Bonviva solution syringe 3mg/3ml 3ml syringe-tubes, 1pc

Composition

1 syringe tube (3 ml) with a solution for intravenous use contains:

Active ingredient:

ibandronic acid 3 mg (as sodium ibandronate monohydrate 3,375 mg),

excipients:

sodium chloride;

sodium acetate trihydrate;

acetic acid ice;

water for injection

Pharmacological action

Pharmacodynamics

Ibandronic acid is a highly active nitrogen-containing bisphosphonate, an inhibitor of bone resorption and osteoclast activity. Ibandronic acid prevents bone destruction caused by gonadal function blockade, retinoids, tumors, and tumor extracts in vivo. Inhibits endogenous resorption in young (fast-growing) rats, which is manifested by a higher bone mass compared to intact animals.

It does not interfere with bone mineralization when administered at doses more than 5,000 times higher than those for the treatment of osteoporosis and does not affect the process of replenishing the osteoclast pool. The selective effect of ibandronic acid on bone tissue is due to its high affinity for hydroxyapatite, which is a mineral matrix of bone.

Ibandronic acid dose-dependently inhibits bone resorption and does not directly affect the formation of bone tissue. In menopausal women, it reduces the increased rate of bone renewal to the level of reproductive age, which leads to an overall progressive increase in bone mass, a decrease in bone collagen breakdown indicators (concentrations of deoxypyridinoline and cross-linked C-and N-telopeptides of type I collagen) in urine and serum, the frequency of fractures, and an increase in BMD.

High activity and therapeutic range provide the possibility of a flexible dosage regimen and intermittent use of the drug with a long period without treatment in relatively low doses.

Efficiency

Taking Bonviva 150 mg once a month for a year increases the average BMD of the lumbar vertebrae, femur, femoral neck and trochanter by 4.9,3.1,2.2 and 4.6%; intravenous use of Bonviva 3 mg once every 3 months for 1 year increases the average BMD of the hip, femoral neck and trochanter by 2.4,2.3 and 3.8%, respectively.

Regardless of the duration of menopause and the degree of initial bone mass loss, the use of Bonviva leads to significantly more pronounced changes in BMD than placebo. The effect of treatment over a year, defined as an increase in BMD, is observed in 83.9% (when taking coated tablets) and 92.1% (when administered intravenously) of patients.

Biochemical markers of bone resorption

Coated tablets,2.5 mg each. Biochemical markers of bone resorption (urinary procollagen type I C-terminal peptide (CTX) and serum osteocalcin) decrease to their level at reproductive age; the maximum decrease is observed after 3-6 months of treatment. A month after starting Bonviva 2.5 mg daily and 20 mg intermittently, a clinically significant decrease in biochemical markers of bone resorption by 50 and 78%, respectively, was achieved; moreover, a slight decrease in these indicators was noted after a week of treatment. A clinically significant decrease in biochemical markers of bone resorption (CTX concentration in urine) is observed one month after the start of treatment.

Daily intake of 2.5 mg of Bonviva for the prevention of postmenopausal osteoporosis (study MF4499) increases the average BMD of the lumbar vertebrae by 1.9% compared to baseline. Regardless of the duration of menopause and the degree of initial loss of the main substance of bone tissue, the use of Bonviva leads to a significantly more pronounced change in the BMD of the lumbar vertebrae. When using the drug Bonviva, the effect of treatment, defined as an increase in BMD, compared to the initial one, is observed in 70% of patients.

Film-coated tablets of 150 mg and a solution for intravenous use. A 28% decrease in serum CTX concentration was observed as early as 24 hours after the first 150 mg Bonviva dose, with a maximum decrease of 68% after 6 days. After the third and fourth use of Bonviva 150 mg, the maximum decrease in serum CTX by 74% was observed after 6 days. 28 days after the fourth dose, the suppression of biochemical markers of bone resorption decreased to 56%.

A clinically significant reduction in serum CTX was obtained after 3,6, and 12 months of therapy. After one year of therapy with Bonviva 150 mg, the decrease was 76%; compared to the initial value, with the use of 3 mg intravenously-58.6%.

A decrease in CTX of more than 50% compared to the initial value was observed in 83.5% of patients who received Bonviva 150 mg once every 28 days.

