Fosamax, pills 70mg, 4pcs

Composition

1 tablet contains:

Active ingredient:  

sodium alendronate 91.37 mg (equivalent to 70 mg of alendronic acid).

Auxiliary substances:  

microcrystalline cellulose 140 mg,

lactose anhydrous 113.4 mg,

croscarmellose sodium 3.5 mg,

magnesium stearate 1.75 mg

Pharmacological action

Pharmacotherapy group: bone resorption inhibitor-bisphosphonate

ATX code:  M 05 VA 04

Pharmacological properties

Pharmacodynamics

The Active ingredient of FOSAMAX® sodium alendronate is a bisphosphonate that inhibits osteoclast-mediated bone resorption without directly affecting the formation of new bone tissue.

Preclinical studies show. that alendronate is mainly localized in areas of active bone resorption. It suppresses the activity of osteoclasts, but does not affect the attraction and attachment of osteoclasts. During treatment with alendronate, normal bone tissue is formed.

Postmenopausal Osteoporosis treatment

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 healthy young people, or as the presence of a history of pathological fracture, regardless of BMD.

The therapeutic equivalence of FOSAMAX 70 mg, taken once a week (n = 519), and alsndronate 10 mg, taken once a day (n = 370), was shown in a one-year study. a multicenter study in women with osteoporosis in postmenopausal women.

The mean increase in lumbar vertebral BMD compared to baseline over one year was 5.1% (95% CI: 4.8,5.4%) in the 70 mg once-weekly group and 5.4% (95% CI: 5.0,5.8%) in the 10 mg once-daily group. The average increase in hip BMD was 2.3% and 2.9%, and hip BMD was 2.9% and 3.1% in the 70 mg once-weekly and 10 mg once-daily groups, respectively.

Both groups also had similar BMD increases in other skeletal regions. The effect of alendronate on bone mass and fracture incidence in postmenopausal women was studied in two initial efficacy studies of the same design (n = 994), as well as in a fracture therapy study (FIT: n = 6459).

In initial efficacy studies, the increase in mean bone mineral density (BMD) with alendronate 10 mg/day compared to placebo after three years was 8.8%,5.9%, and 7.8% for the spine, femoral neck, and trochanter, respectively.

The total BMD of the body also increased significantly. The number of patients with one or more vertebral fractures decreased by 48% (3.2% in the alendronate group compared to 6.2% in the placebo group) among patients treated with alendronate compared to patients treated with placebo. 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 study consisted of two placebo-controlled trials using alendronate daily (5 mg daily for two years and 10 mg daily for one year or two years additionally):

• FIT 1: A three-year study that included 2,027 patients with at least one initial spinal fracture (compression). In this study, daily use of alendronate reduced the incidence of ≥1 new spinal fracture by 47% (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% reduction).
• FIT 2: A four-year study that included 4,432 patients with low bone mass but no initial spinal fracture. In this study, when analyzing a subgroup of women with osteoporosis (37% of the general population with a condition that meets the definition of osteoporosis given above), there was a significant difference in the incidence of hip fractures (1.0% in the alepdronate group compared to 2.2%, in the placebo group, a decrease of 56%) and in the incidence of ≥1 spinal fracture (2.9% compared to 5.8%, a decrease of 50%).

Laboratory test results

In clinical trials, asymptomatic, small, and temporary decreases in serum calcium and phosphate concentrations were observed in approximately 18 and 10% of patients taking alendronate 10 mg/day, respectively, compared to about 12 and 3% of patients taking placebo.

However, the incidence of decreased serum calcium concentrations prior to the use of sodium alendronate has been studied in a small number of patients with osteogenesis imperfecta under the age of 18 years. The results are insufficient to justify the use of sodium alendronate in children with osteogenesis imperfecta.

Application studies in men

Although osteoporosis is not as common in men 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 once a 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%.

Similar results are observed when taking FOSAMAX® at a dose of 70 mg once a week for 1 year. Compared with placebo, the increase in BMD in the lumbar spine is 5.3%, in the femoral neck -2.6%, in the greater trochanter-3.1%, and in the total BMD-1.6%.

When alendronate 10 mg per day was used in men, there was a decrease in the incidence of new spinal fractures, which was 0.8% compared to 7.1% when taking placebo. There was also a decrease in the size of the reduction in height, which was 0.6 mm with alendronate compared to 2.4 mm with placebo.

When using FOSAMAX® 70 mg 1 time per week for 1 year, there is an increase in BMD in the lumbar spine by 2.8%, in the femoral neck-by 1.9%, in the femur – by 2.0%, in other parts of the body – by 1.2% compared to placebo.

