Calcitriol

Pronunciation

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

Introduction

Synthetic vitamin D analog.a b c

Uses for Calcitriol

Hypocalcemia Secondary to Chronic Renal Disease

Management of hypocalcemia and resultant metabolic bone disease in adult patients with chronic renal disease undergoing dialysis.a b c d e

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.b e

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

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Secondary Hyperparathyroidism

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

Serum intact PTH (iPTH) concentrations of ≥100 pg/mL are strongly suggestive of secondary hyperparathyroidism. b e

Hypoparathyroidism and Pseudohypoparathyroidism

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

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.a b c d e 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.b c d e

Administration

Calcitriol is administered orallya b e or by IVc d injection, usually in a single daily dose.a

IV Administration

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

Dosage

Individualize dosageb e based on nature and severity of patient’s hypocalcemiaa c d f and/or secondary hyperparathyroidism;c d maintain serum calcium concentrations at 9–10 mg/dL.a

Individualize dosage adjustments based on PTH, serum calcium and phosphorus concentrations.c d

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

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.b e

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.a b e

≥3 years old: Initially, 0.25 mcg daily.a b e

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

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.a b e

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

If hypercalcemia occurs during titration, withhold dose until normocalcemia ensues; reinstate at a lower dosage.a May consider decreasing dietary calcium intake.a

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

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

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.a b e Patients with normal or slightly reduced serum calcium concentrations require 0.25 mcg every other day.a b e

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.a b e

Usual dosage: 0.5–1 mcg daily.b e

If hypercalcemia occurs, discontinue drug immediately until normocalcemia ensues.a b e

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.c d

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.c d

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

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

Dosage Adjustments based on Patient’s PTH Concentrationscd

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.a b e

May increase if necessary to 0.5 mcg daily.a b e

Hypoparathyroidism and Pseudohypoparathyoidism
Oral

Initially, 0.25 mcg daily given in the morning.a b e

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

Usual dosage: 0.5–2 mcg daily.b e

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.b e

Cautions for Calcitriol

Contraindications

Hypercalcemia or evidence of vitamin D toxicity. b c d e

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

Warnings/Precautions

Warnings

Hypercalcemia

Risk of vitamin D analog toxicity; may require emergency measures.b c d e

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

Do not allow serum calcium × phosphorus (Ca × P) product to exceed 70 mg2/dL2.b c d e

Vitamin D and its analogs should not be used during calcitriol therapy, because of possible additive effects.b c d e

Hyperphosphatemia and Hypercalciuria

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

Hypermagnesemia

Magnesium-containing antacids should not be used concomitantly with calcitriol.b e

Sensitivity Reactions

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

General Precautions

Adequate Patient Monitoring

Measure serum calciumb e and phosphorusc d concentrations at least twice a week during initial and after subsequent dosage adjustments.b c d e

If hypercalcemia develops, discontinue calcitriol therapy immediately and monitor serum calcium and phosphate concentrations daily.a b c d e Once normal serum calcium concentrations are attained, resume calcitriol therapy at a daily dosage of 0.25 mcg lower than that previously used.b e

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

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

In patients undergoing dialysis, determine serum calcium, phosphorus, magnesium, alkaline phosphatase, and 24-hour urinary calcium concentrations periodically.b c d 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.b Determine iPTH every 3 to 4 months.b e

If PTH concentrations are decreased below normal levels, adynamic bone disease may develop.c d PTH concentrations may be used to indicate rate of bone turnover;c d if such concentrations decrease below recommended target range (1.5–3 times ULN), reduce or discontinue IV calcitriol.c d Possible risk of rebound effect upon discontinuation of therapy, titrate downward to an appropriate maintenance dosage.c d

Dehydration

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

Specific Populations

Pregnancy

Category C.b c d e

Lactation

Calcitriol may be distributed into human milk.b e Discontinue nursing or the drug.b e

Pediatric Use

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

Safety and efficacy established in predialysis pediatric patients.b e

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

Geriatric Use

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

Common Adverse Effects

Excessive vitamin D intake (early manifestations): weakness,b e headache, b e somnolence,b e nausea,b e dry mouth,b e constipation,b e muscle or bone pain,b e metallic taste.b e

