Routes are oral, IV, and topical.
Protein binding 99.9% with renal metabolism.
Half-life 5–8 hours in adults, and 27 hours children.
Excretion in feces is 50% with urine 16%.
Calcitriol, also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active metabolite of vitamin D with three hydroxyl groups.
Calcitriol increases the level of calcium (Ca2+) in the blood by increasing the uptake of calcium from the gut into the blood, and possibly increasing the release of calcium into the blood from bone.
Calcitriol usually refers specifically to 1,25-dihydroxycholecalciferol, but may also sometimes include 24,25-dihydroxycholecalciferol the deactivated form of vitamin D.
Calcitriol increases blood calcium levels by promoting absorption of dietary calcium from the gastrointestinal tract and increasing renal tubular reabsorption of calcium, thus reducing the loss of calcium in the urine.
Stimulates release of calcium from bone by its action on the specific type of bone cells ref2242ed to as osteoblasts, causing them to release RANKL, which in turn activates osteoclasts.
Calcitriol acts in concert with parathyroid hormone.
PTH indirectly stimulates osteoclasts.
The main effect of PTH is to increase the rate at which the kidneys excrete inorganic phosphate the counter ion of Ca2+.
The decrease in serum phosphate that results from PTH causes hydroxyapatite (Ca5(PO4)3OH) to dissolve out of bone increasing serum calcium.
PTH stimulates the production of calcitriol.
Many effects of calcitriol are mediated by its interaction with the calcitriol receptor, also called the vitamin D receptor (VDR).
The calcitriol receptor in the intestinal epithelial cells resides in the cytoplasm and when it is bound to calcitriol the ligand-receptor complex translocates to the cell nucleus, where it acts as a transcription factor promoting the expression of a gene encoding a calcium binding protein
The calcium binding protein level increases thus enabling the cells to actively transport more calcium from the intestine across the intestinal mucosa into the blood.
Calcitriol stimulates the intestinal absorption of phosphate.
Calcitriol stimulates the release of calcium from bone appears to contradict fact that sufficient levels of serum calcitriol generally prevent overall loss of calcium from bone.
Increased levels of serum calcium resulting from calcitriol-stimulated intestinal uptake causes bone to take up more calcium than it loses by hormonal stimulation of osteoclasts.
Calcitriol inhibits the release of calcitonin, a hormone which reduces blood calcium primarily by inhibiting calcium release from bone.
Calcitriol is produced in the cells of the proximal tubule of the kidneys by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase, a mitochondrial oxygenase and an enzyme which catalyzes the hydroxylation of 25-hydroxycholecalciferol.
The activity of the enzyme is stimulated by PTH an important control point in Ca2+ homeostasis.
The production of calcitriol is also increased by prolactin,ma process which requires large amounts of calcium.
It is decreased by high levels of serum phosphate and by an increase in the production of the hormone FGF-23 by osteocyte cells in bone.
Calcitriol becomes calcitroic acid through the action of 24-hydroxylase, and it is excreted in the urine.
Prescribed for hypocalcemia associated with hypoparathyroidism, adult osteomalacia, rickets, renal osteodystrophy, chronic kidney disease, osteoporosis, prevention of corticosteroid-induced osteoporosis.
Administered orally for the treatment of psoriasis and psoriatic arthritis.
Main adverse drug reaction is hypercalcaemia, with nausea, vomiting, constipation, anorexia, apathy, headache, thirst, sweating, and/or polyuria.
Compared to other vitamin D compounds in clinical use such as cholecalciferol, ergocalciferol calcitriol has a higher risk of inducing hypercalcemia.
Calcitriol dosage
Usual Adult Dose for Hypocalcemia
Oral
Initial dose: 0.25 mcg orally once a day.
Maintenance dose: May increase by 0.25 mcg/dose at 4 to 8 week intervals.
Parenteral
Initial dose: 0.5 mcg IV 3 times a week.
Maintenance dose: May increase by 0.25 to 0.5 mcg/dose at 2 to 4 week intervals.
Usual Adult Dose for Renal Osteodystrophy
Oral
Initial dose: 0.25 mcg orally once a day.
Maintenance dose: May increase by 0.25 mcg/dose at 4 to 8 week intervals.
Parenteral
Initial dose: 0.5 mcg IV 3 times a week.
Maintenance dose: May increase by 0.25 to 0.5 mcg/dose at 2 to 4 week intervals.
Usual Adult Dose for Hypoparathyroidism
Initial dose: 0.25 mcg orally once a day in the morning.
Maintenance dose: May increase by 0.25 mcg/dose at 2 to 4 week intervals.
Most patients respond to 0.25 to 2 mcg once a day.
Usual Adult Dose for Rickets
1 mcg orally once a day
Usual Adult Dose for Secondary Hyperparathyroidism
Predialysis patients: 0.25 mcg orally once a day in the morning.
