3 times per week regimen (e.g., increase 1 mcg PO 3 times per week to 2 mcg PO 3 times per week) based on iPTH, serum calcium, and serum phosphorus concentrations to maintain an iPTH level within the target range. At any time, each dose may be decreased by 2 mcg. Paricalcitol may be stopped if the patient requires reduction while receiving 1 or 2 mcg 3 times per week, resuming when appropriate.

    Intravenous dosage

    Determine dosage adjustments based on serum calcium and plasma iPTH concentrations. Initially, monitor serum calcium twice weekly until a dose is established; then, monitor monthly. Monitor plasma iPTH concentrations every 2 to 4 weeks after initiation of therapy and dose adjustments. In general, adjust the dose no more frequently than every 2 to 4 weeks.

    Adults

    Initially, 0.04 to 0.1 mcg/kg/dose IV no more frequently than every other day at any time during dialysis. Adjust maintenance dose based on iPTH and serum calcium concentrations. If iPTH is above target and increased or decreased by less than 30%, increase dose by 2 to 4 mcg IV every 2 to 4 weeks. If iPTH is above target and decreased by 30% to 60%, maintain the same dose. If iPTH is above target and decreased by more than 60%, decrease dose per clinical judgement. If iPTH is at target and stable, maintain the same dose. Maximum dosage is 0.24 mcg/kg/dose IV. Suspend or decrease the dose if iPTH is persistently low or if serum calcium is consistently elevated. Restart at a lower dose after laboratory values have normalized.[28490]

    Children and Adolescents 5 to 17 years

    Initially, 0.04 mcg/kg/dose IV bolus 3 times per week if iPTH is less than 500 pg/mL or 0.08 mcg/kg/dose IV bolus 3 times per week if iPTH is 500 pg/mL or more. Administer no more frequently than every other day at any time during dialysis. Adjust maintenance dose based on iPTH and serum calcium concentrations. If iPTH is above target and decreased by less than 30%, increase dose by 0.04 mcg/kg/dose IV every 2 to 4 weeks. If iPTH is 150 pg/mL or more and decreased by 30% to 60%, maintain the same dose. If iPTH is less than 150 pg/mL and decreased by more than 60%, decrease dose by 0.04 mcg/kg/dose IV weekly, or by 50% if decreased dose equals zero. Suspend or decrease the dose if iPTH is persistently low or if serum calcium is consistently elevated. Restart at a lower dose after laboratory values have normalized.[28490]

    For initial dosing and dosage titration in patients with stage 5 chronic kidney disease on dialysis (National Kidney Foundation Guidelines)†.
    NOTE: Serum calcium concentration should be less than 9.5 mg/dL in patients with a serum iPTH less than 1,000 pg/mL. In patients with a serum iPTH more than 1,000 pg/mL, the serum calcium concentration should be less than 10 mg/dL. Serum phosphorous concentration should be less than 5.5 mg/dL and the calcium-phosphorous product should be less than 55.
    Determine dosage adjustments based on serum calcium, serum phosphorous, and plasma iPTH concentrations. Initially and during dosage titration, monitor serum calcium and phosphorous concentrations every 2 weeks for 1 month and then monthly. Monitor plasma iPTH concentration monthly for 3 months then every 3 months once target iPTH concentrations are achieved (150 to 300 pg/mL).
    Intravenous dosage
    Adults with baseline iPTH 300 to 600 pg/mL

    Initially, 2.5 to 5 mcg IV bolus during each hemodialysis session.

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

    Initially, 6 to 10 mcg IV bolus during each hemodialysis session.

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

    Initially, 10 to 15 mcg IV bolus during each hemodialysis session.

    If calcium concentration is more than 10.2 mg/dL

    Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify paricalcitol dose based on phosphorous or iPTH concentrations.

    If calcium concentration is 9.5 to 10.2 mg/dL

    Reduce dose of calcium-containing phosphate binders. If continues to be elevated, modify paricalcitol dose based on phosphorous or iPTH concentrations.

    If phosphorous concentration is more than 6 mg/dL

    Hold paricalcitol until phosphorous concentration is less than 5.5 mg/dL and reduce paricalcitol dosage 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 paricalcitol dosage by 25% to 50%.