FOSAMAX is effective in men regardless of age, sex gland function, and initial BMD in the femoral neck and lumbar spine.

Pharmacokinetics

Suction

The bioavailability of alendroiate 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 0.6% in men. When taking alendroate on an empty stomach an hour or half an hour before a standard breakfast, oiodosunicity decreased to 0.46% and 0.39%, respectively. In osteoporosis studies, alendronate was effective when taken at least 30 minutes before the first meal or drink of the day.

Bioavailability was negligible when alendronate was 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%.

In healthy subjects, no clinically significant changes in the oral bioavailability of alendroiate were observed with oral prednisone (20 mg three times daily for five days) (mean increase in the range of 20% to 44%).

Distribution

The average equilibrium volume of distribution, excluding bones, in humans is at least 28 liters. Plasma concentrations of the drug after oral use of therapeutic doses are too low for analytical detection. There is no evidence that alendronate is metabolized in humans or animals.

Deduction

After a single intravenous dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no excretion in the faeces. The renal clearance of alendroate was 71 ml / min, and the systemic clearance did not exceed 200 ml/min. Plasma concentrations decreased by more than 95% within six hours of intravenous use.

The end-phase elimination half-life in humans is estimated to exceed ten years, reflecting the release of alendronate from the skeleton. Alendronate is not excreted through the acidic and basic transport systems of the kidneys in rats; therefore, it can be expected that it does not interfere with the excretion of other drugs through these systems in humans.

Kidney failure

Preclinical studies have shown that the drug, which does not accumulate in bone tissue, is quickly excreted in the urine. There was no evidence of saturation of bone accumulation after repeated use of cumulative intravenous doses up to 35 mg/kg in animals. Although no clinical data are available, it is likely that, as in animals, renal excretion of alendronate will be reduced in patients with impaired renal function.

Thus, in patients with impaired renal function, a slightly higher accumulation of alsndronate in the 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;
• prevention of osteoporosis if there is a risk of its development in postmenopausal women to reduce the likelihood of fractures;
• treatment of osteoporosis in men to prevent the occurrence of fractures;
• treatment and prevention of glucocorticoid-induced osteoporosis in men and women;
• treatment of Paget’s bone disease in men and women.

Use during pregnancy and lactation

Use during pregnancyalendronate should not be used during pregnancy. There are insufficient data on the use of alendronate in pregnant women.

Animal studies do not indicate the presence of immediate negative effects during pregnancy, embryo and fetal development, or postnatal development. Alendronate administered to rats during pregnancy caused dystocia due to hypocalcemia.

Use during breast-feeding There are no data on the excretion of alendronate in breast milk. Alendronate should not be given to women who are breast-feeding.

CHILDREN

FOSAMAX®preparation It 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.

Contraindications

• Esophageal diseases and other factors that slow down its emptying, such as strictures or achalasia.
• Inability to sit or stand upright for 30 minutes.
• Hypersensitivity to alendronate or any excipient of the drug.
• Hypocalcemia.
• Hereditary lactase deficiency, glucose-galactose malabsorption.
• Severe disorders of mineral metabolism.
• Chronic renal failure (creatinine clearance) Vitamin D deficiency
• Children’s age.

With caution

• Acute diseases of the upper gastrointestinal tract (GI), 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, with the exception of pyloroplasty.
• Predisposition to hypiocalcemia (hypothyroidism, calcium malabsorption).

Side effects

In clinical trials, the following side effects occurred with a frequency of ≥1%:

From the digestive system: abdominal pain, dyspepsia, esophageal ulcer, dysphagia, flatulence, constipation, diarrhea, acid belching, nausea, gastritis, stomach ulcer, including stomach ulcer complicated by bleeding (melena).

From the musculoskeletal system: myalgia, pain in the bones, joints, muscle cramps.

From the central nervous system: headache.

The following side effects have been reported in general clinical practice::

From the digestive system: erosions or ulcers of the esophagus, nausea, vomiting, gastritis, melena, esophagitis, esophageal stricture, perforation, oropharyngeal ulcer; rarely-ulcers of the stomach and duodenum (although the relationship with the drug is not established), local osteonecrosis of the jaw, associated mainly with previous tooth extraction and / or local infection (including osteomyelitis), often with slow recovery.

Musculoskeletal disorders: myalgia, bone pain, joint pain (rarely severe), joint swelling, low-energy fractures of the femoral body.

Dermatological reactions: skin rash, erythema, photosensitization, pruritus, alopecia; rarely-severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Allergic reactions: urticaria; rarely-angioedema.

