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  • Alpha D3
    / Teva


    Active Ingredient
    Alfacalcidol 0.25, 0.5, 1 mcg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Soft Capsules

    30 X 0.25 mcg

    full basket chart 84635 9344

    Soft Capsules

    30 X 1 mcg

    full basket chart 84634 9343

    Oral Drops

    5 ml X 0.25 mcg

    full basket chart 209

    Dosage

    General: The dosage and administration of Alpha D3 should be adjusted according to the indication-specific notes which follow. Alpha D3 may be administered as capsules or drops, however, Alpha D3 capsules are not recommended for children under 20 kg bodyweight.
    The initial dosage for all indications, excepting osteoporosis, is as follows:
    Adults and children 20 kg and over bodyweight: 1 mcg/day
    Elderly patients: 0.5 mcg/day
    Neonates and premature infants: 0.05-0.1 mcg/kg/day
    Children under 20 kg bodyweight: 0.05 mcg/kg/day
    The recommended dosage in osteoporosis is 0.5 mcg/day. It should not be exceeded.
    The dose should subsequently be adjusted to avoid hypercalcemia, according to the biochemical response. Plasma calcium levels (preferably corrected for protein binding) should initially be measured weekly. The dose of Alpha D3 can be increased by increments of 0.25 to 0.5 mcg/day. Most adults respond to doses of 1 to 3 mcg/day. Once the dose is stabilised, calcium levels may be measured every 24 weeks. In osteomalacic patients, the lack of rapid calcemia does not necessitate increasing the dosage. Other indices of response, such as plasma levels of alkaline phosphatase, may be more useful criteria for dose adjustment. Indices of response, in addition to a rise in plasma calcium, may include a progressive reduction in alkaline phosphatase, a reduction in parathyroid hormone levels, an increase in urinary calcium excretion in patients with renal function, and an improvement in bone radiography and histology. After normalisation of biochemical parameters, longer treatment periods may be required before radiological and histological improvements in bone defects can be observed. During the first weeks of therapy, improvement is often observed in clinical symptoms such as bone pain and myalgia. When there is biochemical or radiographic evidence of bone healing (or in hypoparathyroidism when calcium levels have normalised) the dose required for maintenance generally decreases to around 0.25 to 2 mcg/day. Should hypercalcemia occur, Alpha D3 should be stopped until plasma calcium returns to normal (usually about a week) then restarted at one half of the previous dose.
    Renal Bone Disease (Renal Osteostrophy): Patients with already high plasma calcium levels may have autonomous hyperparathyroidism. In this situation they may not respond to alfacalcidol and other therapeutic measures may be indicated.
    In patients with chronic renal disease it is particularly important to check the plasma calcium frequently because prolonged hypercalcemia may further impair renal function. Before and during Alpha D3 treatment, the use of phosphate binding agents to prevent hyperphosphatemia may also be considered. Children with renal osteodystrophy seem to need relatively higher doses than adults and may even need the adult dose.
    Hypoparathyroidism: Low plasma calcium levels can be dangerous and may be restored to normal more quickly with Alpha D3 than with parent Vitamin D. Severe hypocalcemia is corrected more rapidly with higher doses of Alpha D3 (e.g., 3-5 mcg) together with calcium supplements.
    Hyperparathyroidism: In patients needing surgery for primary or tertiary hyperparathyroidsim, preoperative treatment with Alpha D3 for 2-3 weeks can reduce bone pain and myopathy without aggravating hypercalcemia. To decrease the risk of post-operative hypocalcemia, Alpha D3 should be continued until the plasma alkaline phosphatase falls to normal or hypercalcemia occurs.
    Neonate Hypocalcemia: The usual initial dose of Alpha D3 is 0.05-0.1 mcg/kg/day (thereafter carefully titrated). Severe cases may require doses of up to 2 mcg/kg/day. Determination of plasma alkaline phosphatase levels may be more useful than plasma ionised calcium levels which may give guidance to response. Plasma alkaline phosphatase levels approximately 7.5 times greater than the adult range are indicative of active disease. In early neonatal hypocalcemia, in premature infants, a dose of 0.1 mcg/kg/day of alfacalcidol has been shown to be effective.
    Nutritional and Malabsorptive Rickets and Osteomalacia: Malabsorptive osteomalacia, which responds to large doses of I.M. or I.V. parent Vitamin D, will respond to small oral doses of Alpha D3. Nutritional rickets and osteomalacia can also be rapidly cured with Alpha D3.
    Hypophosphatemic Vitamin D-Resistant Rickets and Osteomalacia: Normal doses of Alpha D3 rapidly relieve myopathy, when present, and increase calcium and phosphate retention. Phosphate supplements may also be required in some patients. Neither large doses of parent Vitamin D nor phosphate supplements are entirely satisfactory in these conditions.
    Pseudo-Deficiency (D-Dependent Type I) Rickets and Osteomalacia: As with the nutritional conditions, similar oral doses of Alpha D3 are effective in circumstances which would require high doses of parnet Vitamin D.
    Osteoporosis: Malabsorption of calcium is a common feature of osteoporosis, whether postmenopausal, senile or steroid-induced. The decrease in intestinal calcium absorption is associated with low 1,25-dihydroxyvitamin D3 levels, and can be normalised by small, probably physiological doses of orally administered alfacalcidol (0.5 mcg). Improved calcium absorption is associated with an increase in urinary calcium, the magnitude of which is related to the dose of alfacalcidol and the dietary calcium intake. Accordingly, calcium supplementation is only recommended in osteoporotic patients if dietary intake is clearly inadequate.
    Use in Elderly: Initiation of therapy requires a lower dose in elderly patients. The clinical manifestations of hypo- or hyper calcaemia should be considered especially in elderly patients with pre-existing renal or heart conditions.


