Brand name: Rocaltrol
Drug class: Vitamin D
ATC class: A11CC04
VA class: VT502
CAS number: 32222-06-3

Medically reviewed by Drugs.com on Feb 1, 2024. Written by ASHP.

Introduction

Synthetic vitamin D analog.^{100 101 a}

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.^{100 101 a}

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.¹⁰¹

Has been used in children undergoing dialysis^{† [off-label]} to increase serum calcium and decrease PTH concentrations.^a

Secondary Hyperparathyroidism

Management of secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe CKD (Cl_cr 15–55 mL/minute, corrected for surface area in children) who do not yet require maintenance dialysis therapy (predialysis patients).^{101 a}

Hypoparathyroidism and Pseudohypoparathyroidism

Management of hypocalcemia and its clinical manifestations in patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypoparathyroidism.¹⁰¹

Nutritional Rickets or Osteomalacia

Has been used to control serum calcium concentrations and treat vitamin D-dependent rickets^{† [off-label]} or osteomalacia^{† [off-label]} in a few adult and pediatric patients.^a

Tetany in Premature Infants

Has been used in the prevention of tetany in vitamin D-deficient premature infants with hypocalcemia^{† [off-label]}; also has been used in the treatment of hypocalcemic tetany in premature infants^{† [off-label]}. ^{a f}

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).^{a f}

Related/similar drugs

ergocalciferol, calcium carbonate, Caltrate, Drisdol, Rocaltrol, calcium lactate, calcifediol

Calcitriol Dosage and Administration

General

• Measure serum calcium concentrations at least twice a week during initial therapy and after subsequent dosage adjustments.^{100 101 a} Some clinicians recommend measuring serum calcium concentrations at least weekly for the first 12 weeks of therapy and monthly after stabilization of dosage.^a

• For calcitriol therapy to be effective, patients must have an adequate, but not excessive, daily intake of calcium.^{100 101}

Administration

Administer orally, usually in a single daily dose, or by IV injection, usually 3 times weekly.^{100 101 a}

IV Administration

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

Dosage

Individualize dosage^{100 101} based on nature and severity of patient’s hypocalcemia^{100 a f} and/or secondary hyperparathyroidism;¹⁰⁰ maintain serum calcium concentrations at 9–10 mg/dL.^a

Individualize dosage adjustments based on PTH, serum calcium and phosphorus concentrations.¹⁰⁰ 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.^{126 128}

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.^{128 129}

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 assays¹³⁰ ).¹²⁸ 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.^{126 130 131}

Avoid oversuppression of PTH, which may increase risk of adynamic bone disease.^{126 131}

Administer lowest possible dosage and only increase after careful monitoring of serum calcium concentrations.¹⁰¹

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.¹⁰¹

Hypocalcemia Secondary to Chronic Renal Disease†

Patients Undergoing Dialysis

Oral

0.25–2 mcg daily.^a

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.^{101 a}

≥3 years old: Initially, 0.25 mcg daily.^{101 a}

≥3 years old: May increase if necessary to 0.5 mcg daily.^{101 a}

If hypercalcemia occurs at a dosage of 0.5 mcg daily, reduce dosage to 0.25 mcg daily.¹⁰¹ Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week.¹⁰¹ When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg daily.¹⁰¹

If hypercalcemia occurs at a dosage of 0.25 mcg daily, withhold the drug.¹⁰¹ Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week.¹⁰¹ When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg every other day.¹⁰¹

If hypercalcemia persists at the reduced dosage and serum PTH is normal, discontinue calcitriol and monitor after 3 months.¹⁰¹

Hypoparathyroidism and Pseudohypoparathyoidism

Oral

Children ≥1 years old: Initially, 0.25 mcg daily.^a 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.^{101 a}

If adequate clinical and biochemical responses are not obtained with initial dosage, increase dosage at 2- to 4-week intervals.^{101 a}

Children 1–5 years of age (with hypoparathyroidism) usually require 0.25–0.75 mcg daily.^{101 a}

Most children ≥6 years old: 0.5–2 mcg daily.¹⁰¹

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).¹⁰¹

Nutritional Rickets† or Osteomalacia†

Oral

1 mcg daily has been used.^a

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.^a

Treatment of Tetany Associated with Hypocalcemia†

IV

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

Adults

Hypocalcemia Secondary to Chronic Renal Disease

Patients Undergoing Dialysis

Oral

Initially, 0.25 mcg daily.^{101 a} Patients with normal or slightly reduced serum calcium concentrations may respond to 0.25 mcg every other day.^{101 a}

