Bondronate concentrate solution for infusion 2mg/2ml 2ml, 1pc

Composition

1 ml of concentrate for preparation of infusion solution contains:

Active ingredient:

ibandronic acid 1 mg, as sodium ibandronate monohydrate 1,125 mg,

excipients:

sodium chloride;

sodium acetate;

acetic acid 99%;

water for injection.

Pharmacological action

Pharmacodynamics

Bondronate is an inhibitor of bone resorption, nitrogen-containing bisphosphonate. It has a specific selective effect on bone tissue due to its high affinity for bone mineral components. Suppresses the activity of osteoclasts, reduces the frequency of skeletal complications in malignant diseases.

Ibandronic acid reduces osteoclast-associated release of tumor growth factors, inhibits the spread and invasion of tumor cells, and exhibits a synergistic effect with taxanes in vitro. Ibandronic acid prevents bone destruction caused by gonadal function blockade, retinoids, tumor processes, or in vivo use of tumor tissue extracts.

In doses significantly higher than pharmacologically effective, ibandronic acid does not affect bone mineralization.

In hypercalcemia, the inhibitory effect of ibandronic acid on tumor-induced osteolysis and, in particular, on concomitant hypercalcemia, is accompanied by a decrease in serum calcium levels and urinary calcium excretion. In most cases, the calcium content in the blood normalizes within 4-7 days after use of the drug. The median time to re-increase of serum albumin-corrected calcium to 3 mmol / l is 18-26 days.

Ibandronic acid prevents the development of new bone metastases and reduces the growth of existing bone metastases, which leads to a decrease in the frequency of skeletal complications, the intensity of pain, the need for radiation therapy and surgical interventions for the metastatic process in the bones, thereby leading to a significant improvement in the quality of life of patients.

Ibandronic acid dose-dependently inhibits tumor osteolysis, which is determined by markers of bone resorption (pyridinoline and deoxypyridinoline).

Pharmacokinetics

Suction.

After oral use, ibandronic acid is rapidly absorbed in the upper gastrointestinal tract. The time to reach the maximum concentration (tmax) is 0.5 — 2 hours (median–1 hour) after ingestion on an empty stomach, absolute bioavailability is 0.6%. Simultaneous intake of food or beverages (other than pure water) reduces the bioavailability of ibandronic acid by 90%. Ingestion of food or beverages 30 minutes after ibandronic acid reduces its bioavailability by 30%. When ibandronic acid is taken 60 minutes before meals, there is no significant decrease in bioavailability.

The plasma concentration of ibandronic acid increases in proportion to the dose of the drug administered intravenously (at a dose of up to 6 mg) or taken orally (at a dose of 100 mg).

The bioavailability of ibandronic acid decreases to 75% when taken 2 hours after a meal, and therefore it is recommended to take Bondronate tablets on an empty stomach, followed by a meal no earlier than 30 minutes later.

Distribution.

After entering the systemic circulation, ibandronic acid is rapidly bound in bone tissue or excreted in the urine. The apparent final volume of distribution is 90 liters. Binding to plasma proteins is 87%.

Metabolism.

There is no evidence that ibandronic acid is metabolized.

Output.

Penetrates and accumulates in the bone tissue 40-50% of the amount of the drug circulating in the blood, the remaining drug is excreted unchanged by the kidneys. Unabsorbed drug after oral use is excreted unchanged in the faeces.

Terminal T_1/2 10-60 hours. The concentration of the drug in the blood decreases rapidly and reaches 10% of the maximum 3 hours after intravenous use and 8 hours after oral use.

When ibandronic acid was administered intravenously at 4-week intervals for 48 weeks, no systemic accumulation was observed in patients with metastatic bone damage.

The total clearance of ibandronic acid is 84-160 ml / min. Renal clearance (60 ml / min in healthy menopausal women) accounts for 50-60% of total clearance and depends on creatinine clearance. The difference between total and renal clearance reflects the absorption of substance in bone tissue.

Pharmacokinetics in special groups of patients

, the pharmacokinetics of ibandronic acid do not depend on gender. There were also no clinically significant inter-racial differences in the distribution of ibandronic acid in individuals of South European and Asian race. There is insufficient data on the black race.

