Composition:
Active substance: Alphacalcidol;
1 capsule contains 0.25 microgram of Alphacalcidol.
Additional ingredients: corn oil.
Gelatine coating of capsule: gelatine, glycerine, sorbitol 70% solution (sorbitol E 420), sodium methylparaben (E 219), sodium propylparaben (E 217), titanium dioxide (E 171), purified water.

Pharmaceutical Form: Capsules.

Pharmacotherapeutic group: Preparation of vitamin D and its analogues. Code ATC А11С С03.

Clinical characteristics:
Indications:
- Osteoporosis (including postmenopausal, senile and steroid osteoporosis);
- Osteodystrophy in chronic renal insufficiency (ChRI);
- Hyperparathyreoidism (with bones lesion);
- Hypoparathyreoidism;
- Hypophosphatemic (vitamin-D-resistant) rickets and osteomalacia (as additional therapy);
- Osteomalacia due to inadequate absorption, for example in case of malabsorption and postgastrectomy syndrome.

Contraindications:
Hypersensitivity to any drugs component, signs of vitamin D intoxication, hypercalcemia, hypermagnesemia, hyperphosphatemia (except hyperphosphatemia caused by hypoparathyreoidism), stomach and duodenal ulcer, liver diseases, alkalosis with pH level of venous blood over 7.44 (lactate-alkalosis syndrome, Burnett’s syndrome), pregnancy and lactation, children with body weight less than 20 kg and less than 7 years old.

Administration and Dosage:
The drug is used peroral. Capsule should be swallowed in whole with enough water. The duration of the treatment course is determined individually by a doctor and it depends on the character of the disease and the efficacy of the therapy (in average it lasts from 2–4 weeks to 2 months). In isolated cases the drug is used during a whole life long.
It is recommended to start the treatment with minimal indicated doses and to control the level of calcium and phosphorus in blood plasma once a week. The dosage of the preparation may be increased on 0.25 or 0.5 microgram/day until biochemical indexes stabilization. In reaching of minimal effective dose it is recommended to control calcium level in blood plasma every 3–5 weeks.
In postmenopausal and other types of osteoporosis the daily dose for adults is 0.5–1 microgram for 2 intakes.
In osteodystrophy in patients with chronic liver insufficiency and hyperparathyreoidism (with bones lesion) the daily dose for adults is 0.25–2 micrograms. It is necessary to start the treatment from minimal dose of 0.25 microgram/day, gradually increasing it on 0.25 microgram.
In a case of hypoparathyreoidism and osteomalacia the usual dose of alphacalcidol is 0.5 microgram/day. An average daily dose for adults is 2–4 micrograms.
In hypophosphatemic rickets and osteomalacia (as additional therapy) the preparation is administered from 4 to 20 micrograms per day.
For children with body weight over 20 kg it is administered 1 microgram per day (except osteodystrophy). In osteodystrophy with chronic kidney insufficiency the recommended dose of the preparation is 0.04–0.08 microgram/kg.

Side effects:
Gastrointestinal tract and liver: anorexia, vomiting, heartburn, stomach pain, nausea, dry mouth, discomfort in epigastrium, constipation, diarrhoea; in rare cases it can be increasing of ALT (alanine aminotransferase) and AST (aspartate aminotransferase) in plasma.
Central nervous system: rarely – weakness, fatigability, headache, dizziness, drowse.
Cardiovascular system: tachycardia is in rare cases.
Allergic reactions: rarely – skin rash, itch.
Musculoskeletal system: moderate pain in muscles, bones, joints.
Influence on metabolism: rarely – hypercalcemia; very rarely – insignificant increasing of HDL (high-density lipoproteins) in plasma. In patients with acute kidney function disorders it is possible a development of hyperphosphatemia.

Overdosage:
Cases of overdosage of alphacalcidol can cause hypercalcemia.
Possible symptoms: weakness, flaccidity, dizziness, headache; nausea, dry mouth, constipation, diarrhoea, heartburn, vomiting, pain in epigastrium, bones pain, itch, tachycardia. Polyuria, polydipsia, nocturia, proteinuria in kidney function disorders may occur.
Treatment: It is necessary to stop the drug usage. On the early stage of high overdosage it can be a positive effect from gastric lavage and/or from a prescription of mineral oil (which promotes absorption decrease and increase of the drug excretion with faeces).
Due to hypercalcemia severity it can be used calcium-free or low-calcium diet, liquid intake, dialysis, loop diuretics, glucocorticosteroids and calcitonin.
There is no specific antidote of alphacalcidol.

