Skip to main content

Calcitriol

Class: Vitamin D
ATC Class: A11CC04
VA Class: VT502
CAS Number: 32222-06-3
Brands: Rocaltrol,

Medically reviewed by Drugs.com on Feb 1, 2021. Written by ASHP.

Introduction

Synthetic vitamin D analog.

Uses for Calcitriol

Hypocalcemia Secondary to Chronic Renal Disease

Management of hypocalcemia and resultant metabolic bone disease in adults with chronic kidney disease (CKD) undergoing dialysis.

Enhances calcium absorption, reduces serum alkaline phosphatase concentrations, and may reduce elevated parathyroid hormone (PTH) concentrations and the histologic manifestations of osteitis fibrosa cystica and defective mineralization.

Has been used in children undergoing dialysis to increase serum calcium and decrease PTH concentrations.

Secondary Hyperparathyroidism

Management of secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe CKD (Clcr 15–55 mL/minute, corrected for surface area in children) who do not yet require maintenance dialysis therapy (predialysis patients).

Hypoparathyroidism and Pseudohypoparathyroidism

Management of hypocalcemia and its clinical manifestations in patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypoparathyroidism.

Nutritional Rickets or Osteomalacia

Has been used to control serum calcium concentrations and treat vitamin D-dependent rickets or osteomalacia in a few adult and pediatric patients.

Tetany in Premature Infants

Has been used in the prevention of tetany in vitamin D-deficient premature infants with hypocalcemia; also has been used in the treatment of hypocalcemic tetany in premature infants.

Familial Hypophosphatemia

Has been used in conjunction with phosphate supplements in the treatment of bone disorders in adult patients with familial hypophosphatemia (vitamin D-resistant rickets).

Calcitriol Dosage and Administration

General

  • Measure serum calcium concentrations at least twice a week during initial therapy and after subsequent dosage adjustments. Some clinicians recommend measuring serum calcium concentrations at least weekly for the first 12 weeks of therapy and monthly after stabilization of dosage.

  • For calcitriol therapy to be effective, patients must have an adequate, but not excessive, daily intake of calcium.

Administration

Administer orally, usually in a single daily dose, or by IV injection, usually 3 times weekly.

IV Administration

Administer IV by rapid injection through catheter at the end of a hemodialysis session.

Dosage

Individualize dosage based on nature and severity of patient’s hypocalcemia and/or secondary hyperparathyroidism; maintain serum calcium concentrations at 9–10 mg/dL.

Individualize dosage adjustments based on PTH, serum calcium and phosphorus concentrations. Nephrology experts currently recommend using individual values for serum calcium and phosphorus (evaluated together) instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.

Nephrology experts currently state that optimal intact PTH (iPTH) concentration for predialysis patients with stage 3a (eGFR 45–59 mL/minute per 1.73 m2) to stage 5 (eGFR <15 mL/minute per 1.73 m2) CKD is unknown, but modest elevations may represent an appropriate adaptive response to declining renal function.

For patients with stage 5 CKD undergoing dialysis, some experts suggest maintaining iPTH concentrations within a range of approximately 2–9 times the assay's ULN (may correspond to range of approximately 130–600 pg/mL for commercial assays ). PTH assays exhibit substantial variability; previously recommended range of 150–300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer available.

Avoid oversuppression of PTH, which may increase risk of adynamic bone disease.

Administer lowest possible dosage and only increase after careful monitoring of serum calcium concentrations.

Pediatric Patients

Dosing guidelines not established for pediatric patients <1 year of age with hypoparathyroidism or for pediatric patients <6 years of age with pseudohypoparathyroidism.

Hypocalcemia Secondary to Chronic Renal Disease†
Patients Undergoing Dialysis
Oral

0.25–2 mcg daily.

Secondary Hyperparathyroidism
Predialysis Patients (Clcr 15–55 mL/minute corrected for surface area)
Oral

<3 years old: Initially, 0.01–0.015 mcg/kg once daily.

≥3 years old: Initially, 0.25 mcg daily.

≥3 years old: May increase if necessary to 0.5 mcg daily.

If hypercalcemia occurs at a dosage of 0.5 mcg daily, reduce dosage to 0.25 mcg daily. Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week. When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg daily.

If hypercalcemia occurs at a dosage of 0.25 mcg daily, withhold the drug. Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week. When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg every other day.

