Special Warning : אזהרת שימוש

Warnings
Alfacalcidol should be used with caution for:
• patients being treated with cardioactive glycosides or digitalis as hypercalcaemia may lead to arrhythmia in such patients (see Drug Interactions).
• 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) {see also Precautions}.

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 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.


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Use in Breastfeeding
Although not definitely established, it is likely that increased levels of 1,25- dihydroxyvitamin 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.

Adverse Reactions
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.

Based on data from post-market use the total undesirable effect 'reporting rate' is rare or very rare being approximately 1:10,000 patients treated.

Metabolism and Nutrition Disorders
Hypercalcemia
Hyperphosphatemia

Skin and Subcutaneous Tissue Disorders
Pruritus
Rash
Urticaria

Renal and Urinary Disorders
Nephrocalcinosis
Renal impairment

No other side effects associated directly with alfacalcidol therapy have been noted.

Precautions
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.
Alpha D3, PPI for 0.5 mcg ONLY    15. 6. 2010, RH                      Page 3 of 6 Alfacalcidol should be administered with caution to patients with hypercalciuria, especially those with a history of renal calculi.

Effects on Driving

4.7        Effects on ability to drive and use machines

Alpha D3 has no influence on the ability to drive or use machines