Ibandronate Teva is an Israeli drug that belongs to the group of biosphosphonates and inhibitors of bone tissue resorption (osteoclasts). The average cost of one package of such medicine is 1,500 rubles.
The active ingredient of Ibandronate Teva is ibandronate acid (in the medicine it is presented in the form of sodium ibandronate monohydrate), its dosage in one tablet of the drug is 150 mg.
In addition to it, the drug contains:
- Cellulose microcrystals;
- Polyvinylpyrrolidone and its insoluble low molecular weight form;
- Colloidal silica;
- Octadecanoic acid;
- Titanium dioxide E171;
- Hypromellose 3cP and 6cP;
- PEG 400;
- Polysorbate 80.
The pharmacological form of Ibandronate Teva is tablets. They are white in color, oblong and biconvex in shape, and have “I 150” engraved on one side. The tablets are packed in blister packs.
In pharmacies, Ibandronate Teva is available only with a prescription.
Pharmacological properties of Ibandronate
Ibandronate acid is a highly active nitrogen-containing biophosphonate that inhibits bone destruction and the activity of osteoclasts - these are large multinucleated cells that destroy collagen and dissolve the mineral component of bone.
This substance can stop pathological processes of different nature:
- Blockade of the functions of the sex glands (menopause);
- Retinoids;
- Tumors and their extracts and so on.
Ibandronate does not affect the quantitative value of osteoclasts and does not disrupt the processes of mineralization in bone tissue. Such effects from the acid are ensured due to its high affinity with hydroxypatite (it is part of the mineral matrix of bones).
In case of menopausal destruction of bone tissue, Ibandronate helps to reduce the rate of bone destruction to the level that a woman had during reproductive age. This means that after undergoing therapy with ibandronate acid drugs, bone mass should begin to grow quickly.
The authenticity of these factors is confirmed by a decrease in the blood plasma and urine of the amount of biochemical markers of bone destruction (these are deoxypyridinoline and cross-linked collagen telepeptides of the first type), a decrease in the number of fractures in patients and an improvement in bone mineral density.
Teva Ibandronate is a truly therapeutically active drug. Its effectiveness has been proven by many studies. For example, statistics show that one-year treatment with Ibandronate led to an increase in bone mineral density in more than 85% of patients.
The duration of the menopausal period and the degree of the pathological process were not clinically significant.
Ibandronate-Teva tablets p/o 150 mg No. 1
Name
Ibandronate-Teva tab.p/film.vol. 150 mg per bl. in pack No. 1
Main active ingredient
Ibandronic acid
Release form
Pills
Dosage
150mg
pharmachologic effect
Mechanism of action. 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. Does not interfere with bone mineralization when administered in doses more than 5000 times higher than doses for the treatment of osteoporosis. 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.
Pharmacodynamics
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 bone mineral density (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 Bone mineral density (BMD) Taking Ibandronate-TEVA 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%. Regardless of the duration of menopause and the degree of initial bone loss, the use of Ibandronate-TEVA 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% of patients. Biochemical markers of bone resorption A decrease in the serum concentration of type I procollagen C-terminal peptide (CTX) by 28% was noted within 24 hours after the first dose of 150 mg of Ibandronate-TEVA, the maximum decrease was 68% after 6 days. After the third and fourth doses of Ibandronate-TEVA 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 Ibandronate-TEVA 150 mg, the reduction is 76%. A decrease in CTX of more than 50% compared to the initial value was observed in 83.5% of patients receiving Ibandronate-TEVA 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. 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. The time to reach the maximum concentration of TStax is 0.5-2 hours (median -1 hour) after administration on an empty stomach, absolute bioavailability is 0.6%. 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 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 the bone tissue and accumulates in it. Apparent final volume of distribution 90 l. Connection with blood plasma proteins 85%. Metabolism There is no evidence that ibandronic acid is metabolized. Excretion 40-50% of an orally taken dose absorbed into the bloodstream is bound in the bones, and the rest is excreted unchanged by the kidneys. The drug that is not absorbed is excreted unchanged in the feces. Terminal T1/2 10 - 72 hours. The concentration of the drug in the blood decreases quickly and is 10% of the maximum 8 hours after oral 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 β-substance in 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 (CC). For patients with mild or moderate renal impairment (creatinine clearance >30 ml/min), no dose adjustment is required. In patients with severe renal impairment (CK
Indications for use
Treatment of osteoporosis in postmenopausal women with an increased risk of fractures (see section “Pharmacokinetics”). A reduction in the risk of vertebral fracture has been demonstrated, but the effect on the risk of femoral neck fracture has not been established.
