|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Medication Safety Issues
Sound-alike/look-alike issues:
Calcitriol may be confused with calcifediol, Calciferol®, calcitonin, calcium carbonate, captopril, colestipol, paricalcitol, ropinirole
Dosage is expressed in mcg (micrograms), not mg (milligrams); rare cases of acute overdose have been reported
Pronunciation
(kal si TRYE ole)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes ointment
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
Induces CYP3A4 (weak)
Drug Interactions
Bile Acid Sequestrants: May decrease the serum concentration of Calcitriol. Risk C: Monitor therapy
Cardiac Glycosides: Calcitriol may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
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
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy
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
Take exact dose as prescribed; do not increase dose. Maintain recommended diet and calcium supplementation. Avoid taking magnesium-containing antacids. You may experience nausea, vomiting, loss of appetite, or metallic taste (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report chest pain or palpitations; acute headache; skin rash; change in vision or eye irritation; CNS changes; unusual weakness or fatigue; persistent nausea, vomiting, cramps, or diarrhea; or muscle or bone pain. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
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
Assess effectiveness and interactions of other medications patient may be taking. Assess results of laboratory tests, therapeutic effectiveness, and adverse effects at beginning of therapy and regularly with long-term use. Assess knowledge/teach patient appropriate use, appropriate nutritional counseling, possible side effects/interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, softgel: 0.25 mcg, 0.5 mcg
Rocaltrol®: 0.25 mcg [contains coconut oil]; 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 seed oil]
Pricing: U.S. (www.drugstore.com)
Capsules (Calcitriol)
0.25 mcg (30): $34.99
0.5 mcg (30): $55.99
Capsules (Rocaltrol)
0.25 mcg (30): $67.43
0.5 mcg (30): $63.99
Ointment (Vectical)
3mcg/gm (100): $439.95
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,” Am J Kidney Dis, 2005, 46(4 Suppl 1):1-121.
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 1. Evaluation of Calcium and Phosphorus Metabolism,” Am J Kidney Dis, 2003, 42(4 Suppl 3):52-7.
“K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification, Part 4. Definition and Classification of Stages of Chronic Kidney Disease,” Am J Kidney Dis, 2002, 39(2 Suppl 1):46-75.
“K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 3. Evaluation of Serum Phosphorus Levels,” Am J Kidney Dis, 2003, 42(4 Suppl 3):62-3.
“K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification, Part 6. Serum Calcium and Calcium-Phosphorus Product,” Am J Kidney Dis, 2003, 42(4 Suppl 3):77-84.
“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,” Am J Kidney Dis, 2003, 42(4 Suppl 3):89-92.
“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),” Am J Kidney Dis, 2003, 42(4 Suppl 3):92-98.
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 November 2009
Content last modified November 2009
| 