Patients with impaired renal function. Exposure to ibandronic acid in patients with various renal disorders depends on creatinine clearance. After a single intravenous injection of 6 mg ibandronic acid (15-minute infusion), the mean AUC (0-24) was 14% higher in patients with mild renal impairment (mean creatinine clearance = 68.1 ml/min) and 86% higher in patients with moderate renal impairment (mean creatinine clearance = 41.2 ml/min) compared to healthy subjects (mean creatinine clearance = 120 ml/min). The mean_cmaxdoes not increase in patients with mild renal impairment and increases by 12% in patients with moderate renal impairment. In patients with severe renal impairment (creatinine clearance

However, patients with severe renal impairment (creatinine clearance

Patients with impaired liver function. There are no data on the pharmacokinetics of ibandronic acid in patients with impaired liver function. The liver does not play a significant role in the clearance of ibandronic acid, which is not metabolized, but is excreted through the kidneys or binds in bone tissue. No dose adjustment is required in patients with hepatic impairment. In addition, at therapeutic concentrations, ibandronic acid weakly binds to plasma proteins (87%), so it is likely that hypoproteinemia in severe liver diseases does not lead to a clinically significant increase in the concentration of ibandronic acid in the blood.

Advanced age. The studied pharmacokinetic parameters do not depend on age. Possible impairment of renal function in elderly patients should be considered.

Children. There are no data on the use of Bondronate in persons under 18 years of age.

Indications

Metastatic bone damage in order to reduce the risk of hypercalcemia, pathological fractures, reduce pain, reduce the need for radiation therapy for pain syndrome and the threat of fractures;

Hypercalcemia in malignant neoplasms.

Contraindications

• hypersensitivity to ibandronic acid or other components of the drug;
• childhood (lack of clinical experience);
• pregnancy and lactation.

With caution:

• Cl creatinine
• hypersensitivity to other bisphosphonates;
• when taken orally-in combination with NSAIDs.

Side effects

When administered intravenously: fever, asthenia, headache; sometimes-flu-like syndrome (fever, chills, ossalgia and myalgia), which in most cases do not require specific treatment and disappear after a few hours or days, hypersensitivity reactions; rarely — dyspepsia, diarrhea; bronchospasm in patients with aspirin bronchial asthma.

From the laboratory parameters: often-a decrease in calcium excretion by the kidneys, hypophosphatemia that does not require therapeutic intervention; sometimes — hypocalcemia.

Interaction

Ibandronic acid is excreted only through the kidneys and does not undergo biotransformation. The route of elimination of ibandronic acid does not include any transport systems involved in the elimination of other drugs. Ibandronic acid does not affect the activity of the main isoenzymes of the cytochrome P%^%450 system. At therapeutic concentrations, ibandronic acid weakly binds to plasma proteins, so the possibility of drug interaction due to the displacement of drugs from protein binding sites is small.

Bondronate solution is incompatible with calcium-containing solutions.

Products containing calcium and other polyvalent cations (for example, aluminum, magnesium, iron), including milk and solid foods, may interfere with the absorption of the drug, they should be consumed no earlier than 30 minutes after oral use of Bondronate.

Bisphosphonates and NSAIDs can cause irritation of the gastrointestinal tract.

When administered intravenously, ranitidine increases the bioavailability of ibandronic acid by 20%. Dose adjustment of the drug when used concomitantly with_H2-histamine receptor blockers or other drugs that increase the pH of the stomach is not required.

There is no interaction between Bondronate and tamoxifen, hormone replacement therapy (estrogen therapy) in postmenopausal patients.

How to take it, course of use and dosage

Bondronate in the form of concentrate for the preparation of an infusion solution is usually used in a hospital setting and is administered intravenously by drip within 1-2 hours after preliminary dilution. Concentrate for preparation of infusion solution is diluted in 500 ml of 0.9% sodium chloride solution or 5% dextrose solution.

Metastatic bone damage in breast cancer — 6 mg intravenously drip, for at least 15 minutes, once every 3-4 weeks.The infusion solution concentrate should be diluted in 100 ml of 0.9% sodium chloride solution or 5% dextrose solution. Only in patients with normal renal function or mild impairment (creatinine clearance >50 ml / min), a 15-minute infusion is possible. In patients with Cl creatinine

Hypercalcemia in malignant neoplasms. Bondronate is used only in the form of 1-2-hour intravenous infusions. Bondronate therapy is started after adequate hydration with 0.9% sodium chloride solution. The dose of the drug depends on the severity of hypercalcemia. In patients with severe hypercalcemia (albumin-corrected serum calcium ≥3 mmol / L, or ≥12 mg / dl),4 mg is administered once. Patients with moderate hypercalcemia (albumin-corrected serum calcium

If the first use is not effective enough or if hypercalcemia recurs, repeated use is possible.