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

Interactions for Calcitriol

Specific Drugs

Drug

Interaction

Comments

Calcium supplements

Increased risk of hypercalcemiab e

Uncontrolled intake of additional calcium-containing preparations should be avoided b e

Cardiac glycosides

Concurrent use of vitamin D analogs and cardiac glycosides may result in cardiac arrhythmiasb e

Use concomitantly with cautionb e f

Cholestyramine

Intestinal absorption of calcitriol may be decreasedb e

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 analogsb e f

Ketoconazole

Endogenous serum calcitriol may be reducedb e

Magnesium-containing antacids

Potential additive pharmacologic effect resulting in hypermagnesemiab c d e

Avoid concomitant use in dialysis patientsb c d e

Phenobarbital

Endogenous plasma concentrations of 25-hydroxyvitamin D3 may be reducedb e

May require higher dosage of calcitriol if these drugs are administered simultaneouslyb e

Phenytoin

Endogenous plasma concentrations of 25-hydroxyvitamin D3 may be reducedb e

May require higher dosage of calcitriol if these drugs are administered simultaneouslyb e

Phosphate binders

May require dosage adjustment of phosphate binders b e

Thiazide diuretics

Possible risk of hypercalcemiab e

Use concomitantly with cautionb e

Vitamin D analogs

Possible risk of hypercalcemiab e

Withhold vitamin D analogs during calcitriol therapyb e

Calcitriol Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the intestine following oral administration.b

Duration

3–5 days.f

Serum Concentrations

Peak serum concentrations achieved within 3–6 hours.b e

Distribution

Extent

Calcitriol crosses the placenta and is distributed into milk.b e

Plasma Protein Binding

Approximately 99.9%.b e

Elimination

Metabolism

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

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%).b e

Undergoes biliary excretion and enterohepatic recirculation.b e

Half-life

5–8 hours.b e

Special Populations

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

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.b e

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

Stability

Storage

Oral

Capsules

15–30°C. Protect from light. b

Solution

25°C (may be exposed to 15–30°C).b e Protect from light.b e

Parenteral

Injection

15–30°C.c d Store ampuls in carton to protect from light.c

Actions

  • Synthetic vitamin D analog.a b e

  • 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. b

  • In patients with chronic renal failure, decreased metabolic activation of vitamin D in the kidneys results in secondary hyperparathyroidism and osteodystrophy or rickets. 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.b f

Advice to Patients

  • Importance of diet and calcium supplementation regimen adherence.e b

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

  • Importance of immediate reporting of potential manifestations of hypercalcemia.b e

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

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

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

Preparations

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

* 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*

Rocaltrol (with parabens)

Roche

0.5 mcg*

Rocaltrol (with parabens)

Roche

Solution

1 mcg/mL*

Calcitriol Oral Solution

Roxane

Rocaltrol

Roche

Parenteral

Injection, for IV use only

1 mcg/mL*

Calcitriol Injection

American Regent

Calcijex

Abbott

2 mcg/mL*

Calcitriol Injection

American Regent

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Calcitriol 0.25MCG Capsules (TEVA PHARMACEUTICALS USA): 30/$35.99 or 90/$75.74

Calcitriol 0.5MCG Capsules (TEVA PHARMACEUTICALS USA): 30/$57.99 or 90/$168.98

Rocaltrol 0.25MCG Capsules (VALIDUS PHARMACEUTICALS): 30/$32.99 or 90/$74.97

Rocaltrol 0.5MCG Capsules (VALIDUS PHARMACEUTICALS): 30/$79.99 or 90/$219.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

a. AHFS drug information 2007. McEvoy GK, ed. Calcitriol. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 3640-3641.

b. Roche Pharmaceuticals. Rocaltrol (calcitriol) capsule, and oral solution prescribing information. Nutley, NJ; 2004 July.

c. American Regent, Inc. Calcitriol injection prescribing information. Shirley, NY; 2003 Sept.

d. Abbott Laboratories. Calcijex (calcitriol injection) prescribing information. Lake Forest, IL; 2004 Sept.

e. Boehringer Ingelheim Roxane Laboratories. Calcitriol solution prescribing information. Ridgefield, CT; 2006 Sept.

f. AHFS drug information 2007. McEvoy GK, ed. Vitamin D analogs general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 3634-3640.

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