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Pronunciation
(kal si TRYE ole)
Generic Available (U.S.)
Yes: Excludes ointment
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Oral, injection: Management of hypocalcemia in patients on chronic renal dialysis; management of secondary hyperparathyroidism in patients with chronic kidney disease (CKD); management of hypocalcemia in hypoparathyroidism and pseudohypoparathyroidism
Topical: Management of mild-to-moderate plaque psoriasis
Use: Unlabeled/Investigational
Decrease severity of psoriatic lesions in psoriatic vulgaris; vitamin D-dependent rickets
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects have been observed in animal studies. Mild hypercalcemia has been reported in a newborn following maternal use of calcitriol during pregnancy. If calcitriol is used for the management of hypoparathyroidism in pregnancy, dose adjustments may be needed as pregnancy progresses and again following delivery. Vitamin D and calcium levels should be monitored closely and kept in the lower normal range.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Low levels are found in breast milk (~2 pg/mL)
Contraindications
Hypersensitivity to calcitriol or any component of the formulation; hypercalcemia, vitamin D toxicity
Topical: There are no contraindications listed in the manufacturer's labeling.
Warnings/Precautions
Concerns related to adverse effects:
• Excessive vitamin D: Excessive vitamin D administration may lead to over suppression of PTH, progressive or acute hypercalcemia, hypercalciuria, hyperphosphatemia and adynamic bone disease.
Disease-related concerns:
• Malabsorption syndrome: Use with caution in patients with malabsorption syndromes; efficacy may be limited and/or response may be unpredictable.
• Renal impairment: Use of calcitriol for the treatment of secondary hyperparathyroidism associated with CKD is not recommended in patients with rapidly worsening kidney function or in noncompliant patients. Increased serum phosphate levels in patients with renal failure may lead to ectopic calcification; the use of an aluminum-containing phosphate binder is recommended along with a low phosphate diet in these patients.
Concurrent drug therapy issues:
• Calcium: Adequate dietary (supplemental) calcium is necessary for clinical response to vitamin D.
• Cardiac glycosides: Use with caution in patients taking cardiac glycosides; digitalis toxicity is potentiated by hypocalcemia.
Dosage form specific issues:
• Coconut oil: Products may contain coconut oil (capsule).
• Palm seed oil: Products may contain palm seed oil (oral solution).
• Tartrazine: Some products may contain tartrazine.
• Topical: May cause hypercalcemia; if alterations in calcium occur, discontinue treatment until levels return to normal. For external use only; not for ophthalmic, oral, or intravaginal use. Do not apply to facial skin, eyes, or lips. Absorption may be increased with occlusive dressings. Avoid or limit excessive exposure to natural or artificial sunlight, or phototherapy. The safety and effectiveness has not been evaluated in patients with erythrodermic, exfoliative, or pustular psoriasis.
Other warnings/precautions:
• Calcium-phosphate product: Serum calcium times phosphorus must not exceed 70 mg2/dL2.
Adverse Reactions
Oral, I.V.: Frequency not defined.
Cardiovascular: Cardiac arrhythmia, hypertension
Central nervous system: Apathy, headache, hypothermia, psychosis, sensory disturbances, somnolence
Dermatologic: Erythema multiforme, pruritus
Endocrine & metabolic: Dehydration, growth suppression, hypercalcemia, hypercholesterolemia, hypermagnesemia, hyperphosphatemia, libido decreased, polydipsia
Gastrointestinal: Abdominal pain, anorexia, constipation, metallic taste, nausea, pancreatitis, stomach ache, vomiting, weight loss, xerostomia
Genitourinary: Nocturia, urinary tract infection
Hepatic: ALT increased, AST increased
Local: Injection site pain (mild)
Neuromuscular & skeletal: Bone pain, myalgia, dystrophy, soft tissue calcification, weakness
Ocular: Conjunctivitis, photophobia
Renal: Albuminuria, BUN increased, creatinine increased, hypercalciuria, nephrocalcinosis, polyuria
Respiratory: Rhinorrhea
Miscellaneous: Allergic reaction
Topical:
>10%: Endocrine: Hypercalcemia (≤24%)
1% to 10%:
Dermatologic: Skin discomfort (3%), pruritus (1% to 3%)
Genitourinary: Urine abnormality (4%)
Renal: Hypercalciuria (3%)
Postmarketing and/or case reports: Dermatitis (acute; blistering), erythema, hypercalcemia, kidney stones, skin burning
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Induces CYP3A4 (weak)
Drug Interactions
Aluminum Hydroxide: Vitamin D Analogs may increase the serum concentration of Aluminum Hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Risk D: Consider therapy modification
Calcium Salts: May enhance the adverse/toxic effect of Vitamin D Analogs. Risk C: Monitor therapy
Cardiac Glycosides: Vitamin D Analogs may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
Corticosteroids (Systemic): May diminish the therapeutic effect of Calcitriol. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Magnesium Salts: Calcitriol may increase the serum concentration of Magnesium Salts. Risk D: Consider therapy modification
Mineral Oil: May decrease the serum concentration of Vitamin D Analogs. More specifically, mineral oil may interfere with the absorption of Vitamin D Analogs. Management: Avoid concomitant, oral administration of mineral oil and vitamin D analogs. Consider separating the administration of these agents by several hours to minimize the risk of interaction. Monitor plasma calcium concentrations. Risk D: Consider therapy modification
Orlistat: May decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Risk D: Consider therapy modification
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Sevelamer: May decrease the serum concentration of Calcitriol. Risk C: Monitor therapy
Sucralfate: Vitamin D Analogs may increase the serum concentration of Sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Risk X: Avoid combination
Thiazide Diuretics: May enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Vitamin D Analogs: May enhance the adverse/toxic effect of other Vitamin D Analogs. Risk X: Avoid combination
Storage
Injection: Store at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light.