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.^{101 a}

Usual dosage: 0.5–1 mcg daily.¹⁰¹

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).^{101 a}

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.¹⁰⁰

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.¹⁰⁰

If hypercalcemia or a serum calcium times phosphorous product (Ca × P) >70 mg²/ dL² occurs, discontinue drug immediately until these parameters are appropriate.¹⁰⁰ Then reinitiate at a lower dosage.¹⁰⁰

Adjust dosage of calcitriol according to the patient’s PTH concentrations.¹⁰⁰

Secondary Hyperparathyroidism

Predialysis Patients

Oral

Initially, 0.25 mcg daily.^{101 a}

May increase if necessary to 0.5 mcg daily.^{101 a}

If hypercalcemia occurs at a dosage of 0.5 mcg daily, reduce dosage to 0.25 mcg daily.¹⁰¹ Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week.¹⁰¹ When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg daily.¹⁰¹

If hypercalcemia occurs at a dosage of 0.25 mcg daily, withhold the drug.¹⁰¹ Also reduce or discontinue calcium supplements and measure serum calcium concentration after 1 week.¹⁰¹ When normocalcemia ensues, reinstitute calcitriol at a dosage of 0.25 mcg every other day.¹⁰¹

If hypercalcemia persists at the reduced dosage and serum PTH concentration is normal, discontinue calcitriol and monitor after 3 months.¹⁰¹

Hypoparathyroidism and Pseudohypoparathyoidism

Oral

Initially, 0.25 mcg daily given in the morning.^{101 a}

If a satisfactory response in biochemical parameters and clinical manifestations is not observed, increase dosage at 2- to 4-week intervals.¹⁰¹

Usual dosage: 0.5–2 mcg daily.¹⁰¹

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).¹⁰¹

Nutritional Rickets or Osteomalacia†

Oral

1 mcg daily has been used.^a

Familial Hypophosphatemia (Vitamin D-resistant rickets)†

Oral

2.1 mcg daily has been used.^a

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.¹⁰¹

Cautions for Calcitriol

Contraindications

• Hypercalcemia or evidence of vitamin D toxicity.^{100 101}

• Known hypersensitivity to calcitriol, other vitamin D analogs, or any ingredient in the formulation.^{100 101}

Warnings/Precautions

Warnings

Hypercalcemia

Risk of vitamin D analog toxicity; may require emergency measures.^{100 101}

Chronic hypercalcemia increases risk of soft-tissue calcification, including vascular calcification and nephrocalcinosis.^{100 101} Radiographic evaluation of suspected areas may be useful in early detection of calcification.^{100 101}

Avoid concomitant use of pharmacologic doses of vitamin D or its analogs^{100 101} or use with caution.¹⁰⁰

Risk of hypercalcemia increased in immobilized (e.g., postsurgical) patients.¹⁰¹

Hyperphosphatemia and Hypercalciuria

Risk of hyperphosphatemia.¹⁰¹ Use a non-aluminum-containing phosphate binder and a low-phosphate diet to control serum phosphorus concentrations in patients undergoing dialysis.^{100 101} Risk of hypercalciuria.^{100 101}

Hypermagnesemia

Risk of hypermagnesemia if used concomitantly with magnesium-containing preparations (e.g., antacids);^{100 101} avoid concomitant use in dialysis patients^{100 101} or use with caution.¹⁰⁰

Sensitivity Reactions

Hypersensitivity reactions (e.g., pruritus, rash, urticaria, anaphylaxis) have been reported.^{100 101}

General Precautions

Adequate Patient Monitoring

Measure serum calcium and phosphorus concentrations at least twice a week during initial and after subsequent dosage adjustments.^{100 101}

If hypercalcemia develops in predialysis patients, dosage reduction, temporary interruption, or discontinuance of calcitriol may be required.¹⁰¹ (See Dosage under Dosage and Administration.)

If hypercalcemia develops in patients undergoing dialysis, discontinue calcitriol therapy immediately and monitor serum calcium and phosphate concentrations.^{100 101 a} Once normal serum calcium concentrations are attained, resume calcitriol therapy at reduced dosage.^{100 101} (See Dosage under Dosage and Administration.)

In patients undergoing dialysis, decreases in serum alkaline phosphatase may be indicative of impending development of hypercalcemia.¹⁰¹

Administer vitamin D analogs with caution in patients receiving cardiac glycosides, because hypercalcemia in these patients may result in cardiac arrhythmias.^{100 101}

In patients undergoing dialysis, determine serum calcium, phosphorus, magnesium, alkaline phosphatase, and 24-hour urinary calcium concentrations periodically.^{100 101} 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.¹⁰¹ Determine iPTH every 3–4 months.¹⁰¹

If PTH concentrations are decreased below normal levels, adynamic bone disease may develop.¹⁰⁰ PTH concentrations may be used to indicate rate of bone turnover;¹⁰⁰ if such concentrations decrease below target range, reduce or discontinue IV calcitriol.¹⁰⁰ Possible risk of rebound effect upon discontinuance of therapy; titrate downward to an appropriate maintenance dosage.¹⁰⁰

