Bonviva, 150 mg, 1 pc.

1 coated tablet contains:

active substance:

ibandronic acid 150 mg (as sodium ibandronate monohydrate)

auxiliary substances :

lactose monohydrate,

povidone (K 25),

microcrystalline cellulose,

crospovidone,

stearic acid,

anhydrous colloidal silicon dioxide.

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 blockage of gonads, retinoids, tumors and tumor extracts in vivo. It inhibits endogenous resorption in young (fast-growing) rats, which is manifested by a higher bone mass compared to intact animals.

Does not interfere with bone mineralization when administered in doses more than 5000 times the dose 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 the mineral matrix of the bone.

Ibandronic acid dose-dependently inhibits bone resorption and has no direct effect on bone formation. In menopausal women, it reduces the increased rate of bone turnover to the level of reproductive age, which leads to an overall progressive increase in bone mass, a decrease in the rates of bone collagen degradation (concentration 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.

The high potency and therapeutic range allow for a flexible dosing regimen and intermittent administration of the drug with a long period without treatment at relatively low doses.

Efficiency

Taking Bonviva 150 mg once a month for a year increases the average BMD of the lumbar vertebrae, hip, femoral neck and trochanter by 4.9, 3.1, 2.2 and 4.6%; IV administration of Bonviva 3 mg once every 3 months for 1 year increases the average BMD of the thigh, 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 a significantly more pronounced change in BMD than placebo. The effect of treatment within a year, defined as an increase in BMD, is observed in 83.9% (with coated tablets) and 92.1% (with intravenous administration) of patients.

Biochemical markers of bone resorption

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

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

Film-coated tablets, 150 mg and solution for intravenous administration. A 28% decrease in serum CTX concentration was noted within 24 hours after the first dose of 150 mg Bonviva, the maximum decrease was 68% after 6 days. After the third and fourth doses of Bonviva 150 mg, the maximum decrease in serum CTX by 74% was noted after 6 days. 28 days after taking the fourth dose, there was a decrease in suppression of biochemical markers of bone resorption to 56%.

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

A decrease in CTX of more than 50% compared to the baseline value was noted 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 solution for intravenous administration from 0.5 to 6 mg. The similar efficacy of ibandronic acid has been confirmed with daily and intermittent use, provided that it is the same total dose administered over the period of treatment.

Suction

After oral administration, ibandronic acid is rapidly absorbed in the upper gastrointestinal tract. The concentration in blood plasma increases in a dose-dependent manner with an increase in the dose to 50 mg and much more with a further increase in the dose. The time to reach Cmax (TCmax) is 0.5–2 hours (median is 1 hour) after fasting, absolute bioavailability is 0.6%. Absorption is impaired when the drug is taken with food or drinks (except pure water). Simultaneous intake of food or drinks (except for pure water) reduces the bioavailability of ibandronic acid by 90%. When taking ibandronic acid 60 minutes before meals, there is no significant decrease in bioavailability. Ingestion of food or liquids 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 quickly binds to bone tissue or is 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. Communication with blood plasma proteins when taken orally - 85% and 85–87% - with intravenous administration.

Metabolism

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

Withdrawal

40-50% of the absorbed into the bloodstream taken orally or injected 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.

Terminal T1 / 2 for 2.5 mg tablets is 10-60 hours; for tablets of 150 mg and solution for intravenous administration - 10–72 hours. The concentration of the drug in the blood decreases rapidly and amounts to 10% of the maximum 8 hours after oral administration and 3 hours after intravenous administration.

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

Pharmacokinetics in special patient groups

The pharmacokinetics of ibandronic acid does not depend on gender.

There were no clinically significant interracial differences in the distribution of ibandronic acid in individuals of the South European and Asian races. There is not enough data on the Negroid race.

Patients with impaired renal function. In patients with impaired renal function, the renal clearance of ibandronic acid is linearly dependent on the clearance of creatinine (Cl creatinine). For patients with mild or moderate renal impairment (Cl creatinine ≥30 ml / min), dose adjustment is not required.

In patients with severe renal impairment (Cl creatinine

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 excreted through the kidneys and by capture in bone tissue. Therefore, for patients with impaired liver function, dose adjustment is not required.

Since when taken orally in therapeutic concentrations, ibandronic acid weakly binds to blood plasma proteins (85%), it is likely that hypoproteinemia in severe liver disease does not lead to a clinically significant increase in the concentration of free substance in the blood.

Elderly age. The studied pharmacokinetic parameters do not depend on age. Consideration should be given to the possible decrease in renal function in elderly patients.

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

Postmenopausal osteoporosis to prevent fractures.

Pregnancy. During preclinical studies, no signs of direct embryotoxic or teratogenic action were found; at a drug dose exceeding the human dose 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 reproductive toxicity studies in animals were the same as in all bisphosphonates: a decrease in the number of embryos, impaired delivery, an increase in the frequency of visceral anomalies (syndrome of narrowing of the pelvic-ureteric segment).

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

Breastfeeding 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.

