Expiration date: 01/2025
The composition and form of issue:
Tablets, film-coated. 1 tablet contains:
ibandronova acid 2.5 mg
(in the form of sodium ibandronate monohydrate 2,813 mg)
excipients: lactose monohydrate povidone (K-25) ICC crospovidone stearic acid silica colloidal anhydrous
the shell of the tablet: hypromellose titanium dioxide talc macrogol 6000
blistere in 14 PCs the paper cartons 2 blister.
Tablets, film-coated. 1 tablet contains:
ibandronova acid 150 mg
(in the form of sodium ibandronate monohydrate 168,75 mg)
excipients: lactose monohydrate povidone (K 25) the ICC crospovidone stearic acid silica colloidal anhydrous
shell: Opadry 00A28646 (hypromellose, titanium dioxide (E 171), talc) macrogol 6000
in blister, 1 or 3 PCs the paper cartons of 1 blister.
The intravenous solution 1 PDS.-tub. (3 ml):
ibandronova acid 3 mg
(in the form of sodium ibandronate monohydrate 3,375 mg)
auxiliary substances: sodium chloride sodium acetate trihydrate glacial acetic acid water for injections
in the syringe tube 3 ml (with sterile needle) in the paper cartons 1 set.
Description pharmaceutical form:
The tablets, coated tablets, 2.5 mg: oval, slightly biconvex, film-coated, white or almost white, on one side of the tablet is engraved "I T" on the other — "L 3".
The tablets, coated tablets, 150 mg: oblong, film-coated, white or almost white on one side of the tablet is engraved "BNVA" on the other — "150".
Solution for intravenous injection: clear, colorless liquid.
Pharmacokinetics:
Revealed no direct relation to the efficiency of ibandronova acid from the concentration of the substance in the blood plasma. Concentration in plasma dozozawisimo increases with increasing doses of a solution for/in the introduction of from 0.5 to 6 mg. Similar effectiveness of ibandronova acid is confirmed in daily and intermittent mode of application, provided that it is the same total dose delivered in a treatment period.
Suction
After oral administration ibandronova acid is quickly absorbed in the upper gastrointestinal tract. Concentration in plasma dozozawisimo increases with increasing doses up to 50 mg and much more — with further increase in dose. The time to reach Cmax (TCmax) — 0,5–2 h (median — 1 h) after ingestion on an empty stomach, absolute bioavailability is 0.6%. The absorption is disturbed while taking the drug with food or drinks (except pure water). The simultaneous intake of food or drink (except pure water) reduces the bioavailability of ibandronova acid 90%. When receiving ibandronova acid for 60 min before meals a significant reduction in bioavailability was observed. The food or liquid in less than 60 min after ibandronova acid reduces its bioavailability caused by increase of bone mineral density (BMD).
Distribution
After entering the systemic circulation ibandronova acid rapidly binds to bone or is excreted in the urine. 40-50% of the amount of drug circulating in the blood, penetrates well into bone tissue and accumulates in it. The final apparent volume of distribution of 90 l. the Relationship with blood plasma proteins when administered to 85% and 85-87% in/in the introduction.
Metabolism
Evidence that ibandronova acid is metabolized, no. Ibandronate does not inhibit enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4 of cytochrome P450.
Excretion
40-50% absorbed into the bloodstream accepted oral or injected dose is bound in the bones and the remainder is excreted unchanged by the kidneys.
Not absorbed drug is excreted unchanged in the feces.
Terminal T1/2 for tablets 2.5 mg is 10-60 h for 150 mg tablets and a solution for/in the introduction — 10-72 h. the concentration of the drug in the blood decreases rapidly and is 10% of maximum after 8 h after oral ingestion and 3 h after I/V administration.
Total clearance of ibandronova acid 84-160 ml/min, Kidney klirens (60 ml/min in healthy women in menopause) is 50-60% General clearance and depends on creatinine clearance. The difference between total and renal clearance reflects the capture substances in the bone tissue.
Pharmacokinetics in special patient groups
Pharmacokinetics ibandronova acid does not depend on gender.
No clinically significant race difference distribution of ibandronova acid in persons of South European and Asian race. Regarding Negroid race data is not enough.
