Binosto effervescent pills 70mg, 4pcs

Composition

Composition for 1 tablet:

Active ingredient:

sodium alendronate trihydrate (micronized) (in terms of alendronic acid) -91.37 (70.0) mg.

Auxiliary substances:

sodium citrate anhydrous-1900.00 mg,

citric acid anhydrous-839.63 mg,

sodium bicarbonate-751.00 mg,

sodium carbonate anhydrous-430.00 mg,

strawberry flavor -30.00 mg,

acesulfame potassium-4.00 mg,

sucralose-4.00 mg.

Description

Round flat tablets of white or almost white color with beveled edges with a strawberry smell.

Pharmacological action

Pharmacotherapeutic group of bone resorption inhibitor-bisphosphonate. ATX code: M 05 BA 04 Pharmacological properties The Active ingredient of the preparation Binosto-sodium alendronate trihydrate is a bisphosphonate that inhibits bone resorption caused by osteoclasts, without directly affecting the process of formation of new bone tissue. Preclinical studies have shown that alendronate is mainly localized in areas of active bone resorption. Alendronate suppresses the activity of osteoclasts, but does not affect their accumulation and attachment. During treatment with alendronate, normal bone tissue is formed. The toxic effect on the esophagus during treatment with alendronate is based on many factors, including the main one is local irritation of the esophageal mucosa under the influence of crystals of the substance (tablet esophagitis). Acidic gastroesophageal reflux can act as a concomitant factor, and therefore, reducing acid exposure is the main method of treatment for esophagitis caused by taking alendronate. In the “Side effects” section, you can view data from post-marketing studies of the drug in the United States. Postmenopausal osteoporosis is defined as a decrease in bone mineral density (BMD) of the spine or hip by 2.5 standard deviations (SD) compared to the average value in the population of young people, or as the presence of a history of pathological fracture regardless of BMD. A one-year multicenter study of postmenopausal women with osteoporosis showed the therapeutic equivalence of alendronate 70 mg once a week (n=519) and alendronate 10 mg once a day (n=370). In the group taking alendronate 70 mg once a week, the average increase in BMD in the lumbar spine during the year was 5.1% relative to baseline values (95% CI: 4.8,5.4%>), and in the group taking 10 mg per day, the increase was 5.4% (95% CI: 5.0,5.8%>>). The average increase in BMD in the femoral neck was 2.3% and 2.9%), and for the entire femur-2.9% (and 3.1%) in patients taking 70 mg of alendronate once a week or 10 mg once a day, respectively. Both treatment groups were also comparable to each other in terms of BMD values in other areas of the skeleton. The effect of alendronate on bone mass and fracture incidence in postmenopausal women was studied in two clinical trials of initial efficacy of the same design (n=994), as well as in a fracture therapy study (FIT: n=6459). In the initial efficacy studies, the increase in mean BMD with alendronate 10 mg / day compared to placebo after three years was 8.8% for the spine,5.9% for the femoral neck, and 7.8% for the trochanter. The total BMD of the body also increased significantly. In the alendronate group, the proportion of patients who experienced one or more spinal fractures decreased by 48% compared to the placebo group (3.2% in the alendronate group compared to 6.2% in the placebo group). During the two-year extension period of these studies, the BMD values of the spine and trochanter continued to increase, while the BMD values of the femoral neck and entire body remained unchanged. The FIT fracture therapy trial consisted of two placebo-controlled clinical trials in which patients took alendronate daily (5 mg daily for two years, then 10 mg daily for the next year or two years). * FIT 1: A three-year clinical trial that included 2,027 patients with at least one initial spinal fracture (compression). In this study, daily alendronate treatment resulted in a 47% reduction in the incidence of one or more spinal fractures (7.9% in the alendronate group compared to 15.0% in the placebo group). In addition, there was a statistically significant reduction in the incidence of hip fractures (1.1% vs. 2.2%, a 51% decrease). * FIT 2: A four-year clinical trial that included 4,432 patients with low bone mass but no initial spinal fracture. In this study, when analyzing data from a subgroup of women with osteoporosis (37% of the total population with a condition that meets the above definition of osteoporosis), there was a significant difference in the incidence of one or more spinal fractures (2.9% compared to 5.8%, a 50% decrease) and hip fractures (1.0% in the alendronate group compared to 2.2% in the placebo group, a 56% decrease). Laboratory test resultsin clinical trials, there was an asymptomatic, small and temporary decrease in serum calcium and phosphate concentrations (by 18% and 10%, respectively) in patients taking alendronate 10 mg per day (compared to approximately 12% and 3% in the placebo group). However, the frequency of reduction of serum calcium concentrations to < 8.0 mg / dl (2.0 mmol/L) and serum phosphates toAlthough osteoporosis in men is not as common as in postmenopausal women, a significant proportion of osteoporosis-related fractures occur in men. The prevalence of spinal deformity associated with osteoporosis is similar in men and women. The use of alendronate at a dose of 10 mg per day in men for 2 years reduced the urinary excretion of cross-linked N-telopeptides of type I collagen by approximately 60% and bone-specific alkaline phosphatase by approximately 40%. Pharmacokinetics of absorption The bioavailability of alendronate when taken orally on an empty stomach in the morning two hours before a standard breakfast at a dose of 5-70 mg was 0.64% in women and 0.60% in men. When alendronate was taken on an empty stomach an hour or half an hour before a standard breakfast, the bioavailability decreased to 0.46% and 0.39%, respectively. Bioavailability is almost comparable to that of commonly used alendronate tablets, but for effervescent tablets, intra-individual differences in excretion (and therefore in absorption) are smaller (coefficient of variation in total excretion during the first 48 hours is 32.0 compared to 42.1%, coefficient of variation in the maximum rate of excretion is 37.5 compared to 45.6%). In osteoporosis studies, alendronate was effective when taken at least 30 minutes before the first meal or drink of the day. The bioavailability of alendronate was insignificant when taken during a standard breakfast and for two hours after it. When alendronate was co-administered with coffee or orange juice, bioavailability was reduced by approximately 60%. Distribution Studies in rats have shown that after intravenous use at a dose of 1 mg/kg, alendronate is temporarily distributed to soft tissues, after which it quickly passes into bone tissue or is excreted in the urine. The average equilibrium volume of distribution of alendronate, excluding bones, in humans is at least 28 liters. The plasma concentration of alendronate after oral use of therapeutic doses is too low for analytical detection (less than 5 ng / ml). Binding to plasma proteins in humans is approximately 78%. Metabolism There is no evidence that alendronate is metabolized in humans or animals. Elimination After a single intravenous injection of [ C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no excretion in the faeces. After a single intravenous use of the drug at a dose of 10 mg, the renal clearance of alendronate was 71 ml / min, and the systemic clearance did not exceed 200 ml / min. The plasma concentration decreased by more than 95% within 6 hours after intravenous use. The end-phase elimination half-life in humans exceeds ten years, which reflects the release of alendronate from bone tissue. Studies in rats have shown that alendronate is not excreted through the acidic and basic transport systems of the kidneys. Therefore, it can be expected that it does not interfere with the excretion of other drugs through these systems in humans. Features of use in patients with impaired renal function Clinical studies have shown that the drug, which does not accumulate in bone tissue, is quickly excreted in the urine. It was not possible to establish the maximum saturation capacity of bone tissue in animals with intravenous use of a cumulative dose of 35 mg/kg. Despite the lack of clinical data, a decrease in alendronate excretion is likely in patients with kidney disease (as obtained in animal studies). Thus, in patients with impaired renal function, a slightly higher accumulation of alendronate in bone tissue can be expected (see the section “Dosage and use”).

