Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
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 (67)
- 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.
- ceritinib
ceritinib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- lenacapavir
lenacapavir will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- levoketoconazole
levoketoconazole, 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 (5)
- acetazolamide
acetazolamide will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ribociclib
ribociclib will increase the level or effect of calcifediol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10%
Hyperphosphatemia, at least 1 episode >4.5 mg/dL (ULN) (45%); placebo (44%)
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%); placebo (2.1%)
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 (1.4%)
<1%
Hyperphosphatemia (>5.5 mg/dL x 2) (0.4%)
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
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.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
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)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Rayaldee oral - | 30 mcg capsule |  |
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Formulary
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.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
