Bonefos capsules 400 mg №100

Description for BONEFOS ® capsules. 400 mg:

Pharmacological action

 

Inhibitor of bone resorption, bisphosphonate. Klodronovaya acid belongs to the bisphosphonate and is an analogue of the natural pyrophosphate. Bisphosphonates have high affinity to the mineral components of bone tissue. The main mechanism of action is to inhibit acid klodronovoy osteoclast activity and decrease their mediated bone resorption.

The ability to inhibit acid klodronovoy bone resorption in humans has been confirmed in the histological, kinetic and biochemical studies. However, the exact mechanisms of this process is not fully understood.

Klodronovaya acid inhibits osteoclast activity, reducing the concentration of calcium in the blood serum and excretion of calcium and hydroxyproline excretion.

In vitro bisphosphonates inhibit precipitation of calcium phosphate block its transformation into hydroxyapatite, delay the aggregation of apatite crystals into larger crystals and slow dissolution of these crystals.

In applying klodronovoy acid as monotherapy in doses sufficient to inhibit bone resorption, the effect on normal bone mineralization in humans has not been observed. In patients with breast cancer and multiple myeloma, a decrease of the probability of bone fractures.

Klodronovaya acid reduces the incidence of bone metastases in primary breast cancer. In patients with operable breast cancer to prevent bone metastases and lower mortality was noted.



Pharmacokinetics

 

Absorption

Absorption from the gastrointestinal tract klodronovoy acid occurs rapidly and is approximately 2%. After oral single-dose Cmaxpreparata in serum obtained after 30 minutes. Thanks to the pronounced affinity klodronovoy acid to calcium and other divalent cations absorption klodronovoy acid significantly reduced when taking the drug with food or drugs containing divalent cations. When you receive inside klodronovoy acid for 1 hour before a meal relative bioavailability of 91%, 30 min - 69%, respectively (lower bioavailability while not statistically significant). Significant fluctuations in the absorbability klodronovoy acid from the digestive tract are also seen as among different patients, and at the same patient. Despite significant fluctuations in the absorption of one and the same patient, obtained in the course of long-term treatment klodronovoy acid remains constant.

Distribution

Linking klodronovoy acid to plasma proteins is low.

Klodronovaya acid binds strongly to bone tissue.

Breeding

Withdrawal klodronovoy acid from serum is characterized by two phases: phase distribution with the T1 / 2 about 2 hours and the elimination phase, which flows very slowly as klodronovaya acid binds strongly to bone tissue. Klodronovaya acid is excreted primarily by the kidneys. About 80% determined in the urine for several days after ingestion. Klodronovaya acid associated with the bone (about 20% has grown deep dose) is excreted more slowly. Renal clearance is approximately 75% of plasma clearance.

A clear link between concentration klodronovoy acid in blood plasma and the therapeutic effect or no adverse reactions.

Pharmacokinetics in special clinical situations.

Farmakokineticheksy profile of the drug does not depend on age, drug metabolism or functional impairment, with the exception of renal failure, causes a reduction in renal clearance klodronovoy acid.



Indications for use of the drug BONEFOS ®

 

- Osteolytic metastases of malignant tumors in the bone;

- Multiple myeloma (multiple myeloma);

- Prevention of bone metastasis of primary breast cancer;

- Hypercalcemia due to malignancy.
Dosage regimen

 

The drug is prescribed inside and I / O in the form of infusion.

400 mg capsules should be swallowed without chewing. Tablets 800 mg are divided into two parts, but both sides should be taken simultaneously. You should not crush or dissolve tablets in front of the reception.

The daily dose of 1,600 mg is recommended to take only once in the morning on an empty stomach with a glass of water. After taking the drug, the patient should abstain for an hour of eating, drinking (except for ordinary water) and taking other medicines.

If you exceed a daily dose of 1,600 mg taken in two doses. The first dose should be taken as recommended above. The second dose should be taken between meals, 2 hours after or 1 hour before eating, drinking (except for ordinary water) or intake of any kind whatsoever other medicines.

Bonefos ® should not be taken with milk, food, and also with preparations containing calcium or other divalent cations, since they all violate the absorption klodronovoy acid.

For solution for infusion, the required dose was dissolved in 500 ml 0.9% sodium chloride or 5% dextrose.

Before and during treatment should ensure adequate intake of fluids to the patient and to monitor kidney function and calcium concentration in the serum.

Hypercalcemia due to malignancy

The drug is prescribed to 300 mg / drip for 2 hours (at least) every day (no more than 7 consecutive days) until the normal concentration of serum calcium (which usually occurs within 5 days) or 1500 mg / drip in for 4 hours once. If necessary, the infusion can be repeated or assign Bonefos ® inside. With the development of hypocalcemia is recommended short-term treatment interruption.

If / in the introduction is not possible, Bonefos ® is administered orally at an initial dose of 2.4-3.2 g daily. With a decrease in blood calcium to normal levels gradually reduce the dose to 1600 mg.

Preventing the development of bone metastasis of primary breast cancer

Assign to 1.6 g daily by mouth.

Osteolytic bone changes due to malignant tumors without hypercalcemia

Dose in each case is determined individually. The recommended starting dose is 1.6 g / As clinical indications it may be increased as much as possible - up to 3.2 g /

Patients with renal insufficiency drug should not be administered orally at doses exceeding 1.6 g / in for a long time.

With a / in a dose should be reduced in accordance with the following recommendations:
The degree of renal failure, creatinine clearance (ml / min) dose reduction (%) Light 50-80 25% 12-50 Moderate 25-50% Severe <12 50%