Indications

* Treatment of osteoporosis in postmenopausal women to prevent the development of fractures, including hip fractures and compression fractures of the spine;• treatment of osteoporosis in men to prevent the occurrence of fractures.

Contraindications

• Hypersensitivity to alendronate or any of the components of the drug.
• Violation of esophageal function and other factors that slow down its emptying (for example, strictures, achalasia).
• Inability of the patient to stand or sit upright for 30 minutes.
• Hypocalcemia.
• Vitamin D deficiency.
• Severe disorders of mineral metabolism.
• Severe renal insufficiency – creatinine clearance < 35 ml/min.
• Children’s age.

With caution

When diseases of the upper gastrointestinal tract (GIT) are aggravated, such as dysphagia, esophageal diseases, gastritis, duodenitis or stomach ulcers.

For serious diseases of the gastrointestinal tract that were transferred in the previous 12 months, for example, peptic ulcer, gastrointestinal bleeding, surgery on the upper gastrointestinal tract (except for pyloroplasty).

Predisposition to hypocalcemia (hypothyroidism, calcium malabsorption).

Side effects

In a one-year clinical study in postmenopausal women with osteoporosis, the overall safety profiles of alendronate 70 mg once weekly (n=519) and alendronate 10 mg daily (n=370) were generally similar.