Oral capsule, solution: Store at room temperature of 20°C to 25°C (68°F to 77°F). Protect from light.
Topical: Store at room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not refrigerate; do not freeze.
Compatibility
Stable in D5W, NS, sterile water for injection.
Mechanism of Action
Calcitriol is a potent active metabolite of vitamin D. Vitamin D promotes absorption of calcium in the intestines and retention at the kidneys thereby increasing calcium levels in the serum; decreases excessive serum phosphatase levels, parathyroid hormone levels, and decreases bone resorption; increases renal tubule phosphate resorption
The mechanism by which calcitriol is beneficial in the treatment of psoriasis has not been established.
Pharmacodynamics/Kinetics
Onset of action: Oral: ~2-6 hours
Duration: Oral, I.V.: 3-5 days
Absorption: Oral: Rapid
Protein binding: 99.9%
Metabolism: Primarily to 1,24,25-trihydroxycholecalciferol and 1,24,25-trihydroxy ergocalciferol
Half-life elimination: Children ~27 hours; Normal adults: 5-8 hours; Hemodialysis: 16-22 hours
Time to peak, serum: Oral: 3-6 hours; Hemodialysis: 8-12 hours
Excretion: Primarily feces; urine
Dosage
Hypocalcemia in patients on chronic renal dialysis (manufacturer labeling):
Adults:
Oral: 0.25 mcg/day or every other day (may require 0.5-1 mcg/day); increases should be made at 4- to 8-week intervals
I.V.: Initial: 1-2 mcg 3 times/week (0.02 mcg/kg) approximately every other day. Adjust dose at 2-4 week intervals; dosing range: 0.5-4 mcg 3 times/week
Hypocalcemia in hypoparathyroidism/pseudohypoparathyroidism (manufacturers labeling): Oral (evaluate dosage at 2- to 4-week intervals):
Children <1 year (unlabeled use): 0.04-0.08 mcg/kg once daily
Children 1-5 years: 0.25-0.75 mcg once daily
Children ≥6 years and Adults: Initial: 0.25 mcg/day, range: 0.5-2 mcg once daily
Secondary hyperparathyroidism associated with moderate-to-severe CKD in patients not on dialysis (manufacturer labeling): Oral:
Children <3 years: Initial dose: 0.01-0.015 mcg/kg/day
Children ≥3 years and Adults: 0.25 mcg/day; may increase to 0.5 mcg/day
K/DOQI guidelines for vitamin D therapy in CKD:
Children:
CKD stage 2, 3: Oral:
<10 kg: 0.05 mcg every other day
10-20 kg: 0.1-0.15 mcg/day
>20 kg: 0.25 mcg/day
Note: Treatment should only be started with serum 25(OH) D >30 ng/mL, serum iPTH >70 pg/mL, serum calcium <10 mg/dL and serum phosphorus less than or equal to the age appropriate level.
CKD stage 4: Oral:
<10 kg: 0.05 mcg every other day
10-20 kg: 0.1-0.15 mcg/day
>20 kg: 0.25 mcg/day
Note: Treatment should only be started with serum 25(OH) D >30 ng/mL, serum iPTH >110 pg/mL, serum calcium <10 mg/dL and serum phosphorus less than or equal to the age appropriate level.
