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

Clinical and pharmacological group: & nbsp

Vitamins and vitamin-like remedies

Included in the formulation

Osteotriol®

capsules inwards

Teva Pharmaceutical Enterprises Co., Ltd. Israel

Rocaltrol®

capsules inwards

Hoffmann-La Roche Ltd. Switzerland

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

A.11.C.C.04 Calcitriol

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

Pharmacodynamics:

Calcitriol is an active metabolite of vitamin D₃, possessing all the properties of natural vitamin D₃. By biological activity significantly exceeds the natural vitamin D₃.

The mechanism of action 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 drug increases calcium absorption in the intestine, its reabsorption in the kidneys, promotes the mineralization of bones, participates in the growth and differentiation of bone cells, as well as in the maintenance of neuromuscular transmission, the functioning of striated muscles, modulates immune responses. The effect of the drug is accompanied by a normalization of decreased calcium absorption in the intestine, its reabsorption in the kidneys and an increase in the concentration in the blood plasma, suppression of the secretion of parathyroid hormone. With its application, pain in the bones and muscles is reduced, and the mineralization of the skeleton improves.

Affects the immune processes in the skin, inhibits the proliferation of T-lymphocytes. It inhibits the proliferation of keratinocytes and normalizes their differentiation.

Pharmacokinetics:

After oral administration, it is rapidly absorbed into the intestine. C_maxin the blood serum is achieved in 4-6 hours. Biotransformation occurs with the formation of a number of metabolites, which have a varying degree of activity of vitamin D₃. The half-life period is 3-6 hours, however, because of high lipophilicity, the drug and its metabolites can partially accumulate in adipose tissue, so that the pharmacological effect can last up to 3-5 days. It is excreted with bile and partially subjected to intestinal hepatic recirculation. In patients who are on hemodialysis, the concentration in the blood serum is reduced, and its maximum concentration is reached after a longer period of time.

It penetrates the placental barrier and is excreted into breast milk.

The average absorption for external application is about 10%, the concentration of exogenous calcitriol is lower than the detection level.

Indications:

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

Postmenopausal, senile and steroid osteoporosis;

Postoperative hypoparathyroidism, idiopathic hypoparathyroidism and pseudohypoparathyroidism;

Secondary hyperparathyroidism in patients with moderate and severe degree of chronic renal failure;

Vitamin-D-dependent rickets;

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

Psoriasis of mild and moderate severity (externally).

ICD-10

IV.E20-E35.E20.0 Idiopathic hypoparathyroidism

IV.E20-E35.E20.1 Pseudohypoparathyroidism

IV.E50-E64.E55.0 Rickets active

IV.E70-E90.E83.3 Disorders of phosphorus metabolism

IV.E20-E35.E20.8 Other forms of hypoparathyroidism

XII.L40-L45.L40.0 Psoriasis vulgaris

XIII.M80-M85.M81.0 Postmenopausal osteoporosis

XIII.M80-M85.M81.1 Osteoporosis after removal of ovaries

XIII.M80-M85.M81.2 Osteoporosis caused by immobility

XIII.M80-M85.M81.4 Medicinal osteoporosis

XIII.M80-M85.M81.8 Other osteoporosis

XIII.M80-M85.M82.8 * Osteoporosis in other diseases classified elsewhere

XIV.N25-N29.N25.0 Renal osteodystrophy

Contraindications:

Diseases accompanied by hypercalcemia and hyperphosphatemia, hypervitaminosis D; increased sensitivity to vitamin D preparations; children under 3 years.

Carefully:

Atherosclerosis, sarcoidosis or other granulomatosis, chronic heart failure,nephrolithiasis in the anamnesis, advanced age, chronic renal failure, pregnancy, breast-feeding, children's age till 18 years.

Pregnancy and lactation:

Prescribe to pregnant women should only be on absolute indications if the expected effect for the mother exceeds the possible risk to the fetus. Given the possible hypercalcemia in the mother and adverse reactions in infants, it is not recommended to take the drug during breastfeeding.

The category of FDA recommendations is not defined.

Dosing and Administration:

The initial daily dose is 0.25 μg. The optimal daily dose should be carefully selected for each patient, depending on the calcium content in the serum.

Renal osteodystrophy (dialysis patients)

In patients with normal and slightly reduced serum calcium levels, the drug is usually used at a dose of 0.25 μg per day every other day. In the absence of a satisfactory effect, the dose can be increased by 0.25 μg with an interval of 2-4 weeks. Typically, a dose of 0.5-1.0 μg per day provides the necessary clinical effect. In patients refractory to continuous therapy, pulse (intermittent) therapy is effective at an initial dose of 0.1 mcg / kg 2-3 times a week at night. The maximum total dose should not exceed 12 mcg per week.

Secondary Hyperparathyroidism

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 (corrected for a surface area of 1.73 m²). The daily dose can be increased to 0.5 μg.

Postmenopausal, senile and steroid osteoporosis

0.25 μg 2 times per day, long.