• hypersensitivity to ibandronic acid or other components of the drug;
• hypocalcemia (before starting the use of Bonviva, as well as with the appointment of all bisphosphonates used to treat osteoporosis, hypocalcemia should be eliminated).

Precautions: severe renal impairment (Cl creatinine

From the gastrointestinal tract: dyspepsia, diarrhea, gastritis.

From the musculoskeletal system: arthralgia, myalgia.

From the nervous system: headache, dizziness.

Body as a whole: flu-like syndrome.

On the part of the skin and its appendages: rash.

Hypersensitivity reactions: angioedema, urticaria.

Osteonecrosis of the jaw has been reported very rarely with ibandronic acid.

From the gastrointestinal tract: esophagitis, ulcer or stricture of the esophagus, duodenitis.

From the gastrointestinal tract: nausea, vomiting, abdominal pain, dysphagia, flatulence, gastroesophageal reflux.

On the part of the musculoskeletal system: muscle stiffness, muscle spasm.

Products containing calcium and other polyvalent cations (for example, aluminum, magnesium, iron), incl. milk and solid food may interfere with the absorption of the drug, they should be consumed no earlier than 60 minutes after oral administration of Bonviva.

Calcium supplements, antacids and medicines containing polyvalent cations (eg aluminum, magnesium, iron) can interfere with the absorption of ibandronic acid, so they should be taken no earlier than 60 minutes after taking Bonviva.

Bisphosphonates and NSAIDs can irritate the gastrointestinal mucosa. Special care should be taken when using NSAIDs concurrently with Bonviva. With the simultaneous use of aspirin or NSAIDs and Bonviva for 1 year, the frequency of side effects from the upper gastrointestinal tract was the same.

Ranitidine intravenously increases the bioavailability of ibandronic acid by 20%. No dose adjustment of ibandronic acid is required when used simultaneously with H2-histamine receptor blockers or other drugs that increase the pH in the stomach.

Ibandronic acid does not affect the activity of the main isoenzymes of the cytochrome P450 system. At therapeutic concentrations, ibandronic acid weakly binds to blood 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.

150 mg (1 tablet) once a month (preferably on the same day of each month), 60 minutes before the first meal of the day, liquid (except water) or other drugs and food additives. The tablets should not be chewed or resorbed due to possible ulceration of the upper gastrointestinal tract. You cannot use mineral water that contains a lot of calcium.

In case of missing a scheduled appointment, 1 table should be taken. Bonviva 150 mg, if it is more than 7 days before the scheduled intake, and then take Bonviva 1 time per month in accordance with the established schedule. If there are less than 7 days before the next scheduled appointment, you must wait until the next appointment according to the plan and then continue taking in accordance with the established schedule, because you can not take more than 1 table. in Week.

Symptoms: dyspepsia, heartburn, esophagitis, gastritis, ulcers, hypocalcemia, hypophosphatemia

Treatment: no specific information available. To bind the drug Bonviva, milk or antacids are used. Because of the risk of irritation of the esophagus, vomiting should not be induced and should remain in an erect "standing" position.

Risk factors for the development of postmenopausal osteoporosis and fractures - hereditary 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, and women belonging to South European and Asian race, smoking. These factors are of great importance in deciding whether to prescribe Bonviva 2.5 mg film-coated tablets for the prevention of osteoporosis.

Osteoporosis can be confirmed by detecting low BMD (T index

Before using Bonviva, hypocalcemia and other disorders of bone metabolism and electrolyte balance should be corrected. 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 be additionally taken in the form of dietary supplements.

When taken orally, the side effects of the drug are usually mild or moderate. A transient flu-like syndrome is noted after taking the first dose and resolves on its own without correction of therapy. There was no increase in the frequency of adverse effects from the upper gastrointestinal tract 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, therefore, it is necessary to pay special attention to the implementation of recommendations for taking the drug ("sitting" or "standing" position within 60 minutes after ingestion).

If signs and symptoms of possible damage to the esophagus appear (the appearance or aggravation of swallowing disorders, pain when swallowing, chest pain, heartburn), you should stop taking Bonviva and consult a doctor.

Experience with post-marketing use of Bonviva is limited.

Serum creatinine should be determined before each injection.

Osteonecrosis of the jaw was noted with the appointment of bisphosphonates. The majority of cases were reported in patients with cancer during dental procedures, and a few cases in patients with postmenopausal osteoporosis or other diseases. Risk factors for osteonecrosis of the jaw include an established diagnosis of cancer, concomitant therapy (chemotherapy, radiation therapy, corticosteroids), and other disorders (anemia, coagulopathy, infection, gum disease). Most cases were noted with iv administration of bisphosphonates, but some cases were observed in those who received drugs by mouth.

Surgical dental intervention against the background of bisphosphonate therapy can increase the manifestations of osteonecrosis of the jaw. It is not known whether bisphosphonate withdrawal reduces the risk of osteonecrosis. The decision to conduct treatment must be made for each patient individually after assessing the risk / benefit ratio.

film-coated tablets