Composition, form of production and packaging
Concentrate for the preparation of a solution for infusions in the form of a clear liquid from colorless to pale yellow.
clodronate disodium tetrahydrate 75 mg,
which corresponds to the content of disodium clodronate 60 mg
Excipients: sodium hydroxide 5M (200 g / l) - to a pH of about 5 (4.9-5.1), water d / and up to 1 ml.
5 ml - bottles of glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Clodronic acid belongs to the group of bisphosphonates is an analog of natural pyrophosphate. The action of bisphosphonates is based on a high affinity for the mineral components of bone tissue. The main mechanism of action of clodronic acid is suppression of osteoclast activity and a decrease in bone resorption mediated by them.
The ability of clodronic acid to inhibit bone resorption in humans has been confirmed in the course of histological, kinetic and biochemical studies. Nevertheless, the exact mechanisms of this process are not fully understood.
Clodronic acid suppresses the activity of osteoclasts, reducing the concentration of calcium in the blood serum, as well as the release of calcium and hydroxyproline in the urine.
In vitro bisphosphonates inhibit the precipitation of calcium phosphate, block its transformation into hydroxyapatite, delay the aggregation of apatite crystals into larger crystals, and slow the dissolution of these crystals.
When clodronic acid was used in monotherapy in doses sufficient to inhibit bone resorption, no effect on normal bone mineralization was observed in humans. In patients with breast cancer and multiple myeloma, there was a decrease in the probability of bone fractures.
Clodronic acid reduces the incidence of bone metastases in primary breast cancer. In patients with operable breast cancer for the prevention of metastases in the bone, there was also a decrease in mortality.
The connection of clodronic acid with plasma proteins is low. The volume of distribution is about 20-50 liters. The excretion of clodronic acid from serum is characterized by two phases: a distribution phase with a half-life of about 2 hours and a phase of elimination that proceeds very slowly, as clodronic acid binds firmly to bone tissue. Clodronic acid is excreted mainly by the kidneys. About 80% is detected in the urine within a few days after the administration of the drug. Clodronic acid, bound to bone tissue, is excreted more slowly from the body. Kidney clearance is approximately 75% of
Since clodronic acid binds firmly to bone tissue, there is no clear association between clodronic acid concentrations in blood plasma and the therapeutic effect or adverse reactions of the drug.
Pharmacokinetic profile of the drug does not depend on age, metabolism of the drug or functional disorders, with the exception of renal failure, which causes a decrease in renal clearance of clodronic acid.
- hypercalcemia caused by malignant tumors.
To prepare a solution for infusions, the required dose is dissolved in 500 ml of 0.9% sodium chloride solution or 5% dextrose solution.
Hypercalcemia caused by malignant neoplasms.
- 300 mg intravenously drip slowly for at least 2 hours daily (no more than 7 days in a row) until the normal concentration of calcium in the blood serum (usually occurs within 5 days).
- 1500 mg once a day intravenously drip for 4 hours. If necessary, the infusion can be repeated or appointed Klobir inside.
With the development of hypocalcemia, a brief interruption in treatment is recommended.
Patients with renal insufficiency.
When administered intravenously, doses should be reduced in accordance with the following
Degree of renal failure Creatinine clearance, ml / min Dose reduction,%
Easy 50-80 by 25%
Moderate 12-50 by 25-50%
Heavy <12 by 50%
Most often, approximately 10% of patients experience adverse reactions such as nausea, vomiting, diarrhea; these reactions usually appear in mild form and occur most often when the drug is used in high doses.
Similar reactions can be observed both when taking the drug inside, and with its intravenous administration, although the frequency of occurrence of these reactions may differ.
On the part of the endocrine system: an increase in the concentration of parathyroid hormone in the serum (usually in combination with hypocalcemia).
From the respiratory system: very rarely - in patients with bronchial asthma, with increased sensitivity to acetylsalicylic acid in the anamnesis, there were violations of the respiratory function, bronchospasm.
On the part of the digestive system: often - nausea, vomiting and diarrhea usually in mild form.
From the skin and skin appendages: rarely - skin reactions, according to the clinical picture corresponding to allergic reactions (itching, urticaria, exfoliative dermatitis).
From the urinary system: rarely - renal dysfunction (increased serum creatinine and proteinuria), severe renal failure (especially after rapid intravenous infusion of high doses of clodronic acid).
On the part of laboratory indicators: often - asymptomatic hypocalcemia, rarely, hypocalcemia, accompanied by clinical manifestations. Increase in the level of alkaline phosphatase, aminotransferase and lactate dehydrogenase in blood serum. In patients with metastases, the level of alkaline phosphatase may also increase due to the presence of metastases in the liver and bones.
- Hypersensitivity to clodronic acid, other bisphosphonates or any other components that make up the drug;
- pregnancy and the period of breastfeeding;
- concomitant therapy with other bisphosphonates;
- Children's age (due to lack of clinical experience).
With caution: chronic renal failure.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in chronic kidney failure.
APPLICATION FOR CHILDREN
Contraindicated for children (due to lack of clinical data).
During the Clobir therapy, it is necessary to provide the patient with a sufficient supply of fluid. This is especially important in the appointment of Clobyr in the form of intravenous infusions, as well as for patients with hypercalcemia and renal insufficiency.
Intravenous administration of Clobir in doses far exceeding the recommended levels can cause severe damage to the kidneys, especially if the infusion rate is too high.
The use of Klobir can affect the results of bone scintigraphy. The compatibility of the concentrate for the infusion solution with other drugs or solutions for injection has not been investigated. The drug should be diluted and administered only in accordance with these recommendations.
When intravenous high doses of clodronic acid were reported, an increase in serum creatinine and impaired renal function was reported. In case of an overdose, symptomatic treatment should be given. It is necessary to provide the patient with a sufficient supply of fluid, as well as monitor the kidney function and the calcium content in the blood serum.
There is evidence of a link between the administration of clodronic acid and impaired renal function with the simultaneous administration of non-steroidal anti-inflammatory drugs, most often diclofenac.
Due to the high probability of hypocalcemia, caution should be exercised when administering clodronic acid together with aminoglycosides. It was reported that simultaneous administration of estramustine together with clodronic acid leads to an increase in the concentration of estramustine in the serum up to 80%.
TERMS OF RELEASE FROM PHARMACY
TERMS AND CONDITIONS OF STORAGE
At a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 2 years.