Directions for use and doses
Dosage The recommended dose is one 150 mg film-coated tablet once a month. It is recommended to take the tablet on the same day of each month. Ibandronate-Teva should be taken after an overnight fast (no earlier than 6 hours after the last meal) and one hour before the first meal or drink (not water), any other oral medicinal product, dietary supplement, including calcium, during the day (see section “Interaction with other drugs”). If a dose is missed, the patient is advised to take one Ibandronate-Teva 150 mg tablet in the morning immediately if there are more than 7 days left before the next scheduled dose. In the future, you must adhere to the initially planned intake schedule. If the next scheduled dose is to be taken within 7 days, the patient should wait for the next dose and then continue to take one tablet once a month as originally planned. Patients should not take two tablets in the same week. Patients should additionally take calcium and/or vitamin D if their dietary intake is insufficient (see sections "Precautions" and "Interactions with other drugs"). The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be reassessed periodically based on the benefits and potential risks of using Ibandronate-Teva for each individual patient, especially when used for 5 years or more. Special Populations Patients with Renal Impairment The use of Ibandronate-Teva is not recommended in patients with creatinine clearance below 30 ml/min due to limited clinical experience (see sections "Precautions" and "Pharmacokinetics"). In patients with mild or moderate renal impairment (creatinine clearance 30 ml/min and above), no dose adjustment is required. Patients with hepatic impairment No dose adjustment is required (see section "Pharmacokinetics"). Elderly patients (>65 years) No dose adjustment is required (see section “Pharmacokinetics”). Children There is no information on the use of Ibandronate-Teva in children under 18 years of age; Ibandronate-Teva has not been studied in this population (see sections “Pharmacodynamics” and “Pharmacokinetics”). Method of administration Oral administration - Tablets should be swallowed whole with a full glass of water (180-240 ml), the patient should take the tablets while sitting or standing in an upright position. Do not use water with a high concentration of calcium. If there is a suspicion of high levels of calcium in tap water (hard water), it is recommended to use bottled water with a low mineral content. After taking Ibandronate-Teva, patients should not lie down for 1 hour. Ibandronate-Teva tablets should be taken with water only. The tablet should not be chewed or dissolved due to the potential for oropharyngeal ulceration.
Use during pregnancy and lactation
Pregnancy Ibandronate-Teva is indicated for use only in postmenopausal women and should not be used in women of childbearing potential. There is insufficient data on the use of ibandronic acid in pregnant women. Studies in rats have shown some reproductive toxicity (see Preclinical Safety Data). The potential risk to humans is unknown. Ibandronate-Teva should not be used during pregnancy. Breastfeeding Period It is not known whether ibandronic acid is excreted in a woman's breast milk. Studies in lactating rats have shown the presence of low concentrations of ibandronic acid in milk after intravenous administration. Ibandronate-Teva should not be used during breastfeeding. Fertility There are no data available on the effects of ibandronic acid in humans. Reproductive studies conducted in rats treated orally with the drug showed decreased fertility. In rat studies administered intravenously, ibandronic acid decreased fertility when administered at high daily doses (see Preclinical Safety Data).
Precautionary measures
Hypocalcemia Existing hypocalcemia should be corrected before starting therapy with Ibandronate-Teva. It is also necessary to eliminate other disorders of bone and mineral metabolism. Ensure adequate calcium and vitamin D intake in all patients. Gastrointestinal Irritation Use of oral bisphosphonates may result in local irritation of the upper gastrointestinal mucosa. Due to the possible irritating effect of the drug and the worsening of the existing underlying gastrointestinal disease, caution should be exercised when prescribing Ibandronate-Teva to patients with active pathological processes localized in the upper gastrointestinal tract (for example, established Barrett's esophagus, dysphagia, other diseases of the esophagus , gastritis, duodenitis or ulcers). Adverse reactions such as esophagitis, esophageal ulcers and esophageal erosion, some severe and requiring hospitalization, rarely with bleeding or esophageal narrowing or perforation, have been reported in patients treated with oral bisphosphonates. The risk of severe esophageal adverse effects increases in patients who do not follow dosing recommendations or who continue to take oral bisphosphonates even after symptoms of esophageal irritation have developed. Patients should pay particular attention to and follow dosage recommendations (see section "Dosage and Administration"). Clinicians should be especially alert for any signs or symptoms indicating a possible esophageal reaction, and patients should be warned to stop taking Ibandronate-Teva and seek medical attention if they experience dysphagia, pain with swallowing, or substernal pain. the appearance or worsening of heartburn. Although no increased risk was observed in controlled clinical trials, post-marketing reports of gastric and duodenal ulcers with oral bisphosphonates have been published, some of them severe and with complications. Since the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and bisphosphonates may be accompanied by irritation of the gastrointestinal mucosa, caution should be exercised when using them simultaneously. Osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) has been very rarely reported post-marketing in patients receiving bisphosphonates for the treatment of osteoporosis (see Adverse Reactions section). The initiation of treatment or a new course of treatment should be delayed in patients with non-healing open soft tissue injuries in the oral cavity. A dental examination and individual risk-benefit assessment should be performed before initiating bisphosphonate treatment in patients with underlying risk factors. The following risk factors should be considered when assessing a patient's risk of developing ONJ: Potency of the drug to inhibit bone resorption (higher risk for highly active compounds), route of administration (higher risk for parenteral administration), and cumulative dose of bone resorption therapy Cancer, comorbidities conditions (eg, anemia, coagulopathy, infection), smoking Concomitant medications: corticosteroids, chemotherapy, angiogenesis inhibitors, radiation therapy to the head and neck Poor oral hygiene, periodontal disease, poorly fitting dentures, dental history, invasive dental procedures such as extractions tooth All patients should be advised to maintain good oral hygiene by undergoing regular dental checkups, and should promptly report any oral symptoms such as loose teeth, pain or swelling, or non-healing sores or tooth loss during treatment. While taking the drug, invasive dental procedures should be performed only after a thorough examination and should be avoided before taking the drug. A management plan for patients who develop ONJ should be created in close collaboration between the treating physician and a dentist or oral surgeon with experience in ONJ. If possible, temporary discontinuation of bisphosphonates should be considered until associated risk factors improve. Osteonecrosis of the external auditory canal Osteonecrosis of the external auditory canal is associated mainly with long-term bisphosphonate therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients with symptoms of ear disease, including chronic ear infections, who are receiving bisphosphonates. Atypical femoral fractures Atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonates, primarily in patients receiving long-term treatment for osteoporosis. These transverse and short oblique fractures can be localized along the entire length of the femur from the lesser trochanter to the supracondylar eminence. Atypical fractures occur spontaneously or as a result of minor injuries. In the weeks or months before a complete hip fracture occurs, some patients experience hip or groin pain, which is often accompanied by radiographic evidence of a stress fracture. Because atypical fractures are often bilateral, it is necessary to monitor the other hip in patients with a femoral fracture. Slow consolidation of these fractures was noted. If an atypical fracture is suspected and pending examination results, discontinuation of bisphosphonate therapy should be considered based on an assessment of the benefit/risk ratio in each individual case. Patients should be advised to report any hip or groin pain during bisphosphonate therapy. If these symptoms are present, it is necessary to conduct an examination to identify an incomplete hip fracture. Renal failure Due to limited clinical experience, Ibandronate-Teva is not recommended for use in patients with creatinine clearance below 30 ml/min. (see section "Pharmacokinetics").
