Intravenous Hypocalcaemia, Secondary hyperparathyroidism in chronic kidney disease
Adult: In patients undergoing chronic renal dialysis: Usual dose: Initially, 1-2 mcg 3 times weekly, approx every other day, depending on the severity of condition. Dosing range: 0.5-4 mcg 3 times weekly. Dose may be increased by 0.5-1 mcg at 2- to 4-week intervals if necessary. Dosage adjustment, dosing interruption, or discontinuation may be required according to individual PTH, serum Ca, and phosphorus levels (refer to detailed product guideline). Elderly: Initiate at the lower end of the dosage range.
Oral Secondary hyperparathyroidism in chronic kidney disease
Adult: In patients with moderate to severe chronic kidney disease (CKD) not yet on dialysis: Initially, 0.25 mcg daily, may be increased to 0.5 mcg daily if necessary. Elderly: Initiate at the lower end of the dosage range.
Oral Postmenopausal osteoporosis
Adult: 0.25 mcg bid.
Oral Renal osteodystrophy
Adult: In patients undergoing haemodialysis: Initially, 0.25 mcg daily, or 0.25 mcg every other day (in those with normal or only slightly reduced Ca levels), may be increased by 0.25 mcg at 2- to 4-week intervals if necessary. Usual dosing range: 0.5-1 mcg daily. Dosage adjustment, dosing interruption, or discontinuation may be required according to individual serum Ca levels (refer to detailed product guideline).
Oral Hypoparathyroidism
Adult: In patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, or pseudohypoparathyroidism: Initially, 0.25 mcg daily given in the morning, may be increased at 2- to 4-week intervals if necessary. Dosage adjustment, dosing interruption, or discontinuation may be required according to individual serum Ca levels (refer to detailed product guideline). Elderly: Initiate at the lower end of the dosage range.
Topical/Cutaneous Plaque psoriasis
Adult: In patients with mild to moderately severe cases with up to 35% of BSA involvement: As 3 mcg/g ointment: Apply onto the affected area bid. Max: 30 g daily.
Renal Impairment
Topical:
Contraindicated.
Hepatic Impairment
Topical:
Contraindicated.
Administration
May be taken with or without food. May be taken w/ meals to reduce GI discomfort.
Contraindications
Hypercalcaemia, metastatic calcification, vitamin D toxicity. Topical: History of abnormal Ca metabolism, concomitant systemic treatment of Ca homeostasis; renal and hepatic impairment.
Special Precautions
Patient with malabsorption syndrome. Immobilised patients (e.g. patients who undergone surgery). Renal impairment. Elderly. Pregnancy and lactation. Topical: Not evaluated for use in patients with erythrodermic, exfoliative, or pustular psoriasis.
Adverse Reactions
Significant: Hypercalcaemia which may lead to generalised vascular calcification, other soft tissue calcification, nephrocalcinosis, and exacerbated nephrolithiasis; hypercalciuria, hyperphosphataemia, over suppression of PTH, adynamic bone disease (IV), ectopic calcification; severe irritation and contact allergy (topical). Eye disorders: Photophobia, calcific conjunctivitis. Gastrointestinal disorders: Nausea, abdominal pain, vomiting, constipation, dyspepsia, dry mouth, metallic taste. General disorders and administration site conditions: Asthenia, inj site pain. Immune system disorders: Hypersensitivity. Investigations: Increased blood creatinine, AST/ALT, and BUN; weight loss. Metabolism and nutrition disorders: Polydipsia, decreased appetite, dehydration, anorexia, hypercholesterolaemia. Musculoskeletal and connective tissue disorders: Myalgia, bone pain. Nervous system disorders: Headache, paraesthesia. Psychiatric disorders: Somnolence, apathy. Renal and urinary disorders: UTI, urine abnormality, polyuria, nocturia. Respiratory, thoracic and mediastinal disorders: Rhinorrhoea. Skin and subcutaneous tissue disorders: Rash, pruritus, erythema, skin discomfort or irritation, dry skin, aggravated psoriasis. Vascular disorders: Hypertension.
