calcifediol (Rx)

Brand and Other Names:Rayaldee
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule, extended-release

  • 30mcg

Hyperparathyroidism

Indicated for secondary hyperparathyroidism associated with vitamin D insufficiency in patients with stage 3 or 4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels <30 ng/mL

Ensure serum calcium in <9.8 mg/dL before initiating calcifediol

Initial: 30 mcg PO qHS

Maintenance dose should target serum total 25-hydroxyvitamin D levels to 30-100 mg/mL, intact parathyroid hormone (PTH) levels within the desired therapeutic range, serum calcium (corrected for low albumin) within the normal range, and serum phosphorus <5.5 mg/dL

Also see Administration

Dosage Modifications

Increase dose

  • Increase the dose to 60 mcg PO qHS after ~3 months, if intact PTH remains above the desired therapeutic range
  • Prior to raising the dose, ensure serum calcium is <9.8 mg/dL, serum phosphorus is below 5.5 mg/dL, and serum total 25-hydroxyvitamin D is <100 ng/mL

Suspend dosing

  • Suspend dosing if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease, if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia, or if serum total 25-hydroxyvitamin D is consistently >100 ng/mL
  • Restart at a reduced dose after these laboratory values have normalized

Dosing Considerations

Monitor serum calcium, serum phosphorus, serum total 25-hydroxyvitamin D, and intact PTH levels at a minimum of 3 months after initiation of therapy or dose adjustment, and then at least every 6-12 months

Patients with a history of hypercalcemia prior to initiating therapy should be monitored more frequently for possible hypercalcemia during therapy

Limitations of use

  • Not indicated for secondary hyperparathyroidism in patients with stage 5 CKD or end-stage renal disease on dialysis

Safety and efficacy not established

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Interactions

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              Serious - Use Alternative (7)

              • abametapir

                abametapir will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use is warranted, carefully monitor, particularly during treatment initiation and dose adjustment. Discontinue oliceridine if serotonin syndrome is suspected.

              • apalutamide

                apalutamide will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              • fexinidazole

                fexinidazole will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              • ivosidenib

                ivosidenib will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

              • lonafarnib

                lonafarnib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

              • tucatinib

                tucatinib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              • voxelotor

                voxelotor will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

              Monitor Closely (64)

              • amobarbital

                amobarbital will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • atazanavir

                atazanavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • belzutifan

                belzutifan will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

              • bendroflumethiazide

                bendroflumethiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

              • bosentan

                bosentan, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • carbamazepine

                carbamazepine, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • chlorothiazide

                chlorothiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

              • chlorthalidone

                chlorthalidone increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

              • cholestyramine

                cholestyramine will decrease the level or effect of calcifediol by drug binding in GI tract. Modify Therapy/Monitor Closely. Dose adjustment of calcifediol may be required, and serum total 25-hydroxyvitamin D, intact PTH, and serum calcium concentrations should be monitored closely if cholestyramine is initiated or discontinued.

              • clarithromycin

                clarithromycin, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • cobicistat

                cobicistat, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • conivaptan

                conivaptan, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • dabrafenib

                dabrafenib, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • darunavir

                darunavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • dexamethasone

                dexamethasone, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • digoxin

                calcifediol, digoxin. Other (see comment). Modify Therapy/Monitor Closely. Comment: Calcifediol may cause hypercalcemia which would increase the risk of digitalis toxicity. Monitor both serum calcium levels and for signs and symptoms of digitalis toxicity.

              • efavirenz

                efavirenz, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • elagolix

                elagolix will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • encorafenib

                encorafenib, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

              • enzalutamide

                enzalutamide, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • eslicarbazepine acetate

                eslicarbazepine acetate, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • etravirine

                etravirine, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • fedratinib

                fedratinib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              • fosamprenavir

                fosamprenavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • fosphenytoin

                fosphenytoin, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • grapefruit

                grapefruit, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • hydrochlorothiazide

                hydrochlorothiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

              • idelalisib

                idelalisib, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • imatinib

                imatinib, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • indinavir

                indinavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • isoniazid

                isoniazid, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • istradefylline

                istradefylline will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              • itraconazole

                itraconazole will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Closely monitor when initiating or discontinuing a strong CYP3A4 inhibitor.

              • ketoconazole

                ketoconazole, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • lopinavir

                lopinavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • methyclothiazide

                methyclothiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

              • mifepristone

                mifepristone will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • mitotane

                mitotane, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • nafcillin

                nafcillin, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • nefazodone

                nefazodone, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • nelfinavir

                nelfinavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • nevirapine

                nevirapine, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • nicardipine

                nicardipine, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • oxcarbazepine

                oxcarbazepine, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • pentobarbital

                pentobarbital, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • phenobarbital

                phenobarbital, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • phenytoin

                phenytoin, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • posaconazole

                posaconazole, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • primidone

                primidone, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • rifabutin

                rifabutin, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • rifampin

                rifampin, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • rifapentine

                rifapentine, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • ritonavir

                ritonavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • rucaparib

                rucaparib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

              • saquinavir

                saquinavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • secobarbital

                secobarbital will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • St John's Wort