Patients with impaired renal function. In patients with impaired renal function, the renal clearance of ibandronova acid is linearly related to creatinine clearance (Cl creatinine). For patients with impaired renal function mild or moderate severity (creatinine Cl &,ge30 ml/min) dose adjustment is not required.
In patients with severe impaired renal function (Cl creatinine <,30 10="" 21="" 2="" 3="" 129="" 44="" 0="" 5="" 67="" 77="" 50="" p="">,
Patients with impaired liver function. Data on the pharmacokinetics of ibandronova acid in patients with impaired liver function do not exist. The liver does not play a significant role in the clearance ibandronova acid that is not metabolized, and is excreted through the kidneys and by capturing in the bone tissue. Therefore, for patients with impaired liver dose adjustment is not required.
As when administered in therapeutic concentrations ibandronova acid is weakly associated with blood plasma proteins (85%), it is likely that hypoproteinemia in severe liver disease does not cause clinically significant increase in the concentration of free substance in the blood.
Old age. Studied pharmacokinetic parameters do not depend on age. Consider the decline in renal function in elderly patients (see above section "Patients with impaired renal function").
Children. Data on the use of Bonviva from persons under 18 years are not available.
Description pharmacological action:
Ibandronova acid is a highly active nitrogen-containing bisphosphonate, is an inhibitor of bone resorption activity of osteoclasts. Ibandronova acid prevents bone destruction, caused by the blockade of gonadal function, retinoids, tumours and extracts of tumors in vivo. Inhibits endogenous resorption in young (fast growing) rats, which is manifested higher bone mass compared with intact animals.
Does not disrupt bone mineralization when given in doses more than 5,000 times the dose for the treatment of osteoporosis and does not affect the process of replenishing the pool of osteoclasts. The selective action of ibandronova acid on bone tissue due to its high affinity to hydroxyapatite, the mineral component of the bone matrix.
Ibandronova acid inhibits bone resorption and has no direct effect on bone formation. Women in menopause reduces the increased update rate of bone tissue to the level of reproductive age, resulting in an overall progressive increase in bone mass, reductions in rates of cleavage of bone collagen (concentration deoxypyridinoline and cross-stitched C - and N-telopeptides type I collagen) in the urine and blood serum, the frequency of fractures and increased IPC.
High activity and therapeutic range give the possibility of flexible dosing regime and the intermittent use of the drug for a prolonged period without treatment at relatively low doses.
Efficiency
The tablets, coated tablets, 2.5 mg And continuous and intermittent (one 9-10-week break per quarter) long-term oral use of the drug boniva in the form of tablets, coated 2.5 mg in women in menopause is accompanied by dose-dependent inhibition of bone resorption, including the decline of cleavage of bone collagen (concentration deoxypyridinoline and cross-stitched C - and N-telopeptides type I collagen) in the urine and blood serum, an increase in BMD and a decrease in the frequency of fractures.
After cessation of treatment there is a return to pre-treatment increased rate of bone resorption in postmenopausal osteoporosis.
Histological analysis of samples of bone tissue obtained after 2 and 3 years of treatment in women in menopause, showed normal characteristics of bone tissue and absence of signs of mineralization.
Daily intake of the drug boniva in the form of coated tablets, 2.5 mg for 3 years (randomized, double-blind, placebo-controlled study MF4411) is accompanied by a statistically significant reduction in the frequency rentgenograficheski and morphometry-confirmed vertebral body fractures by 62% and of clinically confirmed vertebral body fractures by 49%. The weakening of bone loss is accompanied by a significantly less pronounced reduction of growth patients compared with use of placebo.
Prevention of fractures was preserved during the whole research period, and the signs of fading effect over time was absent.
Found similar reductions in the relative risk nevertebralnah fractures by 69% in patients from high risk groups (the T ratio of the IPC for femoral neck less is 3.0 SD). These data are consistent with the results of clinical trials of other bisphosphonates.
With daily use of the drug Bonviva within 3 years of the IPC of the lumbar vertebrae increased by 6.5% compared to the baseline.
The tablets, coated tablets, 150 mg and for solution for in/in the introduction. Bone mineral density (BMD)
The drug Bonviva 150 mg 1 time per month during the year increases the average IPC of the lumbar spine, hip, femoral neck and trochanter 4.9, and 3.1, 2.2 and 4.6% in/in the introduction of the drug Bonviva 3 mg 1 every 3 months for 1 year increases the average IPC of the thigh, femoral neck and trochanter 2.4, 2.3 and 3.8%, respectively.
