Expiration date: 07/2025

The composition and form of issue: 

Tablets. 1 tablet contains active substance: 

alendronate sodium of 13.05 mg

91.37 mg

(that corresponds to the content alendronova acid 10, or 70 mg, respectively) 

other ingredients: microcrystalline cellulose lactose anhydrous croscarmellose sodium magnesium stearate 

Tablets 10 mg: blister of 7 or 14 PCs. in cardboard pack 1, 2 or 4 blisters.

Tablets 70 mg: blister of 4 PCs the paper cartons of 1 blister.

Description pharmaceutical form:

Tablets 10 mg: oval, white or almost white, with a reference number 936 on one side.

Tablets 70 mg: oval, white or almost white, with a contoured bone image on one side and a code number 31 on the other.

Pharmacological action:

Inhibiting bone resorption.

Pharmacokinetics:

Suction

The bioavailability of alendronate at a dose of 5-70 mg when administered on an empty stomach at least 2 hours before a standard Breakfast is 0.64% in women and 0.6% in men. Upon receipt of alendronate on an empty stomach 1-1. 5 hours before a standard Breakfast reduced bioavailability by approximately 40%. In patients with osteoporosis and bone Paget's disease Fosamax effective on an empty stomach, at least 30 minutes before the first food or liquid.

The bioavailability of alendronate is insignificant when it is administered with food or within 2 hours after a meal. Joint reception with coffee or orange juice reduces bioavailability of the drug is approximately 60%.

When receiving prednisolone at a dose of 20 mg 3 times a day for 5 days is not happening clinically significant changes in the bioavailability of alendronate.

Distribution

Average Vss Fosamax (except bone tissue) is at least 28 l. When taken in therapeutic doses, the concentration of the drug in plasma is negligible (less 5 ng/ml). The binding of alendronate to plasma proteins is approximately 78%.

Metabolism

There is no evidence that alendronate is subjected to metabolism in humans or animals.

Excretion

After a single on/in the introduction of alendronate labeled with 14C carbon atoms, approximately 50% is excreted in the urine within 72 hours excretion of the labeled drug in the feces was not determined or was negligible. After a single on/in the introduction of alendronate at a dose of 10 mg his kidney klirens is 71 ml/min, and systemic clearance did not exceed 200 ml/min Through 6 h after the/in the reference concentration in plasma is reduced by more than 95%. The final T1/2 is over 10 years, reflecting the release of the drug from bone tissue. Alendronate does not violate the excretion of drugs through the acidic and basic transport system of the kidneys. Somewhat greater accumulation of the drug in the bone tissue can be expected in patients with impaired renal function.

Description pharmacological action:

Alendronate bisphosphonates refers to the connections that localizes in the areas of active bone resorption under osteoclasts, inhibit the process of bone resorption caused by osteoclasts, without exerting direct influence on the formation of new bone tissue. Because bone resorption and new bone tissue is interconnected, bone formation is also reduced, but less so than resorption, leading to progressive increase in bone mass. During treatment with alendronate is formed normal bone, in which the matrix is embedded alendronate, remaining pharmacologically inactive. At therapeutic doses, alendronate does not cause osteomalacia.

Osteoporosis in postmenopausal women

Osteoporosis is characterized by reduced bone mass and consequently increased risk of fractures, especially of the spine, hip and wrist. It is found both in men and women, but most often in women after menopause when the rate of bone resorption exceeds the rate of its formation, leading to bone loss.

Daily intake of alendronate in postmenopausal women causes biochemical changes, indicating a dose-dependent suppression of bone resorption, including reducing the level of calcium in the urine and markers of decomposition of bone collagen (hydroxyproline, deoxypyridinoline and cross-linked N-telopeptides type I collagen) in the urine. These biochemical parameters returned to baseline values after 3 weeks after discontinuation of alendronate, despite the fact that the drug is long-lasting in the bones of the skeleton.