    If iPTH concentrations are more than 300 pg/mL

    Increase paricalcitol dosage by 25% to 50%.

    If iPTH concentration is 200 to 300 pg/mL

    Continue same paricalcitol dosage.

    If iPTH concentration is 150 to 200 pg/mL

    Decrease paricalcitol dosage by 50% for 2 months. Recheck iPTH. If iPTH is greater than 300 pg/mL, increase paricalcitol dosage by 10% to 25%; if iPTH is 200 to 300 pg/mL, continue same dosage; if iPTH is 150 to 200 pg/mL, reduce paricalcitol dosage by 25% to 50%; if iPTH is less than 150 pg/mL, hold paricalcitol for 3 months.

    If iPTH concentration is less than 150 pg/mL

    Hold paricalcitol for 1 month. Recheck iPTH. If iPTH is greater than 300 pg/mL, resume paricalcitol dosage at 75% of initial dose; if iPTH is 200 to 300 pg/mL, continue same dosage; if iPTH is 150 to 200 pg/mL, resume paricalcitol at earlier dosage; if iPTH is less than 150 pg/mL, hold paricalcitol for 3 months.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Specific maximum dosage information is not available for PO or IV formulations; however, doses up to 0.24 mcg/kg (16.8 mcg) IV have been administered safely.

    Geriatric

    Specific maximum dosage information is not available for PO or IV formulations; however, doses up to 0.24 mcg/kg (16.8 mcg) IV have been administered safely.

    Adolescents

    Specific maximum dosage information is not available for PO or IV formulations; however, doses up to 9.6 mcg IV have been administered during clinical trials.

    Children

    10 to 12 years: Specific maximum dosage information is not available for PO or IV formulations; however, doses up to 9.6 mcg IV have been administered during clinical trials.
    5 to 9 years: Safety and efficacy of oral capsules have not been established. Specific maximum dosage information is not available for IV formulation; however, doses up to 9.6 mcg IV have been administered during clinical trials.
    1 to 4 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is required in patients with mild or moderate hepatic impairment. Paricalcitol use has not been studied in patients with severe hepatic impairment.

    Renal Impairment

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

    ADMINISTRATION

    The paricalcitol dose should be individualized based on the iPTH level.
    Monitoring of the PTH level using an intact PTH (iPTH) assay is recommended. See dosage section for monitoring recommendations.
    A ratio of 4:1 (paricalcitol to calcitriol) may be used to convert patients to paricalcitol from calcitriol.

    Oral Administration

    Paricalcitol may be administered once daily every day or once daily 3 times per week. When administered as a 3 times per week regimen, the doses should be administered no more frequently than every other day.

    Oral Solid Formulations

    Paricalcitol capsules may be administered without regard to food.

    Injectable Administration

    After initial vial entry, the contents of the multi-use vial are stable at room temperature for 7 days. Discard unused contents of the single-use vial after use.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Paricalcitol is given intravenously as a bolus injection dose.

    STORAGE

    Zemplar:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Paricalcitol is contraindicated in patients with known hypersensitivity to paricalcitol or any of the inactive ingredients. Hypersensitivity reactions, including angioedema, laryngeal edema, and urticaria have been reported with paricalcitol injection.

    Hypercalcemia

    Paricalcitol is contraindicated in patients with hypercalcemia. Acute hypercalcemia may increase the risk of cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart. Chronic hypercalcemia may lead to generalized vascular calcification and other soft-tissue calcification. Severe hypercalcemia may require emergency treatment. Monitor calcium concentrations twice weekly when initiating paricalcitol or during dose adjustments. Once a maintenance dose has been established, monitor serum calcium at least monthly. If hypercalcemia occurs, reduce the paricalcitol dose or discontinue paricalcitol until serum calcium is normal. Patients with a history of hypercalcemia prior to starting therapy may be at increased risk for developing hypercalcemia during paricalcitol therapy. Hypercalcemia may be worsened by concomitant administration of high doses of calcium-containing preparations, thiazide diuretics, or other vitamin D compounds. Additionally, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. Monitor serum calcium frequently in these situations; dose adjustments of paricalcitol may be necessary. Advise patients of the symptoms of elevated calcium, such as feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst and urination, and weight loss, and to report new or worsening symptoms should they occur.

