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Calcitr Calcitriol iol:: Drug information information Copyright 1978-2013 Lexicomp, Inc. All rights reserved. (For additional information see "Calcitriol: Patient drug information" and information" and see "Calcitriol: Pediatric drug information" ) For abbreviations and symbols that may be used in Lexicomp ( show table ) table )
Brand Names: U.S. Rocaltrol; Vectical Brand Names: Canada Calcijex®; Rocaltrol®; Silkis™ Vit amin D Analog Pharmacologi Pharmacologic c Category Vitamin
Dosing: Adult Hypocalcemia in patients on chronic renal dialysis:
Oral: Initial: Initial: 0.25 mcg daily; may increase dose by 0.25 mc g daily at 4- to 8-week 8-week intervals, intervals, up to t o 0.5-1 mcg daily; patients with normal or mildly decreased serum calcium levels may respond to 0.25 mcg every other day I.V.: U.S. labeling: Initial: 1-2 mcg 3 times weekly approximately every other day. Adjust dose by 0.5-1 mcg at
2- to 4-week intervals; dosing range: 0.5-4 mcg 3 times weekly. Gradual dose reduction and discontinuation of therapy may be necessary as PTH levels decrease below target of (1.5-3 x ULN) in response to therapy. Canadian labeling: Initial: 0.5 mcg 3 times weekly, w eekly, approximately approximately every other day. Adjust dose by 0.25-
0.5 mcg at 2- to 4-week intervals; dosing range: 0.5-3 mcg 3 times weekly Hypocalcemia in hypoparathyroidism/pseudohypoparathyroidism: Oral: U.S. labeling: Initial: 0.25 mcg daily(may adjust dose at 2- to 4-week intervals); range: 0.5-2 mcg once daily Canadian labeling: Initial: 0.25 mcg daily; may increase dose by 0.25 mcg daily at 2- to 4-week intervals.
Discontinue use immediately for hypercalcemia; may resume therapy after calcium levels normalize. Psoriasis: Topical: Apply twice daily to affected areas (maximum: 200 g weekly); Canadian labeling recommends
maximum of 30 g daily Secondary hyperparathyroidism associated with moderate-to-severe CKD in patients not on dialysis: Oral:
0.25 mcg daily; may increase to 0.5 mcg daily KDOQI KDOQI guide line s for for vitamin vitam in D therapy the rapy i n CKD (KD (KDOQI, OQI, 2003):
CKD stage 3: Oral: 0.25 mcg daily. 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 daily. 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 weekly or 0.25 mcg daily 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. Administer per hemodialysis session. 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 Vitamin D-dependent rickets type 1/pseudovitamin D deficiency rickets (PDDR): U.S. unlabeled use: Oral:
Initial: 0.5 mcg twice daily; subsequent dosing adjusted to maintain normal serum calcium and PTH levels; median dose after 2 years: 0.25 mcg daily (range: 0.1-0.5 mcg daily) (Edouard, 2011) Vitamin D-resistant rickets: Canadian labeling (not in U.S. labeling): Oral: Initial: 0.25 mcg daily; may increase
dose by 25 mcg daily at 2- to 4-week intervals if response is inadequate; discontinue use immediately for hypercalcemia and do not resume until calcium levels normalize.
