Kalsidol

Alfacalcidol.

KALSIDOL 0.25: Each soft capsule contains Alfacalcidol 0.25 microgram.
KALSIDOL 1: Each soft capsule contains Alfacalcidol 1 microgram.

Pharmacology: PHARMACODYNAMICS: Summary of Product Characteristics: Alfacalcidol is converted rapidly in the liver to 1,25-dihydroxyvitamin D. This is the metabolite of vitamin D which acts as a regulator of calcium and phosphate metabolism. Since this conversion is rapid, the clinical effects of Alfacalcidol and 1,25-dihydroxyvitamin D are very similar. Impaired 1-α hydroxylation by the kidneys reduces endogenous 1,25-dihydroxyvitamin D production. This contributes to the disturbances in mineral metabolism found in several disorders, including renal bone disease and hypoparathyoidism. These disorders, which require high doses of parent vitamin D for their correction, will respond to small doses of Alfacalcidol. The delay in response and high dosage required in treating these disorders with parent vitamin D makes dosage adjustment difficult. This can result in unpredictable hypercalcaemia which may take weeks or months to reverse. The major advantage of Alfacalcidol is the more rapid onset of response, which allows a more accurate titration of dosage. Should inadvertent hypercalcaemia occur it can be reversed within days of stopping treatment.
PHARMACOKINETICS: Vitamin D substance are well absorbed from the gastrointestinal tract. The presence of bile is essential for adequate intestinal absorption, absorption may be decreased in patients with decreased fat absorption.
Vitamin D and its metabolites circulate in the blood bound to a specific α-globulin. Vitamin D can be stored in adipose and muscle tissue for long periods of time. It is slowly released from such storage sites and from the skin where it is formed in the presence of sunlight or ultraviolet light. Ergocalciferol and colecalciferol have a slow onset and a long duration of action: calcitriol and its analogue alfacalcidol, however, have a more rapid action and shorter half-lives.
Colecalciferol and ergocalciferol are hydroxylated in the liver by the enzyme vitamin D 25-hydroxylase to form 25-hydroxycholecalciferol (calcifediol) and 25-hydroxyergocalciferol respectively. These compounds undergo further hydroxylation in the kidneys by the enzyme vitamin D 1-hydroxylase to form the active metabolites 1,25-dihydroxycholecalciferol (calcitriol) and 1,25-dihydroxyergocalciferol respectively. Further metabolism also occurs in the kidneys, including the formation of the 1,24,25-trihydroxy derivatives. Of the synthetic analogues, alfacalcidol, dihydrotachysterol, and doxercalciferol are converted directly in the liver to their active metabolites (calcitriol, 25-hydroxydihydrotachysterol, and 1,25-dihydroxyergocalciferol respectively).
Vitamin D compounds and their metabolites are excreted mainly in the bile and faeces with only small amounts appearing in urine: there is some enterohepatic recycling but it is considered to have a negligible contribution to vitamin D status. Certain vitamin D substances may be distributed into breast milk.

Hypocalcemia associated with hypoparathyroidism or pseudohypoparathyroidism.
Hypophosphatemia.
Osteomalacia in malabsorption syndrome.
Prevention and treatment of Rickets.

RECOMMENDED DOSE: Dosage depends on the nature and severity of the patient's hypocalcemia and must be individualized to maintain serum calcium concentrations of 9-10 mg/dL.
During therapy with vitamin D analogs, patients should receive adequate amounts of calcium through management of diet or administration of calcium supplements; however, overdosage of calcium may lead to hypercalcemia. Dosage of vitamin D analogs should be decreased when symptoms improve and before biochemical normality or complete bone healing has occurred because requirements for vitamin D analogs often decrease after bone healing occurs. In patients who become bedridden (especially children), dosage reduction may occasionally be needed to avoid hypercalcemia.
Dietary and Replacement Requirements: Children: The American Academy of Pediatrics (AAP) recommends a minimum daily intake of 400 units of vitamin D in all infants, children, and adolescents.
Adults: Bone maintenance is the primary concern in adults 19-50 years of age. Although data on bone health outcomes related to vitamin D generally are more limited in adults 19-50 years of age, National Academy of Sciences (NAS) recommends an average intake of 400 units (10 mcg) daily of vitamin D and an intake of 600 units (15 mcg) daily to cover the needs of nearly all adults in this age group assuming minimal sun exposure.
Adults older than 70 years of age and an intake of 800 units (20 mcg) daily to cover the needs of nearly all adults in this age group assuming minimal sun exposure.
MODE OF ADMINISTRATION: Oral route.