    recommended drugs

    Indications

    Alpha D3 is used for treating conditions in which calcium metabolism is disturbed due to impaired 1-hydroxylation, such as reduced renal function; in other disorders associated with Vitamin D resistance; and in calcium malabsorption of osteoporosis.
    The indications are: Renal bone disease (renal osteodystrophy), Hypoparathyroidism, Hyperparathyroidism (with bone disease)- primary and tertiary, Neonatal hypocalcemia, Rickets and osteomalacia, Osteoporosis.


    Contra-Indications

    Alfacalcidol should not be administered in the presence of hypercalcemia, hyperphosphatemia (except when occurring with hypoparathyroidism) or hypermagnesemia. Metastatic calcification. Alfacalcidol should not be used in patients with evidence of Vitamin D toxicity or known hypersensitivity to the effects of Vitamin D or any of its analogues.


    Special Precautions

    Alfacalcidol should be used with caution for: patients being treated with cardioactive glycosides or digitalis as hypercalcaemia may lead to arrhythmia in such patients, Patients with nephrolithiasis. Hypercalcemia may appear in patients treated with alfacalcidol, the early symptoms are as follows: Polyuria, Polydipsia, Weakness, Headache, Nausea, Constipation, Dry mouth, Muscle and bone pain, Metallic taste.
    Hypercalcaemia can be rapidly corrected by stopping treatment until plasma calcium levels return to normal (in about one week). Alpha D3 treatment may then be restarted at a reduced dose (half the previous dose).  Response to alfacalcidol may be impaired if the diet is markedly deficient in calcium. Healing of bone lesions often indicates a decreased requirement for AlphaD3 in which case appropriate dose adjustments should be made.  Alpha D3 capsules and drops contain arachis oil (peanut oil) and should not be taken by patients known to be allergic to peanut. As there is a possible relationship between allergy to peanut and allergy to soya, patients with soya allergy should also avoid this medicine.
    Use in Pregnancy: There is insufficient evidence on which to assess the safety of alfacalcidol use during pregnancy. Animal studies are insufficient with respect to effects on pregnancy. The potential risks for humans are unknown. Caution should be taken when prescribing to pregnant women as hypercalcemia during pregnancy may produce congenital disorders in the offspring. Alpha D3 should only be used during pregnancy if considered necessary by the physician.
    Use in Breastfeeding: Although not definitely established, it is likely that increased levels of 1,25dihydroxyvitamin D3 will be found in the breast milk of mothers treated with alfacalcidol. This might have some influence on calcium metabolism in a breast-fed infant and discontinuation of breastfeeding should be considered.
    Alfacalcidol increases the intestinal absorption of calcium and phosphate, serum levels of which should be monitored, particularly in patients with renal failure, children and patients receiving high doses. To maintain serum phosphate at an acceptable level in patients with renal bone disease a phosphate binding agent may be used. Throughout treatment with alfacalcidol, regular plasma and urinary (24-hour collection) calcium levels should be determined at weekly to monthly intervals depending on the progress of the patient. Frequent estimations are necessary in the early stages of treatment (particularly when the plasma calcium is already relatively high) and later when there is evidence of bone healing. Alfacalcidol therapy requires regular monitoring of calcium, phosphate, alkaline phosphatase, magnesium and creatinine levels as well as other appropriate biochemical parameters and should only be prescribed when suitable facilities to do so are available.    