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.
DRUG INTERACTIONS
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Aluminum Hydroxide: (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, concomitant use should be avoided, if possible, in patients with chronic renal failure. (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Magnesium-containing antacids, such as magnesium hydroxide, should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, concomitant use should be avoided, if possible, in patients with chronic renal failure. (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D analogs can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with chronic renal failure. Aluminum hydroxide may be used as a phosphate binder in patients receiving vitamin D analogs. The serum phosphate, calcium and calculated calcium-phosphate product (serum Ca x PO4) should be monitored closely. After initiating vitamin D analog therapy, the dose of phosphate binders should be decreased to correct persistent mild hypercalcemia or increased to correct persistent mild hyperphosphatemia.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Amiodarone: (Moderate) 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) 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; 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: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Azilsartan; Chlorthalidone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Bendroflumethiazide; Nadolol: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
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: (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) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium Carbonate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium Carbonate; Magnesium Hydroxide; 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 Carbonate; Risedronate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium Carbonate; Simethicone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium Chloride: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium Gluconate: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Calcium; Vitamin D: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Carbamazepine: (Moderate) 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) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Chlorthalidone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Chlorthalidone; Clonidine: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Cholestyramine: (Moderate) 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.
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. 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.
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. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. 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. cobicistat is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Erythromycin: (Moderate) 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.
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) 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: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Ibritumomab Tiuxetan: (Major) High intake of phosphates concomitantly with vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia.
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) 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.
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.
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) 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.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
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) 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.
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: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Metolazone: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
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.
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) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
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.
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) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Protease inhibitors: (Moderate) 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) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
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.
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.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Magnesium-containing drug products should be used cautiously in patients receiving vitamin D analogs. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of vitamin D analogs and magnesium-containing drug products should be avoided, if possible, in patients with chronic renal failure.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
St. John's Wort, Hypericum perforatum: (Moderate) 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.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
Thiazide diuretics: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine.
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) 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.
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) 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.
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.