Interaction with other drugs
Products containing calcium and other polyvalent cations (for example, aluminum, magnesium, iron), including milk and solid foods, may interfere with the absorption of the drug and should be consumed no earlier than 60 minutes after oral administration of the drug. Calcium supplements, antacids and medications containing polyvalent cations (eg, aluminum, magnesium, iron) may interfere with the absorption of ibandronic acid and should therefore be taken no earlier than 60 minutes after taking the drug. Bisphosphonates and nonsteroidal anti-inflammatory drugs (NSAIDs) can cause GI irritation. Particular caution should be exercised when using NSAIDs concomitantly with Ibandronate-TEVA. When aspirin or NSAIDs were used concomitantly with Ibandronate-TEVA for 1 year, the incidence of upper gastrointestinal side effects was similar. IV ranitidine increases the bioavailability of ibandronic acid by 20%. No dosage adjustment of ibandronic acid is required when used concomitantly with H2-histamine receptor blockers or other drugs that increase gastric pH. Ibandronic acid does not affect the activity of the main isoenzymes of the cytochrome P450 system. At therapeutic concentrations, ibandronic acid binds weakly to plasma proteins and is therefore unlikely to displace other drugs from protein binding sites. Ibandronic acid is excreted only through the kidneys and does not undergo any biotransformation. It appears that the elimination pathway of ibandronic acid does not involve any of the transport systems involved in the elimination of other drugs. If you are taking any other medications, be sure to inform your doctor! While being treated with Ibandronate-TEVA, do not take any other medicines (including over-the-counter medicines) without first consulting your doctor. Uncontrolled treatment can harm your health!
Contraindications
Hypersensitivity to ibandronic acid or any of the components of the drug that are listed in the Composition section Hypocalcemia Abnormalities of the esophagus, with esophageal emptying problems such as stricture or achalasia Inability to stand or sit upright for at least 60 minutes.
Compound
Active ingredient: ibandronic acid 150 mg (in the form of sodium ibandronate monohydrate 168.80 mg). Auxiliary ingredients: microcrystalline cellulose, povidone, crospovidone, colloidal anhydrous silicon dioxide, stearic acid. Film shell: Opadry white YS-1-7003 (titanium dioxide E171, hypromellose, polyethylene glycol, polysorbate).
Overdose
There is no specific information on the treatment of overdose with Ibandronate-Teva. However, based on available information for drugs in this class, overdose with the oral form may result in upper gastrointestinal adverse reactions (such as stomach upset, dyspepsia, esophagitis, gastritis, or ulcers) or hypocalcemia. Milk or antacids should be used to bind Ibandronate-Teva, and any other adverse reactions should be treated symptomatically. Due to the risk of esophageal irritation, vomiting should not be induced and the patient should remain upright.
Side effect
Summary of Safety Profile The most serious adverse reactions reported were anaphylactic reaction/shock, atypical hip fractures, osteonecrosis of the jaw, and inflammatory eye disease (see Description of Selected Adverse Reactions and Precautions). The most common adverse reactions are arthralgia and influenza-like syndrome, which are usually observed after taking the first dose and are characterized by a weak or moderate degree of intensity, short duration and resolve with continued treatment without additional measures (see subsection “Influenza-like syndrome”). Adverse reactions presented in tabular form Table 1 provides a complete list of identified adverse reactions. The safety of daily oral ibandronic acid 2.5 mg was assessed in 1251 patients in four placebo-controlled clinical trials. The majority of patients participating in these studies had previously participated in the main 3-year study of MF4411. In a pivotal two-year study in postmenopausal women with osteoporosis (BM 16549), the overall safety profiles of ibandronic acid 150 mg once monthly and ibandronic acid 2.5 mg daily were similar. The proportion of patients experiencing any adverse reaction was 22.7% and 25.0% after 1 year and 2 years of ibandronic acid 150 mg once monthly, respectively. In most cases, adverse reactions did not lead to discontinuation of the drug. Adverse reactions are listed according to damage to organs and organ systems (MedDRA Medical Dictionary of Regulatory Activities) and frequency of development. Classification of adverse reactions according to the frequency of their development: very frequent (?1/10), frequent (?1/100,
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Pharmacokinetic properties
It is immediately worth noting that the effectiveness of the drug does not greatly depend on the dose administered to the patient. Within a couple of hours after administration, the maximum concentration of ibandronate acid in the blood plasma is reached.
The drug has good bioavailability, but it is significantly reduced if the patient eats less than an hour after taking the drug or drinks it with something other than plain water.
Ibandronate acid is more than 80% bound to plasma proteins. About 45% of the components of the product are absorbed from the blood and settle in the bones. Residues of the drug are excreted in urine or feces.
Ibandronic Acid Sandoz®
The drug should only be administered intravenously. Accidental intra-arterial administration of the drug or contact with surrounding tissues should be avoided, which can lead to tissue damage.