Pregnancy and lactation:
The preparation usage in pregnancy and lactation is contraindicated.

Children:
The preparation is not used in children with body weight less than 20 kg and less than 7 years old.

Special precaution measures:
During the usage of the preparation it is necessary to control the levels of calcium, phosphorus and alkaline phosphatise in plasma and calcium and phosphorus values in urine regularly (not less than 1 time in 3 months), to observe a development of the therapeutic effect and to adjust the dosage of the preparation if there is a need. If there are biochemical symptoms of bones structure normalization (normalization of alkaline phosphatase content in blood plasma) it is necessary an adequate decrease of the preparation dose that enables to avoid the development of hypercalcemia.

Special indications:
For patients who are inclined to hypercalcaemia, especially for patients with urolithiasis it is necessary to administer the drug carefully.
Hypercalcemia may occur in case of sudden calcium entry increase into organism during nutrition change (for example, in increased usage of dairy foods) or during uncontrolled intake of calcium drugs. During Alphaphorcal® usage it s necessary to keep to a diet; it is necessary to teach patients to identify the symptoms of hypercalcemia.
Hypercalcemia and hypercalcuria can be adjusted by stopping of the drug usage and decreasing of calcium usage until normalization of calcium level in blood plasma. As a rule this period is 1 week. Than the therapy can be continued, starting from the half of the last dose.

Influence on velocity reactions in driving motor transport and operating other machines:
If during the treatment by the preparation patients feel dizziness or high fatigability or other symptoms, which were not observed earlier, it is necessary to avoid driving motor transport and other potentially dangerous machines.

Drug interactions:
During the treatment of osteoporosis alphacalcidol can be combined with estrogens and antiresorptive drugs of different groups.
Vitamin D and its derivatives should not be concurrently used with Alphaphorcal® because of the possibility of additive interaction and increased risk of hypercalcemia development.
Glucocorticoids also can decrease the effect of alphacalcidol.
In concurrent use of Alphaphorcal® with Digitalis drugs the risk of arrhythmia development is increased.
In concurrent usage with barbiturates, anticonvulsant drugs and other drugs, which can activate enzymes of microsomal oxidation in liver, the efficacy of Alphaphorcal® is decreased.
Absorption of alphacalcidol is decreased in a case of its concurrent usage with mineral oils (during a long term), colestyramine, colestipol, sucralfate, antacids and albumin preparations.
In concurrent usage of Alphaphorcal® with antacids the risk of hypermagnesemia development is increased.
Concurrent usage of calcium preparations or thiazide diuretics increases a risk of hypercalcemia development.
During the course of the treatment by Alphaphorcal® it is not allowed to prescribe vitamin D and its derivates because of possible additive interaction and increasee of risk of hypercalcemia development.

Pharmacological properties:
Pharmacodynamics: Alphacalcidol is a predecessor of active metabolite of vitamin D3. It increases the absorption of calcium and phosphorus in bowel, increases reabsorption of them in kidneys, intensifies mineralization of bones and decreases the level of parathyroid hormone in blood. Alphaphorcal® renews a positive balance of calcium during the treatment of calcium malabsorption and in this way it decreases the intensity of bones resorption that promotes decreasing of the development of fractures frequency.
During the course of the preparation usage it is observed decreasing of bones and muscular pain caused by disorders of calcium and phosphorus metabolism and improving of movements’ coordination.
Pharmacokinetics: After peroral usage alphacalcidol is absorbed in gastrointestinal tract. Period of reaching of maximal concentration of the preparation in plasma is 8–18 hours.
In liver alphacalcidol is metabolized to the main active metabolite of vitamin D3 – calcitriol (1alpha, 25-dihydroxyvitamin D3). The less part of the preparation is metabolized in bone tissues. In contrast with natural vitamin D3 biotransformation of the drug is not carried out in kidney that enables to use the preparation in patients with kidney pathology.

Pharmaceutical characteristics:
General physic-chemical properties: soft gelatine cream-coloured capsules, containing an oily pale yellow liquid.

Shelf-life:2 years.

Storage: Keep it out of reach of children, in dry, protected from light place at the temperature not more than 25o C.

Package: 10 capsules are in a blister, 3 blisters are in a carton box (№ 10 x 3).

Conditions of supply: By prescription.

Manufacturer: For Kusum Healthcare Pvt. Ltd, India, manufactured by Olive Healthcare, India.