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Other ingredients: purified soybean oil, hydrogenated vegetable oil, soybean lecithin, butylated hydroxyanisole, bees wax.
Gelatine capsule: gelatine, glycerine, sorbitol 70 % solution, sodium methylparaben, sodium propylparaben, dye-stuff Red Oxide, titanium dioxide, purified water.
Pharmaceutical Form: Capsules.
Pharmacotherapeutic group:
Preparation of the Vitamin D and its analogues. Code ATC: А11С С04.
Pharmacological properties:
Pharmacodynamics
Calcitriol is one of the most important metabolites of the vitamin D3. It is arisen from its predecessor, 25-hydroxycholecalciferol in the kidney. As usual, the human organism produces
0,5 – 1,0 microgram of calcitriol per day, during the period of intensive development of the bones (pregnancy or growing) it is produced a little more of the calcitriol. Calcitriol promotes the absorption of the calcium in the bowels and regulates the mineralization of the bones. The duration of pharmacological action of the calcitriol single dose is 3 – 5 days.
The main role of calcitriol in the regulation of the calcium metabolism is to stimulate the activity of the skeletal osteoclasts that is the reliable pharmacological basic for therapeutic action of the drug in osteoporosis.
Calcium carbonate replenishes the calcium deficit, it has also antacidic properties. It inhibits the osteoclasts activity and bones resorption. It also neutralizes the hydrochloric acid and decreases the acidity of the stomach.
Pharmacokinetics
Absorption
Calcitriol is quickly absorbed in gastrointestinal tract. After oral usage of the drug in the single dose of 0,25 – 1,0 microgram the maximal concentration in plasma is reached for 3 – 6 hours. After recurring usage of the drug the equivalent concentrations are reached for 7 days and they are depended on the size of the dosage.
Calcium is absorbed in proximal part of the small intestine in ionized form using the active, vitamin D-dependent transport mechanism.
Allocation
After oral usage of the Phorcal Plus in the single dose of 0,5 microgram the average value of the concentration of calcitriol in plasma increases from 40,0 ± 4,4 pkg/ml to 60,0 ± 4,4 pkg/ml for 2 hours, and for 4 hours it decreases up to 53,0 ± 6,9, for 8 hours it decreases up to 50,7 ± 7,0, for 12 hours it decreases up to 44 ± 4,6 and for 24 hours it decreases up to 41,5 ± 5,1 pkg/ml.
In the blood calcitriol and others metabolites of the vitamin D connect with specific plasma proteins.
Presumably exogenous calcitriol penetrates from the mother blood into the blood of the fetus and into the mother's milk.
Metabolism
There are a lot of calcitriol metabolites, each of them has the different properties of the vitamin D: 1α,25-dihydroxy-24-oxocholecalciferol, 1α,23,25-trihydroxy-24-oxocholecalciferol,
1α,24R,25-dihydroxycholecalciferol, 1α,25R-dihydroxycholecalciferol-26,23S-lacton,
1α,25S,26-tri-hydroxycholecalciferol, 1α,25-dihydroxy-23-oxocholecalciferol,
1α,25R,26-trihydroxy-23-oxocholecalciferol and 1α-hydroxy-23-carboxy-24,25,26,27-tetranorcholecalciferol.
Excretion
The duration of the half life of the drug is 9 -10 hours. However the pharmacological action of the single doge of calcitriol continues for not less then 7 days. Calcitriol is excreted with the bile. After the intravenous administration of the tagged calcitriol in healthy volunteers approximately 27% of it is determined in the faeces and approximately 7% - in the urine. After the internal administration of 1 microgram of the tagged calcitriol in healthy volunteers approximately 10% of it is determined in the urine during 24 hours. On the 6 day it is determined 16% of calcitriol in the urine and 49 % - in the faeces.
Pharmacokinetics in special cases
In patients with the nephrotic syndrome or renal insufficiency, the level of the calcitriol in plasma is decreased and the maximum concentration is reached later.
Indications:
Approved diagnosis of the postmenopausal osteoporosis; secondary hypoparathyreosis and osteoporosis in patients with chronic renal insufficiency; postoperative hypoparathyreosis; idiopathic hypoparathyreosis; pseudohypoparathyreosis; vitamin D-dependent rickets; hypophosphatemic vitamin D-resistant rickets (phosphate diabetes).
Administration and Dosage:
During the treatment the dose is depended on the type and severity of the hypocalcaemia and it should be determined by physician individually for the receiving of the concentration of the calcium in the blood of 9 -10 mg/decilitre.
In renal insufficiency: For the treatment of the secondary hyperparathyreosis and osteoporosis in adults and children above 6 years with moderate or severe renal insufficiency the usual starting dose is 0,25 microgram one time per day. If it is necessary the dose could be increased till 0,5 microgram one time per day.
Hypoparathyreosis, pseudohypoparathyreosis and rickets: For the treatment of hypoparathyreosis, pseudohypoparathyreosis in adults and children above 1 year the usual starting dose of calcitriol is 0,25 microgram/day. The dose should be increased for the term of 2 – 4 weeks. For most adults and children above 6 years the necessary dose of calcitriol is 0,5 - 2,0 microgram/day. For most children from 1 to 5 years with hypoparathyreosis the necessary dose of calcitriol is 0,25 – 0,75 microgram/day.