Long-term (to 5 years) treatment of osteoporosis with Fosamax at a dose of 10 mg/day reduces the urinary excretion of markers of bone resorption of deoxypyridinoline and cross-linked N-telopeptides of type I collagen by approximately 50 and 70%, respectively, to the level observed in healthy women before menopause.

The rate of bone resorption begins to decline already at the 1st month of treatment, reaches a constant value at 3-6 months of therapy and stored at the obtained values throughout the treatment Fosamaxo. Also there is a decrease in levels of markers of bone formation — osteocalcin and alkaline phosphatase casespecifications approximately 50%, and total alkaline phosphatase by approximately 25-30%, reaching a plateau after 6-12 months of therapy. When prophylactic administration of Fosamax at a dose of 5 mg/day decreases the levels of osteocalcin and alkaline phosphatase casespecifications approximately 40 and 15%, respectively. A similar decrease in the rate of bone metabolism and occurs when taken Fosamax at a dose of 70 mg/week for 1 year.

Effect on mineral density of bone tissue. Fosamax at a dose of 10 mg/day in patients with postmenopausal osteoporosis increases mineral bone density (BMD) of the lumbar spine, femoral neck and greater trochanter of the hip after 3 years of therapy compared to placebo on average by 8.82, 5.9 and 7,81%, respectively. Total BMD also increases significantly, and this suggests that the increase in bone mass in the lumbar spine and the femur occurs not at the expense of other parts of the skeleton. An increase in bone mass is observed after 3 months of taking the drug and lasts for 3 years. When extending the deadline to 5 years BMD of the lumbar spine and the greater trochanter of the thigh continues to increase and the additional increase of between 3 and 5 years of therapy is 0.94 and 0.88%, respectively. Thus, Fosamax reverses the development of osteoporosis. The effectiveness of Fosamax does not depend on age, race, baseline rate of bone metabolism, renal function and use of broad-spectrum drugs.

Cancel Fosamax after 1-2 years of taking in a dose of 10 mg is accompanied by a gradual return to the intensity of bone metabolism to reference values, BMD is not increased, but the accelerated bone loss observed. Therefore, therapy with Fosamax should be long to provide a gradual increase in bone mass.

In a study in women with postmenopausal osteoporosis have shown that Fosamax dose 70 mg/week Fosamax therapeutically equivalent to a dose of 10 mg/day. So, the average increase in BMD of the lumbar spine in the first year of receiving Fosamax dose 70 mg/week and at a dose of Fosamax 10 mg/day is 5.1 and 5.4%, respectively. The degree of increase in BMD was also comparable between the data of the therapeutic groups and to other sites of the skeleton. The data obtained support the view that Fosamax dose 70 mg/week is also effective in reducing the frequency of fractures, and Fosamax 10 mg, taken daily.

The impact of PA incidence of bone fractures. It was found that among women with postmenopausal osteoporosis who took Fosamax for 3 years, statistically significantly by 48% reduced the proportion of patients who experienced one or more vertebral fractures (3.2 vs. 6.2% receiving placebo). Moreover, those patients who took Fosamax and suffered fractures of the spine, growth reduction was not as significant as in the placebo group (5,9 and 23.3 mm, respectively), which was explained by the decrease in the number and severity of fractures.

When taking Fosamax for 2-3 years at doses >2.5 mg/day, a decrease in the incidence of nepoznannyj fractures by 29% (9 vs 12.6% in the placebo group). Thus, Fosamax effectively reduce the incidence of fractures, including spine and hip, i.e., sections of the skeleton most vulnerable to osteoporosis and its complications

Histology of bone tissue. Histological study in women with postmenopausal osteoporosis who took Fosamax at doses from 1 to 20 mg/day for 1, 2 or 3 years it was discovered that bone tissue has a normal structure and mineralization, as well as fixed speed reduction bone turnover compared with placebo.

