Synthetic calcitriol is the biologically active form of vitamin D3 which regulates absorption of calcium from the gastrointestinal tract and its utilization in the body.
Mechanism of Action: Calcitriol is one of the most important active metabolites of vitamin D3. It is normally formed in the kidneys from its precursor, 25-hydroxycholecalciferol (25-HCC).
Calcitriol promotes intestinal absorption of calcium and regulates bone mineralization. The pharmacological effect of a single dose of calcitriol lasts for about 3-5 days. The key role of calcitriol in the regulation of calcium homeostasis, which includes stimulating effects on osteoblastic activity in the skeleton, provides a sound pharmacological basis for its therapeutic effects in osteoporosis.
Established postmenopausal osteoporosis; renal osteodystrophy in patients with chronic renal failure, particularly those undergoing hemodialysis; post-surgical hypoparathyroidism; idiopathic hypoparathyroidism; pseudohypoparathyroidism; vitamin D-dependent rickets and hypophosphatemic vitamin D-resistant rickets.
Standard Dosage: The optimal daily dose of calcitriol must be carefully determined for each patient on the basis of the serum calcium level. Calcitriol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of serum calcium.
When the optimal dosage of calcitriol has been determined, serum calcium levels should be checked every month. Samples for serum calcium estimation should be taken without a tourniquet. As soon as the serum calcium levels rise to 1 mg/100 mL above normal, or serum creatinine rises to >120 mmol/L, the dosage of calcitriol should be substantially reduced or treatment stopped altogether until normocalcemia ensues.
During the periods of hypercalcemia, serum calcium and phosphate levels must be determined daily. When normal levels have been attained, treatment with calcitriol can be continued, at a daily dose 0.25 mcg lower than that previously used. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.
A prerequisite for optimal efficacy of calcitriol is adequate but not excessive calcium intake
Adults: Approximately 800 mg daily at the beginning of therapy. Calcium supplements may be necessary.
Because of improved calcium absorption from the GIT, some patients on calcitriol may be maintained on a lower calcium intake. Patients who tend to develop hypercalcemia may require only low doses of calcium or no supplementation at all.
The total daily calcium intake (ie, from food, and where applicable, from drugs) should average approximately 800 mg and should not exceed 1000 mg.
Special Dosage Instruction: Postmenopausal Osteoporosis: Recommended Dosage: 0.25 mcg twice daily. Serum calcium and creatinine levels should be determined at 4 weeks, 3 and 6 months and at 6 monthly intervals thereafter.
Renal Osteodystrophy (Dialysis Patients): Initial Daily Dose: 0.25 mcg. In patients with normal or only slightly reduced serum calcium levels, doses of 0.25 mcg every other day are sufficient. If no satisfactory response in the biochemical parameters and clinical manifestations of the disease is observed within 2-4 weeks, the dosage may be increased by 0.25 mcg/day for 2- to 4-week intervals. During this period, serum calcium levels should be determined at least twice weekly. Most patients respond to between 0.5 and 1 mcg daily.
Hypoparathyroidism and Rickets: Recommended Initial Dose: 0.25 mcg/day given in the morning. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease are not observed, the dose may be increased at 2- to 4-week intervals. During this period, serum calcium levels should be determined at least twice weekly.
Malabsorption is occasionally noted in patients with hypoparathyroidism; hence, larger doses of calcitriol may be needed.
In all diseases associated with hypercalcemia. Patients with known hypersensitivity to calcitriol (or drugs of the same class) and any of the constituents of Meditrol.
There is a close correlation between treatment with calcitriol and the development of hypercalcaemia.
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine.
Immobilized patients eg, those who have undergone surgery, are particularly exposed to the risk of hypercalcemia.
Calcitriol increases inorganic phosphate levels in serum. While this is desirable in patients with hypophosphatemia, caution is called for in patients with renal failure because of the danger of ectopic calcification.
Patients with vitamin D-resistant rickets (familial hypophosphatemia) who are being treated with calcitriol must continue their oral phosphate therapy; however, possible stimulation of intestinal absorption of phosphate by calcitriol should be taken into account since this effect may modify the need for phosphate supplementation. Since calcitriol is the most effective vitamin D metabolite available, no other vitamin D preparation should be prescribed during treatment with calcitriol, thereby ensuring that the development of hypervitaminosis is avoided.
If the patient is switched from ergocalciferol (vitamin D2) to calcitriol, it may take several months for the ergocalciferol level in the blood to return to the baseline values.
Patients with normal renal function who are taking calcitriol should avoid dehydration. Adequate fluid intake should be maintained.
Hypersensitivity reactions may occur in susceptible individuals.
Since calcitriol exerts vitamin D activity, adverse effects may occur which are similar to those found when an excessive dose of vitamin D is taken ie, hypercalcemia syndrome or calcium intoxication (depending on the severity and duration of hypercalcemia). Occasional acute symptoms include anorexia, headache, vomiting and constipation. Chronic effects may include dystrophy, sensory disturbances, fever with thirst, polyuria, apathy, arrested growth and urinary tract infections.
Since calcitriol is one of the most important active metabolites of vitamin D3, pharmacological doses of vitamin D and its derivatives should be withheld during treatment with calcitriol to avoid possible additive effects and hypercalcemia. Dietary instructions, especially calcium supplements should be strictly observed, and uncontrolled intake of additional calcium-containing preparations must be avoided.
Concomitant treatment with a thiazide diuretic increases the risk of hypercalcemia. Calcitriol dosage must be determined with care in patients undergoing treatment with digitalis, as hypercalcemia in such patients may precipitate cardiac arrhythmias.
A relationship of functional antagonism exists between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit it.
Magnesium-containing drugs (eg, antacids) may cause hypermagnesemia and should therefore not be taken during therapy with calcitriol by patients on chronic renal dialysis. Since calcitriol also has an effect on phosphate transport in the intestine, kidneys and bones, the dosage of phosphate binding agents must be adjusted in accordance with the serum phosphate concentration (normal values: 2.5 mg/100 mL or 0.6-1.6 mmol/L).
Administration of enzyme inducers eg, phenytoin or phenobarbital may lead to increase metabolism and, hence, reduced serum concentrations of calcitriol. Therefore, higher doses of calcitriol may be necessary if these drugs are administered simultaneously.
Cholestyramine can reduce intestinal absorption of fat-soluble vitamins and therefore may impair intestinal absorption of calcitriol.
Store below 25°C. Protect from heat and light.
A11CC04 - calcitriol ; Belongs to the class of vitamin D and analogues. Used as dietary supplements.