Osteotriol® (Osteotriol®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceCalcitriolCalcitriol
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  • Osteotriol®
    capsules inwards 
    Teva Pharmaceutical Enterprises Co., Ltd.     Israel
  • Rocaltrol®
    capsules inwards 
    Hoffmann-La Roche Ltd.     Switzerland
    • Dosage form: & nbspcapsules
    Composition:

    1 capsule contains: active substance calcitriol 0.25 or 0.5 μg; Excipients: Butylhydroxyanisole (BGA), butylhydroxytoluene (BHT), glyceryl caprylcaprate.

    Capsule shell composition: gelatin, glycerol 85%, sorbitol 70%, titanium dioxide (E171), dye quinoline yellow (E104), dye blue patented 85% (E131, only in Capsules 0.5 μg).

    Composition of ink: shellac 54%, ferric oxide black oxide (E172) 46%).

    Description:

    Capsules 0.25 μg: yellow oval opaque soft gelatin capsules with the inscription "0.25" ink, containing a transparent oily light-yellow solution.

    Capsules 0.5 μg: green oblong opaque soft gelatin capsules with an inscription "0.5" ink containing a transparent oily light-yellow solution.

    Pharmacotherapeutic group:Vitamin - calcium-phosphorus exchange regulator
    ATX: & nbsp

    A.11.C.C.04   Calcitriol

    A.11.C.C   Vitamin D and its derivatives

    Pharmacodynamics:

    Calcitriol - 1.25α(OH)2D3 - a synthetic preparation identical to the active metabolite of natural vitamin D3, possessing all biological properties of a natural vitamin D3 and the greatest biological activity of all known metabolites of the vitamin D. By biological activity greatly exceeds the natural vitamin D3. Normally formed in the kidneys from the immediate precursor of 25-hydroxycolecalciferol. In physiological concentrations increases the absorption of calcium and phosphate in the intestine and plays an important role in the regulation of bone mineralization. Insufficient formation of calcitriol in chronic renal failure leads to a disruption of mineral metabolism in this pathology. When administered orally in patients with chronic renal failure calcitriol compensates for its reduced endogenous formation, which occurs when the glomerular filtration rate decreases below 30 ml / min. As a result, absorption of calcium and phosphate improves, hypocalcemia decreases. Calcitriol also involved in the growth and differentiation of bone cells, the functioning of the striated muscles. The mechanism of action of calcitriol is associated with interaction with specific receptors localized in the cell nucleus (genomic mechanism), as well as on the plasma membrane of target cells (non-genomic mechanism).The effect of the drug is accompanied by a normalization of calcium absorption in the intestine, an increase in its reabsorption in the kidney and a concentration in the blood plasma, suppression of the secretion of parathyroid hormone. With its application, pain in the bones and muscles decreases, the mineralization of bone tissue improves.

    In patients with postmenopausal osteoporosis calcitriol increases the absorption of calcium in the intestine, the concentration of calcitriol in the blood increases, the frequency of vertebral fractures decreases.

    The action of calcitriol develops faster than other metabolites of the vitamin D, and can also quickly stop. Therefore, dose adjustment can be done earlier and more accurately, which is an advantage of the drug. In case of accidental overdose, symptoms of overdose also go faster.

    Pharmacokinetics:

    After oral administration, it is rapidly absorbed into the small intestine. The maximum concentration in the serum is reached after 4-6 hours. In the blood it binds to specific plasma proteins. It penetrates the placental barrier and is excreted into breast milk. Biotransformation occurs with the formation of a number of active metabolites.The half-life period is 3-6 h, however, due to high lipophilicity, the drug and its metabolites can partially accumulate in adipose tissue, in connection with which the pharmacological effect can be kept up to 3-5 days. After oral administration of 1 μg of radiolabeled calcitriol by healthy volunteers, approximately 10% of the total radioactivity is detected in the urine after 24 hours.

    It is excreted with bile and partially subjected to intestinal hepatic recirculation. In patients on hemodialysis, the concentration in the blood serum is reduced, and for achieving maximum concentration, a longer period of time is required.

    Indications:

    - Renal osteodystrophy in chronic renal failure (especially in patients on hemodialysis).

    - Postmenopausal osteoporosis.

    Contraindications:

    - Diseases accompanied by hypercalcemia.

    - Hypervitaminosis D.

