ALFAD

5 microgram/day The dose of AlfaD should subsequently be carefully adjusted to avoid hypercalcaemia according to the biochemical response of each individual patient. Plasma calcium levels (preferably corrected for protein binding) should initially be measured weekly.

5 micrograms/day. Most adults respond to doses of 1 to 3 micrograms/day. Once the dose of AlfaD is stabilised, calcium levels may be measured every 2-4 weeks. Indices of response, in addition to plasma calcium, may include alkaline phosphatase, parathyroid hormone levels, bone radiography and histological investigations.

25 to 1 microgram/day. Should hypercalcaemia occur, AlfaD should be stopped until plasma calcium returns to normal (usually about a week) then restarted at one half of the previous dose. Renal Osteodystrophy - 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 hypercalcaemia may further impair renal function.

• Before and during AlfaD treatment, the use of phosphate binding agents to prevent hyperphosphataemia may also be considered. Hypoparathyroidism - Low plasma calcium levels may be restored to normal more quickly with AlfaD than with parent Vitamin D.

, 3-5 micrograms) together with calcium supplements. Hyperparathyroidism - In patients needing surgery for primary or tertiary hyperparathyroidism, pre- operative treatment with AlfaD for 2-3 weeks can reduce bone pain and myopathy without aggravating hypercalcaemia.

To decrease the risk of post-operative hypocalcaemia, AlfaD should be continued until the plasma alkaline phosphatase falls to normal or hypercalcaemia occurs. Nutritional and Malabsorptive Rickets and Osteomalacia - Malabsorptive osteomalacia, which responds to large doses of IM or IV parent Vitamin D, will respond to small oral doses of AlfaD.

Nutritional rickets and osteomalacia can also be rapidly cured with AlfaD. Hypophosphataemic Vitamin D-Resistant Rickets and Osteomalacia - Normal doses of AlfaD rapidly relieves 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 AlfaD are effective in circumstance which would require high doses of parent Vitamin D.

Post-menopausal or Glucocorticoid-induced Osteoporosis Adults, including the elderly: Treatment dose: 1 microgram/day Serum calcium and creatinine levels should be determined at 1, 3 and 6 months, and at 6 monthly intervals thereafter.

Use in Children AlfaD capsules are not indicated in children under 20kg as the dosage cannot be titrated adequately. Use in Elderly The clinical manifestations of hypo- or hypercalcaemia should be considered, especially in elderly patients with pre-existing renal or heart conditions.

Method of administration: oral

8. If hypercalcaemia or hypercalciuria occur, this can be corrected rapidly by stopping treatment with AlfaD and any calcium supplements until plasma calcium levels return to normal, usually in about a week. AlfaD may then be restarted at half the last dose used.

Response to AlfaD may be impaired if the diet is markedly deficient in calcium. Healing of bone lesions often indicates a decreased requirement for AlfaD in which case appropriate dose adjustments should be made (see Posology and Method of Administration).

AlfaD 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 AlfaD.

1) and patients with rare hereditary problems of fructose intolerance (HFI) should not take it. This medicinal product contains a small amount of alcohol (ethanol) (less than 2mg per soft capsule, corresponding to less than 1% [w/w]).

The amount of alcohol (ethanol) in one soft capsule of this medicine is equivalent to less than 1 mL of beer or 1 mL of wine. The small amount of alcohol in this medicine has no noticeable effects. 5 Interaction with other medicinal products and other forms of interaction Cardiac glycosides Hypercalcaemia in patients taking digitalis preparations may precipitate cardiac arrhythmias.

4). g. barbiturates, phenytoin, carbamazepine, or primidone) have enzyme-inducing effects resulting in an increased metabolism of alfacalcidol. Patients taking anticonvulsants may therefore require larger doses of AlfaD. , cholestyramine, colestipol) may impair the intestinal absorption of AlphaD.

AlphaD should be administered at least 1 hour before, or 4 to 6 hours after, the intake of the bile acid sequestrant in order to minimise the potential risk of interaction. Aluminium-containing preparations Absorption of aluminium-containing antacids may be enhanced by AlfaD so concomitant use of large amounts of aluminium-containing antacids may result in aluminium-related toxicity.

