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Calcitriol

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

Medically reviewed by Drugs.com. Last updated on Feb 11, 2019.

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 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 (Clcr 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 or osteomalacia 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; also has been used in the treatment of hypocalcemic tetany in premature infants. 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

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 dosage100 101 based on nature and severity of patient’s hypocalcemia100 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

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.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 analogs100 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 patients100 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

Interactions for Calcitriol

Specific Drugs

Drug

Interaction

Comments

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

Anticonvulsants that induce CYP enzymes may increase vitamin D catabolism100 101

Higher calcitriol dosage may be required101

Calcium supplements

Increased risk of hypercalcemia101

Avoid uncontrolled intake of additional calcium-containing preparations101

Cardiac glycosides

Possible cardiac arrhythmias101

Use concomitantly with caution101 f

Cholestyramine

Intestinal absorption of calcitriol may be decreased101

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

Colestipol

Intestinal absorption of calcitriol may be decreasedf

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

Corticosteroids

Corticosteroids may counteract effects of vitamin D analogs100 101 f

Ketoconazole

Endogenous serum calcitriol may be reduced101

Magnesium-containing antacids

Possible hypermagnesemia100 101

Avoid concomitant use in dialysis patients100 101 or use with caution100

Phosphate binders

May require dosage adjustment of phosphate binders101

Thiazide diuretics

Possible risk of hypercalcemia101

Use concomitantly with caution101

Vitamin D analogs

Possible risk of hypercalcemia100 101

Withhold vitamin D analogs during calcitriol therapy100 101 or use with caution100

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

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 2019, 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.

References

100. Akorn, Inc. Calcitriol injection prescribing information. Lake Forest, IL; 2013 Feb.

101. Validus Pharmaceuticals. Rocaltrol (calcitriol) capsules and oral solution prescribing information. Parsippany, NJ; 2010 Aug.

102. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press; 1997. (Uncorrected proofs.)

104. Sakhaee K, Gonzalez GB. Update on renal osteodystrophy: pathogenesis and clinical management. Am J Med Sci. 1999; 317:251-60. http://www.ncbi.nlm.nih.gov/pubmed/10210362?dopt=AbstractPlus

105. Tan AU Jr, Levine BS, Mazess RB et al. Effective suppression of parathyroid hormone by 1 alpha-hydroxy-vitamin D2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism. Kidney Int. 1997; 51:317-23. http://www.ncbi.nlm.nih.gov/pubmed/8995749?dopt=AbstractPlus

126. Kidney Disease: Improving Global Outcomes (KDIGO) CKD–MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease—mineral and bone disorder (CKD–MBD). Kidney Int. 2009; 76 (Suppl 113): S1–S130.

128. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease—mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017; 7:1-59.

129. Isakova T, Nickolas TL, Denburg M et al. KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis. 2017; 70:737-751. http://www.ncbi.nlm.nih.gov/pubmed/28941764?dopt=AbstractPlus

130. Uhlig K, Berns JS, Kestenbaum B et al. KDOQI US commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD-Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis. 2010; 55:773-99. http://www.ncbi.nlm.nih.gov/pubmed/20363541?dopt=AbstractPlus

131. Bover J, Ureña P, Ruiz-García C et al. Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism. Clin J Am Soc Nephrol. 2016; 11:161-74. http://www.ncbi.nlm.nih.gov/pubmed/26224878?dopt=AbstractPlus

a. AHFS Drug Information. McEvoy GK, ed. Calcitriol. Bethesda, MD: American Society of Health-System Pharmacists.

f. AHFS Drug Information. McEvoy GK, ed. Vitamin D analogs general statement. Bethesda, MD: American Society of Health-System Pharmacists.

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