Zemplar

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Zemplar

Classes

Vitamin D Analogues

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.

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

Common Brand Names

Zemplar, Zemplar Multi-Dose Vial Solution, Zemplar Solution

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

Dosage And 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 phosphorus and 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

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.

Drug Interactions

Adagrasib: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and adagrasib, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Paricalcitol is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor approximately doubled the exposure of paricalcitol.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Avoid vitamin D analog coadministration with magnesium hydroxide in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Avoid vitamin D analog coadministration with magnesium hydroxide in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
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. Paricalcitol is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. 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: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Azilsartan; Chlorthalidone: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Burosumab: (Contraindicated) 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) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Carbonate: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Carbonate; Simethicone: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Chloride: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Gluconate: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium; Vitamin D: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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 plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and ceritinib, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Ceritinib is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
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: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Chlorthalidone: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Chlorthalidone; Clonidine: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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. Paricalcitol is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. 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.
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. Paricalcitol is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. 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. Paricalcitol is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. 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.
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.
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 Disoproxil Fumarate: (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.
Elvitegravir; 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. Paricalcitol is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
Elvitegravir; Cobicistat; 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. Paricalcitol is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
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.
Folic Acid, Vitamin B9: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
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.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and ketoconazole, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Paricalcitol is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole approximately doubled the exposure of paricalcitol.
Lansoprazole; Amoxicillin; 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.
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.
Levoketoconazole: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and ketoconazole, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Paricalcitol is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole approximately doubled the exposure of paricalcitol.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Lonafarnib: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and lonafarnib, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Paricalcitol is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
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.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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: (Major) Avoid vitamin D analog coadministration with magnesium citrate in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Magnesium Hydroxide: (Major) Avoid vitamin D analog coadministration with magnesium hydroxide in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Magnesium Salts: (Major) Avoid vitamin D analog coadministration with magnesium-containing products, such as antacids, in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Magnesium: (Major) Avoid vitamin D analog coadministration with magnesium-containing products, such as antacids, in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Methyclothiazide: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Metolazone: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
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.
Nirmatrelvir; 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.
Olanzapine; 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.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
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.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
Pyridoxine, Vitamin B6: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
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.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Major) Avoid vitamin D analog coadministration with magnesium-containing products, such as antacids, in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Thiazide diuretics: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Tucatinib: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and tucatinib, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Paricalcitol is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentrations during concomitant use of thiazide diuretics and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
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.
Vonoprazan; Amoxicillin; 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.
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.

How Supplied

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

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.

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.

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.