Hypercalcaemia is treated by suspending the administration of Alfacalcidol. In severe cases of hypercalcaemia general supportive measures should be undertaken. Keep the patient well hydrated by i.v. infusion of saline (force diuresis), measure electrolytes, calcium and renal function indices; assess electrocardiographic abnormalities, especially in patients on digitalis. More specifically, treatment with glucocorticosteroids, loop diuretics, bisphosphonates, calcitonin and eventually haemodialysis with low calcium content should be considered.

Hypercalcaemia, metastatic calcification.
Hypersensitivity to alfacalcidol or any of the other ingredients.

According to ministry of public health announcement: 1. In order to prevent the accumulation which may occur and be harmful. Please do not take this medicine exceeding recommended daily dose or consecutive long term.
2. Administration unless prescribed by the physician.

Alfacalcidol should be administered with extreme caution, if at all, to patients with impaired renal function and with extreme caution in patients with heart disease, renal stones, or arteriosclerosis. Vitamin D analogs should be administered with caution in patients receiving cardiac glycosides, because hypercalcemia in these patients may result in cardiac arrhythmias. Vitamin D analogs should also be used with caution in patients with increased sensitivity to these drugs. Vitamin D analogs should not be administered concurrently, and these drugs should not be administered to patients with hypercalcemia, vitamin D toxicity, or hypersensitivity to the drug or any ingredient in the formulations.

Pregnancy: A characteristic physiognomy, possibly with aortic valvular stenosis, retinopathy, and mental and/or physical retardation, has occurred following prolonged hypercalcemia in infants and in neonates of mothers with hypercalcemia during pregnancy. Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone concentrations in the neonate resulting in hypocalcemia, tetany, and seizures. Safe use of calcifediol, calcitriol, dihydrotachysterol, paricalcitol, or ergocalciferol during pregnancy has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs.
Lactation: Safe use of calcifediol, calcitriol, dihydrotachysterol, paricalcitol, or ergocalciferol during lactation has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs. Large doses of vitamin D analogs should not be administered to nursing women.

Signs of potential side effects, especially bone pain, constipation, diarrhea, drowsiness, dry mouth, headache (continuing), increased thirst, increase in frequency of urination (especially at night) or in the amount of urine, loss of appetite, metallic taste, muscle pain, nausea or vomiting, unusual tiredness or weakness, cloudy urine, conjunctivitis (calcific), decreased libido, ectopic calcification, high fever, high blood pressure, increased sensitivity of eyes to light or irritation of eyes, irregular heartbeat, itching of skin, lethargy, loss of appetite, pancreatitis, psychosis (overt), rhinorrhea, and weight loss.

Aluminium Hydroxide and Oxide, Cholestyramine, Colestipol (HCl), Cortisone (Acetate), Danazol, Digoxin, Phenobarbitone, Phenytoin (Na), Levothyroxine, Orlistat, Thiazide Diuretics, Other Drugs that is a potent inhibitor of the cytochrome P-450 CYP3A isoenzyme (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole).
These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult the Physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

Store below 30°C. Protect from light and moisture.

Agents Affecting Bone Metabolism

A11CC03 - alfacalcidol ; Belongs to the class of vitamin D and analogues. Used as dietary supplements.

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