Use in men

Although osteoporosis in men is not as common as in postmenopausal women, a significant part of fractures associated with osteoporosis are men. The prevalence of spinal deformity associated with osteoporosis is the same for men and women. The use of Fosamax at a dose of 10 mg/day in men for 2 years reduces the urinary excretion of cross-linked N-telopeptides of type I collagen by approximately 60% and casespecific alkaline phosphatase by approximately 40%. Similar results are observed when taking Fosamax at a dose of 70 mg/week for 1 year. The increase in BMD in the lumbar spine is 5.3% in the femoral neck and 2.6% in the greater trochanter and 3.1%, total BMD of 1.6% compared with placebo.

With the use of Fosamax 10 mg/day in men, the reduction in frequency of new fractures of the spine, which is 0.8% compared to 7.1% when taking a placebo. Also there is a decrease in the magnitude of growth reduction, which is 0.6 mm when taking Fosamax compared to 2.4 mm when taking placebo.

When using Fosamax dose 70 mg/week for 1 year there is an increase in BMD in the lumbar spine, 2.8% in the femoral neck by 1.9% in the femur by 2%, in other parts of the body by 1.2% compared to placebo.

Fosamax is effective in men regardless of age, gonadal function and baseline BMD in the femoral neck and lumbar spine.

Prevention of osteoporosis in postmenopausal women

In women aged 40-60 years, began to take Fosamax at a dose of 5 mg/day for at least 6 months after menopause, the average increase in BMD compared to baseline in the lumbar spine, femoral neck, greater trochanter, and generally in the bones of the skeleton after 2 years of therapy amounts to 3.46, 1.27 mm, 2,98 and 0,67%, respectively, after 3 years of 2.89, 1,10, of 2.71 and 0.32%, respectively. In addition, Fosamax at a dose of 5 mg/day reduces the rate of bone loss in the bones of the forearm by approximately half in comparison with placebo and effective regardless of age, menopause, race and baseline rate of bone turnover.

After 3 years of taking the drug, histological examination reveals normal structure of bone tissue.

The concomitant use with estrogen/hormone replacement therapy (HRT)

During the combination therapy observed a significant increase or tendency to increase BMD in the femur as a whole, as well as in femoral neck and greater trochanter compared with isolated HRT.

Osteoporosis caused by receiving GK

Long-term use of glucocorticoids is associated with osteoporosis and subsequent fracture in men and women at any age. Fosamax reduces the level of biochemical markers of bone resorption and causes a significant increase in BMD in the lumbar spine, femoral neck, greater trochanter of the hip regardless of the dose and duration of use of glucocorticoids. In applying the drug in doses up to 10 mg/day for 1 year, histological examination reveals a normal pattern of bone tissue.

Bone Paget's disease

When the bone Paget's disease Fosamax decreases the rate of bone resorption, which is accompanied by a decrease in bone formation. The use of the drug in a dose of 40 mg/day for 6 months causes a significant decrease in serum alkaline phosphatase, which is an objective indicator of disease severity. In addition, the reception Fosamax leads to the formation of normal lamellar bone in the place of disorganized bone tissue, without disrupting the mineralization of bone. Histological data confirm the influence of the Fosamax is not marked disorders of mineralization and formed normal bone.

Indications:

• treatment of osteoporosis in postmenopausal women to prevent fractures, including hip fractures and compression fractures of the spine
  
• prevention of osteoporosis when 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 osteoporosis induced GK, men and women.
  
• treatment of bone Paget's disease of bone in men and women.
  

Contraindications:

• diseases of the esophagus, slowing emptying (e.g., stricture or achalasia)
  
• inability to sit or stand upright for 30 min
  
• hypocalcemia
  
• hypersensitivity to the drug.
  

Caution: acute diseases of the upper gastrointestinal tract, such as dysphagia, esophageal diseases, gastritis, duodenitis or peptic ulcer patients with renal impairment Cl creatinine <35 ml/min predisposed to hypocalcemia (hypoparathyroidism, vitamin D deficiency, malabsorption of calcium).

Application of pregnancy and breast-feeding:

Fosamax should not be administered during pregnancy and lactation (breastfeeding).