Use the concentrate for preparing a solution for infusion once.
Usually used in a hospital setting.
Use only clear, freshly prepared solution without foreign particles. From a microbiological point of view, the infusion solution for intravenous administration must be used immediately after preparation. If the drug is not used immediately, then the time and storage conditions of the prepared solution are the responsibility of the medical professional.
The prepared solution can be stored for no more than 24 hours at a temperature of 2 to 8 °C if the dilution is carried out under controlled and validated aseptic conditions.
Should not be mixed with solutions containing calcium. Discard unused solution.
Release of the drug into the environment along with waste must be minimized. Do not dispose of with sewage or household waste.
Established systems for drug disposal must be used.
Standard dosage regimen
Metastatic bone lesions
6 mg IV drip over at least 15 minutes, once every 3 to 4 weeks. The concentrate for preparing a solution for infusion should be diluted in 100 ml of 0.9% sodium chloride solution or 5% dextrose solution.
Hypercalcemia in malignant neoplasms
Therapy with Ibandronic acid Sandoz® is started after adequate rehydration with 0.9% sodium chloride solution. The drug is used only in the form of 1-2 hour intravenous infusions. The concentrate for preparing a solution for infusion is diluted in 500 ml of 0.9% sodium chloride solution or 500 ml of 5% dextrose solution.
The dose of the drug depends on the severity of hypercalcemia, as well as on the type of malignancy. As a rule, patients with osteolytic metastases require lower doses of the drug than patients with the humoral type of hypercalcemia. In most cases, patients with severe hypercalcemia (albumin-corrected serum calcium >3 mmol/L or >12 mg/dL) are given a single dose of 4 mg. Patients with moderate hypercalcemia (albumin-corrected serum calcium <3 mmol/l or <12 mg/dl) - 2 mg. The maximum single dose used in clinical studies, 6 mg, does not lead to an increase in effect.
In most cases, elevated serum calcium concentrations return to normal within 7 days. The average time for the development of relapse of hypercalcemia (repeated increase in serum albumin-corrected calcium concentration more than 3 mmol/l) was 18-19 days at doses of 2 and 4 mg. The average time for relapse to develop when 6 mg of the drug was administered was 26 days.
A limited number of patients (n=50) received a second infusion to treat hypercalcemia. If there is insufficient effectiveness or if hypercalcemia recurs, repeated administration is possible.
The concentration of albumin-corrected calcium in serum (mmol/l) is calculated using the formula:
serum calcium (mmol/l) - [0.02 x albumin (g/l)] + 0.8.
Serum albumin-corrected calcium concentration in mg/dL is calculated using the formula:
serum calcium (mg/dL) + 0.8 x [4 - albumin (g/dL)].
Indications and contraindications for use
The main indication for the use of Ibandron Teva is postmenopausal osteoporosis. With osteoporosis, tissues become very fragile and susceptible to fractures (especially the vertebral bones). By inhibiting the destruction of bone tissue and improving the quality of bone mineral density, Ibandronate prevents the occurrence of fractures and inhibits the progression of the disease.
Not everyone can take ibandronate. Some patients should not be treated with this drug:
- If you are hypersensitive to ibandronate acid or the auxiliary components of the drug;
- With low calcium levels;
- For pathologies of the esophagus, which are accompanied by a violation of the passage of food;
- If you are under 18 years of age.
Also, Ibandronate Teva is contraindicated in those patients who cannot remain in an upright position for an hour after taking the drug (meaning the body, so that the person can stand or sit).
Pharmacodynamics and pharmacokinetics
After taking the tablet, the acid is quickly absorbed into the body in the upper parts of the digestive tract and reaches its maximum concentration after 0.5-2 hours if taken on an empty stomach. If you take food or drinks at the same time (not including clean water), bioavailability is reduced by 90 percent. Eating food or drinks half an hour after taking acid reduces bioavailability by 30 percent. Eating food or drinks one hour after taking the acid does not affect bioavailability. If you take acid two hours after eating, bioavailability decreases to 75 percent.
When ibandronic acid enters the systemic circulation, it binds to bone tissue at a high rate or is excreted in the urine. It is 87 percent bound to plasma proteins at therapeutic concentrations. Metabolization data are not available.
On average, from 40 to 50 percent of the acid that circulates in the blood penetrates the bone tissue, where accumulation occurs, the rest is excreted unchanged by the kidneys.
How to take the medicine?
The standard dosage of Ibandronate Teva, which is suitable for almost all patients, is 1 tablet per month, and the medicine should always be taken on the same day (for example, if you started taking the drug on the 20th, then you will need to take it every 20th of each subsequent day month).
The tablet does not need to be chewed (such actions may cause ulcerations to appear in the upper gastrointestinal tract), but should be taken with 200 ml of water. Please note that plain clean water is best for drinking the medicine. It is not recommended to use mineral water and calcium-rich drinks.
IMPORTANT! After taking Ibandronate Teva, you should not lie down for an hour. You can walk, stand or sit.
It happens that due to the infrequency of taking the medicine, patients forget to take it on a certain day. If you miss a scheduled dose of the drug, but you need to wait more than seven days before taking the next dose, take a tablet of the drug and then continue to adhere to the new dosing schedule (take the tablet on the same day each time).
If there are less than 7 days left before the next pill (count from the date of expiration), then you need to wait until the next scheduled dose. In fact, there should be a minimum one-week gap between doses of the medicine; you cannot take the medicine more than once every 7 days.
Old age and the presence of liver disease do not in any way affect the rhythm of treatment with Ibandronate Teva.