    Hypervitaminosis D

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

    Pregnancy

    There are no adequate and well-controlled studies of paricalcitol use during human pregnancy. Paricalcitol should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Paricalcitol has been shown to cause minimal decreases in fetal viability (5%) when administered daily to rabbits at a dose 0.5-times a human dose of 14 mcg or 0.24 mcg/kg (based on body surface area, mcg/m2), and when administered to rats at a dose 2-times the 0.24 mcg/kg human dose (based on body surface area, mcg/m2). At the highest dose tested, 20 mcg/kg administered 3 times per week in rats (13-times the 14 mcg human dose based on surface area, mcg/m2), there was a significant increase in the mortality of newborn rats at doses that were maternally toxic and are known to produce hypercalcemia in rats. No other effects on offspring development were observed. Paricalcitol was not teratogenic at the doses tested. Paricalcitol (20 mcg/kg) has been shown to cross the placental barrier in rats. Based on its pharmacokinetics, paricalcitol probably crosses the human placenta, although exposure to the fetus is expected to be low due to the extensive protein binding and metabolism of paricalcitol. If a pregnant woman is taking paricalcitol, she should not take additional vitamin D or its derivatives.

    Breast-feeding

    There are no data available on the presence of paricalcitol in human breast milk or the effects of paricalcitol on the breast-fed infant or on milk production. Studies have shown that paricalcitol is present in the milk of lactating rats. Because of the potential for serious adverse reactions, including hypercalcemia in a breast-fed infant, breast-feeding is not recommended during treatment with paricalcitol.

    ADVERSE REACTIONS

    Severe

    renal failure (unspecified) / Delayed / 3.3-3.3
    atrial flutter / Early / 0-2.0
    arrhythmia exacerbation / Early / 0-2.0
    cardiac arrest / Early / 0-2.0
    pulmonary edema / Early / 0-2.0
    ocular hypertension / Delayed / 0-2.0
    hyperkalemia / Delayed / 0-2.0
    new primary malignancy / Delayed / 0-2.0
    laryngeal edema / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    hypervitaminosis D / Delayed / Incidence not known
    bone fractures / Delayed / Incidence not known

    Moderate

    edema / Delayed / 5.6-7.0
    hypertension / Early / 0-6.5
    hypotension / Rapid / 0-4.7
    hypoglycemia / Early / 3.3-3.3
    peripheral edema / Delayed / 0-3.3
    palpitations / Early / 3.0-3.0
    skin ulcer / Delayed / 2.8-2.8
    depression / Delayed / 2.8-2.8
    dehydration / Delayed / 2.8-2.8
    chest pain (unspecified) / Early / 0-2.8
    myoclonia / Delayed / 0-2.0
    delirium / Early / 0-2.0
    confusion / Early / 0-2.0
    dyspnea / Early / 0-2.0
    wheezing / Rapid / 0-2.0
    hyperemia / Delayed / 0-2.0
    conjunctivitis / Delayed / 0-2.0
    impotence (erectile dysfunction) / Delayed / 0-2.0
    hypocalcemia / Delayed / 0-2.0
    lymphadenopathy / Delayed / 0-2.0
    anemia / Delayed / 0-2.0
    prolonged bleeding time / Delayed / 0-2.0
    hyperphosphatemia / Delayed / 0-2.0
    hypercalcemia / Delayed / 0-2.0
    elevated hepatic enzymes / Delayed / Incidence not known
    hypercalciuria / Delayed / Incidence not known