Side effects:

In clinical studies the following side effects occurred at a frequency &ge1%

Gastrointestinal: abdominal pain, dyspepsia, esophageal ulcer, dysphagia, flatulence, constipation, diarrhea, sour belching, nausea, gastritis, stomach ulcer, including peptic ulcer, complicated by bleeding (melena).

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

From the nervous system: headache.

Statistics the incidence of side effects in the treatment of osteoporosis by Fosamaxo collected in controlled multicentre clinical trials, the following 3 tables.# (Hereinafter the data marked with "#", taken from the following sources: Physicians Desk Reference.- 63rd ed.- Thomson PDR.- 2009.- 2005 p. www.pharmakonalpha.com/search/query/q/FOSAMAX).

Table 1 includes the results of double-blind, placebo-controlled study of women with osteoporosis in postmenopausal women who took Fosamax at a dose of 10 mg/day (n=196) or placebo (n=397) within 3 years.

Table 1

The frequency of side effects in postmenopausal women

Side effects	Fosamax 10 mg/day, %	Placebo, %
The digestive tract
Abdominal pain	6,6	4,8
Nausea	3,6	4
Dyspepsia	3,6	3,5
Constipation	3,1	1,8
Diarrhea	3,1	1,8
Flatulence	2,6	0,5
Sour belching	2	4,3
Ulcers of the esophagus	1,5	0
Vomiting	1	1,5
Dysphagia	1	0
Bloating	1	0,8
Gastritis	0,5	1,3
Musculoskeletal system
Myalgia, pain in bones, joints	4,1	2,5
Nervous system
Headache	2,6	1,5

Table 2 includes side effects, registered in double-blind clinical trial of women with osteoporosis in postmenopausal women, receiving the drug in doses of 70 mg/week (n=519) or 10 mg/day (n=370).

Table 2

The frequency of side effects in postmenopausal women

Side effects	Fosamax 70 mg/day, %	Fosamax 10 mg/day, %
The digestive tract
Abdominal pain	3,7	3
Dyspepsia	2,7	2,2
Sour belching	1,9	2,4
Nausea	1,9	2,4
Bloating	1	1,4
Constipation	0,8	1,6
Flatulence	0,4	1,6
Gastritis	0,2	1,1
Stomach ulcer	0	1,1
Musculoskeletal system
Myalgia, pain in bones, joints	2,9	3,2
Muscle cramps	0,2	1,1

Table 3 presents data on the frequency of side effects encountered in a double-blind placebo-controlled clinical trial of men with osteoporosis who took Fosamax at doses of 10 mg/day (n=146) or placebo (n=95).

Table 3

The frequency of side effects in men with osteoporosis

Side effects	Fosamax 10 mg/day, %	Placebo, %
The digestive tract
Sour belching	4,1	3,2
Gastroesophageal reflux disease	0,7	3,2
Dyspepsia	3,4	0
Diarrhea	1,4	1,1
Abdominal pain	2,1	1,1
Nausea	2,1	0

In clinical practice (post-marketing studies) reported the following side effects

From the blood: erosion or ulceration of the esophagus, nausea, vomiting, gastritis, melena, esophagitis, esophageal stricture, perforation, ulcers of the oropharynx rarely ulcers of the stomach and duodenum (though the connection to drug not established), local osteonecrosis of the jaw associated mainly with the previous tooth extraction and/or local infection (including osteomyelitis), often with a slow recovery.

From the musculoskeletal: myalgia, bone pain, joint pain, rarely severe, swelling of joints, low-energy body fractures of the femur.

From the skin: skin rash, erythema, photosensitivity, pruritus, alopecia, rarely severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Allergic reactions: hypersensitivity, including urticaria rare angioedema.

From the body as a whole: transient symptoms of the acute phase response in early treatment (myalgia, malaise, asthenia, rarely fever), hypocalcemia rarely — peripheral edema.

From the senses: rarely uveitis, scleritis, episcleritis.

From the nervous system: dizziness, system dizziness, a violation of taste sensations.