CKD stage 5: Oral, I.V.: Note: The following initial doses are based on plasma PTH and serum calcium levels for patients with serum phosphorus <5.5 mg/dL in adolescents or <6.5 in infants and children, and Ca-P product <55 in adolescents or <65 in infants and children <12 years. Adjust dose based on serum phosphate, calcium and PTH levels. Administer dose with each dialysis session (3 times/week). Intermittent I.V./oral administration is more effective than daily oral dosing.
Plasma PTH 300-500 pg/mL and serum Ca <10 mg/dL: 0.0075 mcg/kg (maximum: 0.25 mcg/day)
Plasma PTH >500-1000 pg/mL and serum Ca <10 mg/dL: 0.015 mcg/kg (maximum: 0.5 mcg/day)
Plasma PTH >1000 pg/mL and serum Ca <10.5 mg/dL: 0.025 mcg/kg (maximum: 1 mcg/day)
Adults:
CKD stage 3: Oral: 0.25 mcg/day. Treatment should only be started with serum 25(OH) D >30 ng/mL, serum iPTH >70 pg/mL, serum calcium <9.5 mg/dL and serum phosphorus <4.6 mg/dL
CKD stage 4: Oral: 0.25 mcg/day. Treatment should only be started with serum 25(OH) D >30 ng/mL, serum iPTH >110 pg/mL, serum calcium <9.5 mg/dL and serum phosphorus <4.6 mg/dL
CKD stage 5:
Peritoneal dialysis: Oral: Initial: 0.5-1 mcg 2-3 times/week or 0.25 mcg/day
Hemodialysis: Note: The following initial doses are based on plasma PTH and serum calcium levels for patients with serum phosphorus <5.5 mg/dL and Ca-P product <55. Adjust dose based on serum phosphate, calcium, and PTH levels. Intermittent I.V. administration may be more effective than daily oral dosing.
Plasma PTH 300-600 pg/mL and serum Ca <9.5 mg/dL: Oral, I.V.: 0.5-1.5 mcg
Plasma PTH 600-1000 pg/mL and serum Ca <9.5 mg/dL:
Oral: 1-4 mcg
I.V.: 1-3 mcg
Plasma PTH >1000 pg/mL and serum Ca <10 mg/dL:
Oral: 3-7 mcg
I.V.: 3-5 mcg
Psoriasis: Adults: Topical: Apply twice daily to affected areas (maximum: 200 g/week)
Vitamin D-dependent rickets (unlabeled use): Children and Adults: Oral: 1 mcg once daily
Elderly: No dosage recommendations, but start at the lower end of the dosage range
Dosage adjustment for toxicity: K/DOQI guidelines: Children and Adults: CKD stage 3 and 4:
iPTH below target: Hold calcitriol until levels rise then resume treatment at half the previous dose. If the lowest dose was being used, switch to alternate day therapy.
Corrected total calcium >9.5 mg/dL (adults) or 10.2 mg/dL (children): Hold calcitriol until serum calcium returns to <9.5 mg/dL (adults) or <9.8 mg/dL (children) then resume treatment at half the previous dose. If the lowest dose was being used, switch to alternate day therapy.
Serum phosphorus >4.6 mg/dL (adults) or greater than the age appropriate limits in children: Hold calcitriol (or add/increase dose of phosphate binder) until levels of phosphorous decrease, then resume at half the prior dose.
Dosage: Combination Regimens
Prostate cancer: Estramustine + Docetaxel + Calcitriol
Administration: Oral
May be administered without regard to food. Administer with meals to reduce GI problems.
Administration: I.V.
May be administered as a bolus dose I.V. through the catheter at the end of hemodialysis.
Administration: Topical
Apply externally; not for ophthalmic, oral, or intravaginal use. Do not apply to eyes, lips, or facial skins. Rub in gently so that no medication remains visible. Limit application to only the areas of skin affected by psoriasis.