Regardless of the length of menopause and the degree of initial loss of bone mass, the use of the drug Bonviva leads to a significantly more pronounced change in the IPC, than placebo. The effect of treatment during the year, defined as the increase in IPC is observed in 83,9% (while taking the tablets covered with a shell) and 92.1% (at/in the introduction) of patients.
Biochemical markers of bone resorption
Tablets, film-coated, 2.5 mg. Biochemical markers of bone resorption (concentration of C-terminal peptide of procollagen type I in urine (STH) and osteocalcin in blood serum) are reduced to their level in the reproductive age, the maximum decrease was observed after 3-6 months of treatment. A month after the beginning of the drug Bonviva 2.5 mg daily and 20 mg intermittent mode achieved a clinically significant reduction in biochemical markers of bone resorption by 50 and 78%, respectively moreover, a slight decrease in these parameters were observed after a week of treatment. A clinically significant reduction in biochemical markers of bone resorption (CTX concentration in the urine) is observed a month after the start of treatment.
A daily intake of 2.5 mg of the drug Bonviva for the prevention of postmenopausal osteoporosis (study MF4499) increases the average IPC of the lumbar vertebrae by 1.9% compared to baseline. Regardless of the length of menopause and the degree of initial loss of ground substance of bone tissue, the use of the drug Bonviva leads to a significantly more pronounced change in the IPC of the lumbar vertebrae. In applying the drug Bonviva the effect of treatment, defined as the increase in IPC, compared to baseline, is observed in 70% of patients.
The tablets, coated tablets, 150 mg and for solution for in/in the introduction. The decrease in serum concentrations of STH 28% was observed already after 24 h after the first dose of 150 mg Bonviva, the maximum reduction was 68% after 6 days. After the third and fourth drug Bonviva 150 mg maximum decrease in serum STH 74% was observed after 6 days. 28 days after administration of the fourth dose, a decrease in suppression of biochemical markers of bone resorption up to 56%.
A clinically significant decrease in serum STH received through 3, 6 and 12 months of therapy. After a year of drug therapy Bonviva 150 mg the reduction was 76% compared to the initial value, the application of 3 mg/in to 58.6%.
The decrease in CTX than 50% compared to baseline value was observed in 83.5% of patients receiving the drug Bonviva 150 mg 1 every 28 days.
Indications:
Postmenopausal osteoporosis to prevent fractures.
Contraindications:
For all dosage forms:
- hypersensitivity to ibandronova acid or other components of the drug
- hypocalcemia (before the use Bonviva, as well as in the appointment of all bisphosphonates used to treat osteoporosis, you should correct the hypocalcemia).
For coated tablets, 2.5 mg and mortar for on/in the introduction:
- pregnancy
- the lactation period.
Additionally, for coated tablets, 2.5 mg:
the age of 18 (no clinical experience).
Additionally, the solution for the on/in the introduction:
severe impairment of renal function (creatinine serum >200 µmol/l (2.3 mg/DL) or a creatinine Cl of <30 p="">,
With caution (for coated tablets, 2.5 and 150 mg) is a severe violation of the kidney (Cl creatinine of <30 p="">,
Application of pregnancy and breast-feeding:
Category C.
Pregnancy. During pre-clinical studies not found evidence of direct embryotoxic or teratogenic effects at dose exceeding the dose for a person at least 35 times, adverse effects on development of the offspring in rats F1 is not detected. Adverse effects ibandronova acid in reproductive toxicity studies in animals were the same as all bisphosphonates: reducing the number of embryos, in violation of the birth process, increasing the frequency of visceral anomalies (syndrome of narrowing of the UPJ).
Experience of clinical application of the drug Bonviva in pregnant women no.
The lactation period. Excreted in milk in animals. After 24 h, the concentration of ibandronova acid in blood plasma and milk is the same and corresponds to 5% of the maximum.
Unknown is displayed if ibandronova acid in breast milk in women.
Side effects:
- Common to all dosage forms
- Gastrointestinal: dyspepsia, diarrhea, gastritis.
- From the side of musculoskeletal system: arthralgia, myalgia.