Laboratory indicators: decrease in level of calcium and phosphate in the serum by 18% and 10% respectively.

Drug interactions:

The absorption of Fosamax may be impaired if the drug is taken simultaneously with the calcium supplements, antacids and other oral medications. In this regard, the interval between taking Fosamax and the other drugs, taken by mouth, should be at least 30 min.

When used together Fosamax and HRT (estrogen+progestin) safety and tolerability of combination therapy are similar when using each of these drugs separately.

In clinical studies, Fosamax in men, postmenopausal women and patients receiving GC, no clinically significant drug interactions in relation to effects on protein binding, renal excretion and metabolism. The frequency of adverse events from the upper digestive tract increases when combined Fosamax at a dose of 10 mg/day with drugs containing acetylsalicylic acid. However, this effect was not observed when taken Fosamax at a dose of 70 mg/week.

Method of application and dose:

Fosamax must be taken at least 30 minutes before the first meal, fluids or other drugs, drinking just plain water. Other beverages (including mineral water), food and some medicines can reduce the absorption of Fosamax.

To reduce the risk of side effects from the gastrointestinal tract and especially of the esophagus during therapy with Fosamax should adhere to the following rules:

• take in the morning immediately after rising from bed
  
• drink a full glass of water to facilitate the receipt of the tablets in the stomach
  
• do not chew the tablets and not dissolve them in the mouth because of the possible formation of ulcers in the mouth and throat
  
• patients should not lie down before the first meal, which should be done at least 30 minutes after taking Fosamax
  
• Fosamax should not be taken at bedtime or before getting out of bed.
  

Patients should also take calcium and vitamin D, if intake of these substances with food is not enough.

For elderly patients and patients with mild and moderate renal insufficiency (Cl creatinine clearance 35 to 60 ml/min) dose adjustment is not required. Fosamax is not recommended to appoint patients with severe renal insufficiency (Cl creatinine <35 ml/min) due to lack of experience in these patients.

Treatment of osteoporosis in postmenopausal women and men.The recommended dose is 1 tab. 70 mg 1 time per week or 1 table. 10 mg 1 time per day.

Prevention of osteoporosis in postmenopausal women — 5 mg 1 time per day.

Treatment and prevention of osteoporosis due to the reception of the civil code, men and women — 5 mg 1 time per day. The postmenopausal women who did not receive estrogen, the recommended dose is 10 mg 1 time per day.

Bone Paget's disease in men and women is 40 mg 1 time a day for 6 months.

Repeated treatment of bone Paget's disease.A second course of treatment Fosamax about bone Paget's disease can be performed 6 months after the 1st course in that case, if the patients developed exacerbation of the disease (according to clinical research, the recurrence rate — 9%), diagnosis of which is based on increasing the level of alkaline phosphatase. Repeated treatment can also be carried out in patients whose alkaline phosphatase level does not normalize after initial course of therapy.

Overdose:

Symptoms:hypocalcemia, hypophosphatemia, adverse events from the upper digestive tract including upset stomach, heartburn, esophagitis, gastritis, gastric ulcer and esophagus.

Treatment:Specific information is missing. The patient should take milk or antacids to bind alendronate. To prevent irritation of the esophagus should not cause vomiting. Patients should remain fully upright.

Precautions:

Fosamax, like other bisphosphonates, may cause local irritation of the upper gastrointestinal tract. In patients receiving treatment with Fosamax, there are adverse reactions such as esophagitis, esophageal ulcers and erosion of the esophagus, occasionally resulting in the occurrence of strictures or perforation of the esophagus. In some cases, these adverse events can be severe and require hospitalization. In this regard, physicians should be particularly alert to any signs and symptoms indicating possible violations of the esophagus, and patients should be warned of the need to stop taking Fosamax and consult doctor in case of dysphagia, pain when swallowing or chest, new or increased heartburn. In patients who are unable to fulfill the requirements of the manual for mental disorders, treatment with Fosamax should be under proper control.#

The risk of severe adverse events on the part of the esophagus was higher in patients who violate the guidelines for drug and/or continue to take it at the onset of symptoms of irritation of the esophagus. It is particularly important that the patient had recommendations on receiving the drug, understood them and was informed that the risk of developing esophageal lesions is increased in the event of failure of these recommendations.