In two three-year clinical trials with almost identical design in menopausal women (alendronate 10 mg: n=196, placebo: n=397), the safety profiles of alendronate 10 mg/day and placebo were generally similar.

Adverse events described in these studies as possible, probable, or definitely related to alendronate use are presented in the table below. Adverse events were observed in > 1% of patients in each admission group in the one-year study. In > 1% of patients treated with alendronate at a dose of 10 mg/day, adverse events were observed with a higher frequency than in the placebo group in the three-year study:

The frequency of adverse events are structured as follows: very Pasto (> 1/10), often (> 1/100, < 1/10), infrequently (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000, including individual cases).

1 See the section “Special instructions”.

2 The frequency of occurrence determined by the results of clinical studies was comparable for the drug group and the placebo group.

3 See the sections “Dosage and use” and “Special instructions”.

4 This adverse reaction was identified during post-marketing surveillance.

5 These adverse reactions have been identified for the drug in tablet form, and not all of them can be attributed to the drug Binosto, which is used as an oral buffer solution.

Interaction

The absorption of alendronate may be impaired if Binosto is taken simultaneously with food, beverages (including mineral water), calcium supplements, antacids, and other oral medications. In this regard, the interval between taking Binosto and other medications taken orally should be at least 30 minutes (see the sections “Dosage and use” and “Pharmacological properties”). In a study in healthy volunteers, oral prednisone (20 mg three times daily for 5 days) did not lead to a clinically significant change in the bioavailability of alendronate (the average increase ranged from 20% to 44%). No other clinically significant drug interactions are expected. In clinical trials, some patients received estrogen (intravaginally, transdermally, or orally) while taking alendronate. There were no adverse events associated with their simultaneous use. Since the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with the development of erosive and ulcerative lesions of the gastrointestinal tract, caution should be exercised when using NSAIDs and alendronate simultaneously. Although no specific interaction studies have been conducted, alendronate has been used concomitantly with a wide range of commonly prescribed medications in clinical trials with no evidence of clinical adverse interactions.

How to take, course of use and dosage

Doses

The recommended dose is one effervescent tablet,70 mg once a week.

Patients should be warned that if they miss taking one tablet of Binosto 70 mg, they should take one effervescent tablet in the morning of the next day. You should not take two tablets in one day, but in the future you should continue to take one tablet on the day of the week that was chosen for taking from the very beginning of treatment.

The optimal duration of treatment for osteoporosis with bisphosphonates has not been established. The need to continue bisphosphonate therapy should be evaluated on a regular basis based on the benefit / risk of using Binosto for each patient, especially after 5 or more years of use.

Use in children:

It is not recommended to use alendronate sodium in children under 18 years of age due to insufficient data on the safety and effectiveness of the drug in the treatment of osteoporosis in children.

Use in elderly patients;

In clinical trials, there were no differences in the efficacy or safety profiles of alendronate depending on age. Therefore, no dose adjustment is required for use in elderly patients.

Use in patients with renal insufficiency:

No dose adjustment is required for patients with a glomerular filtration rate (GFR) greater than 35 ml / min. Alendronate is not recommended for use in patients with renal insufficiency, in which GFR is less than 35 ml / min, due to insufficient data on the use.

Method of application

In order to ensure the necessary bioavailability of alendronate, it is necessary to take Binosto at least 30 minutes before the first meal, drink or other medications taken daily, drink only plain water, as other beverages (including mineral water), food and certain medications may reduce the absorption of alendronate (see the section “Interaction with other medications and other forms of interaction”).

To improve gastric intake and thereby reduce the likelihood of local and esophageal irritation/adverse events (see section “Special instructions”):

* Binosto is recommended to be taken dissolved in half a glass of plain water (at least 120 ml or 4.2 fl oz). When the tablet is dissolved in water, a buffer solution is formed with a pH of 4.8-5.4. The resulting solution can be drunk only after the fizzing stops and the tablet is completely dissolved to form a clear or slightly cloudy colorless or almost colorless liquid, after which at least 30 ml of water (1/6 of a glass) is added to the solution. Additional water may be required.

• Do not swallow non-dissolved effervescent tablets, chew or dissolve effervescent tablets due to the risk of irritation of the oropharyngeal mucosa (see sections “Special instructions” and “Side effects”).

* If the tablet is not completely dissolved, the solution should be stirred until it becomes clear or slightly cloudy, colorless or almost colorless.

* Patients should remain upright after the first meal, which should occur no earlier than 30 minutes after consuming the drug solution.

* Patients should remain upright for at least 30 minutes after consuming the drug solution.