Dehydration

Possible risk of dehydration in patients with normal renal function on calcitriol therapy; maintain adequate fluid intake while on therapy.¹⁰¹

Specific Populations

Pregnancy

Category C.^{100 101}

Lactation

Calcitriol may be distributed into human milk.¹⁰¹ Avoid nursing during calcitriol therapy.¹⁰¹

Pediatric Use

Safety and efficacy not established in pediatric patients undergoing dialysis^†.¹⁰¹ Has been used in some children undergoing dialysis.^a

Safety and efficacy established in predialysis pediatric patients.¹⁰¹

Long-term calcitriol therapy is well tolerated in pediatric patients.¹⁰¹ 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.¹⁰¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{100 101} Other clinical experience revealed no substantial differences in safety and efficacy relative to younger adults.^{100 101} Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{100 101}

Common Adverse Effects

Excessive vitamin D intake (early manifestations): Weakness,^{100 101} headache,^{100 101} somnolence,^{100 101} nausea,^{100 101} dry mouth,^{100 101} constipation,^{100 101} muscle or bone pain,^{100 101} metallic taste,^{100 101} anorexia,^{100 101} abdominal pain,^{100 101} epigastric distress.^{100 101}

Excessive vitamin D intake (late manifestations): Polyuria,^{100 101} polydipsia,^{100 101} anorexia,^{100 101} weight loss,^{100 101} nocturia,^{100 101} calcific conjunctivitis,^{100 101} pancreatitis,^{100 101} photophobia,^{100 101} rhinorrhea,^{100 101} pruritus,^{100 101} hyperthermia,^{100 101} decreased libido,^{100 101} elevated BUN,^{100 101} albuminuria,^{100 101} hypercholesterolemia,^{100 101} elevated AST,^{100 101} elevated ALT,^{100 101} ectopic calcification,^{100 101} nephrocalcinosis,^{100 101} hypertension,^{100 101} cardiac arrhythmias,^{100 101} dystrophy,¹⁰¹ sensory disturbances,^{100 101} dehydration,^{100 101} apathy,^{100 101} arrested growth,¹⁰¹ urinary tract infections.¹⁰¹

Drug Interactions

Specific Drugs

Calcitriol Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the intestine following oral administration.¹⁰¹

Duration

3–5 days.^{100 f}

Serum Concentrations

Peak serum concentrations achieved within 3–6 hours.¹⁰¹

Distribution

Extent

Calcitriol crosses the placenta and is distributed into milk.¹⁰¹

Plasma Protein Binding

Approximately 99.9%.¹⁰¹

Elimination

Metabolism

Metabolized by 24-hydroxylase to calcitroic acid and also by stepwise hydroxylation to form a vitamin D₃ lactone ring.¹⁰¹

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%).¹⁰¹

Undergoes biliary excretion and enterohepatic recirculation.¹⁰¹

Half-life

5–8 hours.¹⁰¹

Special Populations

In patients with nephrotic syndrome and those undergoing dialysis, lower predose and peak serum concentrations than in healthy individuals.¹⁰¹

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.¹⁰¹

In pediatric patients (1.8–16 years of age) undergoing peritoneal dialysis, half-life was 27.5 hours.¹⁰¹

Stability

Storage

Oral

Capsules

15–30°C. Protect from light.¹⁰¹

Solution

15–30°C.¹⁰¹ Protect from light.¹⁰¹

Parenteral

Injection

20–25°C.¹⁰⁰ Protect from light.¹⁰⁰

Actions

• Synthetic vitamin D analog.^{100 101 a}

• Calcitriol (activated vitamin D) enhances the efficiency of intestinal calcium absorption along the entire small intestine, but principally in the duodenum and jejunum.¹⁰²

• Enhances phosphorus absorption along the entire small intestine, but principally in the jejunum and ileum.¹⁰²

• Calcitriol is the most active known form of vitamin D₃ in stimulating intestinal calcium transport.¹⁰¹

• In patients with chronic renal failure, decreased metabolic activation of vitamin D in the kidneys results in secondary hyperparathyroidism and metabolic bone disease.^{101 102 104 105} 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.^{101 f}

Advice to Patients

• Importance of diet and calcium supplementation regimen adherence.¹⁰¹

• Importance of serum iPTH, calcium, phosphorus, and alkaline phosphatase monitoring prior to initiation of therapy and periodically thereafter.¹⁰¹

• Importance of immediate reporting of potential manifestations of hypercalcemia.¹⁰¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹⁰¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰¹

  Importance of informing patients of other precautionary information.¹⁰¹ (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

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