Dosing: Pediatric (For additional information see "Calcitriol: Pediatric drug information" ) Hypocalcemia in hypoparathyroidism/pseudohypoparathyroidism: U.S. labeling: Oral:
Children 1-5 years: Usual dosage range: 0.25-0.75 mcg once daily (may adjust dose at 2- to 4-week intervals) Children ≥6 years: Refer to adult dosing. Canadian labeling: Oral: Children: Initial: 0.03-0.05 mcg/kg/day; evaluate response after 2 weeks and increase
dose by 25% if response is inadequate. Dose may be increased or decreased by 25% every 2 weeks thereafter until therapeutic response is achieved. Note: May consider initial dose of 0.05 mcg/kg/day for severe hypocalcemia/ symptoms (hospitalization recommended with close monitoring and dose reduction as soon as clinically possible). Maintenance dose: 0.014-0.04 mcg/kg/day Secondary hyperparathyroidism associated with moderate-to-severe CKD in patients not on dialysis: Oral: U.S. labeling:
Children <3 years: Initial dose: 0.01-0.015 mcg/kg/day Children ≥3 years: Refer to adult dosing. KDOQI guidelines for vitamin D therapy in CKD: Children (KDOQI, 2005):
CKD stage 2, 3: Oral: <10 kg: 0.05 mcg every other day 10-20 kg: 0.1-0.15 mcg daily >20 kg: 0.25 mcg daily 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 daily >20 kg: 0.25 mcg daily 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: Peritoneal dialysis or hemodialysis: 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 weekly). 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 daily) Plasma PTH >500-1000 pg/mL and serum Ca <10 mg/dL: 0.015 mcg/kg (maximum: 0.5 mcg daily) Plasma PTH >1000 pg/mL and serum Ca <10.5 mg/dL: 0.025 mcg/kg (maximum: 1 mcg daily) Vitamin D-dependent rickets type 1/pseudovitamin D deficiency rickets (PDDR): Oral: U.S. unlabeled use: Children: Refer to adult dosing. Canadian labeling: Children: Initial: 0.01-0.025 mcg/kg/day; evaluate response after two weeks and increase
dose by 25% if response is inadequate. Dose may be increased or decreased by 25% every 2 weeks thereafter until therapeutic response is achieved. Note: May consider initial dose of 0.05 mcg/kg/day for severe hypocalcemia/ symptoms (hospitalization recommended with close monitoring and dose reduction as soon as clinically possible). Maintenance dose: 0.0046-0.015 mcg/kg/day. X-linked hypophosphatemic rickets: Canadian labeling (not in U.S. labeling): Children: Oral: Initial: 0.01-0.02
mcg/kg/day; evaluate response after 2 weeks and increase dose by 25% if response is inadequate. Dose may be increased or decreased by 25% every two weeks thereafter until therapeutic response is achieved. Note: May consider initial dose of 0.05 mcg/kg/day for severe hypocalcemia/ symptoms (hospitalization recommended with close monitoring and dose reduction as soon as clinically possible). Maintenance dose: 0.01-0.05 mcg/kg/day.
Dosing: Geriatric Refer to adult dosing. Start at the lower end of the dosage range. Dosing: Renal Impairment No dosage adjustment provided in manufacturer’s labeling. Dosing: Hepatic Impairment No dosage adjustment provided in manufacturer’s labeling. Dosing: Adjustment for Toxicity
KDOQI guidelines:
Children (KDOQI, 2005): CKD stages 2-4: Serum iPTH below target range: Hold calcitriol until levels rise above target range appropriate for CKD stage, than resume treatment at half the previous dose. If the lowest dose was being used, switch to alternate day therapy. Corrected total calcium >10.2 mg/dL: Hold calcitriol until serum calcium returns to <9.8 mg/dL then resume treatment at half the previous dose. If the lowest dose was being used, switch to alternate day therapy. Serum phosphorus greater than the age appropriate limits: Hold calcitriol and add/increase dose of phosphate binder until levels of phosphorous decrease to age appropriate levels, then resume at half the previous dose Adults (KDOQI, 2003): 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: Hold calcitriol until serum calcium returns to <9.5 mg/dL, 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: Hold calcitriol (or add/increase dose of phosphate binder) until levels of phosphorous decrease, then resume at half the prior dose.
Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult s pecific product labeling. Capsule, Oral: Rocaltrol: 0.25 mcg, 0.5 mcg [contains fd&c yellow #6 (sunset yellow), methylparaben, propylparaben] Generic: 0.25 mcg, 0.5 mcg Ointment, External: Vectical: 3 mcg/g (100 g) Generic: 3 mcg/g (100 g) Solution, Intravenous: Generic: 1 mcg/mL (1 mL) Solution, Oral: Rocaltrol: 1 mcg/mL (15 mL) Generic: 1 mcg/mL (15 mL)
Dosage Forms: Canada Excipient information presented when available (limited, particularly for generics); consult s pecific product labeling. Ointment, topical: Silkis™: 3 mcg/g (5 g, 30 g, 100 g)
Generic Equivalent Available: U.S. Yes
Administration I.V.: May be administered as a bolus dose I.V. through the catheter at the end of hemodialysis . Oral: May be administered without regard to food. Administer with meals to reduce GI problems. 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.
