Alfacalcidol

A11C - Vitamin A and D, incl. combinations ATC A11CC03 Small molecule Prodrug Natural product

Active form: Calcitriol.

JFDA label: One-Alpha caps.

Mechanism of Action

Agonist of Vitamin D3 receptor — Vitamin D receptor agonist

Target	Action	Gene / class
Vitamin D3 receptor efficacy	AGONIST	VDR

Indications

Approved

Chronic kidney disease-mineral and bone disorder

Contraindications

Source: Lexicomp

Hypersensitivity to 1-α-hydroxyvitamin D3, vitamin D or its analogues and derivatives, or any component of the formulation Absolute
evidence of vitamin D toxicity Absolute
hypercalcemia Absolute
hyperphosphatemia 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 (2)

Not Known Cardiac arrhythmia · hypertension

Nervous system disorders (4)

Not Known drowsiness · Headache · hyperthermia · psychosis (rare)

Hepatobiliary disorders (2)

Not Known Increased serum ALT · increased serum AST

Renal and urinary disorders (3)

Not Known Increased blood urea nitrogen · Nocturia · polyuria

Metabolism and nutrition disorders (6)

Not Known Decreased libido · hypercalcemia · hypercholesterolemia · hyperphosphatemia · polydipsia · weight loss

Gastrointestinal disorders (7)

Not Known Anorexia · constipation · dysgeusia · nausea · pancreatitis · vomiting · xerostomia

Skin and subcutaneous tissue disorders (1)

Not Known Pruritus

Musculoskeletal and connective tissue disorders (3)

Not Known Myalgia · ostealgia · weakness

Eye disorders (3)

Not Known Conjunctivitis · corneal deposits (calcification) · photophobia

Respiratory, thoracic and mediastinal disorders (1)

Not Known Rhinorrhea

Dosing

Source: Lexicomp

Chronic kidney disease-mineral and bone disorder (hypocalcemia, secondary hyperparathyroidism, or osteodystrophy): Note: Patients taking calcium supplements should limit intake to ≤500 mg/day (elemental calcium). Oral: Predialysis patients: Initial: 0.25 mcg/day for 2 months; if necessary, may titrate dose upward in increments of 0.25 mcg/day every 2 months. Maintenance (usual dose): 0.5 mcg/day; up to 1 mcg/day may be necessary to maintain desired serum calcium concentrations. Dialysis patients: Initial: 1 mcg/day for up to 4 weeks; if necessary, may titrate dose upward in increments of 0.5 mcg/day every 2 to 4 weeks. Usual effective dose: 1 to 2 mcg/day; up to 3 mcg/day may be required in some patients. Maintenance (usual dose): 0.25 to 1 mcg/day; dosing interval may be increased (every other day or less frequently) in patients who develop hypercalcemia. Note: In some studies, intermittent dosing (on dialysis days) in dialysis patients has been shown as efficacious as daily dosing (Tarrass 2006). IV: Dialysis patients: Initial: 1 mcg per dialysis (2 to 3 times weekly); if inadequate response after 1 week, may titrate dose upward in weekly increments of 1 mcg per dialysis (maximum dose: 12 mcg/week). Total titration period should not exceed 6 weeks. Maintenance: 1.5 to 12 mcg per week (divided equally between hemodialysis sessions); usual effective dose: 6 mcg/week.

No dosage adjustment necessary.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Excessive vitamin D

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

Hypercalcemia

Monitor calcium levels closely; patients with chronic renal failure are at an increased risk for hypercalcemia. Dose reduction or discontinuation of therapy may be necessary. Withhold calcium supplementation until calcium levels normalize. Discontinue use with hypercalcemia in dialysis patients; may reinstitute therapy at 50% of previous dose 1 week after calcium levels have normalized. Chronic hypercalcemia may result in generalized vascular and soft tissue calcification and exacerbate nephrolithiasis.

Hyperphosphatemia

Monitor serum phosphate; hyperphosphatemia may require the use of phosphate-binding agents. Disease-related concerns:

Cardiovascular

Avoid prolonged hypercalcemia; may aggravate arteriosclerosis or cardiac valve sclerosis. Use with caution in patients with calcification of pulmonary tissue; may result in cardiac disease. Severe hypercalcemia may increase risk of cardiac arrhythmias.