On the part of the body as a whole: transient symptoms of an acute phase reaction at the beginning of treatment (myalgia, malaise, asthenia, less often – fever), hypocalcemia; rarely – peripheral edema.

From the sensory organs: rarely-uveitis, scleritis, episcleritis.

From the central nervous system: dizziness, systemic dizziness, impaired taste sensations.

On the part of laboratory parameters: a decrease in serum calcium and phosphate levels (usually mild, asymptomatic, and transient) by 18% and 10%, respectively.

Fosamax is generally well tolerated, and side effects are usually mild and do not require discontinuation.

Interaction

Absorption of alendronate may be impaired if the drug is taken simultaneously with food, beverages (including mineral water), calcium supplements, antacids, and other oral medications. Therefore, the interval between taking FOSAMAX and other oral medications should be at least 30 minutes.

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

The recommended dose is one tablet of 70 mg once a week. 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 FOSAMAX® for each patient, especially after 5 or more years of use.

To ensure sufficient absorption of alendronate:FOSAMAX® it should be taken at least 30 minutes before the first dose of pisha. drinks or medicines taken daily, washed down only with plain water. Other beverages (including mineral water), food, and certain medications may reduce the absorption of alendronate.

To facilitate the entry of the tablet into the stomach and reduce the likelihood of local irritation and irritation of the esophagus/adverse events:

• FOSAMAX® should be taken only after getting out of bed, washed down with a full glass of water (at least 200 ml);
• Patients should swallow the entire FOSAMAX tablet. The tablet should not be crushed, chewed or dissolved in the mouth due to the possible formation of ulcers in the oral cavity and pharynx;
• Patients should not go to bed before the first meal, which should be at least 30 minutes after taking the pill;
• Patients should not go to bed for at least 30 minutes after taking FOSAMAX®;
• FOSAMAX® do not take it before going to bed or before getting out of bed.

Patients should take additional calcium and vitamin D supplements if their intake from food is insufficient.

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

Use in patients with renal insufficiency: No dose adjustment is required for patients with glomerular filtration rate (GFR) greater than 35 ml / min.

Alendronate is not recommended for patients with renal insufficiency, in which GFR is less than 35 ml / min, due to insufficient data on the use. The use of FOSAMAX 70 mg once a week in the treatment of glucocorticoid-induced osteoporosis has not been studied.

Overdose

Symptoms: hypocalcemia, hypophosphatemia, adverse events from the upper gastrointestinal tract, including dipepsia, heartburn, esophagitis, gastritis, stomach and esophageal ulcers.

Treatment: 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. Data on specific therapy are not available.

Special instructions

The patient should be informed that if symptoms of gastrointestinal damage occur (for example, pain when swallowing or behind the sternum, the appearance or increase of heartburn), it is necessary to stop taking the drug and consult a doctor.

The risk of developing severe esophageal adverse reactions increases in patients who violate the rules for taking the drug (they are in a horizontal position after taking Fosamax, drink an incomplete glass of water, continue to take Fosamax after symptoms of esophageal irritation appear). Therefore, the patient should be clearly informed about the rules for taking the drug.

With caution, Fosamax should be prescribed to patients with exacerbation of diseases of the upper gastrointestinal tract (dysphagia, esophageal diseases, gastritis, duodenitis, ulcers) due to the possible irritant effect of Fosamax on the mucous membrane and worsening of the underlying disease.

The patient should be informed that if you accidentally miss taking the drug at a dosage of 1 once a week, you should take 1 tablet in the morning of the next day. You should not take 2 tablets in 1 day, but in the future you should continue to take 1 tablet on the day of the week that was chosen for admission from the very beginning of treatment.

Before starting treatment with Fosamax, the blood calcium content should be normalized and the lack of vitamin D should be compensated.

Due to the fact that Fosamax increases the content of minerals in the bones, there may be a slight asymptomatic decrease in serum calcium and phosphate levels (including in patients receiving corticosteroids, in which calcium absorption may be reduced).

Patients should take dietary supplements containing calcium and vitamin D if the intake of these substances from food is insufficient.

No age-related differences in the efficacy or safety profile of Fosamax were observed in clinical trials.

In double-blind, multicenter, controlled trials,18% and 10% of patients treated with Fosamax and 12% and 3% of patients treated with placebo experienced asymptomatic, mild, and transient decreases in serum calcium and phosphate levels. However, the rate of decrease in calcium content less than 8 mg/dl and phosphate content less than 2 mg / dl was similar in both groups.

Form of production

Pills.

Storage conditions

At a temperature of 15-30 °C

Shelf life

2 years

Active ingredient

Alendronic Acid

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

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

Indications

Osteoporosis, Menopause