Known rare cases of stomach ulcers and duodenal ulcers, sometimes severe and complicated. However, in these cases a causal relationship to drug intake is not installed.

It is believed that therapy with Fosamax can be combined with oral NSAIDs. According to the results of a 3-year controlled trials, in which the majority of patients received concomitant NSAIDs, the frequency of adverse events from the upper gastrointestinal tract in patients who received Fosamax at doses of 5 and 10 mg/day, was comparable to those taking placebo. However, because NSAIDs administration is associated with irritation of the mucous membranes of the upper GI tract, then care should be taken in case of their simultaneous application with Fosamax.#

Fosamax should be administered with caution to patients with exacerbations of diseases of the upper gastrointestinal tract, such as dysphagia, esophageal diseases, gastritis, duodenitis or ulcers because of possible irritant action of Fosamax on the mucosa of the upper gastrointestinal tract and the worsening of the underlying disease.

Known cases of the appearance of local osteonecrosis of the jaw (ESP), associated mainly with the previous tooth extraction and/or local infection (including osteomyelitis), often with a slow recovery.

In most cases, ESP in patients receiving bisphosphonates occurs in cancer patients receiving bisphosphonates. Known risk factors include VLF cancer, concomitant therapies (e.g. chemotherapy, radiotherapy, corticosteroids), poor oral hygiene and comorbidities (for example diseases of the periodontium and/or other dental disease, anemia, coagulopathy, infection) and Smoking. Patients who develop together, should be provided specialized medical assistance oral and maxillofacial surgeon, and the question of the abolition of bisphosphonates therapy should be considered based on individual assessment of risk/benefit. Dental surgery may worsen the condition.

Treatment tactics of each patient requiring invasive dental surgery (e.g. tooth extraction, implants), including the bisphosphonates therapy should be based on clinical judgment of the attending physician and/or oral and maxillofacial surgeon and individual evaluation of risk/benefit.

Reported occurrence of pain in the bones, joints and/or muscles in patients receiving bisphosphonates. These symptoms rarely are severe and/or lead to disability. Time to onset of symptoms varied from one day to several months from the start of therapy. In the majority of patients after cessation of therapy the symptoms recede, but some patients appear again after resuming the same drug or another bisphosphonate.

It was reported on the pathological (i.e., when exposed to a small force or spontaneous) intertrochanteric fractures or fractures of the proximal diaphysis of the femur in a small number of patients taking bisphosphonates. Some of the fractures were classified as stress (also known as stress fracture, March fracture, fracture of Deuscleaner), resulting in no injuries. Some patients for weeks or months before the occurrence of full fracture had experienced prodromal pain in the affected area, often associated with a characteristic radiographic picture of a stress fracture. The number of messages was very small, in addition, stress fractures with similar clinical features occur in patients not taking bisphosphonates. Patients with stress fractures should be evaluated with the assessment of known causes and risk factors (e.g. vitamin D deficiency, malabsorption, corticosteroids, stress fracture history of arthritis or fracture of the lower limbs, excessive or prolonged load, diabetes mellitus, chronic alcoholism) and to provide adequate orthopedic care. Pending the results of the survey should consider the suspension of acceptance of bisphosphonates in patients with stress fractures based on an assessment of the benefit/risk in each case.

Patients should be warned that accidental omission of the drug Fosamax 1 per week, they should take one tablet in the morning, the nearest day. You should not take two doses in one day, but later need to go back to taking the drug 1 time per week same day of the week that was selected at the beginning of treatment.

Fosamax is not recommended for patients with creatinine Cl <35 ml/min.

Should take into account other causes of osteoporosis, in addition to estrogen deficiency, age and treatment of CC.