The only situation where it is necessary to reconsider the dosage and, possibly, the frequency of taking the drug, is renal failure with creatine clearance less than 30 ml/minute.
Side effects and overdose
High doses of Ibandronate may cause side effects in certain body systems:
- Gastrointestinal tract: symptoms of dyspepsia, attacks of vomiting and nausea, pain in the abdomen, increased gas formation, swallowing disorders, diarrhea, narrowing of the esophagus or the appearance of ulcers in it, inflammation of various mucous membranes in different parts of the gastrointestinal tract;
- CNS: headaches and loss of coordination;
- Musculoskeletal system: pain in muscles and joints, limited mobility, cramps;
- Allergic reactions: nettle rash, allergic edema (up to angioedema).
Other side effects from high doses of Ibandronate include flu-like symptoms. Patients develop body aches, a rise in temperature (even fever), chills, weakness, and severe weakness.
Note! When the first side effects and overdose syndromes appear, you should definitely call a doctor.
The main symptoms of an overdose of Ibandronate are exacerbation of dyspepsia (digestive upset) and heartburn. In some cases, an overdose is manifested by the appearance of ulcers, gastritis (inflammation of the gastric mucosa) or esophagitis (inflammation of the esophageal mucosa).
The first measure of overdose treatment is artificial induction of vomiting. After this, the patient must remain in a sitting position; lying down or sitting is strictly forbidden. The second stage of therapy is binding of drug residues. This is done with milk or antacids (baking soda, calcium or magnesium carbonate, magnesium oxide, Rennie, Times, Andrews type drugs).
Instructions for use (Method and dosage)
Used orally or intravenously. The treatment regimen and dose depend on the clinical situation and indications. The tablets should not be taken with water containing large amounts of calcium. As a rule, the tablets are taken one hour before the first meal and liquid (not including water) of the day. The tablet must be swallowed whole in a standing or sitting position with a glass of clean water. After taking the pill, you should not lie down for an hour. Also, tablets containing acid should not be sucked or chewed, as ulceration of the upper gastrointestinal tract may occur.
It is used intravenously only in hospital settings. Before use, the contents of the ampoule are diluted with the required amount of a five percent dextrose or isotonic sodium chloride .
Similar medicines
As already indicated, the main active component of Ibandronate Teva is ibandronate acid. There are other drugs based on this substance on the pharmacological market:
- Bandon Health (tablets, powder for injection solution);
- Boniva (tablets - from 1000 to 4000 rubles, injection solution - about 5000 rubles);
- Ibandronic acid Accord/Vista/Pharmex (tablets - approximately 2000 rubles, injection solution and concentrate for infusion solution);
- Ossica (tablets);
- Rezerban (injection solution).
There are other drugs that coincide with Ibandronate in ATC coding, but differ in the active substance.
Price, where to buy
You can purchase Ibandronic acid in Russia for an average of 20 rubles.
- Online pharmacies in UkraineUkraine
Pharmacy24
- Ibandronic acid-Pharmex 1 mg/ml 3 ml No. 1 solution for injection
1138 UAH. order - Ibandronic acid-Pharmex 1mg/ml 6ml No. 1 concentrate
1621 UAH. order
- Ibandronic acid-Vista 150 mg No. 3 tablets Sinton Spain, S.L., Spain
850 UAH. order
- Ibandronic acid-Vista 50 mg N30 tablets Sinton Spain, S.L., Spain
2200 UAH order
- Ibandronic acid-Vista 1 mg/ml 6 ml (6 mg) bottle No. 1 concentrate solution for infusion
1850 UAH order
Reviews of Ibandronate
Vladimir (traumatologist). Osteoporosis is a common disease today. It mainly affects older women and is always chronic. It is impossible to cure osteoporosis completely, you can only slow down the pathological process. To do this, we use an integrated approach, which includes exercise therapy and diet. However, its basic component is drug therapy. It includes treatment with estrogens and selective modulators of their receptors, calcium preparations and biosphosphonates. It is the latter that play the most important role. Teva Ibandronate is one of the best biosphosphonates. This is the remedy I prescribe to most of my patients. After just a few months of treatment, bones susceptible to osteoporosis become stronger, and the disease goes into remission.
Olga (patient 41 years old). At what seemed like a young age, I was diagnosed with focal osteoporosis. As my attending physician said, the stage is early, so it will not be difficult to prevent the development of the disease and achieve remission. The main impact of therapy was the use of Ibandronate. I have been taking it for a year now and tests show that there are positive results. And indeed, despite the decrease in bone density, I have not yet had any fractures. The medicine is good, I don’t feel any side effects from it. The only drawback is the rather high price. Although we took into account how many techniques it has, the cost is quite justified.
Maria (orthopedic doctor). I have extensive experience in treating different types and etiologies of osteoporosis. During my practice, I have encountered many types of drug therapy for this disease, but I believe that treatment with biophosphonates is the most effective. These medications work well against bone destruction, but do not have an overly aggressive effect on the body. If you correctly combine the use of Ibandronate with other medications, vitamins, a well-structured diet and light but regular physical activity, then the chances of remission are very high.
Valentina (patient, 62 years old). After the onset of menopause (at age 51), osteoporosis began. At the age of 53, I suffered a vertebral fracture for the first time. To treat my illness and stimulate bone healing, doctors prescribed Ibandronate. The fracture actually healed relatively quickly. Now I continue to take medications, go in for sports (I really like water aerobics) and constantly monitor my diet. Everything is normal with the integrity of the musculoskeletal system.