Compatibility Stable in D5W, NS, sterile water for injection. Use Management of hypocalcemia in patients on chronic renal dialysis (oral, injection); management of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) (oral); management of hypocalcemia in patients with hypoparathyroidism and pseudohypoparathyroidism (oral); management of mild-to-moderate plaque psoriasis (topical) Canadian labeling: Additional uses (not in U.S. labeling): Vitamin D-resistant rickets (oral)
Use - Unlabeled Vitamin D-dependent rickets type I/pseudovitamin D deficiency rickets (PDDR) Medication Safety Issues Sound-alike/look-alike issues:
Calcitriol may be confused with alfacalcidol, Calciferol™, calcitonin, calcium carbonate, captopril, colest ipol, paricalcitol, ropinirole Administration issues:
Dosage is expressed in mcg (micrograms), not mg (milligrams); rare cases of acute overdose have been reported
Adverse Reactions Significant Oral, I.V.: Frequency not defined.
Cardiovascular: Cardiac arrhythmia, hypertension Central nervous system: Apathy, headache, hyperthermia, psychosis, sensory disturbances, somnolence Dermatologic: Erythema multiforme, erythematous skin disorders, pruritus, rash, urticaria Endocrine & metabolic: Dehydration, growth suppression, hypercalcemia, hypercholesterolemia, 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, hypersensitivity reactions <1% (Limited to important or life-threatening): Anaphylaxis Topical:
>10%: Endocrine: Hypercalcemia (24%) 1% to 10%: Dermatologic: Psoriasis (4%), skin discomfort (3%), pruritus (1% to 3%) Genitourinary: Urine abnormality (4%) Renal: Hypercalciuria (3%) <1% (Limited to important or life-threatening): Kidney stones
Contraindications U.S. labeling:
Oral, injection: Hypersensitivity to calcitriol or any component of the formulation; hypercalcemia, vitamin D toxicity Topical: There are no contraindications listed in the manufacturer's labeling. Canadian labeling:
Oral, injection: Hypersensitivity to calcitriol, vitamin D or its analogues or derivatives, or any component of the formulation or container; hypercalcemia, vitamin D toxicity Topical: Ophthalmic or internal use; hypercalcemia or a history of abnormal calcium metabolism; concurrent systemic treatment of calcium homeostasis; severe renal impairment or end-stage renal disease (ESRD)
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. Withhold pharmacologic doses of vitamin D and its derivatives during therapy to avoid the potential for hypercalcemia to develop. In addition, several months may be required for ergocalciferol levels to return to baseline in patients switching from ergocalciferol therapy to calcitriol.
• Hypercalcemia: Monitor calcium levels closely with initiation of therapy and with dose adjustments; discontinue use promptly in patients who develop hypercalcemia. Avoid abrupt dietary modifications (eg, increased intake of dairy products) which may lead to hypercalcemia; adjust calcium intake if indicated and maintain adequate hydration. Chronic hypercalcemia can result in generalized vascular and soft tissue calcification. Immobilized patients may be at a higher risk for hypercalcemia. Disease-related concerns:
• Hepatic impairment: Canadian labeling (topical formulation) does not recommend use in patients with hepatic impairment. • Malabsorption syndrome: Use oral calcitriol 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. Canadian labeling (topical formulation) does not recommend use in patients with mild-tomoderate renal impairment. 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 hypercalcemia. • Magnesium-containing products: Concomitant use with magnesium-containing products such as antacids may lead to hypermagnesemia in patients receiving chronic renal dialysis. 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: Discontinue use immediately in patients with a calcium-phosphate product (serum calcium times phosphorus) >70 mg 2/dL2; may resume therapy at decreased doses when levels are appropriate.