                St John's Wort, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

              • stiripentol

                stiripentol, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              • tazemetostat

                tazemetostat will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tecovirimat

                tecovirimat will decrease the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

              • tipranavir

                tipranavir, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              • voriconazole

                voriconazole, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

              Minor (1)

              • ribociclib

                ribociclib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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              Adverse Effects

              >10%

              Hyperphosphatemia, at least 1 episode >4.5 mg/dL (45%)

              1-10%

              Anemia (4.9%)

              Nasopharyngitis (4.9%)

              Increased blood creatinine (4.9%)

              Dyspnea (4.2%)

              Hypercalcemia, at least 1 episode >10.5 mg/dL (4.2%)

              Cough (3.5%)

              Congestive heart failure (3.5%)

              Constipation (3.2%)

              Bronchitis (2.8%)

              Hyperkalemia (2.5%)

              Osteoarthritis (2.1%)

              Hyperuricemia (1.8%)

              Contusion (1.8%)

              Pneumonia (1.4%)

              COPD (1.5%)

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              Warnings

              Contraindications

              None

              Cautions

              Adynamic bone disease with subsequent increased risk of fractures may develop if intact PTH levels are suppressed by calcifediol to abnormally low levels; monitor intact PTH levels and adjust calcifediol dose accordingly (see Dosage Modifications)

              Hypercalcemia

              • Hypercalcemia may occur
              • Acute hypercalcemia may increase risk of cardiac arrhythmias, and seizures and may potentiate the effect of digitalis on the heart
              • Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification
              • Severe hypercalcemia may require emergency attention
              • Hypercalcemia may be exacerbated by concomitant administration of high doses of calcium-containing preparations, thiazide diuretics, or other vitamin D compounds
              • Careful and regular monitoring of serum calcium levels is necessary
              • Inform patients about the symptoms of hypercalcemia and to contact their physician if they develop; symptoms include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, and weight loss

              Interaction overview

              • Calcifediol may cause hypercalcemia, which would increase the risk of digitalis toxicity; monitor both serum calcium levels and for signs and symptoms of digitalis toxicity
              • Coadministration of calcifediol and thiazide diuretics may cause hypercalcemia
              • Cholestyramine may impair the absorption of calcifediol
              • Phenobarbital or other anticonvulsants or other compounds that stimulate microsomal hydroxylation reduce the half-life of calcifediol
              • CYP3A inhibitors
                • CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1)
                • This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol
                • Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor
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              Pregnancy

              Pregnancy

              There are no human data with use in pregnant women to identify a drug-associated

              risk for major birth defects, miscarriage or adverse maternal or fetal outcomes; there are risks to mother and fetus associated with chronic kidney disease in pregnancy

              Animal data

              • In animal reproduction studies, drug increased skeletal and soft tissue malformation when rabbits were given once daily oral doses representing ≥6 times the human
              • dose of 60 mcg/day, based on body surface area (mg/m2), during the period of organogenesis
              • No adverse developmental effects were observed in rats given up to 15 times the human dose, based on body surface area (mg/m2) during organogenesis
              • Chronic kidney disease in pregnancy increases the maternal risk for hypertension, miscarriage,
              • preterm labor, and preeclampsia; chronic kidney disease increases fetal risk for intrauterine
              • growth restriction (IUGR), prematurity, polyhydramnios, still birth, and low birth weight

              Lactation

              There is no information available on presence of drug in human milk, effects of drug on breastfed infant, or on milk production; infants potentially exposed to drug through breast milk should be monitored for signs and symptoms of hypercalcemia; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

              Monitor infants exposed to calcifediol through breast milk for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation and weight loss; consider monitoring of serum calcium in infant

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Extended-release formulation of calcifediol (25-hydroxyvitamin D3), a prohormone of the active form of vitamin D3

              Calcifediol is converted to calcitriol by CYP27B1, also called 1-alpha hydroxylase, primarily in the kidney; calcitriol binds to the vitamin D receptor in target tissues and activates vitamin D responsive pathways that result in increased intestinal absorption of calcium and phosphorus and reduced parathyroid hormone synthesis

              Absorption

              Steady-state: Levels of serum total 25-hydroxyvitamin D are reached after ~3 months

              Distribution

              Protein bound: >98%

              Vd, steady-state: 8.8 L (healthy volunteers); 30.1 L (stage 4 CKD)

              Metabolism

              Production of calcitriol from calcifediol is catalyzed by the 1-alpha-hydroxylase enzyme, CYP27B1, located in the kidney and other tissues

              CYP24A1, located in all vitamin D responsive tissues, catabolizes both calcifediol and calcitriol to inactive metabolites

              Elimination

              Excretion: Primarily through biliary fecal route

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              Administration

              Oral Administration

              Swallow capsule whole

              Missed dose

              • Instruct patients to skip a missed dose and resume taking at the next regularly scheduled time
              • Do not administer an extra dose

              Storage

              Store at controlled room temperature (20-25°C [68-77°F]); excursions permitted to 15-30°C (59-86°F)

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              Rayaldee oral
              -
              30 mcg capsule

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

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              • View the formulary and any restrictions for each plan.
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              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.