Mineral oil and sucralfate Absorption of AlfaD may be impaired by concurrent use of mineral oil (prolonged use) and sucralfate. Magnesium-containing preparations Caution should be exercised in the use of magnesium-based antacids or laxatives for patients taking AlfaD who are on chronic renal dialysis.

Hypermagnesaemia may occur. Thiazide-diuretics and calcium-containing preparations The risk of hypercalcaemia is increased in patients taking calcium-containing preparations or thiazide diuretics concurrently with AlfaD. Other Vitamin D-containing preparations AlfaD is a potent derivative of Vitamin D.

Pharmacological doses of Vitamin D, or its analogues, should not be given during AlfaD treatment because of the possibility of additive effects and an increased risk of hypercalcaemia. 6 Fertility, pregnancy and lactation Pregnancy There are no or limited data from the use of AlfaD in pregnancy women.

Animal studies have shown reproductive toxicity at high doses. AlfaD is not recommended during pregnancy and in women of child-bearing potential not using contraception. Breast-feeding 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 AlfaD.

This might have an influence on calcium metabolism in a breast-fed infant; consequently, breast-fed infants of AlfaD-treated mothers should be closely monitored for hypercalcaemia. Fertility There are no clinical studies on the effect of AlfaD on fertility.

Animal studies showed adverse effects on fertility at high doses. 7 Effects on ability to drive and use machines AlfaD has no or negligible influence on the ability to drive and use machines. 8 Undesirable effects Adverse effects generally relate to abnormally elevated serum calcium levels (hypercalcaemia) leading to signs or symptoms that may include abdominal pain/discomfort, anorexia, asthenia, confusional state, dehydration, dry mouth, fatigue/lassitude, nausea, vomiting, constipation or diarrheoa, weight loss, muscle or bone pain, metallic taste, kidney stones, renal impairment, somnolence, sweating, headache, polyuria and polydipsia, vertigo, and raised plasma and urine concentrations of calcium and phosphate.

Hypercalcaemia can be rapidly corrected by stopping treatment until plasma calcium levels return to normal (about 1 week). AlphaD treatment may then be re-started at half the previous dose. In the case of renal impairment, elevated serum phosphate levels may be induced by AlfaD therapy.

The dosage should be adjusted to the patient’s requirements. Undesirable effects are listed by MedDRA system organ class (SOC) and individual undesirable effects are listed starting with the most frequently reported one. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness: Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data).

• Metabolism and nutrition disorders Common: Hypercalcaemia; Hyperphosphataemia • Skin and subcutaneous tissue disorders Common: Rash, Pruritus Not known: Urticaria • Renal and urinary disorders Common: Hypercalciuria Uncommon: Nephrocalcinosis • General disorders and administration site conditions Uncommon: Calcinosis (ectopic, or metastatic calcifications) Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product […]

AlfaD 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 • patients with granulomatous diseases, such as sarcoidosis, where sensitivity to vitamin D may be increased due to increased hydroxylation activity and vitamin D toxicity can occur.

AlfaD increases the intestinal absorption of calcium and phosphate, serum levels of which should be monitored, particularly in children, patients with renal failure, and patients receiving high doses. Parathyroid hormone, alkaline phosphatase, and calcium x phosphate should be monitored as clinically indicated.

To maintain serum phosphate at an acceptable level in patients with renal bone disease a phosphate binding agent may be used. 8. If hypercalcaemia or hypercalciuria occur, this can be corrected rapidly by stopping treatment with AlfaD and any calcium supplements until plasma calcium levels return to normal, usually in about a week.

AlfaD may then be restarted at half the last dose used. Response to AlfaD may be impaired if the diet is markedly deficient in calcium. Healing of bone lesions often indicates a decreased requirement for AlfaD in which case appropriate dose adjustments should be made (see Posology and Method of Administration).

AlfaD 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 AlfaD.

1) and patients with rare hereditary problems of fructose intolerance (HFI) should not take it. This medicinal product contains a small amount of alcohol (ethanol) (less than 2mg per soft capsule, corresponding to less than 1% [w/w]).

The amount of alcohol (ethanol) in one soft capsule of this medicine is equivalent to less than 1 mL of beer or 1 mL of wine. The small amount of alcohol in this medicine has no noticeable effects.

Hypercalaemia; metastatic calcification. AlfaD 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. 1.