    Mild

    pharyngitis / Delayed / 0-8.2
    infection / Delayed / 0-8.2
    dizziness / Early / 0-6.6
    arthralgia / Delayed / 5.0-5.0
    influenza / Delayed / 5.0-5.0
    chills / Rapid / 5.0-5.0
    fever / Early / 5.0-5.0
    insomnia / Early / 0-4.9
    headache / Early / 0-4.7
    vertigo / Early / 4.7-4.7
    rash / Early / 0-3.7
    anxiety / Delayed / 0-3.3
    sinusitis / Delayed / 2.8-3.3
    fatigue / Early / 0-3.3
    malaise / Early / 3.0-3.0
    muscle cramps / Delayed / 2.8-2.8
    back pain / Delayed / 2.8-2.8
    pruritus / Rapid / 0-2.8
    syncope / Early / 0-2.8
    cough / Delayed / 0-2.8
    myalgia / Early / 0-2.0
    alopecia / Delayed / 0-2.0
    urticaria / Rapid / 0-2.0
    acne vulgaris / Delayed / 0-2.0
    night sweats / Early / 0-2.0
    hirsutism / Delayed / 0-2.0
    paresthesias / Delayed / 0-2.0
    agitation / Early / 0-2.0
    hypoesthesia / Delayed / 0-2.0
    restlessness / Early / 0-2.0
    weight loss / Delayed / 0-2.0
    injection site reaction / Rapid / 0-2.0
    asthenia / Delayed / 0-2.0
    rhinitis / Early / Incidence not known
    urinary urgency / Early / Incidence not known