Efficacy and safety of ibandronate: evidence base
Osteoporosis is a chronic disease associated with the development of pathological fractures, the prevention of which is an important task of modern medicine. The article discusses pathophysiologically based approaches to the treatment of osteoporosis, including the use of drugs whose action is aimed at inhibiting bone resorption. The importance of patient adherence to therapy is emphasized to improve the effectiveness of treatment. The results of the main international clinical studies of ibandronate (BONE, MOBILE, etc.) are presented, which demonstrated the effectiveness and safety of the prolonged dosage form of the drug for monthly use.
Table. Characteristics of factors causing low adherence to medical programs
Rice. 1. Changes in spine BMD due to long-term use of Bonviva
Rice. 2. Significant increase in BMD in the lumbar vertebrae while taking Bonviva once a month
*Higher (p < 0.05) compared to the 2.5 mg daily regimen. Rice. 3. MOBILE study: increase in BMD in the proximal femur after two years of taking Bonviva
Rice. 4. Significant reduction in the risk of non-vertebral fractures during the use of Bonviva in patients at high risk
Osteoporosis (OP) is a chronic progressive skeletal disease, which remains a pressing medical, social and economic health problem throughout the world, due to its widespread prevalence, which increases with age, late diagnosis and negative impact on the quality and life expectancy [1–4] .
In the future, this problem will become even more global, as there is a trend of population aging. Thus, according to the official demographic forecast, in 2030 the number of people aged 65 years and older will increase to 18% [5].
With AP, bone strength decreases, which leads to fractures with minimal trauma [1, 6–8].
Most often, women suffer from AP, since they initially have lower bone mass, strength of the vertebrae due to their smaller size, longer average life expectancy and, accordingly, loss of bone mass throughout life (due to menopause) [9–11].
Among all forms of the disease, primary AP predominates. Taking into account clinical features, hormonal changes and the relationship of the disease with age and menopause, it has been proposed to distinguish between several types of primary AP (postmenopausal, senile, juvenile and idiopathic).
Primary AP is an independent disease that develops at any age, but most often in women over 50 years of age in the postmenopausal period [1, 3, 10].
During the first five years after menopause, a woman's bone loss can amount to up to one-third of the total bone mass lost over a lifetime, increasing the risk of fractures from even minimal stress [10, 12].
With prolonged imbalance, the trabeculae become thinner, lose their lamellar structure and become cylindrical, and biomechanical load and tension increase. This leads to perforation and destruction of trabeculae. Bone mineral density (BMD) decreases and the quality of bone tissue deteriorates [1, 4, 11].
The share of secondary forms in the overall structure of AP accounts for 15–20% of cases. As a rule, this is a manifestation of other diseases or a consequence of taking drugs that negatively affect bone tissue [1, 13]. The potential risk of fractures in secondary AP is comparable to that in primary AP [14].
Late diagnosis and untimely initiation of treatment for osteoporosis are observed in 75% of women and 90% of men [4]. According to the US National Committee for Healthcare Quality, more than 90% of adults with cardiovascular disease receive beta blockers, and only 19% of adults with frequent fractures receive therapy for osteoporosis [8].
Since AP is asymptomatic for a long time, it is called a silent epidemic. The first manifestation is usually osteoporotic fractures without an obvious cause or with minimal physical activity. Regardless of BMD values, the presence of a low-energy fracture allows a diagnosis of “severe osteoporosis” to be made [3, 9].
Fractures can cause pain, in particular back pain, which intensifies after physical activity or when staying in one position for a long time. For pain, patients either do not go to the doctor at all, or for a long time are ineffectively treated for osteochondrosis, radiculitis and other diseases of the musculoskeletal system [4].
A characteristic symptom of AP is a gradual decrease in linear growth and poor posture.
Fractures that occur spontaneously or are associated with a fall from a height (on the floor) are late manifestations of AP. Fractures of the vertebral bodies, which usually occur earlier than osteoporotic fractures of any other location, account for about half of all fractures [1, 6, 9]. Fractures of the distal radius and vertebral bodies are more often observed in postmenopausal AP and some forms of secondary AP [3, 10]. Osteoporosis is the leading cause of hip fracture in women over 65 years of age [7, 12].
Unfortunately, low-energy fractures are not always given due importance. It is known that after the first fracture, a “cascade” of fractures begins, with the risk of repeated osteoporotic vertebral fracture increasing fourfold, hip fracture – twofold [3, 9, 12].
Mechanism of action of bisphosphonates
Currently, therapy for OP involves the use of non-drug and drug methods. The first include, first of all, quitting smoking, reducing alcohol consumption, and increasing physical activity depending on the condition [3].
The goal of pharmacotherapy is to increase BMD and reduce the risk of fractures.
Several groups of drugs of different types and with different mechanisms of action are currently used to treat AP. Depending on the effect on bone remodeling, antiresorptive and anabolic agents are distinguished. Antiresorptive drugs reduce the activity of remodeling processes and increase the mineralization of bone tissue [2, 15, 16].
Today it is difficult to imagine anti-osteoporotic therapy without bisphosphonates (BPs), which have been successfully used for many years [15–17]. BFs have demonstrated effectiveness in postmenopausal, senile, glucocorticosteroid-induced AP and AP in men [10, 13, 16].
Bisphosphonates are stable analogs of natural inorganic phosphates. The oxygen atom in the pyrophosphate molecule is replaced by a carbon atom (P-C-P) and there are two radicals in the side chains: R1-OH - a group that increases the physicochemical binding of BP to hydroxyapatite, and R2 - which determines the biological effect of drugs on bone cells [ 15, 18].
The selective effect of BP on bone tissue is primarily due to its high affinity for bone hydroxyapatite crystals, which allows them to be deposited at sites of new bone formation. BFs remain in places of bone formation until the old bone is replaced by a new one [16, 19, 20].