- From the nervous system: headache, dizziness.
- Body as a whole: flu-like syndrome.
- The skin and its appendages: rash.
- Hypersensitivity reactions: angioedema, urticaria.
- Very rarely in the appointment of ibandronova acids was noted that osteonecrosis of the jaw.
- Total for coated tablets
- Gastrointestinal: esophagitis, ulcers or esophageal stricture, duodenitis.
Additionally, for coated tablets, 2.5 mg:
The skin and its appendages: urticaria.
The body as a whole: weakness, back pain.
Laboratory parameters: decrease in the activity of alkaline phosphatase.
Additionally, coated tablets, 150 mg
Gastrointestinal: nausea, vomiting, abdominal pain, dysphagia, flatulence, gastro-oesophageal reflux esophageal.
From the side of musculoskeletal system: muscle stiffness, muscle spasm.
Additionally, for solution for I/V administration
Bonviva, like other bisphosphonates, when administered intravenously, may cause a temporary decrease in the level of calcium in the blood serum.
Gastrointestinal: constipation, gastroenteritis.
From the side of musculoskeletal system: pain in the limbs and bones, osteoarthritis.
From the nervous system and psychic sphere: insomnia, depression.
The body as a whole: weakness, reaction at the injection site, phlebitis, thrombophlebitis, nasopharyngitis, cystitis, infections of the urinary tract, bronchitis, upper respiratory tract infection, arterial hypertension, hypercholesterolemia, uveitis, scleritis.
Drug interactions:
For tablets, coated
Products containing calcium and other multivalent cations (such as aluminium, magnesium, iron), including milk and solid food, can disrupt the absorption of the drug should be consumed no earlier than 60 min after oral administration Bonviva.
Food calcium supplements, antacids and medications containing polyvalent cations (e.g. aluminium, magnesium, iron), can disrupt the absorption of ibandronova acid and should be taken no earlier than 60 min after administration Bonviva.
Bisphosphonates and NSAIDs can cause irritation of the gastrointestinal mucosa. You should exercise particular caution when using NSAIDs at the same time with the drug Bonviva. With simultaneous use of aspirin or NSAIDs and drug Bonviva for 1 year, the incidence of side effects from the upper gastrointestinal tract was the same.
Ranitidine/increases the bioavailability of ibandronova acid 20%. Dose adjustment ibandronova acid with the simultaneous use with blockers of H2-histamine receptors or other drugs that increase the pH in the stomach, not required.
For solution for in/in the introduction
Bonviva incompatible with calcium-containing solutions and other solutions for on/in the introduction.
For both dosage forms
Ibandronova acid does not affect the activity of the major isoenzyme of cytochrome P450. In therapeutic concentrations ibandronova acid is weakly bound to plasma proteins the blood, so it is unlikely that it will be displaced from plots of protein binding of other drugs. Ibandronova acid is excreted only through the kidneys and does not undergo any biotransformation. Apparently, the way out ibandronova acid does not include any transport system involved in the excretion of other drugs.
Method of application and dose:
Inside, in/V.
Inside, whole with a full glass (180-240 ml) clean water in position "sitting" or "standing", should not lie down within 60 minutes after administration Bonviva.
The tablets, coated tablets, 2.5 mg
2.5 mg (1 table.) once a day for 60 min prior to the first day of this meal, liquids (except water) or other medications and supplements. You cannot use mineral water that contain many calcium. Tablets should not be chewed or sucked due to possible ulceration of the esophagus.
The tablets, coated tablets, 150 mg
150 mg (1 table.) 1 once a month (preferably on the same day of each month), for 60 min prior to the first day of this meal, liquids (except water) or other drugs and nutritional supplements. Tablets should not be chewed or sucked due to possible ulceration of the upper gastrointestinal tract. You cannot use mineral water, which contains a lot of calcium.
In case of missing a scheduled appointment should take 1 tab. drug Bonviva 150 mg if prior to the scheduled appointment more than 7 days, continue to take the drug Bonviva 1 time per month in accordance with the established timetable. If, prior to the next scheduled appointment less than 7 days, you must wait until the next admission plan to continue the reception in accordance with a set schedule, because you can not make more than 1 table. a week.
Solution for the on/in the introduction
The Medication only for/in use!
