Alfacalcidol

From Drugs Prescribing Information
Jump to: navigation, search

Click on "►" to expand:

Alfacalcidol is a type of vitamin D. Vitamin D controls the levels of calcium and phosphate in the body and both of these substances are needed for healthy bones and teeth.

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Alfacalcidol.png

[edit] MECHANISM OF ACTION

To be effective vitamin D must undergo two metabolic conversions, first in the liver to 25-hydroxyvitamin D3 (abbreviated 25(OH)D) and then in the kidney to the physiologically active metabolite, calcitriol also called 1,25-dihydroxy vitamin D3 or 1,25-(OH)2D3). In patients with chronic renal failure, progressive nephron destruction blocks the production of 1,25-(OH)2 D3 by the kidneys resulting in diminished serum levels of this metabolite.


Alfacalcidol (1-alpha-hydroxycholecalciferol or 1-alpha-OHD3) is rapidly converted in the liver to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), the active metabolite of vitamin D, effectively bypassing the critical renal metabolic conversion.

Vitamin D stimulates intestinal calcium and phosphorus absorption, the reabsorption of calcium from bone and possibly the renal reabsorption of calcium.

Impaired endogenous production of 1,25-dihydroxyvitamin D3 by the kidneys appears to contribute to the disturbances in mineral metabolism found in several disorders, including renal bone disease, hypoparathyroidism, and vitamin D-dependent rickets.

As compared to vitamin D, the main advantage of Alfacalcidol is more rapid onset and offset of action. This allows a more accurate titration of dosage and decreases the risk of prolonged hypercalcemia.

[edit] INDICATIONS

  • Osteoporosis
  • Management of hypocalcemia
  • Secondary hyperparathyroidism due to physiological secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels)
  • Osteodystrophy in patients with chronic renal failure.
  • Neonatal hypocalcaemia and Rickets (the childhood form of osteomalacia)
  • Osteomalacia
  • Hypoparathyroidism which is decreased function of the parathyroid glands with underproduction of parathyroid hormone. This can lead to low levels of calcium in the blood.

[edit] DOSAGE

Initial dose for all indications:

  • Adults: 1 microgram/day
  • Elderly: 0.5 microgram/day
  • Neonates and premature infants: 0.05 - 0.1 microgram/kg/day
  • Children under 20 kg bodyweight: 0.05 microgram/kg/day
  • Children over 20 kg bodyweight: 1 microgram/day

The dose should be adjusted thereafter to avoid hypercalcaemia according to the biochemical response. Indices of response include plasma levels of calcium (ideally corrected for protein binding), alkaline phosphatase, parathyroid hormone, as well as radiographic and histological investigations.

Plasma levels should initially be measured at weekly intervals. The daily dose may be increased by increments of 0.25 - 0.5 microgram. When the dose is stabilised, measurements may be taken every 2 - 4 weeks.

Most adult patients respond to doses between 1 and 3 micrograms per day. When there is biochemical or radiographic evidence of bone healing, (and in hypoparathyroid patients when normal plasma calcium levels have been attained), the dose generally decreases. Maintenance doses are generally in the range of 0.25 to 1 microgram per day. If hypercalcaemia occurs, Alfacalcidol should be stopped until plasma calcium returns to normal (approximately 1 week) then restarted at half the previous dose.

[edit] CONTRAINDICATIONS

Alfacalcidol is contraindicated when there is biochemical evidence of hypercalcemia, hyperphosphatemia, or evidence of vitamin D overdose

[edit] WARNINGS AND PRECAUTIONS

  • Alfacalcidol should not be used concomitantly with other vitamin D products or derivatives.
  • During treatment with Alfacalcidol, progressive hypercalcemia either due to hyper-responsiveness or overdose may become so severe as to require emergency treatment. Chronic hypercalcemia can lead to generalized vascular calcification, nephrocalcinosis or calcifications of the cornea or other soft tissues. During treatment with Alfacalcidol, the TOTAL SERUM CALCIUM (mg/dL) (TIMES) SERUM INORGANIC PHOSPHATE (mg/dL) PRODUCT (Ca x P) should not exceed 70 mg2/dl2. In early treatment during dosage adjustment, serum calcium should be determined at least twice weekly. In the later stages of treatment when there is evidence of bone healing (e.g., when the plasma alkaline phosphatase level falls toward normal), weekly estimations are recommended.
  • In patients on digitalis hypercalcemia may precipitate cardiac arrhythmias. In such patients Alfacalcidol should be used with extreme caution.

[edit] INTERACTIONS

  • Patients taking barbiturates or anticonvulsants (e.g. carbamazepine, phenobarbitone, phenytoin, and primidone) may require larger doses of Alfacalcidol to produce the desired effect due to the induction of hepatic detoxification enzymes.
  • Concomitant administration of colestyramine may interfere with the intestinal absorption of alfacalcidol.
  • Use with caution in patients being treated with thiazide diuretics (e.g., hydrochlorothiazide). as they may have an increased risk of developing hypercalcemia.
  • Alfacalcidol should be used with extreme caution in patients on digitalis (Digoxin - Lanoxin), as hypercalcemia may trigger cardiac arrhythmias.
  • Absorption of magnesium-containing antacids may be enhanced by alfacalcidol, increasing the risk of hypermagnesemia
  • Alfacalcidol may increase the serum concentration of aluminium. Patients taking aluminium containing preparations (e.g. aluminium hydroxide, sucralfate) should be monitored for signs of aluminium related toxicities.

[edit] PREGNANCY AND LACTATION

  • Alfacalcidol should not be used in pregnancy unless clearly necessary as there is a risk that hypercalcaemia during pregnancy may produce congenital disorder in the offspring.
  • Breastfeeding: Alfacalcidol is excreted in human milk. A decision must be made whether to discontinue breastfeeding or to discontinue Alfacalcidol therapy taking into account the benefit of breast-feeding for the child and the benefit of Alfacalcidol therapy for the woman.

[edit] SIDE EFFECTS

In general, the adverse effects of Alfacalcidol are similar to those encountered with excessive vitamin D intake.

The early and late signs and symptoms associated with vitamin D intoxication and hypercalcemia may include:

  • Early: Pruritus, weakness, headache, "red-eyes", somnolence, nausea, cardiac arrhythmia, vomiting, excessive thirst, dry mouth, constipation, muscle pain, bone pain and metallic taste.
  • Late: Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis, corneal calcification, photophobia, rhinorrhea, pancreatitis, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SGOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis.


Because of the short biological half-life of calcitriol the active metabolite of Alfacalcidol, pharmacokinetic investigations have shown normalization of elevated serum calcium within a few days of treatment withdrawal, much faster than in treatment with vitamin D

[edit] RELATED LINKS

Calcium and phosphate homeostasis, including discussion of vitamin D metabolism and the actions of PTH
How osteoporosis develops

[edit] BIBLIOGRAPHY

[edit] REFERENCES