If hypercalcemia persists at the reduced dosage and serum PTH is normal, discontinue calcitriol and monitor after 3 months.

Hypoparathyroidism and Pseudohypoparathyoidism
Oral

Children ≥1 years old: Initially, 0.25 mcg daily. Since only a limited number of children <6 years of age with pseudohypoparathyroidism have received the drug, dosage recommendations for such children currently do not exist.

If adequate clinical and biochemical responses are not obtained with initial dosage, increase dosage at 2- to 4-week intervals.

Children 1–5 years of age (with hypoparathyroidism) usually require 0.25–0.75 mcg daily.

Most children ≥6 years old: 0.5–2 mcg daily.

If hypercalcemia occurs, discontinue drug immediately, institute a low-calcium diet, withdraw calcium supplements, and measure serum calcium concentrations daily; when normocalcemia ensues (generally in 2–7 days), reinstitute calcitriol at a reduced dosage (0.25 mcg daily lower than the prior dosage).

Nutritional Rickets† or Osteomalacia†
Oral

1 mcg daily has been used.

Tetany in Premature Infants†
Prevention of Tetany Associated with Vitamin D Deficiency and Hypocalcemia†
Oral

1 mcg daily for first 5 days of life has been used.

Treatment of Tetany Associated with Hypocalcemia†
IV

0.05 mcg/kg daily for 5–12 days has been used.

Adults

Hypocalcemia Secondary to Chronic Renal Disease
Patients Undergoing Dialysis
Oral

Initially, 0.25 mcg daily. Patients with normal or slightly reduced serum calcium concentrations may respond to 0.25 mcg every other day.

If adequate clinical and biochemical responses are not obtained with initial dosage, increase dosage by 0.25 mcg daily at 4- to 8-week intervals.

Usual dosage: 0.5–1 mcg daily.

If hypercalcemia occurs, discontinue drug immediately, institute a low-calcium diet, withdraw calcium supplements, and measure serum calcium concentrations daily; when normocalcemia ensues (generally in 2–7 days), reinstitute calcitriol at a reduced dosage (0.25 mcg daily lower than the prior dosage).

IV

Initially, 1 mcg (0.02 mcg/kg) to 2 mcg administered 3 times weekly, approximately every other day; however, initial dosages may range from 0.5–4 mcg 3 times weekly.

If a satisfactory response is not observed, increase the dose given 3 times weekly by 0.5–1 mcg at 2- to 4-week intervals.

If hypercalcemia or a serum calcium times phosphorous product (Ca × P) >70 mg2/ dL2 occurs, discontinue drug immediately until these parameters are appropriate. Then reinitiate at a lower dosage.

Adjust dosage of calcitriol according to the patient’s PTH concentrations.

Manufacturer-recommended Dosage Adjustments based on Patient’s PTH Concentrations100

PTH Concentrations

Calcitriol Dosage

Remain the same or increase

Increase

Decrease by <30%

Increase

Decrease by >30 to <60%

Maintain

Decrease by >60%

Decrease

1.5–3 times the ULN

Maintain

Secondary Hyperparathyroidism
Predialysis Patients
Oral

Initially, 0.25 mcg daily.

May increase if necessary to 0.5 mcg daily.

If hypercalcemia occurs at a dosage of 0.5 mcg daily, reduce dosage to 0.25 mcg daily. Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week. When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg daily.

If hypercalcemia occurs at a dosage of 0.25 mcg daily, withhold the drug. Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week. When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg every other day.

If hypercalcemia persists at the reduced dosage and serum PTH concentration is normal, discontinue calcitriol and monitor after 3 months.

Hypoparathyroidism and Pseudohypoparathyoidism
Oral

Initially, 0.25 mcg daily given in the morning.

If a satisfactory response in biochemical parameters and clinical manifestations is not observed, increase dosage at 2- to 4-week intervals.

Usual dosage: 0.5–2 mcg daily.

If hypercalcemia occurs, discontinue drug immediately, institute a low-calcium diet, withdraw calcium supplements, and measure serum calcium concentrations daily; when normocalcemia ensues (generally in 2–7 days), reinstitute calcitriol at a reduced dosage (0.25 mcg daily lower than the prior dosage).

Nutritional Rickets or Osteomalacia†
Oral

1 mcg daily has been used.