* Binosto should not be taken before bedtime or before getting out of bed in the morning.

* Binosto may be prescribed to patients who are unable or unwilling to swallow the pill.

Patients should take additional calcium and vitamin D supplements if their dietary intake is insufficient (see section “Special instructions”).

Overdose

Overdose may cause hypocalcemia, hypophosphatemia, and upper gastrointestinal side effects, including stomach upset, heartburn, esophagitis, gastritis, and stomach and esophageal ulcers. There is no specific treatment for alendronate overdose. The patient should take milk or antacids to bind alendronate. To prevent irritation of the esophagus, do not induce vomiting. Patients should maintain an upright position.

Special instructions

Use during pregnancy

Alendronate should not be used during pregnancy. There are insufficient data on the use of alendronate in pregnant women. Animal studies have shown no immediate negative effects during pregnancy, embryo and fetal development, or postnatal development.

There are no data on the effect of alendronic acid on the fetus when using the drug during pregnancy. However, there is a theoretical risk of negative effects on the fetus (especially on bone tissue) if pregnancy occurs after undergoing a course of bisphosphonate therapy. After ingestion, bisphosphonates are embedded in the bone matrix, from where they are gradually released over several years.

The amount of bisphosphonates embedded in the bone matrix and able to get back into the systemic circulation directly depends on the dose and duration of use of the drug. In animal studies, violations of fetal bone formation with high doses of alendronic acid and labor dysfunction associated with hypocalcemia were identified.

Use during breastfeeding

There are no data on the excretion of alendronate in breast milk. Alendronate should not be used during breastfeeding.

Children

Binosto should not be used in children under 18 years of age due to insufficient data on safety and efficacy in diseases associated with childhood osteoporosis.

Alendronate may cause local irritation of the upper gastrointestinal mucosa. In this regard, caution should be exercised when prescribing Binosto to patients with diseases of the upper gastrointestinal tract, for example, dysphagia, esophageal disease, gastritis, duodenitis, ulcer, serious gastrointestinal disease that was transferred in the previous 12 months, for example, with peptic ulcer, as well as with active gastrointestinal bleeding, surgery on the upper gastrointestinal tract, with the exception of pyloroplasty. For patients with diagnosed Barrett’s esophagus, alendronate should be considered individually based on an assessment of the expected benefit-to-risk ratio.

When treated with alendronate, there are known cases of adverse reactions from the esophagus (esophagitis, erosion or esophageal ulcer), sometimes severe and requiring hospital treatment and in rare cases complicated by the formation of stricture.

In this regard, doctors should pay special attention to any signs or symptoms that indicate possible esophageal disorders, and patients should be warned to stop taking alendronate and consult a doctor if symptoms of esophageal irritation appear, such as dysphagia, pain when swallowing or behind the sternum, the appearance or increase of heartburn.

The risk of severe esophageal adverse events is higher in those patients who violate the recommendations for taking the drug and / or continue to take it when symptoms of esophageal irritation appear. It is especially important to give the patient recommendations on taking the drug, so that he understands that the risk of developing esophageal damage increases if these recommendations are not followed (see the section “Dosage and use”).

Although no increased risk was observed in extended clinical trials of alendronate, rare cases of gastric and duodenal ulcers, sometimes severe and complicated, were reported in post-marketing reports.

In cancer patients treated with intravenous bisphosphonates, there have been cases of local osteonecrosis of the jaw, mainly associated with previous tooth extraction and/or local infection (including osteomyelitis). Many of the patients also received chemotherapy and glucocorticosteroids. There are also known cases of osteonecrosis of the jaw in patients with osteoporosis who have taken bisphosphonates orally. When assessing the individual risk of developing jaw necrosis, the following risk factors should be taken into account::

bisphosphonate activity (highest in zolendronic acid), route of use (see above) and total dose;

cancer, chemotherapy, radiotherapy, corticosteroids, smoking;

a history of dental diseases, poor oral hygiene, periodontal disease, invasive dental procedures and poorly selected dentures. Before starting oral bisphosphonate therapy, patients with unsatisfactory dental status are recommended to undergo a dental examination and preventive medical measures.

During the course of taking bisphosphonates, such patients are advised to avoid invasive dental procedures as much as possible. If a patient develops osteonecrosis of the jaw during bisphosphonate therapy, surgical dental treatment may worsen the condition. It is not known whether discontinuation of bisphosphonates reduces the risk of osteonecrosis of the jaw in patients who require dental procedures. In each case, the decision should be made by the attending physician based on an assessment of the ratio of expected benefit to possible risk for a particular patient.