    DRUG INTERACTIONS

    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) Concomitant use of amiodarone, a CYP3A4 inhibitor, and paricalcitol, a CYP3A4 substrate, may result in increased paricalcitol concentrations. A paricalcitol dose reduction may be necessary if these drugs are used together.
    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.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as clarithromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as clarithromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Amprenavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if paricalcitol and aprepitant, fosaprepitant are used concurrently and monitor for an increase in paricalcitol-related adverse effects for several days after administration of a multi-day aprepitant regimen. Paricalcitol is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of paricalcitol. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Atazanavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Atazanavir; Cobicistat: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and cobicistat, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol. (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    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.
    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.
    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.
    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.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering paricalcitol with boceprevir due to an increased potential for paricalcitol-related adverse events. If paricalcitol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of paricalcitol. Paricalcitol is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated paricalcitol plasma concentrations.
    Bosentan: (Moderate) Serum concentrations of paricalcitol may be reduced when administered with drugs known to induce the CYP3A4 enzyme, such as bosentan. Dosage adjustments of paricalcitol may be required. Clinicians should monitor plasma PTH and serum calcium and phosphorous concentrations.
    Burosumab: (Severe) Vitamin D analogs are contraindicated in patients receiving burosumab; discontinue vitamin D analogs 1 week prior to initiation of burosumab.
    Calcifediol: (Major) Withhold calcifediol treatment when using other vitamin D analogs, like paricalcitol, 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 paricalcitol 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 paricalcitol.
    Calcium Acetate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Carbonate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Carbonate; 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 Carbonate; Simethicone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Chloride: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Citrate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium Gluconate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Calcium; Vitamin D: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
    Candesartan; Hydrochlorothiazide, HCTZ: (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) Antiepileptic drugs can increase the metabolism of endogenous vitamin D, thereby lowering serum concentrations and decreasing its activity. In addition, carbamazepine is a CYP3A4 inducer and thus may further lower serum concentrations of paricalcitol. Dosage adjustments of paricalcitol may be required.
    Ceritinib: (Moderate) Monitor serum calcium and iPTH levels if coadministration of paricalcitol and ceritinib are necessary; a paricalcitol dosage adjustment may be necessary. Ceritinib is a CYP3A4 inhibitor and paricalcitol is metabolized by CYP3A4. Coadministration with a strong CYP3A4 inhibitor approximately doubled the AUC of paricalcitol, although the Cmax was minimally affected; the mean half-life of paricalcitol also increased from 9.8 hours to 17 hours. The degree of CYP3A4 inhibition by ceritinib is unknown.
    Chloramphenicol: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as chloramphenicol. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    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 soluble vitamins including vitamin D analogs, such as oral paricalcitol. If a patient must receive treatment with both of these drugs, separate administration of paricalcitol by 1 hour before or 4 to 6 hours after a cholestyramine dose to help limit absorption interactions.
    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.
    Clarithromycin: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as clarithromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Cobicistat: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and cobicistat, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and cobicistat, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and cobicistat, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
    Colestipol: (Moderate) Separate administration of paricalcitol 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 paricalcitol.
    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.
    Conivaptan: (Major) According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as paricalcitol, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with paricalcitol. Treatment with paricalcitol may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Danazol: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as danazol. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Darunavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Darunavir; Cobicistat: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and cobicistat, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol. (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and cobicistat, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol. (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Delavirdine: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as delaviridine. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Digoxin: (Moderate) Paricalcitol 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 paricalcitol 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 paricalcitol.
    Dihydrotachysterol: (Major) The use of dihydrotachysterol with paricalcitol is not recommended because of the increased potential for additive effects and toxicity.
    Diltiazem: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as diltiazem. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Doxercalciferol: (Major) The use of doxercalciferol with paricalcitol is not recommended because of the increased potential for additive effects and toxicity.
    Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Paricalcitol is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
    Efavirenz: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paricalcitol.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paricalcitol.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as paricalcitol.
    Elbasvir; Grazoprevir: (Moderate) Administering paricalcitol with elbasvir; grazoprevir may result in elevated paricalcitol plasma concentrations. Paricalcitol is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    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) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as erythromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Erythromycin; Sulfisoxazole: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as erythromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Fluconazole: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as fluconazole. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Fluoxetine: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as fluoxetine. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Fluoxetine; Olanzapine: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as fluoxetine. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Fosamprenavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    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.
    Grapefruit juice: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol strong CYP3A4 inhibitors; dose adjustments of paricalcitol may be required. Plasma PTH and serum calcium and phosphorous concentrations should be closely monitored if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor, such as grapefruit juice.
    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) Antiepileptic drugs, such as barbiturates (i.e., phenobarbital and primidone), and phenytoin (or fosphenytoin which is metabolized to phenytoin) can increase the metabolism of endogenous vitamin D, thereby lowering serum concentrations and decreasing its activity. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. In addition, hydantoins are CYP3A4 inducers and thus may further lower serum concentrations of paricalcitol through increased CYP3A4-mediated metabolism. Dosage adjustments of vitamin D analogs may be required in patients who are receiving chronic treatment with antiepileptic drugs.
    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.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with paricalcitol, a CYP3A substrate, as paricalcitol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Imatinib: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as imatinib. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Indinavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) According to the manufacturer of oral iron sucrose, sucroferric oxyhydroxide an interaction was seen with paricalcitol in in vitro studies. Consider separating the administration of the two drugs and monitor for clinical response to paricalcitol.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with paricalcitol may result in increased serum concentrations of paricalcitol. Paricalcitol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring for adverse effects, such as GI effects, are advised if these drugs are used together.