If there is biochemical evidence of bone healing (e.g., return towards normal serum alkaline phosphatase levels), hypercalcemia may develop if the dose of Alpha D3 is not decreased appropriately. If hypercalcemia or hypercalciuria occur, this can be corrected rapidly by stopping treatment with Alpha D3 and any calcium supplements until plasma calcium levels return to normal, usually in about a week. Alpha D3 may then be restarted at half the last dose used. Alfacalcidol should be administered with caution to patients with hypercalciuria, especially those with a history of renal calculi.


    Side Effects

    The most frequently reported undesirable effects are hypercalcemia, various skin reactions and, in the case of renal impairment, hyperphosphatemia which may be induced by alfacalcidol therapy. In hypercalcemic dialysis patients, the possibility of calcium influx from the dialysate should be considered. Elevated serum calcium levels lead to symptoms of anorexia, lassitude, nausea, vomiting, diarrhea, weight loss, polyuria, sweating, headache, thirst, vertigo, and raised plasma and urine concentrations of calcium and phosphate. Hypercalcemia can be rapidly corrected by stopping treatment until plasma calcium levels return to normal (about 1 week). Alpha D3 treatment may then be re-started at half the previous dose.
    For full details see prescribing information.


    Drug interactions

    Anticonvulsants, barbiturates, rifampicin. Danazol, digitalis. Mineral oils, cholestyramine, colestipol, sucralfate, aluminum-based antacids. Calcium-containing preparations, thiazides. Magnesium-based antacids, laxatives. Vitamin D or its analogs.
    For full details see prescribing information.


    Pregnancy and Lactation

    Pregnancy: There is insufficient evidence on which to assess the safety of alfacalcidol use during pregnancy. Animal studies are insufficient with respect to effects on pregnancy. The potential risks for humans are unknown. Caution should be taken when prescribing to pregnant women as hypercalcemia during pregnancy may produce congenital disorders in the offspring. Alpha D3 should only be used during pregnancy if considered necessary by the physician.
    Breastfeeding: Although not definitely established, it is likely that increased levels of 1,25dihydroxyvitamin D3 will be found in the breast milk of mothers treated with alfacalcidol. This might have some influence on calcium metabolism in a breast-fed infant and discontinuation of breastfeeding should be considered.


    Overdose

    Manifestations: Hypercalcemia which may manifest clinically: as malaise, fatigue, weakness, dizziness, drowsiness, headache, anorexia, nausea, dry mouth, constipation, diarrhea, heartburn, vomiting, weight loss, polyuria, sweating, thirst, vertigo, abdominal pain or other gastrointestinal discomfort, muscle pain, bone pain, joint pain, pruritus or palpitations, and raised plasma and urine concentrations of calcium and phosphate.
    Treatment: Administration of Alpha D3 should be stopped if hypercalcemia occurs. 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. In acute overdose, early treatment with gastric lavage and/or the administration of mineral oil may reduce absorption and promote fecal elimination.


    Manufacturer
    Teva Pharmaceutical Industries Ltd, Israel
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