Avoid excessive and uncontrolled intake of vitamin D and additional Ca-containing supplements; maintain appropriate daily fluid intake. Topical: Avoid or limit excessive exposure to natural or artificial sunlight (including tanning booths or sun lamps) and phototherapy. Avoid applying to >35% of BSA during daily treatments or covering affected area with occlusive dressings.
Monitoring Parameters
Monitor serum Ca and phosphorus (more frequently during initial phase, e.g. at least twice weekly); Mg, alkaline phosphatase, PTH levels, renal function tests, 24-hour urinary Ca and phosphorus periodically during treatment initiation and dose adjustments. Measurement frequency should be dependent on patient stability, presence and magnitude of abnormalities, rate of CKD progression, and treatments used for CKD-mineral and bone disorder. Assess for signs of high Ca levels (e.g. weakness, constipation, confusion, bone pain).
Overdosage
Symptoms: Headache, anorexia, constipation, vomiting, dystrophy, apathy, sensory disturbances, possible fever with thirst, polyuria, dehydration, arrested growth, UTI; hypercalcaemia, hypercalciuria, and hyperphosphatemia. Management: Supportive treatment. In case of hypercalcaemia, discontinue supplemental Ca and institute low Ca diet. Induce vomiting or perform gastric lavage to prevent further absorption. Administer liquid paraffin or mineral oil to promote faecal excretion. Monitor serum Ca levels and urinary Ca excretion; assess for ECG abnormalities. In case of persistent or markedly increased serum Ca levels, may give phosphates and corticosteroids, or induce appropriate forced diuresis. May consider peritoneal dialysis and haemodialysis against a Ca-free dialysate.
Drug Interactions
Increased risk of hypercalcaemia with thiazide diuretics. May cause cardiac arrhythmias with digitalis. May reduce and impair the intestinal absorption with bile acid sequestrants (e.g. colestyramine, sevelamer). May result to hypermagnesaemia with Mg-containing agents (e.g. antacids) in dialysis patients. May decrease the effects with CYP450-inducing anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin). Bone and mineral metabolism effects may be antagonised by corticosteroids. May enhance toxic effects with other vitamin D analogues.
Food Interaction
Increased intake of Ca (e.g. dairy products) may lead to hypercalcaemia.
Action
Description: Mechanism of Action: Calcitriol, the active form of vitamin D3 (cholecalciferol), binds to and activates the vitamin D receptors in the intestine, kidneys, parathyroid gland and bone, thus stimulating intestinal Ca transport and absorption. It also stimulates bone resorption and increases renal tubular reabsorption of Ca, thereby decreasing PTH levels and improving Ca-phosphate homeostasis. In the treatment of psoriasis, it blocks the proliferation of keratinocytes and T-cells thereby stimulating keratinocytes differentiation and normalising the production of various inflammation factors, respectively.
Synonym: 1α,25-dihydroxyvitamin D3, 1,25-dihydroxycholecalciferol, 1,25-dihydroxyvitamin D3, 1α, 25-dihydroxycholcalciferol. Onset: 2 hours (oral). Duration: 3-5 days (oral, IV). Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: Oral: Within 2-6 hours; 8-12 hours (on haemodialysis). Distribution: Enters breast milk (small amounts). Plasma protein binding: 99.9%, mainly to a specific vitamin D binding protein (DBP) and to a lesser extent to albumin and lipoproteins. Metabolism: Metabolised in the liver and kidney via hydroxylation and oxidation by CYP24A1 isoenzyme primarily into calcitroic acid and a lactone metabolite. Excretion: Mainly via faeces (27%); urine (7% as unchanged drug in 24 hours). Elimination half-life: 5-8 hours; 16-22 hours (on haemodialysis).
Chemical Structure
Calcitriol Source: National Center for Biotechnology Information. PubChem Database. Calcitriol, CID=5280453, https://pubchem.ncbi.nlm.nih.gov/compound/Calcitriol (accessed on Jan. 21, 2020)
Storage
Store between 15-30°C. Protect from light and moisture. Ointment: Do not refrigerate or freeze.
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