Dialysis patients: 0.25 mcg orally once a day in the morning.
Increase dose, if needed, by 0.25 mcg/dose at 2 to 4 week intervals.
For some patients 0.25 mcg orally every other day may be enough.
Most patients respond to doses of 0.25 to 1 mcg once a day.
Alternatively, 0.5 to 4 mcg IV may be administered three times per week at the end of each dialysis.
Pulse oral therapy: Patients on Continuous Ambulatory Peritoneal Dialysis:
5 mcg orally given twice per week.
Patients on hemodialysis:
4 mcg orally given twice per week.
Usual Pediatric Dose for Hypoparathyroidism
Less than 1 year: 0.04 to 0.08 mcg/kg orally once a day.
1 to 5 years: 0.25 to 0.75 mcg orally once daily.
May increase by 0.25 mcg/dose at 2 to 4 week intervals.
Greater than or equal to 6 years: 0.5 to 2 mcg.
May increase by 0.25 mcg/dose at 2 to 4 week intervals.
Usual Pediatric Dose for Rickets
Vitamin D dependent rickets: 1 mcg orally once a day.
Vitamin D resistant rickets (familial hypophosphatemia): Initial: 0.015 to 0.02 mcg/kg orally once daily;
maintenance: 0.03 to 0.06 mcg/kg orally once daily; maximum dose: 2 mcg once daily.
Usual Pediatric Dose for Hypocalcemia
Hypocalcemia secondary to hypoparathyroidism:
Neonates: 1 mcg orally once daily for the first 5 days of life, or 0.02 to 0.06 mcg/kg/day.
Hypocalcemic tetany:
Neonates: 0.05 mcg/kg IV once daily for 5 to 12 days or 0.25 mcg orally once daily followed by 0.01 to 0.10 mcg/kg/day divided in 2 doses daily (maximum daily dose: 2 mcg).
Management of hypocalcemia in patients with chronic kidney disease (CKD) is indicated when serum levels of 25(OH)D are greater than 30 ng/mL and serum levels of intact parathyroid hormone are above the target range for the stage of CKD, serum levels of corrected total calcium are less than 9.5 to 10 mg/dL and serum levels of phosphorus are less than upper limits of normal (ULN)..
Children and Adolescents: CKD Stages 2 to 4:
Less than 10 kg: 0.05 mcg orally every other day.
10 to 20 kg: 0.1 to 0.15 mcg orally daily.
Greater than 20 kg: 0.25 mcg orally daily.
If PTH decrease is less than 30% after 3 months of therapy and serum levels of calcium and phosphorus are within the target ranges based upon the CKD Stage, increase dosage by 50%.
If PTH decrease is less than the target range for CKD stage, hold calcitriol therapy until iPTH increases to above target range; resume therapy at half the previous dosage (if dosage is less than 0.25 mcg capsule or 0.05 mcg liquid, use every other day therapy).
If serum levels of total corrected calcium exceed 10.2 mg/dL, hold calcitriol therapy until serum calcium decreases to less than 9.8 mg/dL; resume therapy at half the previous dosage (if dosage is less than 0.25 mcg capsule or 0.05 mcg liquid, use every other day therapy).
If serum levels of phosphorus increase to greater than the age appropriate upper limits, hold calcitriol therapy (initiate or increase phosphate binders until the levels of serum phosphorus decrease to age appropriate limits); resume therapy at half the previous dosage.
Children and Adolescents with CKD Stage 5: Serum calcium times phosphorus product (Ca x P) should not exceed 65 mg(2)/dL(2) for infants and children less than 12 years of age and 55 mg(2)/dL(2) for adolescents, serum phosphorus should be within target, serum calcium less than 10 mg/dL.
PTH 300 to 500 pg/mL: 0.0075 mcg/kg orally or IV per dialysis session (3 times/week); not to exceed 0.25 mcg daily.
PTH greater than 500 to 1000 pg/mL: 0.015 mcg/kg orally or IV per dialysis session (3 times/week); not to exceed 0.5 mcg daily.
PTH greater than 1000 pg/mL: 0.025 mcg/kg orally or IV per dialysis session (3 times/week); not to exceed 1 mcg daily.
Dosage adjustment: If iPTH decrease is less than 30% after 3 months of therapy and serum levels of calcium and phosphorus are within the target ranges based upon the CKD Stage 5, increase dosage by 50%.
No adjustments for renal impairment is recommended, however, patients with renal insufficiency are more prone to the development of hypercalcemia.
Some patients may respond to as little as 0.25 mcg every other day.
Most patients respond to 0.5 to 1 mcg orally once a day or 0.5 to 3 mcg IV 3 times a week.
Calcitriol should be withheld if hypercalcemia develops.
Serum calcium should be monitored once to twice a week during dose titration, and approximately once a month after stabilization of the dosage.