The main target of BP is osteoclasts [21, 22]. Penetrating into bone tissue and creating a high concentration in resorption lacunae, BFs are concentrated around osteoclasts. Within these cells, they cause numerous changes, including loss of the brush border, destruction of the cytoskeleton, inability to move, decreased chemotaxis to sites of resorption, and induction of apoptosis [15, 21]. The activity of osteoclasts slows down, as a result, the rate of bone remodeling decreases with inhibition of the resorption phase [20, 22].
However, the antiresorptive activity of different BPs varies significantly due to the characteristics of the chemical structure of the molecule. It is most pronounced in nitrogen-containing BPs (aminobisphosphonates), which block the synthesis of farnesyl diphosphate synthase [23, 24]. As a result, the formation of mevalonate, a substance necessary to maintain normal cytoarchitecture and vital activity of osteoclasts, is reduced [25].
Nitrogen-containing BPs are considered stronger inhibitors of osteoclast activity and osteolysis than nitrogen-free compounds [3, 16].
Structural differences in the nitrogen chain of BP also influence the inhibition of bone resorption. The presence of a nitrogen atom in the side chain explains their ability to inhibit protein modification in osteoclasts, which leads to apoptosis of mature cells. Confirmation is the appearance of specific changes in the cell and the structure of the nucleus [19, 20, 26]. In this case, osteoclast precursor cells lose the ability to differentiate and mature, which also contributes to a decrease in the osteoclast population. It should be noted that some details of the mechanism of action of BF continue to be studied.
Osteoblasts are a potential target of FD. In vitro data
indicate that under the influence of BP, osteoblasts reduce the secretion of osteoclast-stimulating factor [15, 20].
Other effects of BF are anabolic in nature. The drugs are able to increase the survival of osteoblasts and osteocytes by blocking their apoptosis, increase the synthesis of type 1 collagen by osteoblasts, which leads to changes in microarchitecture (in particular, thickening of bone trabeculae) and an increase in the mineral component of bone. As a result, bone loss is prevented and the risk of osteoporotic fractures is reduced [19, 27].
Efficacy and adherence to therapy
In the treatment of any chronic disease, including AP, there is a significant problem - careful adherence to recommendations for taking medications, which in turn affects the effectiveness of the therapy. It was found that the risk of osteoporotic fractures increases by 40% in patients who took less than half the recommended course dose, compared with those whose adherence to therapy was 90% [28].
According to the World Health Organization, treatment adherence is the compliance of the patient's behavior with the doctor's recommendations, including taking medications, diet and/or lifestyle changes. The table presents factors that may influence patients' compliance with doctor's recommendations.
One of the effective ways to increase patient adherence to anti-osteoporotic therapy is to simplify the pharmacotherapy regimen, a simple regimen [29, 30]. Therefore, reducing the frequency of drug administration while maintaining the therapeutic effect is one of the effective strategies, since it limits the possibility of deviations from the recommended dosage regimen.
Clinical potential of the first monthly bisphosphonate
The new generation of BFs has broad prospects. Their advantages include not only greater antiresorptive activity, but also the possibility of intermittent treatment regimens [16].
The nitrogen-containing third-generation BP ibandronate (Bonviva) is one of the modern and highly effective anti-osteoporotic agents [23, 31–33]. This drug has a prolonged effect, so it is used not daily, not weekly, but once a month, 150 mg [34, 35]. In addition, another dosage form for intravenous infusion in a dose of 3 mg is registered in Russia, the regimen of use is once every three months.
At the stage of preclinical studies, it was shown that the relative activity of ibandronate is two, ten and 50 times higher than the activity of risedronate, alendronate and pamidronate, respectively [36].
Ibandronate is the first DF for which long-term intermittent treatment has been shown to be effective [31, 37, 38].
The effectiveness of Bonviva is confirmed by data from large clinical studies that studied the effect of therapy on BMD and bone quality, the risk of developing new fractures, the safety of therapy, etc., involving more than 13 thousand patients from different countries [23, 32, 33, 35, 38 –42]. It has been proven that Bonviva has a positive effect on the BMD of not only the spine, but also the femoral neck, preventing the development of osteoporotic fractures, which are unfavorable for the life prognosis (Fig. 1). In addition, ibandronate was found to be safe and well tolerated [23].
The results of the MOBILE study are of great interest. This was a multicenter, randomized, double-blind study that included 1609 women (age 55–80 years) with a postmenopausal duration of five years or more who had AP in the lumbar spine (BMD T-score -2.5 to -5.0 CO) [ 38]. According to the study design, patients were assigned to Bonviva or placebo. At the same time, there were several options for their dosage regimen: 2.5 mg of Bonviva per day orally and placebo once a month; Bonviva 100 mg orally once a month and placebo daily; 100 mg Bonviva orally once a month, 50 mg per day for two days in a row (50 mg/50 mg) and daily placebo; Bonviva 150 mg orally once a month and placebo daily. All study participants also took calcium (500 mg) and vitamin D (400 IU) supplements daily.
The primary endpoint for assessing the effectiveness of ibandronate was the change in lumbar vertebrae BMD after one year of treatment compared to baseline. Additionally, changes in BMD of the lumbar vertebrae were studied after two years of therapy, in the proximal femur after one and two years, and changes in the level of bone turnover markers (C-terminal type I procollagen peptide (CTX)) after one and two years.