    Itraconazole: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as itraconazole. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Ketoconazole: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as ketoconazole. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of paricalcitol; monitor for potential reduction in efficacy. Paricalcitol is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of paricalcitol; monitor for potential reduction in efficacy. Paricalcitol is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) An increase in in the plasma concentration of paricalcitol may occur if given with letermovir. Dosage adjustment of paricalcitol may be necessary in patients also receiving cyclosporine, because the magnitude of the interaction may be increased. Closely monitor serum intact parathyroid hormone (iPTH) and calcium concentrations. Paricalcitol is a CYP3A4 substrate and letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In one pharmacokinetic study, paricalcitol exposure approximately doubled and the half-life increased from 9.8 hours to 17 hours in the presence of a strong CYP3A4 inhibitor.
    Lopinavir; Ritonavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of paricalcitol by decreasing its systemic exposure; if used together, monitor intact parathyroid hormone (iPTH), serum calcium, and serum phosphorus concentrations and adjust the paricalcitol dosage as necessary. Paricalcitol is partially metabolized via CYP3A4 and lumacaftor is a strong CYP3A inducer.
    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.
    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.
    Mineral Oil: (Moderate) Separate administration of oral vitamin D analogs by 1 hour before or 4 to 6 hours after mineral oil to limit effects on absorption and availability of the vitamin D analog. Absorption of fat-soluble vitamins may be decreased with concomitant administration of mineral oil. The bioavailability of orally administered vitamin D analogs may also be decreased.
    Mitotane: (Moderate) Use caution if mitotane and paricalcitol are used concomitantly, and monitor for decreased efficacy of paricalcitol and a possible change in dosage requirements. Clinicians should monitor plasma iPTH and serum calcium and phosphorous concentrations when mitotane is initiated or discontinued. Mitotane is a strong CYP3A4 inducer and paricalcitol is partially metabolized by CYP3A4; coadministration may result in decreased plasma concentrations of paricalcitol.
    Nefazodone: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as nefazodone. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Nelfinavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Nevirapine: (Moderate) Serum concentrations of paricalcitol may be reduced when administered with drugs known to induce the CYP3A4 enzyme, such as nevirapine. Dosage adjustments of paricalcitol may be required. Clinicians should monitor plasma PTH and serum calcium and phosphorous concentrations with this combination.
    Nicardipine: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as nicardipine. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Nilotinib: (Moderate) Concomitant use of nilotinib, a moderate CYP3A4 inhibitor, and paricalcitol, a CYP3A4 substrate, may result in increased paricalcitol levels. A paricalcitol dose reduction may be necessary if these drugs are used together.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Oritavancin: (Moderate) Paricalcitol is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of paricalcitol may be reduced if these drugs are administered concurrently. Paricalcitol dosage adjustments may be required. Monitor plasma iPTH and serum calcium and phosphorous concentrations when oritavancin is initiated or discontinued.
    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.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and paricalcitol, a CYP3A4 substrate, may cause an increase in systemic concentrations of paricalcitol. Use caution when administering these drugs concomitantly.
    Phosphorated Carbohydrate Solution: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Phosphorus: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Polycarbophil: (Moderate) The concurrent use of vitamin D analogs, like paricalcitol 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).
    Posaconazole: (Moderate) Posaconazole and paricalcitol should be coadministered with caution due to an increased potential for paricalcitol-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of paricalcitol. These drugs used in combination may result in elevated paricalcitol plasma concentrations, causing an increased risk for paricalcitol-related adverse events.
    Potassium Phosphate: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Potassium Phosphate; Sodium Phosphate: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
    Protease inhibitors: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Ranolazine: (Moderate) Ranolazine may theoretically increase plasma concentrations of CYP3A4 substrates like paricalcitol, potentially leading to adverse reactions.
    Ribociclib: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and ribociclib, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Ribociclib is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
    Ribociclib; Letrozole: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and ribociclib, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Ribociclib is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
    Rifamycins: (Moderate) Serum concentrations of paricalcitol may be reduced when administered with drugs known to induce the CYP3A4 enzyme, such as rifampin, rifabutin, and rifamycin. Dosage adjustments of paricalcitol may be required. Clinicians should monitor plasma PTH and serum calcium and phosphorous concentrations when these drugs are initiated or discontinued.
    Ritonavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Rufinamide: (Minor) Rufinamide is not metabolized through hepatic CYP isozymes; however, it is a weak inducer of CYP3A4. In theory, decreased exposure of drugs that are extensively metabolized by CYP3A4, such as paricalcitol, may occur during concurrent use with rufinamide.
    Saquinavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of paricalcitol, which is a CYP3A4 substrate. Monitor patients for adverse effects of paricalcitol, such as nausea and vomiting. Plasma PTH and serum calcium and phosphorous concentrations should be closely monitored.
    St. John's Wort, Hypericum perforatum: (Moderate) Serum concentrations of paricalcitol may be reduced when administered with drugs known to induce the CYP3A4 enzyme, such as St. John's Wort. Dosage adjustments of paricalcitol may be required. Clinicians should monitor plasma PTH and serum calcium and phosphorous concentrations with this combination.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering paricalcitol with telaprevir due to an increased potential for paricalcitol-related adverse events. If paricalcitol dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of paricalcitol. Paricalcitol is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated paricalcitol plasma concentrations.
    Telithromycin: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as telithromycin. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and paricalcitol is necessary, as the systemic exposure of paricalcitol may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of paricalcitol; consider increasing the dose of paricalcitol if necessary. Paricalcitol is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    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.
    Tipranavir: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as protease inhibitors. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Trandolapril; Verapamil: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as verapamil. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Vemurafenib: (Moderate) Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as paricalcitol, could be expected with concurrent use. Use caution, and monitor therapeutic effects of paricalcitol when coadministered with vemurafenib.
    Verapamil: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as verapamil. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Voriconazole: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and voriconazole, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Voriconazole is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
    Zafirlukast: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as zafirlukast. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
    Zileuton: (Moderate) Paricalcitol is partially metabolized by CYP3A4. Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as zileuton. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of paricalcitol use during human pregnancy. Paricalcitol should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Paricalcitol has been shown to cause minimal decreases in fetal viability (5%) when administered daily to rabbits at a dose 0.5-times a human dose of 14 mcg or 0.24 mcg/kg (based on body surface area, mcg/m2), and when administered to rats at a dose 2-times the 0.24 mcg/kg human dose (based on body surface area, mcg/m2). At the highest dose tested, 20 mcg/kg administered 3 times per week in rats (13-times the 14 mcg human dose based on surface area, mcg/m2), there was a significant increase in the mortality of newborn rats at doses that were maternally toxic and are known to produce hypercalcemia in rats. No other effects on offspring development were observed. Paricalcitol was not teratogenic at the doses tested. Paricalcitol (20 mcg/kg) has been shown to cross the placental barrier in rats. Based on its pharmacokinetics, paricalcitol probably crosses the human placenta, although exposure to the fetus is expected to be low due to the extensive protein binding and metabolism of paricalcitol. If a pregnant woman is taking paricalcitol, she should not take additional vitamin D or its derivatives.

