Rocaltrol - instructions for use, dose, side effects, contraindications

Active substanceCalcitriolCalcitriol

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Osteotriol®

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Teva Pharmaceutical Enterprises Co., Ltd. Israel

Rocaltrol®

capsules inwards

Hoffmann-La Roche Ltd. Switzerland

Dosage form: & nbspcapsules

Composition:

One capsule contains: calcitriol - 0.25 μg or 0.5 μg;

Excipients: butylhydroxyanisole 16.0 μg, butyl hydroxytoluene 16.0 μg, medium chain triglycerides up to 160.0 mg;

shell capsules: gelatin - 71.08 mg, glycerol (glycerol) 85% - 16.83 mg, Carion 83 (contains 2-4% mannitol, 27-35% sorbitol, 61-71% hydrogenated hydrolysed starch) -11.56 mg, titanium dioxide (E171) -0.33 mg, iron dye red oxide (E172) - 0.04 mg, ferric oxide yellow oxide (E172) - 0.06 mg.

Description:

Capsules 0.25 μg: soft gelatin capsules oval, opaque; one half of the capsule from brown-orange to red-orange, the other half of the capsule from white to gray-yellow or gray-orange; length 9.1-10.2 mm; the diameter is 6.3-7.3 mm.

Contents of capsules: clear oily liquid from colorless to slightly yellowish, slightly brownish or slightly brownish-yellowish in color.

Capsules 0.5 mcg: soft gelatin capsules oval, opaque; from brown-orange to red-orange; length 9.1-10.2 mm; diameter of 6.3-7.3 mm.

Contents of capsules: clear oily liquid from colorless to slightlyyellowish, slightly brownish or slightly brownish-yellowish in color.

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 is one of the most important active metabolites of the vitamin D₃. Calcitriol promotes absorption of calcium in the intestine and regulates the mineralization of bones. The pharmacological effect of a single dose of calcitriol lasts 3-5 days.

The key role of calcitriol in the regulation of calcium metabolism, which is to stimulate the activity of osteoblasts of the skeleton, is a reliable pharmacological basis for its therapeutic effect in osteoporosis.

In individuals with severe renal insufficiency, the synthesis of endogenous calcitriol decreases or may even cease altogether. Insufficiency of calcitriol plays a major role in the onset of renal osteodystrophy.

In patients with renal osteodystrophy, Rocaltrol® (synthetic calcitriol) normalizes the reduced absorption of calcium in the intestines, eliminates hypocalcemia, elevated levels of alkaline phosphatase and parathyroid hormone in the serum.It reduces pain in the bones and muscles, as well as eliminates the histological changes that occur with fibrous osteitis and other mineralization disorders.

In patients with postoperative and idiopathic hypoparathyroidism and pseudohypoparathyroidism, Rocaltrol® reduces hypocalcemia and its clinical manifestations.

In patients with vitamin-D-dependent rickets, the concentration of calcitriol in the serum is low or completely absent. Given the inadequate endogenous synthesis of calcitriol in the kidneys, the administration of Rocaltrol® can be considered in such patients as substitution therapy.

In patients with vitamin-D-resistant rickets and hypophosphatemia with a low level of calcitriol in plasma, treatment with Rocaltrol® reduces tubular phosphate excretion and, in conjunction with the intake of phosphorus preparations, normalizes the development of bones.

Treatment with Rocaltrol® also helps in other forms of rickets, for example, caused by neonatal hepatitis, atresia of the biliary tract, cystinosis, as well as nutritional deficiencies in calcium and vitamin D.

Pharmacokinetics:

Suction

Calcitriol is rapidly absorbed into the intestine.After a single oral intake of 0.25-1.0 μg of Rocaltrol®, the maximum serum concentration is achieved after 3-6 hours. With repeated administration, equilibrium concentrations are reached within 7 days and depend on the dose value.

Distribution

After a single oral intake of 0.5 mcg of Rocaltrol®, the average concentration of calcitriol in the serum rose from the initial value of 40.0 ± 4.4 pg / ml to 60.0 ± 4.4 pg / ml after 2 hours, and then decreased to 53.0 ± 6.9 after 4 hours, to 50.0 ± 7.0 across 8 hours, to 44 + 4.6 in 12 hours and 41.5 + 5.1 pg / ml after 24 hours.

In blood calcitriol and other metabolites of the vitamin D bind to specific plasma proteins.

It can be assumed that the exogenous calcitriol penetrates the placental barrier and into breast milk.