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: As signment of Major/Minor
substrate status based on clinically relevant drug interaction potential; Induces CYP3A4 (weak/moderate)
Drug Interactions (For additional information: Launch Lexi-Interact™ Drug Interactions Program )
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 ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor clinical response. Reduce the oral aripiprazole dose to 10-15 mg/day if the inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with extendedrelease injectable aripiprazole. Risk D: Consider therapy modification Axitinib: CYP3A4 Inducers (Weakly to Moderately Effective) may decrease the serum concentration of Axitinib. 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 c alcium concentrations. Risk D: Consider therapy modification
Calcium Salts: May enhance the adverse/toxic effect of Vitamin D Analogs. Risk C: Monitor therapy Cardiac Glyc osides: Vitamin D Analogs may enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination Corticosteroids (Systemic): May diminish the therapeutic effect of Calcitriol. Risk C: Monitor therapy CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification 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
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification Danazol: May enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy 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. Management: Consider avoiding CYP3A4 inducing herbs in order to avoid therapeutic failure of the substrate. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy Magnesium Salts: Calcitriol may increase the serum concentration of Magnesium Salts. Risk D: Consider therapy modification
Mifepristone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus,
and tacrolimus. 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 Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Vitamin D Analogs. Risk X: Avoid combination
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Vitamin D Analogs. Risk X: Avoid combination
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
Pregnancy Risk Factor C (show table) Pregnancy Implications Teratogenic effects have been observed in some animal reproduction studies. Mild hypercalcemia has been reported in a newborn following maternal use of calcitriol during pregnancy. Adverse effects on fetal development were not observed with use of calcitriol during pregnancy in women (N=9) with pseudovitamin D-dependent rickets. Doses were adjusted every 4 weeks to keep calcium concentrations within normal limits (Edouard, 2011). 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) 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.
Pricing: U.S. (Medi-Span®) Capsules (Calcitriol Oral)
0.25 mcg (100): $120.95 0.5 mcg (100): $193.38 Capsules (Rocaltrol Oral)
0.25 mcg (30): $51.18 0.5 mcg (100): $268.60 Ointment (Calcitriol External)
3 mcg/g (100 g): $640.25 Ointment (Vectical External)
3 mcg/g (100 g): $713.82 Solution (Calcitriol Intravenous)
1 mcg/mL (1 mL): $6.00 Solution (Calcitriol Oral)
1 mcg/mL (15 mL): $179.00 Solution (Rocaltrol Oral)
1 mcg/mL (15 mL): $214.80 Disclaimer: The pricing data provided represent a median AWP and/or AAWP price for the brand and/or generic
product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for charging or reimbursement functions. Pricing data is updated monthly.
Monitoring Parameters Manufacturer’s labe ling:
Oral therapy: Dialysis patients: Serum calcium, phosphorus, magnesium, and alkaline phosphate monitored periodically Hypoparathyroid patients: Serum calcium, phosphorus, 24 hour urinary calcium monitored periodically Predialysis patients: Serum calcium, phosphorus, alkaline phosphatase, creatinine, and intact PTH, initially; then serum calcium, phosphorus, alkaline phosphatase, and creatinine monthly x 6 months, then periodically. Intact PTH should be monitored every 3-4 months. During titration periods (all patients), monitor serum calc ium levels at least twice weekly. I.V. therapy: Serum calcium and phosphorus twice weekly (following initiation and during dosage adjustments) and periodically during therapy; periodic magnesium, alkaline phosphatase, 24 hour urinary calcium and phosphorous KDOQI Guidelines: Oral and I.V. therapy: Note: More frequent monitoring may be necessary depending on the
presence and magnitude of abnormalities, the rate of progression of CKD, and the use of treatments for CKDmineral and bone disorders. Children (KDOQI, 2005): Serum calcium and phosphorous: CKD stages 2-4: At least monthly for first 3 months following initiation of therapy and at least every 3 months thereafter CKD stage 5: At least every 2 weeks for one month following initiation of therapy and dose increases and monthly thereafter Serum iPTH:
