SUPRA CALCI

Alfacalcidol, or 1-alpha-hydroxycholecalciferol or 1-alpha-hydroxyvitamin D3, is a non-endogenous analogue of vitamin D.

It plays an essential function in calcium homeostasis and bone metabolism.

Alfacaldisol is activated by the enzyme 25-hydroxylase in the liver to mediate its effects in the body, or most importantly, the kidneys and bones.

The pharmacological actions of alfacalcidol are prolonged than vitamin D because a negative feedback mechanism regulates the final activation step of vitamin D in the kidneys. 1, 2 Alfacalcidol is available in oral and intravenous formulations.

In Canada, it is marketed as ONE-ALPHA, which manages hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in adults with chronic renal failure.

In approving

European countries, alfacalcidol is also indicated for managing nutritional and malabsorptive rickets and osteomalacia, vitamin D-dependent rickets and osteomalacia, and hypophosphataemic vitamin D resistant rickets and osteomalacia. 11, 12.

Alfacalcidol is indicated in adult patients with chronic renal failure for the management of hypocalcemia, secondary hyperparathyroidism, or osteodystrophy.

Alfacalcidol is indicated in the management of nutritional and malabsorptive rickets and osteomalacia, vitamin D-dependent rickets and osteomalacia, and hypophosphataemic vitamin D resistant rickets and osteomalacia. 11,

Alfacalcidol works to increase serum levels of calcium by stimulating intestinal calcium absorption, reabsorption of calcium from bone, and possibly the renal reabsorption of calcium.

It also modestly promotes intestinal phosphorus absorption.

In patients with renal failure, alfacalcidol increased intestinal calcium and phosphorus absorption in a dose-related manner.

This increase in calcium and phosphorus levels occurs within three days following drug administration: this effect was reversed within three days of drug discontinuation.

In patients with chronic renal failure, serum calcium levels were elevated while parathyroid hormone and alkaline phosphatase levels returned to normal levels within five days following alfacalcidol administration.

Since alfacalcidol suppresses parathyroid hormone, a reduction in parathyroid hormone levels is achieved more rapidly in patients on intermittent intravenous therapy, with significant reductions occurring within three months of therapy.

In patients receiving daily oral therapy of alfacalcidol, the time it takes alfacalcidol to normalize plasma calcium levels may be up to several months, possibly reflecting calcium being utilized for bone mineralization.

In patients with nutritional osteomalacia, alfacalcidol increased calcium absorption with six hours of oral administration and the effects peaked at 24 hours.

Alfacalcidol is absorbed passively and almost completely in the small intestine.

Alfacalcidol is rapidly converted in the liver to 1,25-dihydroxyvitamin D, which is essentially the metabolite of vitamin D that regulates calcium and phosphate metabolism.

Alfacalcidol is further metabolized to other polar inactive metabolites, excreted primarily through the bile.

The half-life of alfacalcidol ranges from three to four hours. 9, 12.

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There is a discrepancy across a number of reported LD 50 values for alfacalcidol, which can be attributed to differences in the procedures used in laboratories.

LD in mice ranges from 440-490 mcg/kg.

LD in rats ranges from 340-720 mcg/kg.

In case of an acute accidental overdose following oral administration, emesis or gastric lavage can be induced to prevent further drug absorption.

Mineral oil may be used to promote fecal drug elimination in instances where the drug was already absorbed in the stomach.

Alfacalcidol overdose can lead to hypercalcemia, hypercalciuria, and hyperphosphatemia.

Similarly, a high intake of calcium and phosphate concurrently with a therapeutic dose of alfacalcidol can result in those conditions.

Hypercalcemia most commonly presents with headache, weakness, hypertension, somnolence, dizziness, sweating, anorexia, nausea, vomiting, diarrhea, constipation, polyuria, polydipsia and muscle and bone pain, and metallic taste.

Hypercalcemia should be responded to with discontinuation of alfacalcidol, a low calcium diet and withdrawal of calcium supplements.

Prolonged hypercalcemia can lead to nephrocalcinosis, nephrolithiasis, and reduced kidney function.

In cases of severe hypercalcemia, general supportive measures are recommended, which may include forced diuresis and close monitoring of renal function, electrolytes, and electrocardiographs.

Monitoring for abnormalities is especially critical in patients receiving digitalis glycosides.

Management with glucocorticosteroids, loop diuretics, bisphosphonates, and calcitonin, as well as hemodialysis with low calcium content, may be considered.