Metabolism

Several metabolites of calcitriol have been identified, each of which has different properties of the vitamin D: 1α, 25-dihydroxy-24-oxoxolecalciferol, 1α, 23,25-trihydroxy-24-oxoxolecalciferol, 1а, 24R, 25-trihydroxycolecalciferol, 1α, 25R-dihydroxycolecalciferol-26.23S-lactone, 1α, 258,26-trihydroxycolecalciferol, 1α, 25-dihydroxy-23-oxoxolecalciferol, 1α, 25R, 26-trihydroxy-23-oxocolecalciferol and 1α-hydroxy-23-carboxy-24,25,26,27-tetranorocolecalciferol.

Excretion

The half-life of calcitriol from serum is 9-10 hours. However, the pharmacological effect of a single dose of calcitriol lasts not less than 7 days. Calcitriol is excreted with bile and subjected to intestinal hepatic recirculation. After intravenous administration of labeled calcitriol to healthy volunteers within 24 hours, about 27% of the radioactivity is found in the feces and about 7% in the urine. After oral administration 1 μg of labeled calcitriol by healthy volunteers at about 10% of the total radioactivity is detected in the urine within 24 hours. On 6The first day after intravenous administration of labeled calcitriol in urine, 16% is detected, and in stool - 49% of the total radioactivity.

Pharmacokinetics in special cases

In patients with nephrotic syndrome or in patients on hemodialysis, serum calcitriol levels are decreased, and the maximum concentration is somewhat slowed.

Indications:

Confirmed postmenopausal osteoporosis.

Renal osteodystrophy in patients with chronic renal failure, especially in those on hemodialysis.

Secondary hyperparathyroidism in patients with moderate and severe degree of chronic renal failure (pre-dialysis).

Postoperative hypoparathyroidism.

Idiopathic hypoparathyroidism.

Pseudohypoparathyroidism.

Vitamin-D-dependent rickets.

Hypophosphatemic vitamin-D-resistant rickets (phosphate-diabetes).

Contraindications:

All diseases accompanied by hypercalcemia; hypersensitivity to the drug (or to medicines of the same class) or to any other component of the drug; hypervitaminosis D, children's age up to 3 years.

Carefully:

Atherosclerosis, pulmonary tuberculosis, heart failure, phosphate nephrolithiasis, sarcoidosis and other granulomatosis, old age (may contribute to the development of atherosclerosis).

Pregnancy and lactation:

For oral administration of sublethal doses of vitamin A D Pregnant rabbits developed a supralvular aortic stenosis in the fetuses. Data on the teratogenicity of the vitamin D, even very large doses, for a person there. Appointment of Rocaltrol® to pregnant women follows only in absolute indications, if the expected effect for the mother exceeds the possible risk to the fetus.

Apparently, exogenous calcitriol penetrates into breast milk. Given the possible hypercalcemia in the mother and adverse reactions in infants, it is not recommended to take the drug during breastfeeding.

Dosing and Administration:

Standard dosing regimen

Inside. The initial daily dose is 0.25 μg. The optimal daily dose of Rocaltrol® should be carefully selected for each patient, depending on the calcium content in the serum. Treatment with Rocaltrol® should always be started with as low a dose as possible and increased only with careful monitoring of serum calcium levels.

A necessary condition for the optimal effectiveness of therapy with Rocaltrol® is sufficient, but not excessive, intake of calcium from food from the beginning of treatment (for adults - about 800 mg per day). In some cases, the patient may need to take calcium preparations. By improving absorption of calcium in the gastrointestinal tract, some patients receiving Rocaltrol® may also have a low intake of calcium. Patients with a tendency to hypercalcemia should be prescribed drugs only in small doses or in general to abolish them.

The total daily intake of calcium (with food and, if it is, with drugs) should be, on average, about 800 mg and not exceed 1000 mg.

At the stage of stabilizing therapy with Rocaltrol®, the serum calcium concentration should be determined at least twice a week. After choosing the optimal dose of Rocaltrol®, serum calcium levels should be checked monthly (or according to recommendations for individual indications, see below). Blood to determine calcium should be taken without the use of a tourniquet.

Once the serum calcium level is 1 mg / 100 ml (250 μmol / L) exceeds the norm (9-11 mg / 100 ml or 2250-2750 μmol / L) or the serum creatinine exceeds 120 μmol / l, take Rocaltrol® immediately before the normalization of the level of calcium in the blood.

With hypercalcemia, the levels of calcium and phosphate in the serum should be determined daily. After their normalization, treatment with Rocaltrol® can be continued, reducing the previous dose by 0.25 μg. You should estimate the daily intake of calcium from food and, if necessary, make adjustments to the diet.