CKD stages 2-4: At least every 3 months CKD stage 5: Monthly for at least 3 months following initiation of therapy or dose increases; once target levels are achieved monitor at least every 3 months thereafter Adults (KDOQI, 2003): Serum calcium and phosphorous: CKD stages 3 and 4: At least monthly for first 3 months following initiation of therapy and every 3 months thereafter CKD stage 5: At least every 2 weeks for one month following initiation of therapy or dose increases and monthly thereafter Serum iPTH: CKD stages 3 and 4: At least every 3 months for 6 months and every 3 months thereafter CKD stage 5: Monthly for at least 3 months following initiation of therapy or dose increases and at least every 3 months once target levels are achieved
Reference Range Corrected total serum calcium (KDOQI, 2003): CKD stages 3 and 4: 8.4-10.2 mg/dL (2.1-2.6 mmol/L); CKD stage 5: 8.4-9.5 mg/dL (2.1-2.37 mmol/L); KDIGO guidelines recommend maintaining normal ranges for all stages of CKD (3-5D) (KDIGO, 2009) Phosphorus (KDOQI, 2003): CKD stages 3 and 4: 2.7-4.6 mg/dL (0.87-1.48 mmol/L) (adults); maintain within age-appropriate limits (children) CKD stage 5 (including those treated with dialysis): 3.5-5.5 mg/dL (1.13-1.78 mmol/L) (children >12 years and adults); 4-6 mg/dL (1.29-1.94 mmol/L) (children 1-12 years) KDIGO guidelines recommend maintaining normal ranges for CKD stages 3-5 and lowering elevated phosphorus levels toward the normal range for CKD stage 5D (KDIGO, 2009) Serum calcium-phosphorus product (KDOQI, 2003): CKD stage 3-5: <55 mg 2/dL2 (children >12 years and adults); <65 mg2/dL2 (children ≤12 years) PTH: Whole molecule, immunochemiluminometric assay (ICMA): 1.0-5.2 pmol/L; whole molecule, radioimmunoassay (RIA): 10.0-65.0 pg/mL; whole molecule, immunoradiometric, double antibody (IRMA): 1.06.0 pmol/L Target ranges by stage of chronic kidney disease (KDIGO, 2009): CKD stage 3-5: Optimal iPTH is unknown; maintain normal range (assay-dependent); CKD stage 5D: Maintain iPTH within 2-9 times the upper limit of normal for the assay used
International Brand Names Altrol (MX); Bocatriol (DE); Bonky (HK, KP); Cacare (TH); Calcijex (AU, CL, GB, HU, LU, MY, TW); Calcit (ID); Calcit SG (TH); Calcitriol (CO); Caleobrol (PY); Caraben (KP); Decostriol (DE, TH); Ecatrol (ID); Gyneamsa (MX); Hitrol (ID); Kolkatriol (ID); Kosteo (AU); Lemytriol (MX); Macolol (TW); Meditrol (TH); Nafartol (MX); Neobon (KP); Osteo-D (TW); Osteocap (MY); Osteotriol (DE); Poscal (KP); Raquitriol (AR); Renatriol (DE); Rocaltriol (DK); Rocaltrol (AE, AT, AU, BB, BE, BG, BH, BM, BR, BS, BZ, CH, CL, CN, CO, CY, CZ, DE, EC, EE, EG, ES, FI, FR, GB, GH, GY, HK, HN, HR, HU, IE, IL, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LU, LY, MT, MX, NL, NO, NZ, OM, PE, PH, PK, PL, PT, QA, RU, SA, SE, SG, SK, SR, SY, TH, TR, TT, TW, TZ,
UG, UY, VE, YE, ZM); Roical (MY); Rolsical (IN); Sical (AU); Silkis (ES, FR, GB, GR, HK, IE, MX, NO, SG, TW); Tariol (KP); Tirocal (MX); Triocalcit (PE)
Mechanism of Action Calcitriol, the active form of vitamin D (1,25 hydroxyvitamin D 3), binds to and activates the vitamin D receptor in kidney, parathyroid gland, intestine, and bone, stimulating intestinal calcium transport and absorption. It reduces PTH levels and improves calcium and phosphate homeostasis by stimulating bone resorption of calcium and increasing renal tubular reabsorption of calcium. Decreased renal conversion of vitamin D to its primary active metabolite (1,25 hydroxyvitamin D) in chronic renal failure leads to reduced activation of vitamin D receptor, which subsequently removes inhibitory suppression of parathyroid hormone (PTH) release; increased serum PTH (secondary hyperparathyroidism) reduces calcium excretion and enhances bone resorption. The mechanism by which calc itriol is beneficial in the treatment of psoriasis has not been established.
Pharmacodynamics/Kinetics Duration: Oral, I.V.: 3-5 days Absorption: Oral: Rapid Protein binding: 99.9% Metabolism: Primarily to calcitroic acid and a lactone metabolite Half-life elimination: Children ~27 hours; Healthy adults: 5-8 hours; Hemodialysis: 16-22 hours Time to peak, serum: Oral: 3-6 hours; Hemodialysis: 8-12 hours Excretion: Primarily feces; urine Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES
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Topic 9183 Version 55.0