    There are no data available on the presence of paricalcitol in human breast milk or the effects of paricalcitol on the breast-fed infant or on milk production. Studies have shown that paricalcitol is present in the milk of lactating rats. Because of the potential for serious adverse reactions, including hypercalcemia in a breast-fed infant, breast-feeding is not recommended during treatment with paricalcitol.

    MECHANISM OF ACTION

    Paricalcitol reduces parathyroid hormone (PTH) concentrations with only small changes in serum calcium and phosphorus. This unique mechanism of action may be due to a different dose response of paricalcitol and calcitriol on the regulation of intestinal vitamin D receptor (VDR) content, parathyroid gland growth, and bone resorption. In animal studies, calcitriol is effective at suppressing PTH but only at doses which cause significant hypercalcemia and hyperphosphatemia. Paricalcitol, at all doses studied, decreases PTH concentrations with no significant difference in serum ionized calcium or phosphorus concentrations. In additional animal trials, paricalcitol reduced parathyroid gland weight compared to controls while calcitriol had no effect on parathyroid gland growth. Paricalcitol also does not upregulate intestinal VDR content as does calcitriol. Serum phosphorus, calcium, and calcium-phosphorus product may increase during paricalcitol administration; however, there is no significant difference in the incidence of hypercalcemia or hyperphosphatemia when compared to placebo. At higher doses, paricalcitol loses its selectivity for PTH suppression.

    PHARMACOKINETICS

    Paricalcitol is administered orally and intravenously as a bolus infusion. It is highly bound to plasma proteins (>= 99.8%). After administration, it is metabolized, with approximately 2% of the dose eliminated unchanged in the feces, and no parent drug found in the urine. In vitro data suggest that paricalcitol is metabolized by multiple non-hepatic and hepatic enzymes including CYP3A4, UGT1A4, and mitochondrial CYP24. Only one metabolite, which is less active than paricalcitol, has been identified as 24-R-hydroxy paricalcitol. The average half-life is 4 to 6 hours in healthy subjects. The major route of elimination is hepatobiliary with approximately 63% to 70% and 18% to 19% of the dose recovered in feces and urine, respectively. There is no accumulation with repeated administration.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP24, CYP3A4, UGT1A4
    Paricalcitol is partially metabolized by CYP3A4 and CYP24; however, it is not expected to inhibit or induce the clearance of drugs metabolized by the CYP450 isozyme system. Paricalcitol is also a UGT1A4 substrate.

    Oral Route

    Following an oral dose, paricalcitol is well-absorbed with a mean absolute bioavailability of 72% to 86%. Food delays the time to maximum plasma concentration by roughly 2 hours, but the extent of absorption is not altered.

    Intravenous Route

    Following paricalcitol doses ranging from 0.04 to 0.24 mcg/kg IV in chronic renal failure patients, concentrations of paricalcitol decrease rapidly within 2 hours; thereafter, concentrations decline linearly. In patients with chronic renal failure, the half-life of intravenous paricalcitol is around 15 hours.