Hypoparathyroidism and rickets

Treatment begins with a dose of 0.25 μg 1 time per day in the morning. If necessary, the dose can be increased at intervals of 2-4 weeks from 0.25 μg to 0.5-1.0 μg per day.

Psoriasis (externally)

Adults and children over 12 years of age should be applied a thin layer on the affected skin areas (for previously cleaned and dried skin) 2 times a day (morning and evening). The maximum daily dose is 30 mcg. Daily use of the ointment should not be more than 35% of the skin surface. The average duration of treatment is 6 weeks, if necessary, longer treatment is possible, as well as the use of the drug as maintenance therapy.

Side effects:

Hypercalcemia, hypercalciuria, the symptoms of which are nausea, vomiting, constipation, abdominal pain, anorexia, lethargy, headache, drowsiness and apathy.

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

In very rare cases (especially in the presence of hypercalcemia and hyperphosphataemia) calcification of soft tissues may develop.

Early symptoms: weakness, prolonged headache, drowsiness, nausea, vomiting, dry mouth, constipation, myalgia, bone pain, metallic taste in the mouth, decreased appetite, abdominal pain, thirst, increased frequency of urination, especially at night, or polyuria, arrhythmia.

Late symptoms: pain in the bones, polydipsia, anorexia, nocturia, conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, increased blood urea nitrogen, albuminuria, hypercholesterolemia, increased hepatic transaminase activity, ectopic calcification, nephrocalcinosis, arterial hypertension, dystrophy , weight loss), impaired sensation, dehydration, apathy, developmental delay, urinary tract infections; rarely - psychosis.

Allergic reactions: itching, rash, hives; very rarely - erythematous skin lesions.

With topical application: dermatitis.

Overdose:

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

Symptoms of chronic poisoning: dystrophy, weakness, weight loss, sensitivity disorder, fever with thirst, polyuria, dehydration, apathy, urinary tract infections, foci of calcification in internal organs.

Treatment: with an accidental overdose - a gastric lavage or the use of an emetic to prevent further absorption of the drug.

With the development of hypercalcemia, calcitriol therapy should be stopped, a diet with a low calcium content should be prescribed and the patient should be kept under medical supervision until the calcium concentration in the blood plasma is normalized. After this, therapy can be resumed either with a reduced dose, or the same, but with large intervals of drug intake. In the case of acute hypercalcemia, the patient needs to hydrate to increase diuresis.

Interaction:

When used simultaneously with preparations of cardiac glycosides, the risk of arrhythmia increases.

When used simultaneously with magnesium-containing drugs, including antacids,the risk of hypermagnesemia increases, and therefore these funds should not be administered to patients on hemodialysis who receive calcitriol.

Application of inducers hepatic enzymes can increase the metabolism of calcitriol and reduce its concentration in the blood serum, which may require higher doses of calcitriol.

Kolestyramin can reduce the intestinal absorption of fat-soluble vitamins, including calcitriol.

The use of calcitriol together with thiazide diuretics increases the risk of hypercalcemia.

When calcitriol is used because of the risk of hypercalcemia, simultaneous prescription of other preparations of vitamin D and its derivatives is not allowed.

Glucocorticoids, calcitonin preparations are antagonists of vitamin D.

Special instructions:

With caution, the drug is used for cardiac and renal failure, phosphate nephrolithiasis, sarcoidosis and other granulomatosis.

In elderly patients, a meticulous individual dosage adjustment is required to prevent hypercalcemic complications.

During the treatment with calcitriol, do not consume a significant amount of foods enriched with vitamin D (butter, eggs).

During the period of treatment, it is necessary to regularly monitor the level of calcium and inorganic phosphates in blood and urine, especially in patients with renal osteodystrophy, as well as long-term bed rest (in particular, after surgery).

To prevent hypercalcemia, the dose of calcitriol is calculated based on the patient's reaction to the drug and is selected individually. The effectiveness of treatment is provided by determining an adequate daily dose of calcium, including, if necessary, changes in diet, as well as taking calcium-containing supplements or preparations. By improving the absorption of calcium in the digestive tract, some patients receiving calcitriol, can do with a lower intake of calcium preparations, and in some cases (with a tendency to hypercalcemia) dispense with their intake.

It is necessary to monitor the serum calcium level at least twice a week during the period of application of the drug.If the serum calcium level is exceeded by 1 mg / 100 ml (250 μmol / L), compared to the accepted standard - 9-11 mg / 100 ml (2250-2750 μmol / l), or the serum level of serum creatinine up to 120 μmol / L and higher, the reception of calcitriol should be stopped immediately. Renewal of treatment is allowed only after the normalization of the serum calcium level within the permissible regulatory range using a 0.25 μg dose of the drug.

With the simultaneous administration of barbiturates or anticonvulsants, an increase in the dosage of calcitriol may be required.

In the initial period of treatment of osteoporosis, it is necessary to measure the concentration of calcium in the serum and creatinine 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.

Patients with normal renal function receiving calcitriol, you must avoid dehydration, keeping in mind that the fluid is sufficient.

Instructions

Calcitriol (Calcitriolum)