    - Hypersensitivity to any component of the drug, as well as to other preparations of the vitamin D.

    - Children under 18 years.

    Carefully:

    Atherosclerosis, pulmonary tuberculosis (active form), chronic heart failure, hyperphosphataemia, phosphate nephrourolythiasis,sarcoidosis and other granulomatosis, old age (may contribute to the development of atherosclerosis).

    Pregnancy and lactation:

    Safety of calcitriol in pregnant women is not established. Clinical studies of the effect of exogenous calcitriol on pregnancy and fetal development have not been conducted. Concerning calcitriol should be prescribed during pregnancy only if the possible benefit of using the drug exceeds the possible risk to the fetus. It should be borne in mind that calcitriol penetrates into breast milk. Given the possible hypercalcemia in the mother and the development of adverse reactions in infants, it is not recommended to take the drug during breastfeeding.

    Dosing and Administration:

    Inside, washing down with water.

    In order to prevent hypercalcemia, the dose is selected individually, based on the patient's reaction to the drug. The effectiveness of treatment is provided by determining an adequate daily dose of calcium, taking into account changes in diet (if necessary) and taking calcium-containing drugs.

    It is shown that oral pulse therapy (taking 2 or 3 times a week) is effective in patients with osteodystrophy refractory to continuous therapy.

    Renal osteodystrophy

    The recommended initial dose is 0.25 μg / day.In patients with normal and slightly reduced serum calcium levels, the drug is usually used at a dose of 0.25 μg / day every other day.

    In the absence of therapeutic effect, the dose can be increased by 0.25 μg with an interval of 2-4 weeks. During the use of the drug should monitor the level of calcium in the blood serum at least 2 times a week. In case of exceeding the level of calcium in the blood serum by 1 mg / 100 ml (250 μmol / l) compared with the accepted norm 9-11 mg / 100 ml (2250-2750 μmol / l), or an increase in serum creatinine levels above 120 μmol / L, osteotriol should be immediately discontinued until the serum calcium level is normalized within the allowable range.

    As a rule, a dosage of 0.5-1.0 μg per day provides the necessary clinical effect, however, simultaneous administration of barbituric acid derivatives or anticonvulsants may require an increase in the dose of osteotriol.

    Postmenopausal osteoporosis

    25 micrograms 2 times a day.

    In the initial period of treatment of osteoporosis, the concentrations of calcium and creatinine in serum should be measured after 4 weeks, 3 months and 6 months. At the end of this period, it is necessary to conduct control analyzes of these indicators at intervals of 6 months.

    Use in children

    Doses in children are not established.

    Application in elderly patients

    Experience with calcitriol in elderly patients suggests that dose adjustment is not required. It is necessary to adhere to general recommendations for monitoring the level of calcium and creatinine in the blood.

    Side effects:

    The main side effects of the drug, hypercalciuria and hypercalcemia, develop when the dose is exceeded. The likelihood of hypercalcemia is higher in patients with renal insufficiency, hyperparathyroidism, or permanently on hemodialysis. Symptoms of hypercalcemia: nausea, vomiting, constipation, anorexia, lethargy, headache, drowsiness and apathy. More severe symptoms: dehydration, thirst, nocturia, polyuria, cardiac arrhythmias, paralytic intestinal obstruction and abdominal pain. In rare cases, metastatic calcification and psychosis may develop. Because the calcitriol has a short half-life, the symptoms of hypercalcemia disappear within 2-7 days after drug withdrawal, i.e. much faster than after the withdrawal of other vitamin derivatives D.

    In patients with normal renal function, chronic hypercalcemia may be associated with an elevated serum creatinine level.

    Sensitized patients may develop hypersensitivity reactions.

    Overdose:

    Symptoms of acute overdose: anorexia, headache, vomiting, constipation.

    Symptoms of chronic overdose: dystrophy (weakness, weight loss), fever, thirst, polyuria, dehydration, apathy, urinary tract infection, foci of calcification in the internal organs, hypercalcemia.

    Treatment

    In case of accidental overdose: gastric lavage for 6-8 hours from the time of acute overdose or the use of emetics to prevent further absorption of the drug.

    With the development of hypercalcemia, therapy with osteotriol should be stopped and a diet with a lower calcium content should be prescribed before the normalization of calcium concentration in the blood plasma. After that, the therapy can be resumed either with a lower dose or in the dose used earlier, but at longer intervals of admission. In the case of acute hypercalcemia, measures should be taken to increase diuresis, with increased bone resorption calcitonin helps to lower the level of calcium in the blood serum.