Dosing in special cases in adults

Postmenopausal osteoporosis: 0.25 μg 2 times a day.The content of calcium and creatinine should be determined after 4 weeks, 3 and 6 months after initiation of treatment, and then every 6 months.

Renal osteodystrophy / patients with dialysis): the initial daily dose is 0.25 μg. Patients with a normal or only slightly reduced serum calcium level have a dose of 0.25 μg every other day. If the biochemical parameters and the clinical picture do not improve, the daily dose should be increased by 0.25 μg at intervals of 2-4 weeks. During this period, serum calcium should be determined at least twice in a week. In most patients, the therapeutic effect occurs at a daily dose of 0.5- 1.0 mcg.

In patients refractory to continuous therapy, pulse (intermittent) therapy with Rocaltrol® is effective at an initial dose of 0.1 mcg / kg 2-3 times a week at night. The maximum total dose of Rocaltrol® should not exceed 12 mcg per week.

Secondary hyperparathyroidism (pre-dialysis): in patients with moderate and severe renal insufficiency (creatinine clearance 15-55 ml / min), the initial daily dose is 0.25 μg per day for adults and children over 3 years (adjusted for a surface area of 1.73 m²). The daily dose can be increased to 0.5 mcg.

Hypoparathyroidism and rickets: the initial dose is 0.25 μg per day in the morning. If there is no improvement in biochemical parameters and a clinical picture, the dose can be increased at intervals of 2-4 weeks. During this period, serum calcium should be determined at least twice a week. With hypercalcemia, the administration of Rocaltrol® should be immediately discontinued until the level of calcium in the blood is normalized. It is necessary to reduce the intake of calcium from food.

In patients with hypoparathyroidism, absorption disorders, including calcium, can sometimes occur, which may require an increase in the dose of Rocaltrol®.

If Roctalrol® is prescribed to a pregnant woman with hypoparathyroidism, then in the second half of pregnancy an increase in the dose of the drug may be required, and after delivery and during lactation, it decreases.

Dosing in patients of senile age

For patients of senile age, dose adjustment is not required. It is necessary to adhere to the general recommendations for monitoring the level of calcium and creatinine in the serum.

Side effects:

Since Rocaltrol® has a vitamin activity D, its side effects are similar to those that occur with an overdose of a vitamin D, those. syndrome of hypercalcemia or calcium intoxication (depending on the severity and duration of hypercalcemia). Acute symptoms may include anorexia, headache, vomiting, gastralgia or abdominal pain and constipation. Due to the short biological half-life of calcitriol, the serum calcium level is normalized a few days after the cancellation of Rocaltrol®, that is, much faster than with vitamin A D₃. With prolonged admission, dystrophy, sensitivity disorders, fever, thirst, polyuria, dehydration, apathy, stunting and urinary tract infections can occur.

The frequency of each of the adverse reactions described in the clinical application of Rocaltrol® for all indications over 15 years is very low (including hypercalcemia) and does not exceed 0.001%.

With simultaneous hypercalcemia and hyperphosphataemia >6 mg / 100 ml or> 1.9 mmol / l, calcification of soft tissues may occur, which can be detected radiographically.

In patients with normal renal function, chronic hypercalcemia may lead to an increase in serum creatinine.

Sensitive individuals may develop hypersensitivity reactions (pruritus, rash, urticaria and very rarely erythematous skin lesions).

Overdose:

Treatment of asymptomatic hypercalcemia (see. See section "Dosing and Administration"). Since Rocaltrol® is a derivative of the vitamin D, it is characterized by the same symptoms of an overdose. Taking large doses of calcium and phosphate simultaneously with Rocaltrol® can cause similar symptoms. The index of the product of the concentration of calcium and phosphorus in the serum (СахР) should not exceed 70 mg²/ dL². The development of hyperkappaemia can be promoted by a high content of calcium in the dialysate.

Symptoms of acute vitamin poisoning D: anorexia, headache, vomiting, constipation.

Symptoms of chronic poisoning: dystrophy (weakness, weight loss), sensitivity disorders, fever with thirst, polyuria, dehydration, apathy, growth retardation and urinary tract infections. Consequences of hypercalcemia are focal calcification of the cortical layer of the kidneys, myocardium, lungs and pancreas.

Treatment of accidental overdose: immediate gastric lavage or taking vomiting medications to prevent further absorption. To excrete the drug with feces, Vaseline oil is used as a laxative. It is recommended to re-determine the serum calcium level. If the elevated serum calcium level persists, phosphates and corticosteroids can be prescribed, and measures can be taken to ensure sufficient diuresis.