Enter only specialist. It should not be intra-arterial administration or falling into the surrounding tissue.
Before administration is necessary to examine the solution for the absence of impurities or discoloration.
Use the needle supplied with the syringe-tubes.
The EpiPen is intended only for single administration.
The standard dosing regimen
3 mg IV bolus (within 15-30 s) 1 time in 3 months.
Additionally, the patient should take calcium and vitamin D.
In the case of missing a scheduled injection should be injected as soon as an opportunity arises. Further, the introduction of the drug to continue every 3 months after the last injection.
It is impossible to prescribe the drug more than 1 time in 3 months.
During treatment should monitor kidney function, serum calcium, phosphorus and magnesium.
Dispensing from specific patient groups
The liver dysfunction. Dose adjustment is not required (see section "Pharmacokinetics").
The impairment of renal function. For weak and moderately expressed violation of the kidney (Cl creatinine &,ge30 ml/min) dose adjustment is not required. When Cl creatinine of <30 p="">,
Old age. Dose adjustment is not required.
Children. Safety and effectiveness in persons younger than 18 years have not been established.
Overdose:
For tablets, coated
Symptoms: dyspepsia, heartburn, esophagitis, gastritis, ulcers, hypocalcemia, hypophosphatemia
Treatment: specific information is missing. For binding of the drug Bonviva use milk or antacids. Due to the risk of esophageal irritation, should not induce vomiting and should remain in an erect standing position.
For solution for in/in the introduction
Symptoms: hypocalcemia, hypophosphatemia, hypomagnesemia.
Treatment: specific information is missing. A clinically significant decrease in calcium, phosphate and magnesium in blood serum can be korrigirovat/with the introduction of calcium gluconate, potassium or sodium phosphate and magnesium sulfate, respectively. Dialysis is ineffective if assigned after 2 h after drug administration.
Special instructions:
Risk factors for development of postmenopausal osteoporosis and fractures — family history, a history of bone fractures, early menopause, active bone metabolism, low BMD (at least 1.0 SD below the average IPC in reproductive age), fragile Constitution, and whether the women of South European and Asian race, Smoking. These factors are important when deciding on the appointment of the drug Bonviva of tablets, coated tablets, 2.5 mg to prevent osteoporosis.
Osteoporosis may be confirmed in identifying low BMD (T index <,than -2.0 sd="" standard="" deviation="" -2="" 5="" p="">,
Prior to use of the drug Bonviva should korrigirovat hypocalcaemia and other disturbances of bone metabolism and electrolyte balance. Patients should consume enough calcium and vitamin D.
If the patient gets from food is not enough calcium and vitamin D, you should additionally take them as supplements.
In oral administration drug side effects usually weakly or moderately expressed. Transient flu-like syndrome observed after the first dose and resolved on their own without treatment. No marked increase in the frequency of undesirable effects from the upper gastrointestinal tract in patients with gastrointestinal disease (including peptic ulcer without hemorrhage and hospitalization, dyspepsia or reflux-disease).
The use of oral bisphosphonates is often accompanied by violation of the swallowing, esophagitis and ulceration of the esophagus and stomach, so it is necessary to pay special attention to the implementation guidelines for the use of the drug (position "sitting" or "standing" within 60 min after administration).
At the onset of signs and symptoms of possible lesions of the esophagus (the emergence or strengthening of swallowing, pain when swallowing, pain behind the breastbone, heartburn) should stop taking Bonviva and consult a doctor.
Experience in post-marketing use Bonviva limited.
Before each injection, you must determine the creatinine in the blood serum.
In the appointment of bisphosphonates was noted that osteonecrosis of the jaw. Most cases reported in patients with cancer during dental treatments, several cases of patients with postmenopausal osteoporosis or other diseases. Risk factors for development of osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapy (chemotherapy, radiotherapy, corticosteroids) and other violations of the (anemia, coagulopathy, infection, gum disease). The majority of the cases observed in the on/in the appointment of bisphosphonates, but individual cases were observed in treated with the drugs inside.
Surgical dental intervention during therapy with bisphosphonates may increase symptoms of osteonecrosis of the jaw. It is unknown whether it reduces the risk of osteonecrosis of bisphosphonates cancel. The decision on treatment must be taken for each patient individually after assessing the risk/benefit.
