Alfacalcidol (X-bone) is used for treating conditions in which calcium metabolism is disturbed due to impaired 1α hydroxylation, (i.e. reduced renal function), in other disorders associated with Vitamin D resistance and in calcium malabsorption of osteoporosis.
The main indications are renal bone disease (renal osteodystrophy), hypoparathyroidism (with bone disease), nutritional and malabsorptive rickets and osteomalacia, hypophosphatemic Vitamin D resistant rickets and osteomalacia, pseudo-deficiency (D dependent Type I) rickets with osteomalacia and osteoporosis.
DOSAGE & ADMINISTRATION:
The daily dose must be carefully individualized and titrated according to such factors as the state of renal function, degree of bone mineralization and initial plasma calcium and alkaline phosphatase concentrations. Other factors which may be taken into account are urinary calcium excretion, plasma PTH and phosphorus.
The success of Alfacalcidol (X-bone) is also based on the assumption that the patient is receiving an adequate daily intake of calcium during treatment. The recommended daily allowance of calcium in adults is about 800 to 1000 mg (from all sources such as dialysate, diet and calcium supplements). The physician should ensure that each patient receives an adequate daily intake of calcium by prescribing a calcium supplement or instructing the patients in appropriate dietary measures. Dose Titration: Predialysis Patients: A dose of Alfacalcidol (X-bone) that maintains serum calcium (adjusted for albumin concentration) within the normal range should be selected. An initial dose of 0.25 µg/day is recommended, followed by dose adjustment until an appropriate dose is achieved. Alfacalcidol (X-bone)has been shown to be safe and effective in the prevention of renal bone disease when doses were maintained at or below 1 µg/day. Alfacalcidol (X-bone) is usually administered as a single dose each day taken with food.
Protocol for Dosage Adjustment: An initial dose of 0.25µg/day should be administered for 2 months unless hypercalcemia develops. If hypercalcemia occurs then the dose should be reduced to 0.25µg on alternate days. If serum calcium is below the desired range, the dose may be adjusted in increments of 0.25 µg/day every 2 months. Most patients will be maintained on a dose of 0.5 µg/day. However, doses up to 1 µg/day may be necessary to maintain serum calcium within the desired range. If hypercalcemia develops at any time during treatment then the dose of Alfacalcidol (X-bone) should be reduced by 50% and all calcium supplements stopped until calcium levels return to normal. Serum calcium and phosphate levels should be monitored at monthly intervals or as is considered necessary if hypercalcemia develops. Calcium supplements should not exceed 500mg of elemental calcium per day.
Dose Titration for Hemodialysis Patients: The recommended initial dose is 1µg daily. If a satisfactory response in the biochemical parameters and Antacids containing magnesium should be avoided as they may contribute towards hypermagnesemia clinical manifestation is not observed within 4 Patients and their immediate relatives should be informed about the need for compliance with the dosage instructions, strict adherence to prescribed calcium intake, dietary and supplementary and avoidance of unapproved nonprescription drugs or medications.
Patients should be made aware of symptoms of hypercalcemia and should be instructed to seek medical attention if such symptoms appear.
ADVERSE DRUG REACTIONS:
In general, the adverse effects of Alfacalcidol (X-bone) are similar to those encountered with excessive vitamin D intake.
Early symptoms: Pruritus, weakness, headache, red eyes, somnolence, nausea, cardiac arrhythmia, vomiting, excessive thirst, dry mouth, constipation, muscle pain, bone pain and metallic taste. Late symptoms: Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis, corneal calcification, photophobia, rhinorrhea, pancreatitis, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis.
Hypercalcemia and possibly an exacerbation of hyperphosphatemia are the most frequent adverse reactions that have been reported with Alfacalcidol (X-bone) in patients with renal osteodystrophy. Elevated levels of calcium and phosphorus increase the risk of metastatic calcification and may accelerate the decline in renal function in some patients with chronic renal failure.
PRECAUTIONS:
Alfacalcidol (X-bone) should not be used concomitantly with other vitamin D products or derivatives. As with all vitamin D preparations and metabolites, hypercalcemia must be anticipated when using Alfacalcidol (X-bone). Regular monitoring of plasma calcium is essential. Indeed, Alfacalcidol (X-bone) should only be used when adequate facilities are available for monitoring of blood and urine chemistries on a regular basis. During treatment with Alfacalcidol (X-bone), progressive hypercalcemia either due to hyperresponsiveness or overdose may become severe enough 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 (X-bone), the total serum calcium (mg/dL) times serum inorganic phosphate (mg/dL) should be maintained at accepted levels. A dialysate calcium level of 7.0mg/dL (1.75 mmol/L) or above, in addition to excess dietary calcium supplements may lead to frequent episodes of hypercalcemia. To control serum inorganic phosphate levels and dietary phosphate absorption, appropriate oral phosphate binding agents in association with a low phosphate diet may be necessary to prevent hyperphosphatemia and extraskeletal calcifications. Serum phosphate levels were maintained below 2 mmol/L in the study that demonstrated the benefits of Alfacalcidol (X-bone) on the development of bone disease in predialysis patients. In patients on digitalis, hypercalcemia may precipitate cardiac arrhythmias. Use Alfacalcidol (X-bone) with extreme caution in these patients.
The therapeutic margin with Alfacalcidol (X-Bone) is narrow, the optimal daily dose must be carefully titrated for each individual patient. The occurrence of hypercalcemia depends on such factors as the degree of bone mineralization, the state of renal function and the dose of Alfacalcidol (X-bone). Excessive doses of the drug induce hypercalcemia and hypercalciuria.
DRUG-DRUG INTERACTION
Alfacalcidol (X-bone) should be used with extreme caution in patients on digitalis, as hypercalcemia may trigger cardiac arrhythmias. Resins such as cholestyramine and mineral oil used as a laxative may interfere with the intestinal absorption of Alfacalcidol. Patients concurrently treated with barbiturates and other anticonvulsant drugs may require higher doses of Alfacalcidol (X-bone), as these drugs may interfere with the action of vitamin D.
STORAGE:
Storage: Do not store above 30°C.
Protect from sunlight & moisture.
Habit Forming: No
Sedation: No
Child Safety: No
Route of Administration: Oral