Familial Hypophosphatemia (Vitamin D-resistant rickets)†
Oral

2.1 mcg daily has been used.

Special Populations

Geriatric Patients

Select dosage with caution (generally starting at the low end of the dosing range) because of age-related decreases in hepatic, renal, and/or cardiac function, and concomitant disease and drug therapy.

Cautions for Calcitriol

Contraindications

  • Hypercalcemia or evidence of vitamin D toxicity.

  • Known hypersensitivity to calcitriol, other vitamin D analogs, or any ingredient in the formulation.

Warnings/Precautions

Warnings

Hypercalcemia

Risk of vitamin D analog toxicity; may require emergency measures.

Chronic hypercalcemia increases risk of soft-tissue calcification, including vascular calcification and nephrocalcinosis. Radiographic evaluation of suspected areas may be useful in early detection of calcification.

Avoid concomitant use of pharmacologic doses of vitamin D or its analogs or use with caution.

Risk of hypercalcemia increased in immobilized (e.g., postsurgical) patients.

Hyperphosphatemia and Hypercalciuria

Risk of hyperphosphatemia. Use a non-aluminum-containing phosphate binder and a low-phosphate diet to control serum phosphorus concentrations in patients undergoing dialysis. Risk of hypercalciuria.

Hypermagnesemia

Risk of hypermagnesemia if used concomitantly with magnesium-containing preparations (e.g., antacids); avoid concomitant use in dialysis patients or use with caution.

Sensitivity Reactions

Hypersensitivity reactions (e.g., pruritus, rash, urticaria, anaphylaxis) have been reported.

General Precautions

Adequate Patient Monitoring

Measure serum calcium and phosphorus concentrations at least twice a week during initial and after subsequent dosage adjustments.

If hypercalcemia develops in predialysis patients, dosage reduction, temporary interruption, or discontinuance of calcitriol may be required. (See Dosage under Dosage and Administration.)

If hypercalcemia develops in patients undergoing dialysis, discontinue calcitriol therapy immediately and monitor serum calcium and phosphate concentrations. Once normal serum calcium concentrations are attained, resume calcitriol therapy at reduced dosage. (See Dosage under Dosage and Administration.)

In patients undergoing dialysis, decreases in serum alkaline phosphatase may be indicative of impending development of hypercalcemia.

Administer vitamin D analogs with caution in patients receiving cardiac glycosides, because hypercalcemia in these patients may result in cardiac arrhythmias.

In patients undergoing dialysis, determine serum calcium, phosphorus, magnesium, alkaline phosphatase, and 24-hour urinary calcium concentrations periodically. In predialysis patients, determine serum calcium, phosphorus, alkaline phosphatase, creatinine, and iPTH initially; thereafter, monitor serum calcium, phosphorus, alkaline phosphatase, and creatinine concentrations monthly for 6 months, and periodically thereafter. Determine iPTH every 3–4 months.

If PTH concentrations are decreased below normal levels, adynamic bone disease may develop. PTH concentrations may be used to indicate rate of bone turnover; if such concentrations decrease below target range, reduce or discontinue IV calcitriol. Possible risk of rebound effect upon discontinuance of therapy; titrate downward to an appropriate maintenance dosage.

Dehydration

Possible risk of dehydration in patients with normal renal function on calcitriol therapy; maintain adequate fluid intake while on therapy.

Specific Populations

Pregnancy

Category C.

Lactation

Calcitriol may be distributed into human milk. Avoid nursing during calcitriol therapy.

Pediatric Use

Safety and efficacy not established in pediatric patients undergoing dialysis. Has been used in some children undergoing dialysis.

Safety and efficacy established in predialysis pediatric patients.

Long-term calcitriol therapy is well tolerated in pediatric patients. Most common adverse effects include mild, transient episodes of hypercalcemia, hyperphosphatemia, and increased Ca × P; usually managed effectively by dosage adjustment or temporary discontinuance of vitamin D therapy.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Other clinical experience revealed no substantial differences in safety and efficacy relative to younger adults. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Common Adverse Effects

Excessive vitamin D intake (early manifestations): Weakness, headache, somnolence, nausea, dry mouth, constipation, muscle or bone pain, metallic taste, anorexia, abdominal pain, epigastric distress.

