Calcifediol

A11C - Vitamin A and D, incl. combinations ATC A11CC06 Small molecule approved 1980 Oral

JFDA label: Dedrogyl

Mechanism of Action

Agonist of Vitamin D3 receptor — Vitamin D receptor agonist

Target	Action	Gene / class
Vitamin D3 receptor efficacy	AGONIST	VDR

Indications

Approved

Secondary hyperparathyroidism

Contraindications

Source: Lexicomp

There are no contraindications listed in the manufacturer's labeling Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Very Common Cardiac failure

Renal and urinary disorders (1)

Very Common Increased serum creatinine

Blood and lymphatic system disorders (2)

Very Common Anemia · bruise

Metabolism and nutrition disorders (3)

Very Common Hypercalcemia · hyperkalemia · hyperuricemia

Musculoskeletal and connective tissue disorders (1)

Very Common Osteoarthritis

Other (1)

Very Common Hematologic & oncologic: Abnormal phosphorus levels (increased: 45%; hyperphosphatemia: 1% to 10%:

Respiratory, thoracic and mediastinal disorders (6)

Very Common bronchitis · chronic obstructive pulmonary disease · cough · dyspnea · Nasopharyngitis · pneumonia

Dosing

Source: Lexicomp

Secondary hyperparathyroidism: Oral: Initial: 30 mcg once daily at bedtime; may increase to 60 mcg once daily at bedtime after 3 months if intact PTH remains above desired therapeutic range. Note: Ensure corrected serum total calcium is below 9.8 mg/dL prior to initiating therapy. Maintenance dose should target total 25-hydroxyvitamin D levels between 30 and 100 ng/mL, intact PTH levels within desired therapeutic range, serum calcium

Refer to adult dosing.

No dosage adjustment necessary.

There are no dosage adjustments provided in the manufacturer's labeling; has not been studied.

Warnings & Precautions

Source: Lexicomp

Excessive vitamin D

Excessive vitamin D administration may lead to over suppression of PTH, progressive or acute hypercalcemia, hypercalciuria, hyperphosphatemia and adynamic bone disease.

Hypercalcemia

Progressive and/or acute hypercalcemia may increase risk of cardiac arrhythmias and seizures; chronic hypercalcemia may lead to generalized vascular and other soft-tissue calcification. Risk of hypercalcemia may be increased by concomitant use of calcium-containing supplements, vitamin D containing compounds, and/or medications that increase serum calcium (eg, thiazide diuretics). Monitor calcium levels closely with initiation of therapy and with dose adjustments; discontinue use promptly in patients who develop hypercalcemia. Patients with a history of hypercalcemia prior to therapy should be monitored more frequently.

Hyperphosphatemia

Should be corrected before initiating therapy; exacerbates secondary hyperparathyroidism, diminishing the effect of calcifediol. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in animal reproduction studies. Endogenous calcifediol crosses the placenta in concentrations generally lower than those in the maternal plasma; supplementation increases cord blood 25OHD concentrations (IOM 2011).

Lactation

Endogenous calcifediol is poorly excreted into breast milk, but milk concentrations may be increased with supplementation (IOM 2011). The manufacturer recommends that caution be used if administered to a nursing woman.

Monitoring

Clinical pearl	Serum calcium, serum phosphorus, serum total 25-hydroxyvitamin D and intact PTH levels within 3 months after initiation of therapy or dose adjustment, and subsequently at least every 6 to 12 months; signs and symptoms of hypercalcemia.

Chemistry & Properties

Formula	C27H46O3
Molecular weight	418.66 g/mol
IUPAC name	(1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol
CAS	19356-17-3
PubChem CID	5283731
InChIKey	`WRLFSJXJGJBFJQ-WPUCQFJDSA-N`
logP	6.73 (XLogP 6.2)
Polar surface area	40.46 Å²
H-bond acceptors / donors	2 / 2
Drug-likeness (QED)	0.52
Lipinski violations	1

SMILES

C=C1CC[C@H](O)C/C1=C/C=C1\CCC[C@]2(C)[C@@H]([C@H](C)CCCC(C)(C)O)CC[C@@H]12.O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.389 h
Volume of distribution	0.536 L/kg
Protein binding	70.0%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C8	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (57, DDInter)

Interacting drug	Severity	Management
Burosumab	major
Calcitriol	major
Cholecalciferol	major
Dihydrotachysterol	major
Doxercalciferol	major
Erdafitinib	major
Ergocalciferol	major
Paricalcitol	major
Aluminum hydroxide	moderate
Amobarbital	moderate
Bendroflumethiazide	moderate
Benzthiazide	moderate
Butabarbital	moderate
Butalbital	moderate
Calcipotriol (topical)	moderate
Calcitriol (topical)	moderate
Carbamazepine	moderate
Chlorothiazide	moderate
Chlorthalidone	moderate
Cholestyramine	moderate
Colesevelam	moderate
Colestipol	moderate
Digitoxin	moderate
Digoxin	moderate
Felbamate	moderate
Fosphenytoin	moderate
Hydrochlorothiazide	moderate
Hydroflumethiazide	moderate
Indapamide	moderate
Iron sucrose	moderate
Isoniazid	moderate
Magnesium carbonate	moderate
Magnesium chloride	moderate
Magnesium citrate	moderate
Magnesium gluconate	moderate
Magnesium glycinate	moderate
Magnesium hydroxide	moderate
Magnesium oxide	moderate
Magnesium sulfate	moderate
Methylphenobarbital	moderate

Showing 40 of 57.

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Everdi 15mg/100ml Oral Drops	Oral Drops 15 mg/100 ml	10 ml	Hayat Pharmaceutical Industries CO.PLC/JORDAN	4.920
Dedrogyl	Injection 0.15 mg/ml	10 ml	Awtar Pharmaceutical Co	5.240