Pharmacokinetics

There was no direct dependence of the effectiveness of ibandronic acid on the concentration of the substance in the blood plasma. The concentration in blood plasma increases dose-dependently with an increase in the dose of the solution for intravenous use from 0.5 to 6 mg. Similar efficacy of ibandronic acid was confirmed with daily and intermittent use, provided that its total dose was the same during the treatment period.

Suction

After oral use, ibandronic acid is rapidly absorbed in the upper gastrointestinal tract. The concentration in blood plasma increases dose-dependently with an increase in the dose to 50 mg and significantly more with a further increase in the dose. Time to reach Cmax (TCmax)–0.5 — 2 hours (median — 1 hour) after fasting, absolute bioavailability-0.6%. Absorption is impaired when the drug is taken with food or beverages (except pure water). Simultaneous intake of food or beverages (other than pure water) reduces the bioavailability of ibandronic acid by 90%. When ibandronic acid is taken 60 minutes before meals, there is no significant decrease in bioavailability. Ingestion of food or fluids less than 60 minutes after ibandronic acid reduces its bioavailability and the resulting increase in bone mineral density (BMD).

Distribution

After entering the systemic circulation, ibandronic acid is rapidly bound in bone tissue or excreted in the urine. 40-50% of the amount of the drug circulating in the blood penetrates well into the bone tissue and accumulates in it. The apparent final volume of distribution is 90 liters. The relationship with plasma proteins when taken orally is 85% and 85-87% – when administered intravenously.

Metabolism

There is no evidence that ibandronic acid is metabolized. Ibandronate does not inhibit the cytochrome P450 enzymes 1A2,2A6,2C9,2C19,2D6,2E1, and 3A4.

Elimination

40-50% of the absorbed oral or intravenous dose is bound in the bones, and the rest is excreted unchanged by the kidneys.

The unabsorbed drug is excreted unchanged in the feces.

The terminal T 1/2 for 2.5 mg tablets is 10-60 hours; for 150 mg tablets and intravenous solution-10-72 hours. The concentration of the drug in the blood decreases rapidly and is 10% of the maximum 8 hours after oral use and 3 hours after intravenous use.

The total clearance of ibandronic acid is 84-160 ml / min. Renal clearance (60 ml / min in healthy menopausal women) It is 50-60% of the total clearance and depends on the 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 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. In patients with impaired renal function, the renal clearance of ibandronic acid is linearly dependent on creatinine clearance (Cl creatinine). No dose adjustment is required in patients with mild or moderate renal impairment (creatinine clearance ≥30 ml / min).

In 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 and captured in bone tissue. Therefore, no dose adjustment is required in patients with hepatic impairment.

Since ibandronic acid is weakly bound to plasma proteins (85%) when taken orally at therapeutic concentrations, it is likely that hypoproteinemia in severe liver diseases does not lead to a clinically significant increase in the concentration of free substance 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 Bonviva in people under 18 years of age.

Indications

Postmenopausal osteoporosis to prevent fractures.

Use during pregnancy and lactation

Pregnancy. During preclinical studies, no signs of direct embryotoxic or teratogenic effects were found; at a dose of the drug exceeding the dose for humans by at least 35 times, no adverse effect on the development of offspring in F1 rats was found. The adverse effects of ibandronic acid in animal reproductive toxicity studies were the same as in all bisphosphonates: a decrease in the number of embryos, a violation of the delivery process, an increase in the frequency of visceral abnormalities (pelvic-ureteral narrowing syndrome).

There is no experience of clinical use of Bonviva in pregnant women.

Breast-feeding period. It is excreted in milk in animals.After 24 hours, the concentration of ibandronic acid in blood plasma and milk is the same and corresponds to 5% of the maximum.

It is not known whether ibandronic acid is excreted in breast milk in women.

Contraindications

• hypersensitivity to ibandronic acid or other components of the drug;
• hypocalcemia (before using Bonviva, as well as when prescribing all bisphosphonates used for the treatment of osteoporosis, hypocalcemia should be eliminated).
• pregnancy;
• breast-feeding period.
• severe renal impairment (serum creatinine >200 mmol / L (2.3 mg / dl) or Cl creatinine>

Side effects

From the gastrointestinal tract: dyspepsia, diarrhea, gastritis.

Musculoskeletal disorders: arthralgia, myalgia.

Nervous system disorders: headache, dizziness.

Body as a whole: flu-like syndrome.

From the skin and its appendages: rash.

Hypersensitivity reactions: angioedema, urticaria.