Granulomatous diseases

Use with caution in patients with granulomatous diseases (eg, sarcoidosis) due to increased sensitivity to vitamin D. 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

Adverse events have been observed in animal reproduction studies.

Lactation

Avoid

Alfacalcidol may be present in breast milk. Breastfeeding is not recommended by the manufacturer.

Monitoring

Clinical pearl	Serum calcium and phosphorus: Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of CKD, and the use of treatments for CKD-mineral and bone disorders (KDIGO 2009): CKD stage 3: Every 6 to 12 months CKD stage 4: Every 3 to 6 months CKD stage 5 and 5D: Every 1 to 3 months Periodic 24-hour urinary calcium and phosphorus; magnesium; alkaline phosphatase every 12 months or more frequently in the presence of elevated PTH; creatinine, BUN, albumin; intact parathyroid hormone (iPTH) every 3 to 12 months depending on CKD severity; periodic ophthalmologic exams; symptoms of hypercalcemia

Clinical pearl

Serum calcium and phosphorus: Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of CKD, and the use of treatments for CKD-mineral and bone disorders (KDIGO 2009): CKD stage 3: Every 6 to 12 months CKD stage 4: Every 3 to 6 months CKD stage 5 and 5D: Every 1 to 3 months Periodic 24-hour urinary calcium and phosphorus; magnesium; alkaline phosphatase every 12 months or more frequently in the presence of elevated PTH; creatinine, BUN, albumin; intact parathyroid hormone (iPTH) every 3 to 12 months depending on CKD severity; periodic ophthalmologic exams; symptoms of hypercalcemia

Chemistry & Properties

Formula	C27H44O2
Molecular weight	400.65 g/mol
IUPAC name	trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
CAS	41294-56-8
PubChem CID	5282181
InChIKey	`OFHCOWSQAMBJIW-AVJTYSNKSA-N`
logP	6.59 (XLogP 6.8)
Polar surface area	40.46 Å²
H-bond acceptors / donors	2 / 2
Drug-likeness (QED)	0.53
Lipinski violations	1

SMILES

C=C1/C(=C\C=C2/CCC[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@H]23)C[C@@H](O)C[C@@H]1O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.681 h
Volume of distribution	0.618 L/kg
Protein binding	98.4%
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)

Registered Products (13)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Osteo Alfa Cap	Capsule 0.25 mcg	30 cap pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	3.240
One-Alpha caps.	Capsule 0.25 mcg	30 cap	Shawi & Rushedat Drug Store	3.980
Adicule	Tablet 0.5 mcg	30 tab	Argon drug store	4.750
Osteo Alfa Cap	Capsule 1 mcg	30 cap pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	6.470
Alfost	Capsule 0.25 mcg	100 cap	ÙØ³ØªÙØ¯Ø¹ Ø£Ø¯ÙÙØ© Ø§ÙÙÙÙÙÙÙ	6.790
One-Alpha caps.	Capsule 0.5 mcg	30 cap pack varies	Shawi & Rushedat Drug Store	7.910
Osteo Alfa Cap	Capsule 0.25 mcg	100 cap pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	10.180
Alfost	Capsule 0.5 mcg	100 cap	ÙØ³ØªÙØ¯Ø¹ Ø£Ø¯ÙÙØ© Ø§ÙÙÙÙÙÙÙ	11.140
One-Alpha Drops .	Oral Drops 2 mcg/ml	20 ml pack varies	Shawi & Rushedat Drug Store	13.230
Osteo Alfa Cap	Capsule 1 mcg	100 cap pack varies	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	20.350
One-Alpha 2mcg/ml	Solution 2 mcg/ml	0.5 ml pack varies	Khoury Drug Store	22.760
One-Alpha caps.	Capsule 0.5 mcg	100 cap pack varies	Shawi & Rushedat Drug Store	24.780
One-Alpha caps.	Capsule 1 mcg	100 cap	Shawi & Rushedat Drug Store	33.180