    If the patient is on dialysis, then you can also reduce the concentration of calcium in the dialysate.

    Interaction:

    With the simultaneous use of osteotriol with digitalis preparations, the risk of arrhythmia increases, and with magnesium-containing drugs (eg antacids), the risk of hypermagnesemia increases, and therefore these drugs should not be administered to hemodialysis patients receiving Osteotriol®.

    The use of drugs that are inducers of hepatic enzymes (phenytoin, phenobarbital , etc.) may cause an increase in the metabolism of the drug and a decrease in the concentration of calcitriol in the blood serum, and therefore, with the simultaneous use of Osteotriol® and these drugs, higher doses of calcitriol may be required.

    Kolestyramin can reduce the intestinal absorption of fat-soluble vitamins and, in particular, calcitriol.

    The use of osteotriol® together with thiazide diuretics can increase the risk of hypercalcemia.

    When using Osteotriol® because of the risk of hypercalcemia, simultaneous administration of other vitamin preparations D and its derivatives.

    Increases the toxicity of cardiac glycosides and increases the risk of arrhythmia due to the development of hypercalcemia.

    Incompatible with vitamin D and its derivatives (increases the risk of hypervitaminosis D).

    Thiazide diuretics, calcium-containing drugs increase the risk of hypercalcemia (require monitoring of calcium concentration in the blood).

    Inductors of microsomal oxidation (incl. phenytoin, phenobarbital, primidos) reduce the action of calcitriol.

    Toxic effect weakens vitamin A, alpha-tocopherol, ascorbic acid, pantothenic acid, thiamine, riboflavin, pyridoxine.

    Long-term therapy with the drug against the background of simultaneous use of antacids containing aluminum and magnesium increases its concentration in the blood and the risk of intoxication (especially in chronic kidney failure).

    Calcitonin, derivatives of etidronic and pamidronic acids, plikamycin, gallium nitrate and glucocorticosteroid drugs reduce the effect (due to the opposite effect on calcium absorption in the intestine).

    Kolestyramin, colestipol and mineral oils reduce absorption in the gastrointestinal tract of fat-soluble vitamins and require an increase in their dosage.

    Increases the absorption of phosphorus-containing drugs and the risk of hyperphosphataemia.

    Special instructions:

    To avoid complications, use strictly according to the doctor's prescription!

    During the treatment with osteotriol, you should not prescribe other vitamin preparations D, including its derivatives. Do not also eat a significant amount of foods rich in vitamin D (butter, eggs, etc.).

    The use of osteotriol® does not eliminate the requirement for phosphate control in blood plasma for the administration of phosphate binding drugs. Because the calcitriol affects the transport of phosphate in the intestines and bones, it may be necessary to reduce the dose of these drugs.

    Since the drug has a narrow therapeutic latitude, concentration in the blood of calcium, phosphate, creatinine, urea nitrogen, the activity of alkaline phosphatase should be determined first once a week, then periodically during the entire period of drug administration at therapeutic doses.

    The calcium / creatinine index is recommended to be determined every 1-3 months until the patient's condition is stabilized. The concentration of calcium should not exceed 8.8 - 10.3 mg / 100 ml. The index of the product of the concentration of calcium on the concentration of phosphates (Ca x P) should not exceed 60 mg / dL.

    A daily dose of 5 mg or more should be administered with great care (clinical examination, as well as determination of the concentration of calcium, phosphates and alkaline phosphatase activity in the blood should be done 2 times a week).

    Every 3-6 months, an X-ray examination should be performed.

    Effect on the ability to drive transp. cf. and fur:

    He is established.

    Form release / dosage:Capsules 0,25, 0,5 g.
    Packaging:

    Capsules 0.25 μg

    For 30 or 100 capsules in bottles of polypropylene with a lid of low density polyethylene with control of the first opening; 1 bottle with instructions for use in a cardboard box.

    Capsules 0.5 μg

    30 capsules in polypropylene bottles with a lid of low density polyethylene with control of the first opening; 1 bottle with instructions for use in a cardboard box.

    Storage conditions:

    At a temperature of no higher than 30 ° C. Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015032 / 01
    Date of registration:18.06.2009
    Expiration Date:Unlimited
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp15.06.2017
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