After a year, there was a significant increase of 4.3% in the BMD of the lumbar spine relative to the initial values when taking 50 mg/50 mg of Bonviva, by 4.1% when taking 100 mg, by 4.9% when taking 150 mg monthly and on 3.9% – with a daily dose of 2.5 mg of Bonviva [38]. The increase in BMD of the lumbar vertebrae after two years of the study was 5.3, 5.6 and 6.6% when taking 50 mg/50 mg, 100 mg and 150 mg Bonviva, respectively, and 5.0% when taking the drug daily (Fig. 2) . Similar results were obtained for hip BMD. A significant increase in BMD of the total hip, femoral neck and greater trochanter area was observed in all treatment groups after a year of therapy and persisted during the second year of treatment.
Bonviva 150 mg once monthly compared with daily was associated with the largest and most progressive increase in BMD at all proximal femoral sites (p
A study of the level of bone turnover markers showed a decrease in their levels after just three months of treatment, which continued throughout the entire observation period. In particular, after two years in the treatment groups, the concentration of CTX in the blood decreased by 56.1–61.5%. The greatest reduction was observed in the group receiving 150 mg ibandronate. The study also showed a good safety profile for once-monthly Bonviva therapy.
It should be emphasized that Bonviva was the first drug for once-monthly use for AP. The results of the MOBILE study demonstrated that the use of Bonviva at a dose of 150 mg once a month provides not only high therapeutic efficacy (restoration of bone metabolism to premenopausal values), a reduction in the risk of pathological fractures, but also accurate compliance with doctor's prescriptions in the long term. A positive effect was observed after a year of using ibandronate. In particular, 9 out of 10 patients receiving the drug showed an increase in BMD either in the lumbar vertebrae or in the lumbar vertebrae and hip [38]. The results of the extended phase of the study indicate the feasibility of using Bonviva for at least five years (Fig. 1) [35, 41, 42].
The BONE study confirmed the effectiveness of ibandronate in preventing vertebral and non-vertebral fractures over a three-year follow-up period [33]. At the same time, therapy with Bonviva helped reduce the risk of developing vertebral fractures by 62% compared with other DFs. The effectiveness of a similar course of alendronate in relation to this indicator was about 50%.
Other important evidence for the effectiveness of ibandronate comes from a retrospective analysis of the BONE study, which included 375 patients at high risk of nonvertebral fractures (baseline femoral neck BMD T-score
The quality of bone tissue is an important characteristic that determines bone strength. In this regard, it is of interest to follow-up histological and histomorphometric analysis of bone biopsies in a subgroup of patients from the BONE study who participated in a program to evaluate the effect of intermittent and daily ibandronate on the quality and microarchitecture of bone tissue [33]. We examined 110 women randomized to undergo iliac wing biopsy (at 22 and 34 months of therapy). Biopsy results showed that both oral Bonviva regimens promoted new bone formation without evidence of disruption of bone matrix mineralization, and there was clear improvement in bone microarchitecture.
Indicative were the results of the multicenter BALTO study, which compared different treatment regimens, analyzed patient preferences and the convenience of using anti-osteoporotic drugs. 66.1% of patients with postmenopausal AP preferred monthly 150 mg ibandronate to weekly 70 mg alendronate [39].
The practical advantages of using ibandronate are also evidenced by a survey of participants in the BALTO study. They noted that monthly use of the drug is more convenient: this treatment regimen is easier to maintain for a long time, and it is more acceptable for the usual lifestyle. This ensures greater adherence to therapy, which means better outcomes of AP.
Of interest are the results of the VIBE retrospective cohort study, one of the goals of which was to determine the risk of developing fractures in patients adherent to treatment with oral BD who received either ibandronate (150 mg/month) or any other BD (alendronate at doses of 35 and 70 mg/week, risedronate at a dose of 35 mg/week) [40]. The primary analysis included 64,182 patients who took ibandronate for more than 90 days (n = 7345), weekly BP (n = 56,837). The average duration of therapy was seven months. The risks of nonvertebral fractures, hip fractures, and all clinical fractures were comparable in both groups. In particular, the incidence of fractures in the group receiving BF weekly was 1.5%, in the group receiving ibandronate - 1.4%, that is, it was minimal. It is significant that the number of vertebral fractures when taking ibandronate was half as much (0.11 versus 0.24%, respectively, p
A recently published comparative study assessed the effectiveness of different dietary supplements over a two-year period [43]. Patients with postmenopausal AP (n = 172) were randomized into three groups: ibandronate (150 mg/month), alendronate (70 mg/week), risedronate (35 mg/week). All participants received daily calcium (1200 mg) and vitamin D (800 IU) supplements. A greater increase in BMD of the lumbar vertebrae was achieved in the groups receiving ibandronate and alendronate.
Overall, the results of all clinical studies demonstrated that the relatively large dose required for once-monthly dosing of ibandronate did not have a significant effect on tolerability. The oral dosage form of Bonviva is characterized by a low risk of side effects from the gastrointestinal tract [18, 23, 32, 33, 35, 37, 44].
Features of application
Bonviva should be taken at a dose of 150 mg (one tablet) once a month on an empty stomach, 60 minutes before meals, liquids (except water) or other medications to ensure maximum absorption. There is no need to change the dose of the drug in elderly people. There is no need for dose adjustment for mild and moderately severe renal dysfunction (glomerular filtration rate > 30 ml/min/1.73 m2), liver dysfunction.
It is important to remember that one of the conditions for effective treatment of AP with ibandronate, like any other FD, in the presence of hypocalcemia is the mandatory correction of this shift before starting therapy. Additionally, patients should be advised to take calcium and vitamin D supplements.
Conclusion
Bonviva is a highly effective treatment for AP that can be taken once a month. This mode of application leads to increased adherence to therapy and, as a consequence, its effectiveness.