Administration: I.V. Detail
pH: 5.9-7.0
Monitoring Parameters
Signs and symptoms of vitamin D intoxication; alkaline phosphatase, serum creatinine
Serum calcium and phosphorus:
CKD stage 2-4: Every month for the first 3 months, then every 3 months
CKD stage 5: Every 2 weeks for 1 month, then monthly
Serum or plasma intact PTH (iPTH):
CKD stage 3 and 4: Every 3 months for 6 months, then every 3 months
CKD stage 5: Monthly for 3 months, then every 3 months
Reference Range
CKD K/DOQI guidelines definition of stages; chronic disease is kidney damage or GFR <60 mL/minute/1.73 m2 for ≥3 months:
Stage 2: GFR 60-89 mL/minute/1.73 m2 (kidney damage with mild decrease GFR)
Stage 3: GFR 30-59 mL/minute/1.73 m2 (moderate decrease GFR)
Stage 4: GFR 15-29 mL/minute/1.73 m2 (severe decrease GFR)
Stage 5: GFR <15 mL/minute/1.73 m2 or dialysis (kidney failure)
Target range for iPTH:
Stage 2 CKD: 35-70 pg/mL (children)
Stage 3 CKD: 35-70 pg/mL (children and adults)
Stage 4 CKD: 70-110 pg/mL (children and adults)
Stage 5 CKD: 150-300 pg/mL (adults); 200-300 pg/mL (children)
Serum phosphorus:
Stage 3 and 4 CKD: ≥2.7 to <4.6 mg/dL (adults); within age appropriate limits (children)
Stage 5 CKD: 3.5-5.5 mg/dL (children >12 years and adults); 4-6 mg/dL (children 1-12 years)
Serum calcium-phosphorus product:
Stage 3-5 CKD: <55 mg2/dL2 (children >12 years and adults); <65 mg2/dL2 (children ≤12 years)
Dietary Considerations
May be taken without regard to food. Give with meals to reduce GI problems. Adequate calcium intake should be maintained during therapy; dietary phosphorous may need to be restricted.
Patient Education
Maintain recommended diet and calcium supplementation. You may experience nausea, vomiting, loss of appetite, or metallic taste. Report CNS changes, unusual weakness or fatigue, or persistent nausea or vomiting.
Topical: Avoid or limit excessive exposure to sun or phototherapy. Protect skin with sunblock and protective clothing.
Geriatric Considerations
Recommended daily allowances (RDA) have not been developed for persons >65 years of age; vitamin D, folate, and B12 (cyanocobalamin) have decreased absorption with age, but the clinical significance is yet unknown. Calorie requirements decrease with age and therefore, nutrient density must be increased to ensure adequate nutrient intake, including vitamins and minerals. Therefore, the use of a daily supplement with a multiple vitamin with minerals is recommended. Elderly consume less vitamin D, absorption may be decreased, and many elderly have decreased sun exposure; therefore, elderly should receive supplementation with 800 units of vitamin D (20 mcg)/day. This is a recommendation of particular need to those with high risk for osteoporosis.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Metallic taste and xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause sedation or irritability
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Provide appropriate nutritional counseling.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, softgel, oral: 0.25 mcg, 0.5 mcg
Rocaltrol®: 0.25 mcg, 0.5 mcg [contains coconut oil]
Injection, solution: 1 mcg/mL (1 mL)
Calcijex®: 1 mcg/mL (1 mL) [contains aluminum]
Ointment, topical:
Vectical™: 3 mcg/g (100 g)
Solution, oral: 1 mcg/mL (15 mL)
Rocaltrol®: 1 mcg/mL (15 mL) [contains palm oil]
Pricing: U.S. (www.drugstore.com)
Capsules (Calcitriol)
0.25 mcg (30): $35.99
0.5 mcg (30): $54.99
Capsules (Rocaltrol)
0.25 mcg (30): $55.99
Ointment (Vectical)
3mcg/gm (100): $530.01
References
Callies F, Arlt W, Scholz HJ, et al, “Management of Hypoparathyroidism During Pregnancy -- Report of Twelve Cases,” Eur J Endocrinol, 1998, 139(3):284-9.
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Children With Chronic Kidney Disease.” Available at http://www.kidney.org/professionals/KDOQI/guidelines_pedbone/index.htm
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 1. Evaluation of Calcium and Phosphorus Metabolism.” Available at http://www.kidney.org/professionals/KDOQI/guidelines_pedbone/guide1.htm
“K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification, Part 4. Definition and Classification of Stages of Chronic Kidney Disease.” Available at http://www.kidney.org/professionals/KDOQI/guidelines_ckd/p4_class.htm
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 3. Evaluation of Serum Phosphorus Levels.” Available at http://www.kidney.org/professionals/KDOQI/guidelines_bone/Guide3.htm
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 6. Serum Calcium and Calcium-Phosphorus Product.” Available at http://www.kidney.org/professionals/KDOQI/guidelines_bone/Guide6.htm
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 8A. Active Vitamin D Therapy in Patients With Stages 3 and 4 CKD.” Available at http://www.kidney.org/professionals/KDOQI/guidelines_bone/Guide8A.htm
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 8B. Vitamin D Therapy in Patients on Dialysis (CKD Stage 5).” Available at http://www.kidney.org/professionals/KDOQI/guidelines_bone/Guide8B.htm
Letsou AP and Price LS, “Health Aging and Nutrition: An Overview,” Clin Geriatr Med, 1987, 3(2):253-60.
Myrianthopoulos M, “Dietary Treatment of Hyperlipidemia in the Elderly,” Clin Geriatr Med, 1987, 3(2):343-59.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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