The concentration of albumin-corrected calcium in serum (mmol / l) is calculated by the formula: serum calcium (mmol/L) − [0.02 × albumin (g/l)] + 0.8, or in mg / dl: serum calcium (mg/dl) + 0.8 × [4-albumin (g/dl)].

Dosage for special patient groups

Impaired liver function. No dose adjustment is required.

Impaired renal function

Infusion solution concentrate: an increase in the systemic concentration of Bondronate does not worsen the tolerability of the drug in patients with impaired renal function of varying severity. However, the following guidelines should be followed in patients with metastatic bone damage in breast cancer:

Table of contents

1 when administered 1 time in 3-4 weeks.

2 0.9% sodium chloride solution or 5% dextrose solution.

In patients with Cl creatinine

Advanced age. No dose adjustment is required.

Children. Safety and efficacy in persons under 18 years of age have not been established.

Bed rest. There are no data on the safety of using oral Bondronate in patients who are unable to stand or sit for 60 minutes after taking the drug.

Overdose

There are no reports of acute overdose of Bondronate.

Due to possible toxic effects on the liver and kidneys, it is necessary to monitor the function of these organs. With an overdose of the drug taken orally, it is possible to increase dyspeptic phenomena, the appearance of heartburn, the development of esophagitis, gastritis, gastrointestinal ulcers.

Treatment: intravenous calcium gluconate, hemodialysis. Milk or antacids should be used to bind the drug taken orally. Because of the risk of irritation of the esophagus, vomiting should not be induced and it is necessary to remain in a straight “standing” position.

Special instructions

Hypocalcemia and other disorders of bone metabolism and electrolyte balance should be corrected before starting Bondronate therapy. Patients should consume adequate amounts of calcium and vitamin D.

If the patient receives insufficient calcium and vitamin D from food, then they should also be taken in the form of dietary supplements.

The drug for parenteral use is administered only intravenously. Intra-arterial use or contact with surrounding tissues should be avoided.

Unlike other bisphosphonates, there are no data on impaired renal function with prolonged use of Bondronate. During treatment, renal function, serum calcium, phosphorus, and magnesium levels should be monitored.

There are no recommendations on the dosage of the drug in patients with hepatic insufficiency, due to the lack of experience with the use of Bondronate in this category of patients.

Hyperhydration with intravenous Bondronate should be avoided in patients at risk of developing heart failure.

The use of oral bisphosphonates is often accompanied by impaired swallowing, esophagitis and the formation of ulcers of the esophagus and stomach, so special attention should be paid to the implementation of recommendations for taking the drug.

If there are signs and symptoms of possible esophageal damage (the appearance or increase of dysphagia, pain when swallowing and/or behind the sternum, heartburn), you should stop taking Bondronate and consult a doctor.

Given that NSAIDs are associated with gastrointestinal irritation, caution should be exercised when co-prescribing NSAIDs and Bondronate.

When prescribing bisphosphonates, osteonecrosis of the jaw was rarely observed. Most cases have been reported in cancer patients during dental procedures, with a few cases occurring in patients with postmenopausal osteoporosis or other medical conditions. Risk factors for developing osteonecrosis of the jaw include an established cancer diagnosis, concomitant therapy (chemotherapy and radiation therapy, corticosteroids), and other disorders (anemia, coagulopathy, infection, gum disease). Most cases were reported with intravenous use of bisphosphonates, but some cases were observed in patients who received the drugs orally.

Surgical dental intervention on the background of bisphosphonate therapy can increase the manifestations of osteonecrosis of the jaw. It is not known whether the elimination of bisphosphonates reduces the risk of osteonecrosis. The decision on treatment should be made for each patient individually after assessing the risk / benefit ratio.

Influence on the ability to drive vehicles and work with machines and mechanisms. Studies on the effect of Bondronate on the ability to drive vehicles or work with machines and mechanisms have not been conducted.

Form of production

Concentrate for preparation of solution for infusions

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

5 years

Active ingredient

Ibandronic Acid

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Osteoporosis, Bone Fractures, Menopause