Excessive vitamin D intake (late manifestations): Polyuria, polydipsia, anorexia, weight loss, nocturia, calcific conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated AST, elevated ALT, ectopic calcification, nephrocalcinosis, hypertension, cardiac arrhythmias, dystrophy, sensory disturbances, dehydration, apathy, arrested growth, urinary tract infections.

Interactions for Calcitriol

Specific Drugs

Drug

Interaction

Comments

Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)

Anticonvulsants that induce CYP enzymes may increase vitamin D catabolism

Higher calcitriol dosage may be required

Calcium supplements

Increased risk of hypercalcemia

Avoid uncontrolled intake of additional calcium-containing preparations

Cardiac glycosides

Possible cardiac arrhythmias

Use concomitantly with caution

Cholestyramine

Intestinal absorption of calcitriol may be decreased

Allow as long a time interval as possible between ingestion of calcitriol and cholestyramine

Colestipol

Intestinal absorption of calcitriol may be decreased

Allow as long a time interval as possible between ingestion of calcitriol and colestipol

Corticosteroids

Corticosteroids may counteract effects of vitamin D analogs

Ketoconazole

Endogenous serum calcitriol may be reduced

Magnesium-containing antacids

Possible hypermagnesemia

Avoid concomitant use in dialysis patients or use with caution

Phosphate binders

May require dosage adjustment of phosphate binders

Thiazide diuretics

Possible risk of hypercalcemia

Use concomitantly with caution

Vitamin D analogs

Possible risk of hypercalcemia

Withhold vitamin D analogs during calcitriol therapy or use with caution

Calcitriol Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the intestine following oral administration.

Duration

3–5 days.

Serum Concentrations

Peak serum concentrations achieved within 3–6 hours.

Distribution

Extent

Calcitriol crosses the placenta and is distributed into milk.

Plasma Protein Binding

Approximately 99.9%.

Elimination

Metabolism

Metabolized by 24-hydroxylase to calcitroic acid and also by stepwise hydroxylation to form a vitamin D3 lactone ring.

Elimination Route

Calcitriol and its metabolites are mainly excreted in feces (up to about 50%), with only small amounts eliminated in urine (up to 16%).

Undergoes biliary excretion and enterohepatic recirculation.

Half-life

5–8 hours.

Special Populations

In patients with nephrotic syndrome and those undergoing dialysis, lower predose and peak serum concentrations than in healthy individuals.

In patients with nephrotic syndrome or those undergoing dialysis, peak serum concentrations were achieved within 4 or 8–12 hour, respectively, while half-lives were 16.2 or 21.9 hours, respectively.

In pediatric patients (1.8–16 years of age) undergoing peritoneal dialysis, half-life was 27.5 hours.

Stability

Storage

Oral

Capsules

15–30°C. Protect from light.

Solution

15–30°C. Protect from light.

Parenteral

Injection

20–25°C. Protect from light.

Actions

  • Synthetic vitamin D analog.

  • Calcitriol (activated vitamin D) enhances the efficiency of intestinal calcium absorption along the entire small intestine, but principally in the duodenum and jejunum.

  • Enhances phosphorus absorption along the entire small intestine, but principally in the jejunum and ileum.

  • Calcitriol is the most active known form of vitamin D3 in stimulating intestinal calcium transport.

  • In patients with chronic renal failure, decreased metabolic activation of vitamin D in the kidneys results in secondary hyperparathyroidism and metabolic bone disease. In such patients, calcitriol increases GI absorption of calcium, decreases elevated blood concentrations of PTH and serum alkaline phosphatase, and corrects renal osteodystrophy, muscle weakness, and bone pain in such patients.

Advice to Patients

  • Importance of diet and calcium supplementation regimen adherence.

  • Importance of serum iPTH, calcium, phosphorus, and alkaline phosphatase monitoring prior to initiation of therapy and periodically thereafter.

  • Importance of immediate reporting of potential manifestations of hypercalcemia.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

    Importance of informing patients of other precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Calcitriol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

0.25 mcg*

Calcitriol Capsules

Rocaltrol

Validus

0.5 mcg*

Calcitriol Capsules

Rocaltrol

Validus

Solution

1 mcg/mL*

Calcitriol Oral Solution

Rocaltrol

Validus

Parenteral

Injection, for IV use only

1 mcg/mL*

Calcitriol Injection

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 11, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Show article references