Very rarely, when ibandronic acid was prescribed, osteonecrosis of the jaw was noted.

Bonviva, like other bisphosphonates, can cause a short-term decrease in serum calcium levels when administered intravenously.

From the gastrointestinal tract: constipation, gastroenteritis.

From the musculoskeletal system: pain in the limbs and bones, osteoarthritis.

From the nervous system and mental sphere: insomnia, depression.

Body as a whole: weakness, injection site reactions, phlebitis, thrombophlebitis, nasopharyngitis, cystitis, urinary tract infections, bronchitis, upper respiratory tract infections, arterial hypertension, hypercholesterolemia, uveitis, scleritis.

Interaction

Bonviva is incompatible with calcium-containing solutions and other solutions for intravenous use.

Ibandronic acid does not affect the activity of the main isoenzymes of the cytochrome P450 system.

At therapeutic concentrations, ibandronic acid is weakly bound to plasma proteins, and therefore it is unlikely that it will displace other drugs from the protein binding sites.

Ibandronic acid is excreted only through the kidneys and does not undergo any biotransformation. Apparently, the route of elimination of ibandronic acid does not include any transport systems involved in the elimination of other drugs.

How to take, course of use and dosage

Intravenously. The drug is intended for intravenous use only!

Entered only by a specialist. Intra-arterial use or contact with surrounding tissues should be avoided.

Before use, it is necessary to inspect the solution for the absence of foreign impurities or discoloration.

You should use the needles included with the syringe tubes.

The syringe tube is intended for a single injection only.

The standard dosage regimen

is 3 mg intravenously bolus (for 15-30 s) 1 time in 3 months.

The patient should also take calcium and vitamin D.

If you miss a routine injection, you should perform the injection as soon as possible. Then continue the drug use every 3 months after the last injection.

Do not prescribe the drug more often than 1 time in 3 months.

During treatment, renal function, serum calcium, phosphorus, and magnesium levels should be monitored.

Dosage for special patient groups

Impaired liver function. No dose adjustment is required.

Impaired renal function. In patients with mild to moderate renal impairment (creatinine clearance ≥30 ml/min), no dose adjustment is required. 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.

Overdose

Symptoms: hypocalcemia, hypophosphatemia, hypomagnesemia.

Treatment: no specific information available. Clinically significant decreases in serum calcium, phosphate, and magnesium can be corrected by intravenous use of calcium gluconate, potassium, or sodium phosphate, and magnesium sulfate, respectively. Dialysis is ineffective if prescribed 2 hours after the drug is administered.

Special instructions

Risk factors for postmenopausal osteoporosis and fractures include a family history, previous bone fractures, early menopause, active bone metabolism, low BMD (at least 1.0 SD less than the average BMD at reproductive age), fragile physique, as well as belonging to the South European and Asian race, smoking. These factors are of great importance when deciding whether to prescribe Bonviva 2.5 mg coated tablets for the prevention of osteoporosis.

Osteoporosis can be confirmed by detecting a low BMD (T index).

Hypocalcemia and other disorders of bone metabolism and electrolyte balance should be corrected prior to the use of Bonviva. Patients should consume adequate amounts of calcium and vitamin D.

If the patient does not receive enough calcium and vitamin D from food, then they should also be taken in the form of dietary supplements.

When taken orally, the side effect of the drug is usually mild or moderate. Transient flu-like syndrome is noted after taking the first dose and resolves independently without correction of therapy. There was no increase in the incidence of upper gastrointestinal adverse events in patients with gastrointestinal diseases (including peptic ulcer without bleeding and hospitalization, dyspepsia or reflux disease).

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 (sitting or standing position for 60 minutes after use).

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

The experience of post-marketing use of Bonviva is limited.

Serum creatinine should be determined before each injection.

When prescribing bisphosphonates, osteonecrosis of the jaw was noted. Most cases were reported in patients with cancer during dental procedures, while a few cases were reported in patients with postmenopausal osteoporosis or other diseases. Risk factors for developing osteonecrosis of the jaw include an established cancer diagnosis, concomitant therapy (chemotherapy, radiation therapy, corticosteroids), and other disorders (anemia, coagulopathy, infection, gum disease). Most cases were observed with intravenous use of bisphosphonates, but some cases were observed in those 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.

Form of production

Solution for intravenous use.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

2 years

Active ingredient

Ibandronic Acid

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution