Bonviva solution and tablets: instructions for use, price, reviews from doctors and analogues

Compound

The tablets contain the active ingredient ibandronic acid (2.5 mg or 150 mg), as well as additional ingredients: povidone, anhydrous colloidal silicon dioxide, lactose monohydrate, stearic acid, crospovidone, MCC.
The tablet shell consists of titanium dioxide, hypromellose, talc, macrogol 6000. Bonviva IV contains the active substance ibandronic acid (3 mg), as well as auxiliary ingredients: sodium chloride, sodium acetate trihydrate, glacial acetic acid, water.

Release form

The drug Bonviva is produced in the form of tablets and a solution for intravenous administration.

2.5 mg tablets are film-coated, slightly biconvex, oval, white or slightly white in color. “IT” is engraved on one side of the tablet and “L 3” on the other side. Tablets containing 2.5 mg of ibandronic acid, 14 pcs in a blister, two blisters in a pack.
Bonviva 150 mg tablets are film-coated, oblong, oval, white or slightly white in color. “BNVA” is engraved on one side of the tablet and “150” on the other side. Tablets containing 150 mg of ibandronic acid, 1 or 3 pcs in a blister, one blister in a pack.
The medicine in the form of a solution is a colorless transparent liquid. It is contained in a special 3 ml syringe tube; the kit also includes a sterile needle. The syringe is placed in a cardboard box.

Use during pregnancy and breastfeeding

Category C.

Pregnancy. During preclinical studies, no evidence of direct embryotoxic or teratogenic effects was found; at a dose of the drug exceeding the human dose by at least 35 times, no adverse effect on the development of offspring in F1 rats was detected. The adverse effects of ibandronic acid in reproductive toxicity studies in animals were the same as for all bisphosphonates: decreased embryo production, disruption of labor, increased incidence of visceral abnormalities (stenosis of the ureteropelvic segment).

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

Breastfeeding period. 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.

pharmachologic effect

The component ibandronic acid is a highly active bisphosphonate containing nitrogen. This substance is an inhibitor of bone resorption and osteoclast activity. Under its influence, bone destruction is prevented, which is caused by blockade of the function of the sex glands, retinoids , tumors .

The product does not disrupt the process of bone mineralization and does not affect the replenishment of the osteoclast pool. The active component selectively affects bone tissue, which is due to its significant affinity for hydroxyapatite , which makes up the mineral matrix of bone.

The active component of the drug Bonviva stops bone resorption and does not directly affect the process of bone tissue formation. When taking drugs during menopause , there is a decrease in the rate of bone tissue renewal to the level observed during reproductive age. As a result, there is a general increase in bone mass, the breakdown of bone collagen decreases, and the incidence of fractures decreases.

Due to the high activity of the drug and the wide therapeutic range, flexible dosing and intermittent administration of Bonviva with a long period without treatment is permissible.

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 blockade, retinoids, tumors and tumor extracts in vivo. Inhibits endogenous resorption in young (fast-growing) rats, which is manifested by higher bone mass compared to intact animals.

Does not interfere with bone mineralization when administered in doses more than 5000 times higher than doses for the treatment of osteoporosis and does not affect the process of replenishment of the osteoclast pool. The selective effect of ibandronic acid on bone tissue is due to its high affinity for hydroxyapatite, which constitutes the mineral matrix of bone.

Ibandronic acid inhibits bone resorption in a dose-dependent manner and does not have a direct effect on bone formation. In menopausal women, it reduces the increased rate of bone tissue turnover to the level of reproductive age, which leads to a general progressive increase in bone mass, a decrease in the breakdown of bone collagen (concentrations of deoxypyridinoline and cross-linked C- and N-telopeptides of type I collagen) in urine and blood serum , incidence of fractures and increased BMD.

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

Efficiency

Film-coated tablets, 2.5 mg. Both continuous and intermittent (one 9-10 week break per quarter) long-term oral use of Bonviva® in the form of 2.5 mg film-coated tablets in menopausal women is accompanied by dose-dependent inhibition of bone resorption, incl. a decrease in the breakdown of bone collagen (the concentration of deoxypyridinoline and cross-linked C- and N-telopeptides of type I collagen) in urine and blood serum, an increase in BMD and a decrease in the incidence of fractures.

After cessation of treatment, there is a return to the pre-treatment increased rate of bone resorption in postmenopausal osteoporosis.

Histological analysis of bone tissue samples obtained after 2 and 3 years of treatment in menopausal women showed normal bone tissue characteristics and no signs of mineralization disorders.

Daily administration of Bonviva® in the form of film-coated tablets, 2.5 mg for 3 years (randomized, double-blind, placebo-controlled study MF4411) is accompanied by a statistically significant reduction in the incidence of radiographic and morphometrically confirmed vertebral fractures by 62%, and clinically confirmed vertebral body fractures by 49%. The reduction in bone loss was accompanied by a significantly less pronounced decrease in the height of patients compared to placebo.

Prevention of fractures was maintained throughout the study, and there was no evidence of the effect fading over time.

A similar reduction in the relative risk of non-vertebral fractures was revealed by 69% in patients from the high-risk group (BMD T coefficient for the femoral neck less than -3.0 SD). These data are consistent with the results of clinical studies of other bisphosphonates.

With daily use of Bonviva® for 3 years, the BMD of the lumbar vertebrae increases by 6.5% compared to the baseline.

Film-coated tablets, 150 mg each, and solution for intravenous administration. Bone Mineral Density (BMD)

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 femur, 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 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% (when taking film-coated tablets) and 92.1% (when administered intravenously) of patients.

Biochemical markers of bone resorption

Film-coated tablets, 2.5 mg. Biochemical markers of bone resorption (urinary concentrations of type I procollagen C-terminal peptide (CTX) and serum osteocalcin) decline to their levels during reproductive age; the maximum reduction is observed after 3-6 months of treatment. Just one month after starting the use of Bonviva 2.5 mg daily and 20 mg intermittently, a clinically significant reduction 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 concentrations) is observed one month after the start of treatment.

Bonviva 2.5 mg daily for the prevention of postmenopausal osteoporosis (study MF4499) increased mean lumbar spine BMD by 1.9% compared with baseline. Regardless of the duration of menopause and the degree of initial loss of basic 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 treatment effect, defined as an increase in BMD compared to the baseline, is observed in 70% of patients.

Film-coated tablets, 150 mg each, 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®, with a maximum decrease of 68% after 6 days. After the third and fourth doses of Bonviva® 150 mg, the maximum decrease in serum CTX by 74% was observed after 6 days. 28 days after taking the fourth dose, a decrease in the suppression of biochemical markers of bone resorption was noted 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 reduction was 76%; compared with the initial value, when using 3 mg IV - 58.6%.

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

Pharmacokinetics and pharmacodynamics

There was no direct dependence of the effect of ibandronic acid on the concentration of the component in plasma.

After oral administration, rapid absorption of ibandronic acid is observed, absorption occurs in the upper gastrointestinal tract. There is a dose-dependent increase in the concentration of the active substance in plasma. The highest concentration is achieved 0.5–2 hours after the drug has been taken on an empty stomach. The level of absolute bioavailability is 0.6%. When taken with food, the absorption process is disrupted; you can take the tablets with clean water. When taken simultaneously with food, the level of bioavailability decreases by 90%. When using the product 1 hour before meals, the level of bioavailability does not decrease.

After the substance enters the bloodstream, it quickly binds to bone tissue or is excreted from the body. Approximately 40–50% of the substance that circulates in the blood penetrates the bone tissue and accumulates.

It binds to blood proteins by 85% when taken orally and by 85–87% when taking Bonviva intravenously.

There is no evidence that the active substance is metabolized.

Approximately half the dose is bound in bone tissue, the part that remains unbound is excreted unchanged in the urine.

The half-life for 2.5 mg tablets is 10-60 hours, for Bonviva 150 mg and IV solution - 10-72 hours. After oral administration, 8 hours later and 3 hours after IV administration, the concentration of the active substance decreases to 10%.

Pharmacokinetics

There was no direct relationship between the effectiveness of ibandronic acid and the concentration of the substance in the blood plasma. The concentration in blood plasma increases in a dose-dependent manner as the dose of the solution for intravenous administration increases from 0.5 to 6 mg. Similar effectiveness of ibandronic acid was confirmed with daily and intermittent use, provided that the total dose administered during the treatment period was the same.

Suction

After oral administration, ibandronic acid is rapidly absorbed from the upper gastrointestinal tract. Plasma concentrations increase dose-dependently when the dose is increased to 50 mg and significantly more when the dose is further increased. Time to reach Cmax (TCmax) - 0.5–2 hours (median - 1 hour) after administration on an empty stomach, absolute bioavailability - 0.6%. Absorption is impaired when taking the drug with food or drinks (except pure water). Concomitant consumption of food or drinks (except pure water) reduces the bioavailability of ibandronic acid by 90%. When taking ibandronic acid 60 minutes before meals, no significant decrease in bioavailability is observed. Ingestion of food or liquid 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 bone tissue and accumulates in it. Apparent final volume of distribution 90 l. Communication with blood plasma proteins when administered orally is 85% and 85–87% when administered intravenously.

Metabolism

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

Removal

40–50% of an orally or intravenously administered dose absorbed into the bloodstream 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 150 mg and solution for intravenous administration - 10–72 hours. The concentration of the drug in the blood decreases quickly and is 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) accounts for 50–60% of the total clearance and depends on creatinine clearance. The difference between total and renal clearance reflects the uptake of the substance into bone tissue.

Pharmacokinetics in special groups of patients

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 Southern European and Asian races. There is not enough data regarding the Negroid 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). For patients with mild or moderate renal impairment (creatinine Cl ≥30 ml/min), no dose adjustment is required.

In patients with severe renal impairment (Cl creatinine <30 ml/min) who received the drug at a dose of 10 mg orally for 21 days, the concentration of ibandronic acid in the blood plasma was 2-3 times higher than in people with normal renal function ( total clearance 129 ml/min). In severe renal impairment, the total clearance of ibandronic acid is reduced to 44 ml/min. In patients receiving the drug at a dose of 0.5 mg IV, total, renal and non-renal clearances of ibandronic acid were reduced by 67, 77 and 50%, respectively. However, an increase in systemic concentration does not impair the tolerability of the drug.

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 by uptake into bone tissue. Therefore, for patients with impaired liver function, no dose adjustment is required.

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

Elderly age. The studied pharmacokinetic parameters do not depend on age. The possible decline in renal function in elderly patients should be taken into account (see section “Patients with impaired renal function” above).

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

Contraindications

The drug Bonviva in all forms is contraindicated in the following cases:

high sensitivity to drug ingredients;
hypocalcemia (must be eliminated before starting treatment).

Contraindications for Bonviva 2.5 mg and IV solution:

pregnancy and breastfeeding;
patient age under 18 years (tablets);
severe renal dysfunction (solution).

Prescribe the medicine with caution for acute conditions in the stomach and esophagus, duodenitis , Barrett's esophagus , dysphagia , gastritis .

BONVIVA film-coated tablets 150 mg No. 1

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 blockade, retinoids, tumors and tumor extracts in vivo. Inhibits endogenous resorption in young (fast-growing) rats, which is manifested by higher bone mass compared to intact animals. Does not interfere with bone mineralization when administered in doses more than 5000 times higher than doses for the treatment of osteoporosis and does not affect the process of replenishment of the osteoclast pool. The selective effect of ibandronic acid on bone tissue is due to its high affinity for hydroxyapatite, which constitutes the mineral matrix of bone. Ibandronic acid inhibits bone resorption in a dose-dependent manner and does not have a direct effect on bone formation. In menopausal women, it reduces the increased rate of bone tissue turnover to the level of reproductive age, which leads to a general progressive increase in bone mass, a decrease in the breakdown of bone collagen (concentrations of deoxypyridinoline and cross-linked C- and N-telopeptides of type I collagen) in urine and blood serum , incidence of fractures and increased BMD. High activity and therapeutic range provide the possibility of a flexible dosage regimen and intermittent administration of the drug with a long period without treatment in relatively low doses. Efficacy 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 femur, 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 loss, Bonviva resulted in a significantly greater change in BMD than placebo. The effect of treatment within a year, defined as an increase in BMD, is observed in 83.9% (when taking film-coated tablets) and 92.1% (when administered intravenously) of patients. Biochemical markers of bone resorption Film-coated tablets, 2.5 mg. Biochemical markers of bone resorption (urinary concentrations of type I procollagen C-terminal peptide (CTX) and serum osteocalcin) decline to their levels during reproductive age; the maximum reduction is observed after 3-6 months of treatment. Just one month after starting the use of Bonviva 2.5 mg daily and 20 mg intermittently, a clinically significant reduction 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 concentrations) is observed one month after the start of treatment. Bonviva 2.5 mg daily for the prevention of postmenopausal osteoporosis (study MF4499) increased mean lumbar spine BMD by 1.9% compared with baseline. Regardless of the duration of menopause and the degree of initial loss of basic bone tissue, the use of Bonviva leads to a significantly more pronounced change in BMD of the lumbar vertebrae. When using Bonviva, the treatment effect, defined as an increase in BMD compared to the baseline, 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, with a maximum decrease of 68% after 6 days. After the third and fourth doses of Bonviva 150 mg, the maximum decrease in serum CTX by 74% was observed after 6 days. 28 days after taking the fourth dose, a decrease in the suppression of biochemical markers of bone resorption was noted to 56%. Clinically significant reductions in serum CTX were obtained after 3, 6 and 12 months of therapy. After a year of therapy with Bonviva 150 mg, the reduction 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 initial value was observed in 83.5% of patients receiving Bonviva 150 mg once every 28 days. Pharmacokinetics There was no direct relationship between the effectiveness of ibandronic acid and the concentration of the substance in the blood plasma. The concentration in blood plasma increases in a dose-dependent manner as the dose of the solution for intravenous administration increases from 0.5 to 6 mg. Similar effectiveness of ibandronic acid was confirmed with daily and intermittent use, provided that the total dose administered during the treatment period was the same. Absorption Following oral administration, ibandronic acid is rapidly absorbed from the upper gastrointestinal tract. Plasma concentrations increase dose-dependently when the dose is increased to 50 mg and significantly more when the dose is further increased. Time to reach Cmax (TCmax) - 0.5–2 hours (median - 1 hour) after administration on an empty stomach, absolute bioavailability - 0.6%. Absorption is impaired when taking the drug with food or drinks (except pure water). Concomitant consumption of food or drinks (except pure water) reduces the bioavailability of ibandronic acid by 90%. When taking ibandronic acid 60 minutes before meals, no significant decrease in bioavailability is observed. Ingestion of food or liquid less than 60 minutes after ibandronic acid reduces its bioavailability and the resulting increase in bone mineral density (BMD). Distribution Once in the systemic circulation, ibandronic acid is rapidly bound to bone tissue or excreted in the urine. 40–50% of the amount of the drug circulating in the blood penetrates well into bone tissue and accumulates in it. Apparent final volume of distribution 90 l. Communication with blood plasma proteins when administered orally is 85% and 85–87% when administered intravenously. Metabolism There is no evidence that ibandronic acid is metabolized. Ibandronate does not inhibit enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4 of the cytochrome P450 system. Excretion: 40–50% of an orally or intravenously administered dose absorbed into the bloodstream 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 150 mg and solution for intravenous administration - 10–72 hours. The concentration of the drug in the blood decreases quickly and is 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) accounts for 50–60% of the total clearance and depends on creatinine clearance. The difference between total and renal clearance reflects the uptake of the substance into bone tissue. Pharmacokinetics in special groups of patients 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 Southern European and Asian races. There is not enough data regarding the Negroid 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). For patients with mild or moderate renal impairment (creatinine Cl ≥30 ml/min), no dose adjustment is 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 is excreted through the kidneys and by uptake 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 plasma proteins (85%), it is likely that hypoproteinemia in severe liver diseases does not lead to clinically significant increase in the concentration of free substance in the blood. Elderly. The studied pharmacokinetic parameters do not depend on age. A possible decrease in renal function in elderly patients should be taken into account. Children. There are no data on the use of Bonviva in persons under 18 years of age.

Side effects

During treatment, a number of side effects common to all forms of Bonviva may occur:

digestive system: gastritis , dyspepsia , diarrhea ;
nervous system: dizziness , headaches ;
skin: rash ;
allergic manifestations: urticaria , angioedema ;
other manifestations: flu-like syndrome, in very rare cases - osteonecrosis of the jaw .

Side effects when using Bonviva tablets:

digestive system: duodenitis , ulcer or stricture of the esophagus , esophagitis ;
general manifestations: weakness, back pain.

Side effects when using Bonviva 150 mg tablets:

digestive system: dysphagia , vomiting , nausea , abdominal pain, reflux , flatulence ;
musculoskeletal system: muscle spasm, muscle stiffness.

Side effects when using Bonviva IV:

short-term decrease in calcium levels in the blood;
digestive system: gastroenteritis , constipation ;
musculoskeletal system: osteoarthritis , pain in the limbs, bones;
nervous system: depression , insomnia ;
general manifestations: reactions at the injection site, weakness, phlebitis , thrombophlebitis , cystitis , nasopharyngitis , bronchitis , urinary tract infections, scleritis , upper respiratory tract infections, hypertension , uveitis , hypercholesterolemia .

Instructions for use of Bonviva (Method and dosage)

Bonviva tablets, instructions for use

The drug in tablet form should be taken orally with water (a full glass), in a standing or sitting position. You should not drink mineral water because it contains a large amount of calcium. After taking the tablet, do not lie down for 60 minutes. Do not suck or chew the tablet, as the risk of ulcers on the esophagus increases.

Bonviva 2.5 mg should be taken once a day, one tablet. This should be done 1 hour before the first meal of the day.

Bonviva 150 mg should be taken 1 tablet once a month. You should take the tablet on the same day. If the next dose was missed, you need to take the pill as soon as the opportunity presents itself. Next, you need to follow the dosage schedule established by your doctor. It is strictly forbidden to take two 150 mg tablets per week.

Bonviva solution, instructions for use

Used for intravenous use only. Do not allow the medicine to get into surrounding tissues. For administration, use those needles that are included with the syringe tube. It is indicated to administer 3 mg intravenously as a bolus (infusion lasts 15–30 s) once every three months. Additionally, taking calcium and vitamin D .

If an injection is missed, it should be given as soon as possible. Further administration of the drug is continued 3 months after the last administration. The product should not be administered more often than once every three months.

During the treatment period, it is important to monitor the levels of phosphorus, magnesium, calcium in the serum, as well as control of kidney function.

Directions for use and doses

Inside, intravenously.

Orally, whole, with a glass (180–240 ml) of clean water in a sitting or standing position; you should not lie down for 60 minutes after taking Bonviva®.

Film-coated tablets, 2.5 mg

2.5 mg (1 tablet) once a day 60 minutes before the first meal of the day, liquid (except water) or other medications and nutritional supplements. Do not use mineral waters that contain a lot of calcium. The tablets should not be chewed or sucked due to the possible formation of esophageal ulcers.

Film-coated tablets, 150 mg

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 nutritional supplements. The tablets should not be chewed or sucked due to possible ulceration of the upper gastrointestinal tract. Do not use mineral water, which contains a lot of calcium.

If you miss a scheduled appointment, you should take 1 tablet. Bonviva® 150 mg, if there are more than 7 days before the scheduled dose, and then take Bonviva® once a 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 scheduled appointment and then continue taking it in accordance with the established schedule, because You cannot take more than 1 tablet. in Week.

Solution for intravenous administration

IV. The drug is for intravenous use only!

Entered only by a specialist. Its intra-arterial administration or contact with surrounding tissue should be avoided.

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

Needles should be used in combination with syringe tubes.

The syringe tube is intended for single administration only.

Standard dosage regimen

3 mg IV bolus (over 15–30 s) once every 3 months.

The patient should additionally take calcium and vitamin D.

If you miss a scheduled injection, you should give the injection as soon as possible. Further administration of the drug should be continued every 3 months after the last administration.

The drug should not be prescribed more than once every 3 months.

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

Dosing in special patient groups

Liver dysfunction. No dose adjustment is required (see section "Pharmacokinetics").

Renal dysfunction. For mild and moderately severe renal dysfunction (creatinine Cl ≥30 ml/min), no dose adjustment is required. When creatinine Cl <30 ml/min, the decision to use Bonviva® should be based on an individual assessment of the risk/benefit ratio for a particular patient (see section “Pharmacokinetics”).

Elderly age. No dose adjustment is required.

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

Overdose

In case of an overdose of tablets, the patient may experience esophagitis , gastritis , hypocalcemia , dyspepsia , heartburn , hypophosphatemia , and ulcers .

In order to bind ibandronic acid, you need to take antacids and milk. Do not induce vomiting, as there is a risk of irritation of the esophagus. You need to remain in a standing position.

In case of an overdose of a solution for intravenous administration, hypophosphatemia , hypocalcemia , and hypomagnesemia . of calcium gluconate , potassium or magnesium sulfate and sodium phosphate is indicated Dialysis is not effective.

Interaction

Interaction of Bonviva tablets may occur in the following cases:

Absorption of the active substance of Bonviva may interfere with the intake of calcium-containing products, as well as products containing iron , magnesium , and aluminum . After oral administration of the drug, they can be taken no earlier than 1 hour later. Similarly, you need to take nutritional supplements containing these minerals.
Taking bisphosphonates and NSAIDs can cause irritation of the gastrointestinal mucosa. This combination must be practiced very carefully.
Intravenous administration of ranitidine increases the level of bioavailability of ibandronic acid by 20%.

Interactions with Bonviva solution may occur in the following cases:

The solution is incompatible with solutions that contain calcium, as well as with other solutions for intravenous administration.

Recommendations for patients taking Zometa or Bonviva:

If the patient comes to the dentist with a history of taking bisphosphonates, then it is necessary to notify the doctor about the fact of taking them (drugs of the group: Zometa, Bonviva, Zoledronate, Bondronat, Boniva, etc. ). There is NO statute of limitations on these medications. Even if you only took bisphosphonates once five years ago, you should tell your dentist.
The dentist you notify about taking bisphosphonates should try to avoid any surgical dental treatment that requires bone healing (tooth extraction, dental implants, etc.). If treatment is still necessary, for example, tooth extraction, then you should be prepared for complications in order to cope with them more easily.

For all questions regarding dental treatment while taking bisphosphonates, please contact the relevant government medical institutions.

special instructions

Before using Bonviva, you need to take into account all risk factors for fractures and postmenopausal osteoporosis .

Before starting to use the drug, it is necessary to correct all disturbances in electrolyte balance, as well as bone metabolism, in particular hypocalcemia . For this purpose, the patient is prescribed a sufficient amount of vitamin D. It is important that the patient receives enough calcium and vitamin D during treatment with Bonviva.

When taking drugs orally, side effects are usually mild or moderate. The manifestation of influenza-like syndrome can be observed after the first dose; it goes away without adjusting the dosage of the drug.

It is important to take into account all recommendations for taking the medication in order to avoid side effects such as ulcers , swallowing problems , and esophagitis . If such symptoms occur, you should stop treatment and consult a doctor.

Serum creatinine should be monitored before each injection.

Cases of osteonecrosis of the jaw when bisphosphonates were prescribed against the background of cancer. The risk of such manifestations increases with surgical intervention to treat dental diseases.

Bonviva is a powerful anti-osteoporotic bisphosphonate.

The article discusses the pathogenesis of osteoporosis, non-drug and drug methods of its treatment, and methods for assessing the effectiveness of the latter. The results of clinical studies of the effectiveness and tolerability of the third generation nitrogen-containing bisphosphonate, Bonviva, in patients with osteoporosis are presented.

Rice. 1. Bone mineralization during Bonviva therapy

Rice. 2. Microarchitecture of developing bone

Osteoporosis (OP) is a systemic metabolic disease of the skeleton, characterized by a decrease in bone mass and a violation of its quality (microarchitecture), which leads to a decrease in bone strength and an increased risk of fractures. Primary AP, predominantly postmenopausal, accounts for 85% of cases.

In AP, there are no characteristic early pathognomonic symptoms, except for previous fractures [1]. Epidemiological studies show a lower incidence of hip and forearm fractures in men compared to women [2]. At the same time, the prevalence of vertebral fractures is the same in patients of both sexes. Mortality rates due to osteoporotic fractures are higher in men.

The state of bone mass is reflected by the indicator “bone mineral density” (BMD). Low BMD in old age may be a consequence of both insufficient accumulation of peak bone mass in youth and accelerated loss of bone mass in later life.

On average, peak bone mass (maximum bone density values) is reached between 25 and 30 years of age, followed by a plateau period. According to G.P. Kotelnikov and S.V. Bulgakova (2010), the rate of bone turnover of the skeleton per year is 8–10%. Moreover, the rate of bone turnover in cortical bone is seven times lower than in trabecular bone (4 and 28%, respectively) [3]. From 35–40 years old, age-related physiological loss of bone mass begins, which in men reaches 0.5–2% per year. Cortical bone tissue accounts for 20%, trabecular bone tissue accounts for up to 30% [4].

Trabecular bone is most susceptible to pathological changes, since metabolic processes occur more actively in it [5]. Thus, the decrease in BMD per unit volume in trabecular bone begins earlier than in cortical bone.

There is an assumption that the high rate of bone turnover of the cancellous layer, along with maintaining mechanical strength (sufficient thickness and density of vertical and horizontal trabeculae) determine adequate resistance to standard loads and play an important role in bone homeostasis [6].

With AP, the trabeculae of the spongy substance become thinner and perforated, the integration of bone structures is disrupted until they disappear in certain areas. Free bone beams do not bear a functional load and undergo autolysis.

Pathogenesis

Refinement of bone structures, decrease in bone mass, as well as disruption of bone microarchitecture are a consequence of changes in the function of osteoblasts (OB), osteocytes (OC) and a decrease in their enzymatic activity.

An imbalance in bone remodeling processes can be expressed by increased activity of osteoclasts (OC) with normal OB function (high metabolic rate), normal OC activity with reduced functional activity of OC (low metabolic rate), reduced activity of OC and OB. Most often, with AP, an increase in the pool of active OCs is observed, accompanied by intensification of bone resorption and a decrease in bone mass [7, 8].

In addition, bone tissue is a target for systemic sex hormones, as well as for their local metabolism and synthesis. Androgens and estrogens directly regulate the activity of osteogenic cells and indirectly (through the metabolism of hormone D) - inhibition of parathyroid hormone [5].

Estrogen receptors have been identified on both OB and OC [9]. The results of many studies confirm the positive effect of estrogens on the differentiation, proliferation and functional activity of OB. Estrogens stimulate the synthesis of collagen proteins, promoting an increase in trabecular bone mass [10]. These steroids inhibit the differentiation and activity of TC, including apoptosis [11, 12].

EP Paschalis et al. (2003) using histomorphometry confirmed the positive effect of estrogens on the bone matrix. Namely: an increase in the percentage of minerals in the trabecular structure of the bone and the number of collagen cross-links. Significant signs of suppression of resorptive activity with a decrease in the number of osteoclastic resorptive lacunae have also been demonstrated [13].

The presence of androgen receptors (AR) in various bone tissue cells (on OB, OC and progenitor cells) [14] suggests the presence of widespread androgenic activity. Androgens stimulate proliferation and differentiation of OB and promote bone mineralization by increasing the production of alkaline phosphatase and collagen by these cells [15]. Evidence has been obtained that the possible indirect effect of androgens is associated with the influence on the synthesis of growth factors (transforming growth factor and insulin-like growth factor 1), which also indicates activation of the OB function [16].

Expression of AR on human OC has not been detected. Therefore, it has been suggested that androgens act on OCs indirectly – through cells of the osteoblastic phenotype [17]. At the same time, a number of studies have shown that sex steroids can also have a direct effect, causing apoptosis of TC. Thus, AG Ruetsche et al. (2005) demonstrated that androgens promote periosteal bone growth in men [18]. Androgens also reduce osteoclastogenesis through inhibition of interleukin 6 production by bone marrow stromal cells, which prevents the maturation and differentiation of TC [15].

In bone tissue, androgens can be converted to estrogens by the enzyme aromatase and influence it through both AR and estrogen receptors [15].

Treatment

Treatment for AP is aimed at:

to prevent new fractures;
slowing down or stopping bone loss (ideally, its gain);
normalization of bone remodeling processes;
reduction of pain, expansion of motor activity;
improving the patient's quality of life.

Non-drug treatment

Non-drug treatment of AP includes educational programs, walking and exercises with body weight, strength, balance training (jumping and running are contraindicated), nutritional correction (consumption of foods rich in calcium (Ca)), cessation of smoking and alcohol abuse, in case of high risk falls – measures aimed at reducing them (treatment of concomitant diseases, vision correction, changing the home environment, teaching the correct pattern of movements, using a cane, wearing stable shoes, etc.).

Non-drug treatment also includes taking calcium and vitamin D supplements. These drugs are used to prevent AP and complement basic therapy.

Calcium is actively involved in physiological processes occurring in bone tissue (mineralization, remodeling). According to clinical recommendations, adequate consumption of this microelement with food helps maintain BMD, slows down age-dependent bone loss, enhances the antiresorptive effect of sex steroids, and therefore should be an important part of the treatment and prevention of AP [1, 5, 19]. During a screening program conducted in several regions of Russia, O.A. Nikitinskaya and N.V. Toroptsova (2012), it was found that the usual daily human diet does not contain enough Ca2+ - no more than 600–800 mg [20]. Similar data were obtained in other European countries [21, 22]. At the same time, the lowest level of microelement intake from food was recorded in men and women over 55 years of age [23].

L. D. McCabe et al. (2004) showed that the use of Ca2+ supplements in persons over 60 years of age reduces bone loss in the femur [24]. The work of BL Riggs et al. (1998) demonstrated that Ca2+ supplementation at a dose of 1600 mg per day for four years reduced the rate of bone loss in the proximal skeleton [25]. F. Scopacasa et al. (1998) found that the administration of 1000 mg Ca2+ per day helps to reduce the level of bone resorption markers and can have an effect on BMD with long-term use [26].

It should be noted that to date, a large number of studies have been conducted to determine the dose of calcium that causes side effects: the formation of stones, calcification of the vascular wall. Data from recent systemic reviews indicate that additional consumption of Ca2+ does not cause the formation of stones in organs, and the process of calcification of the vascular wall does not depend on the level of Ca2+ in the blood or its consumption, it is a consequence of passive deposition in areas of active inflammation. This protective effect, according to the authors, is due to calcium binding of oxalates and phosphates in the intestine, preventing their excessive excretion in the urine, which contributes to the formation of stones [27].

It has been proven that Ca2+ monotherapy is less effective in preventing bone loss than combination therapy with vitamin D. Vitamin D preparations promote better absorption of calcium salts. In their absence, no more than 10% of the macronutrient entering the body can be absorbed [28].

Vitamin D is fat soluble and is stored in adipose tissue. An increase in the number of overweight individuals leads to an increase in the prevalence of vitamin D deficiency, which is explained by its deposition in subcutaneous fat and inaccessibility to the central bloodstream.

In addition, the global trend towards reducing sun exposure and the use of sunscreens, as well as low levels of insolation in some regions of residence, reduce vitamin D synthesis in the skin by 95–98%.

Drug treatment

Many previously recommended drugs for AP are limited in use (strontium ranelate) or discontinued (calcitonin drugs) due to non-compliance with modern safety criteria.

Currently, bisphosphonates are considered the gold standard for drug treatment of AP.

Bisphosphonates were developed at the beginning of the 19th century, but it was only in 1960 that the first study of their effect on bone metabolism was conducted; since 1990, they have been included in treatment regimens for AP [29].

The mechanism of action of bisphosphonates is physicochemical binding to hydroxyapatite on the resorptive surface; accumulation around the OC and creating a high concentration in resorption lacunae. Absorption of bisphosphonates by OCs leads to suppression of the mevalone pathway of cholesterol biosynthesis. In this case, the formation of the cytoskeleton and corrugated border is disrupted, adhesion to the bone matrix is suppressed and the secretion of lysosomal enzymes is reduced. As a consequence, inhibition of OC migration, disruption of metabolism, functional activity, reduction of chemotaxis to sites of resorption and induction of their apoptosis [30–33].

Thus, the main pharmacological effect of this group of drugs is to reduce the rate of bone remodeling with inhibition of the resorption phase [34, 35].

Among the anabolic effects of bisphosphonates, they include the ability to increase the survival of BC and OB by blocking their apoptosis, and increase the synthesis of OB collagen type 1. This is accompanied by positive changes in bone microarchitecture and an increase in the mineral component. As a result, bone trabeculae thicken and bone loss is prevented [36, 37].

E.V. Rudenko et al. (2011) showed that 20–50% of the drug entering the body is deposited in bone tissue [28].

Bisphosphonates have a protective effect on the vascular wall: they suppress the uptake of low-density lipoproteins involved in the development of atherosclerosis [7].

A large number of large randomized clinical trials have been devoted to the use of bisphosphonates in AP. It has been established that with their use, a significant increase in BMD is observed after three months in the area of the vertebral bodies and after a year in the area of the femur [34]. In studies by DM Black et al. (2006–2007) treatment with bisphosphonates for three to five years was associated with a significant increase in BMD and a 70% reduction in vertebral fractures. On the contrary, cessation of therapy led to an increase in bone turnover markers over the next five years [35].

Today, nitrogen-containing bisphosphonates (alendronate, ibandronate) are recognized as one of the most effective drugs for AP in both women and men [34]. The presence of a nitrogen atom in the side chain of drugs determines their ability to inhibit the modification of proteins in the TC, which leads to specific changes and apoptosis of the latter. In addition, preosteoclasts, under the influence of nitrogen-containing ibandronates, lose the ability to differentiate and mature, as a result of which the OC population decreases.

The antiresorptive activity of individual drugs in this group varies significantly, which is associated with the characteristics of their chemical structure and reflects the levels of effective pharmacological and therapeutic doses [7, 38]. In accordance with the increase in antiresorptive potential, the relative activity of alendronate is 100–1000, ibandronate – 1000–10,000.

Monitoring treatment effectiveness

The effectiveness of treatment is assessed using dual-energy X-ray absorptiometry one to three years after the start of therapy, but not more than once a year (it is recommended to use a device from the same manufacturer). Peripheral dual-energy X-ray absorptiometry should not be used for monitoring.

In addition, markers of bone resorption are analyzed.

Treatment is considered effective if BMD increases or remains at the original level. Continued loss of BMD on dual-energy x-ray absorptiometry or a new fracture may indicate poor patient adherence to treatment.

Bonviva

Bonviva (ibandronate) is a third-generation nitrogen-containing bisphosphonate. The drug is taken orally at a dose of 150 mg once a month. After absorption, 40–50% of the drug dose in the systemic circulation binds to bone tissue and accumulates in it, which corresponds to the concept of a high affinity of the drug for bone hydroxyapatite. Once bound, the release of the drug occurs extremely slowly.

It should be noted that when Bonviva is taken one hour before meals, there is no significant decrease in bioavailability.

Like other bisphosphonates, Bonviva is not metabolized in the body and is excreted unchanged in the urine. Clearance of ibandronate depends on renal function. The part of the drug that is bound to bone tissue is not eliminated from the body until the remodeling process is completed in the bone area. The half-life of Bonviva from bones is about a year.

The clinical effectiveness of ibandronate is confirmed by data from a number of multicenter studies that studied its effect on BMD and bone quality, the risk of developing new fractures, and tolerability. In total, 13,000 patients took part in them.

After a year of monthly administration of Bonviva at a dose of 150 mg, BMD in the lumbar spine significantly increased by 4.3%, and after two years – by 6.6%. A significant increase in BMD in the general hip, femoral neck and greater trochanter area was noted after a year of therapy. The achieved values were maintained during the second year of treatment. Thus, on average, BMD relative to the initial level after two years in the femoral neck increased by 3.1%, the greater trochanter - by 6.2%, and in the general hip - by 4.2%. A decrease in the level of bone turnover markers was recorded after three months of treatment and continued throughout the entire observation period.

The results of the multicenter, randomized, double-blind MOBILE trial showed that BMD in the lumbar spine in patients with postmenopausal AP increased with ibandronate administered once a month as effectively as with daily dosing of the drug at a dose of 2.5 mg [39].

Bonviva 150 mg once a month was associated with the largest and most progressive increase in BMD at all proximal femoral sites (at two years p

After three years of ibandronate therapy, the increase in BMD in the femoral neck was 3.5%, in the greater trochanter - 6.2%, in the total hip - 4.1%, in the lumbar spine - 7.6%.

As part of the BONE study, histological and histomorphometric analyzes of bone biopsies were performed to evaluate the effect of ibandronate on the quality and microarchitecture of bone tissue [40]. Oral Bonviva was associated with new bone formation without evidence of impaired bone matrix mineralization (Figure 1). At the same time, an improvement in its microarchitecture was noted (Fig. 2).

The results of numerous studies have shown that taking aminobisphosphonates increases BMD in the lumbar spine and proximal femur and reduces the incidence of fractures by 40−70% [38, 41]. An increase in BMD and a reduction in bone loss are largely associated with an increase in the mineral component of bone, which contributes to the thickening of trabeculae [37, 42].

It should be noted that the effectiveness of therapy for any chronic disease is largely determined by the patient’s adherence to treatment. The results of the multicenter BALTO study on the comparative assessment of patient adherence to treatment showed that 66.1% of patients with postmenopausal AP preferred monthly administration of Bonviva at a dose of 150 mg to weekly administration of alendronate at a dose of 70 mg [43].

The results of the studies showed that a relatively large dose of Bonviva did not have a significant effect on the tolerability of therapy. Additionally, Bonviva was not associated with an increased risk of upper gastrointestinal side effects [44].

The literature describes cases of osteonecrosis of the jaw in patients receiving bisphosphonates. Their frequency is 6.5–12.5% [45–47]. Osteonecrosis of the jaw is a condition characterized by exposure of the bone of the lower and/or upper jaw and persists for at least eight weeks, in the absence of previous radiation or metastases to the jaw [48]. Moreover, only 4% of all cases of osteonecrosis of the jaw were recorded in patients with AP [7]. This complication was more often observed with intravenous administration of long-acting drugs (pamidronate, zoledronic acid) than with oral administration [47, 49].

The pathogenesis of osteonecrosis of the jaw is not fully understood. Some authors associate its development with an imbalance in bone remodeling processes, increased formation of proinflammatory cytokines, and the presence of pathogenic microflora in the oral cavity [46, 47]. Other authors believe that with long-term use, bisphosphonates block OB function by inhibiting OC activity [50].

A cause-and-effect relationship between necrotic changes in the jaw and treatment of AP with bisphosphonates has not been established [48, 51].

One of the advantages of aminobisphosphonates is the minimal risk of jaw necrosis [34].

The above allows us to conclude: Bonviva is an effective drug for the treatment of AP. Its long-term use promotes an increase in BMD in the lumbar spine and proximal femur, as well as a reduction in the risk of fractures.

Bonviva's analogs

Level 4 ATC code matches:
Tevanat

Alendronic acid

Rizendros

Zolerix

Aklasta

Forosa

Xydiphone

Zometa

Ibandronic acid

Fosamax

Ostalon

Alendronate

Bonviva analogues are medicines that contain the same active ingredient. These are the drugs Bondronat , Ossika , Bandron-Zdorovye , Ibandronat .

There are also a number of drugs that have a similar effect on the body. These are the drugs Kalcemin , Veprena , Aquadetrim , Andriol , Bivalos , etc.

Bonviva price, where to buy

You can buy the drug in pharmacies or order it online. The price of Bonviva in tablets is from 1,700 rubles per 1 tablet. 150 mg. The price of Bonviva injections is on average 5,000 rubles. per syringe tube 3 mg.

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine
Online pharmacies in KazakhstanKazakhstan

LuxPharma* special offer

Bonviva tablets 150 mg No. 3 (Hoffmann–La Roche)
RUB 4,380 order

Pharmacy24

Bonviva 150 mg N3 tablets Hoffman-La Roche Ltd, Switzerland
1304 UAH order
Bonviva 150 mg N1 tablets Hoffman-La Roche Ltd, Switzerland
452 UAH order
Bonviva 3 mg 3 ml solution in syringe
2387 UAH. order