Other cases: In adults and children above 6 years with vitamin D-dependent rickets the dosage of calcitriol is 1 microgram/day. It is necessary for control of the calcium level in the plasma and for the treatment of the rickets or osteomalacia. Phosphate salts could be used synchronously.
Side effects:
Usually the Phorcal Plus is good transmitted. It could be following side effects: nausea, vomiting, anorexia, constipation, diarrhoea, stomach pain, thirst, weakness, headache, drowse, dizziness, bones pain, dry mouth, dysuria, and in rare cases it could be increasing of alanine aminotransferase and aspartate aminotransferase in plasma. It could be allergic reactions, such as skin rash, itch.
Contraindications:
Hypersensitivity for some of drugs components; -
hypercalcinemia, hypermagnesemia; -
hyperphosphatemia (except hyperphosphatemia, caused by hypoparathyreosis);
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pregnancy and lactation; -
stomach and duodenal ulcer; -
liver diseases; -
renal insufficiency; -
nephrolithiasis.
Overdosage:
Possible symptoms of the overdosage could be: weakness, headache, anorexia, nausea, vomiting, stomach spasms, dizziness, buzzing in the ears.
It is no the specific antidote. In a case of the overdosage it should be the symptomatic treatment.
Special indications:
There is the close relation between the treatment by calcitriol and hypercalcaemia appearing. Hypercalcaemia could arise in a case of unexpected entry of calcium into the organism if the nutrition is changed (for example in increase usage of the milk products) or in a case of uncontrolled usage of calcium drugs. During the treatment by Phorcal Plus in is necessary to keep to a diet and it is necessary also to teach the patients to identify the symptoms of the hypercalcaemia.
There is the biggest risk for patients, which are bedridden during the long time, for example patients, which were operated.
Calcitriol increases the amount of ino
1rganic phosphates in the plasma. This is desired effect for patients with hypophosphatemia, but it is dangerous to patients with renal insufficiency because of the ectopic calcification. In such cases it is necessary to hold the normal level of the phosphates in the plasma (2 – 5 mg / 100 ml or 0,65 – 1,62 millimole /litre) by hypophosphate diet and by the usage of the drugs, which connect the phosphates.
Patients with vitamin D-dependent rickets (family hypophosphatemia), which received Phorcal Plus should continue oral usage of the phosphates. However it is necessary to remember about the possibility of Phorcal Plus to stimulate the intestinal absorption of the phosphates that it could replace the additional usage of the phosphates. It is also necessary to determine the level of the calcium, phosphorus, magnesium and the alkaline phosphatase in plasma and the level of the calcium, phosphorus in the daily urine. During the stabilizing phase of the treatment by Phorcal Plus it is necessary to control the level of the calcium in the plasma not less than two times a week.
Inasmuch as calcitriol is the most effective metabolite of the vitamin D the other vitamin D’ preparations are not administered during the treatment by Phorcal Plus for the avoidance of hypervitaminosis D.
In a case of changing the therapy from ergocalciferol (vitamin D2) to calcitriol the normalisation of the ergocalciferol in the blood could go on several months.
Patients with the normal function of the kidney, which are treated with Phorcal Plus, should use an adequate amount of the liquid.
Drug interactions:
Inasmuch as calcitriol is one of the most important metabolites of the vitamin D3 the other
Vitamin D’ derivates should not be administered during the treatment by Phorcal Plus for the avoidance of the possible additive effects and hypercalcaemia.
It is necessary to keep to a diet, especially calcium usage relating and to avoid the uncontrolled usage of calcium drugs.
There is the increased risk of hypercalcaemia in a case of the synchronous usage the thiazide diuretics. The dose for patients, receiving the digitalis preparations should be selected very carefully, because the risk of the arrhythmia in such patients is increased.
There is some functional antagonism between the vitamin D analogists, which intensify the calcium absorption and corticosteroids, which reduce it.
Drugs, which contain magnesium (for example, antacids) could cause the hypermagnesemia and during the treatment by Phorcal Plus should not be administered to patients, receiving the program haemodialysis
Inasmuch as Phorcal Plus influents to the transport of the phosphates in the bowels, kidney and bones the dose of the drugs, which connect phosphates should be corrected according to the level of the phosphates in the plasma (as norm, 2 – 5 mg/100 ml or 0,65 – 1,62 millimole /litre).
The drugs, such as phenitoin and phenobarbital could intensify the metabolism and in this way to decrease the concentration of calcitriol in the blood, therefore in a case of such combination it is necessary to use more high doses of calcitriol. Colestyramine could decrease the intestine absorption of the liposoluble vitamins including calcitriol.
It is necessary to be wary for patients, which use digoxin, colestyramine, colestipol, mineral oils, thiazide diuretics, phenobarbital, phenitoin, steroids.
Storage and Shelf-life: Keep out of reach of children, in dry, protected from light place; at the temperature not more than 25oC. Shelf-life – 24 months.
Conditions of supply: On prescription.
Package: 10 capsules are in a blister, 3 blisters are in a carton box (No10x3).
Manufacturer.
Kusum Healthcare Pvt. Ltd., India
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