Interaction:

Because the calcitriol - one of the most important active metabolites of the vitamin D3, To avoid possible additive effects and hypercalcemia for the duration of treatment with Rocaltrol®, medication doses should be stopped D and its derivatives. Patients should strictly follow dietary recommendations, especially regarding calcium intake, and avoid uncontrolled supplemental intake of calcium-containing drugs.

Simultaneous treatment with thiazide diuretics increases the risk of hypercalcemia. Patients receiving digitalis preparations, a dose of calcitriol should be selected very carefully, since hypercalcemia in them can provoke arrhythmias.There is a functional antagonism between the analogs of the vitamin D, which increase calcium absorption, and corticosteroids, which suppress it.

Preparations containing magnesium (for example, antacids) can cause hypermagnesemia and therefore should not be given to patients on chronic hemodialysis during treatment with Rocaltrol®.

Since Rocaltrol® affects phosphate transport in the intestines, kidneys and bones, the dose of phosphate binding drugs should be adjusted depending on serum phosphate levels (normally 2-5 mg / 100 ml or 0.65-1.62 mmol / L).

The use of such enzyme inducers as phenytoin or phenobarbital, can increase metabolism and thereby reduce the concentration of calcitriol in the serum, so the simultaneous use of these drugs may require higher doses of calcitriol.

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

Special instructions:

There is a close relationship between the treatment of calcitriol and the onset of hypercalcemia. Hypercalcemia can develop with an increase in calcium intake in the body when food changes (for example, increased consumption of dairy products) or uncontrolled intake of calcium preparations.Patients and their families should be informed of the need for strict adherence to the prescribed diet; they should also be trained to recognize the symptoms of hypercalcemia.

Particularly high risk for the development of hypercalcemia is experienced by patients who have been in bed for a long time, for example, who underwent surgery.

Calcitriol increases the content of inorganic phosphates in the serum. This effect, being desirable in patients with hypophosphatemia, requires caution in patients with renal insufficiency because of the danger of ectopic calcification. In such cases, the phosphate content in the plasma should be maintained at a normal level (2-5 mg / 100 ml, or 0.65-1.62 mmol / L) by oral administration of phosphate binding drugs and a low-phosphate diet.

The index of the product of the concentration of calcium and phosphorus in the serum (СахР) should not exceed 70 mg²/ dL².

Patients with vitamin-D-resistant rickets (familial hypophosphatemia) receiving Rocaltrol®, one should continue oral intake of phosphates. It should, however, be remembered that stimulation of intestinal absorption of phosphates by the action of Rocaltrol®, since this effect may change the need for additional prescription of phosphates.It is necessary to regularly determine the content of calcium, phosphorus, magnesium and alkaline phosphatase in the serum, as well as calcium and phosphate in the daily urine. During the stabilizing (initial) phase of treatment with Rocaltrol®, the calcium content in the blood serum should be monitored at least twice a week.

Because the calcitriol - the most pharmacologically active metabolite of the vitamin D of all existing, during treatment with Rocaltrol® should not be prescribed other vitamin preparations D to avoid the development of hypervitaminosis D.

If the patient is transferred from ergocalciferol (vitamin D₂) on calcitriol, the normalization of ergocalciferol in the blood can take several months (see the section "Overdose").

Patients with normal kidney function who take Rocaltrol® should avoid dehydration, ensuring that they receive sufficient fluid.

Special care should be taken when prescribing to children under 18 years of age.

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

FROM taking into account the known profile of pharmacodynamics and described side effects, it is considered that the drug does not affect or is unlikely to affect such activities.

Form release / dosage:

Capsules 0.25 μg or 0.5 μg

Packaging:

10 capsules per blister of polyvinylchloride film and aluminum foil. For 3 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

List B.

Store at a temperature of no higher than 25 ° C in a dry, protected from light place.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:Without recipe

Registration number:П N014565 / 01

Date of registration:24.03.2009

The owner of the registration certificate:Hoffmann-La Roche Ltd.Hoffmann-La Roche Ltd. Switzerland

Manufacturer: & nbsp

Catalan Germany Eberbach GmbH, Germany Germany

Representation: & nbspF.Hoffmann-La Roche Ltd. F.Hoffmann-La Roche Ltd. Switzerland

Information update date: & nbsp09.09.2015

Illustrated instructions

Instructions

Rocaltrol® (Rocaltrol®)