During bisphosphonate therapy, patients should be taught the importance of proper oral hygiene, routine checkups, and be warned to report any oral symptoms, such as tooth mobility, pain, or the appearance of swelling.

Cases of bone, joint, and/or muscle pain have been reported during the course of bisphosphonate therapy.

Post-marketing experience with the use of bisphosphonates shows that in rare cases these symptoms were severe and/or led to disability (see the section “Side effects”). The time of onset of symptoms ranged from one day to several months after the start of treatment. In most patients, symptoms disappeared after discontinuation of treatment. Some of them experienced symptoms again when they resumed taking the same drug or another bisphosphonate drug. Cases of atypical subtrochanteric or diaphyseal femoral fractures have been reported with bisphosphonates, mainly in patients receiving long-term therapy for the treatment of osteoporosis. These transverse or oblique fractures can occur along the entire length of the femur from the lesser trochanter of the femur to the supracondylar extension. These fractures occur after a minor injury or without it, and some patients experience severe pain in the hip or groin area, which is often combined with radiographic symptoms of stress fractures, several weeks or months before the full picture of the hip fracture appears.

Fractures are often bilateral, so the second (contralateral) hip should be examined in patients with a hip fracture who are taking bisphosphonates. These fractures do not heal well. If an atypical hip fracture is suspected, discontinuation of bisphosphonate therapy should be considered until the expected benefit-to-risk ratio is individually assessed. During bisphosphonate therapy, patients should be advised to report any pain in the hip or groin area. All patients admitted with such complaints should be examined for an incomplete femoral fracture.

An adverse event such as osteonecrosis of the external auditory canal, which was mainly associated with prolonged use of alendronate, has been reported. Possible risk factors for developing osteonecrosis of the external auditory canal include the use of steroids, chemotherapy, infections, and injuries.

Severe skin reactions, including Stevens-Johnson syndrome and Lyell’s syndrome (toxic epidermal necrolysis), have been reported infrequently during post-marketing use.

Patients should be warned that if they accidentally miss taking Binosto once a week, they should take 1 tablet in the morning of the next day after they remember. You should not take two tablets in one day, but in the future it is necessary to return to taking the drug 1 time a week on the day of the week that was chosen at the beginning of treatment.

The drug Binosto is not recommended for patients with renal insufficiency with a glomerular filtration rate of less than 35 ml / min (see the section “Dosage and use”).

Other causes of osteoporosis should also be taken into account, in addition to estrogen deficiency and age.

In the presence of hypocalcemia, the concentration of calcium in the blood should be normalized before starting treatment with alendronate (see the section “Contraindications”). Other mineral metabolism disorders (such as vitamin D deficiency and hypoparathyroidism) should also be treated effectively before starting alendronate therapy. In patients with these disorders, during therapy with Binosto, it is necessary to monitor the concentration of calcium in the blood serum and the symptoms of hypocalcemia.

Since alendronate increases bone mineral content, there may be a decrease in serum calcium and phosphate concentrations, especially in patients taking glucocorticosteroids, in which calcium absorption may be reduced.

Usually, this decrease is small and asymptomatic. However, there are rare cases of symptomatic hypocalcemia, which sometimes reached a severe degree and developed in patients with a corresponding predisposition (for example, hypoparathyroidism, vitamin D deficiency, calcium malabsorption).

Ensuring adequate intake of calcium and vitamin D is especially important for patients taking glucocorticosteroids.

Binosto contains 26.2 mmol (or 602.54 mg) of sodium in one tablet. This should be taken into account when treating patients on a controlled sodium diet.

Features of use in children

It is not recommended to use alendronate sodium in children under 18 years of age due to insufficient data on the safety and effectiveness of the drug in the treatment of osteoporosis in children (see the section “Dosage and use”).

Influence on the ability to drive vehicles and mechanisms

No studies have been conducted to study the effect on the ability to drive a vehicle and work with mechanisms. However, some of the adverse reactions observed with Binosto may affect the ability of some patients to drive vehicles or other mechanisms. Individual reactions to the drug Binosto may differ (see the section “Side effects”).

Form of production

Tablets are effervescent. The number of tablets in a package is 4 pcs.

Storage conditions

In a dark place at a temperature not exceeding 30 °C. Keep out of reach of children.

Shelf

life is 4 years. Do not use the product after the expiration date indicated on the package.

Active ingredient

Alendronic Acid

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets

Purpose

For adults as prescribed by a doctor, For postmenopausal women, For women in the menopausal period

Indications

Menopause, Osteoporosis