Фосамакс®

General characteristics. Structure:

Active ingredient: 91,37 mg of an alendronat of sodium (that is equivalent to 70 mg of alendronovy acid).

Excipients: cellulose microcrystallic, lactose anhydrous, croscarmellose sodium, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Inhibitor of a bone resorption. Treats group of bisfosofonat which, локализуясь in zones of an active resorption of a bone, under osteoclasts, inhibit the process of a resorption of a bone tissue caused by osteoclasts without exerting a direct impact on process of formation of a new bone tissue. As the resorption of a bone and emergence of a new bone tissue are interconnected, formation of a bone also decreases, but to a lesser extent, than a resorption that leads to the progressing increase in bone weight. During treatment alendronaty the normal bone tissue which matrix it is built in алендронат forms, remaining pharmacological inactive. In therapeutic doses алендронат does not cause osteomalacy.

Osteoporosis at women in a postmenopause. Osteoporosis is characterized by decrease in bone weight and thereof, the increased risk of changes, especially a backbone, a hip and a wrist. It occurs both at men, and at women, but is especially frequent at women after a menopause when the speed of a resorption of a bone exceeds the speed of its education that leads to loss of bone weight.

Daily reception of an alendronat in a postmenopause causes the biochemical changes testimonial of dozozavisimy suppression of a bone resorption in women, including decrease in level of calcium in urine and bone collagen disintegration markers (hydroxyproline, a deoksipiridinolin and the cross and connected N-telopeptidov of collagen I of type) in urine. These biochemical indicators are returned to reference values in 3 weeks after cancellation of an alendronat in spite of the fact that drug it is long remains in skeleton bones.

Long (up to 5 years) treatment of osteoporosis by Fosamaks in a dose of 10 mg/days reduces removal with urine of markers of a resorption of a bone of a deoksipiridinolin and the cross and connected N-telopeptidov of collagen I of type approximately by 50% and 70% respectively, to the level observed at healthy women before a menopause.

Speed of a bone resorption begins to decrease on the first month of treatment, reaches constant value on 3-6 month of therapy and remains on the reached values throughout treatment by Fosamaks. Also decrease in levels of markers of formation of a bone - osteocalcine and a kostespetsifichesky alkaline phosphatase approximately for 50%, and the general alkaline phosphatase approximately for 25-30% is noted, reaching the plateau in 6-12 months of therapy. At preventive appointment of Fosamaks in a dose of 5 mg/days there is a decrease in levels of osteocalcine and a kostespetsifichesky alkaline phosphatase approximately by 40% and 15% respectively. Similar reduction in the rate of bone metabolism happens also at Fosamaks's reception in a dose of 70 mg within one year once a week.

Treatment of postmenopauzny osteoporosis. Influence on the mineral density of a bone tissue. Фосамакс® in a dose of 10 mg/days at patients with postmenopauzny osteoporosis increases the mineral density of a bone tissue (MPK) of lumbar department of a backbone, neck of a hip and a big spit of a hip in 3 years of therapy in comparison with placebo on average for 8.82%, 5.9% and 7.81% respectively. The general MPK also considerably increases, and it demonstrates that increase in bone weight and in a femur happens in lumbar department of a backbone not at the expense of other sites of a skeleton. Increase in bone weight is observed in 3 months after administration of drug and continues within 3 years. At prolongation of reception up to 5 years of MPK of lumbar department of a backbone and a big spit of a hip continues to increase, and the additional gain during the period between 3 and 5 of therapy makes 0.94% and 0.88% respectively. Thus, Fosamaks® causes osteoporosis involution. Fosamaks's efficiency does not depend on age, race, the initial speed of metabolism of a bone tissue, function of kidneys and use of a wide range of medicines.

Fosamaks's cancellation after 1-2 years of reception in a dose of 10 mg is followed by gradual return of intensity of bone metabolism to reference values, MPK does not increase, but also the accelerated loss of bone weight is not observed. Therefore therapy by Fosamaks should be carried out it is long to provide gradual increase in bone weight.

In a research at women with postmenopauzny osteoporosis it was shown that Fosamaks® in a dose of 70 mg therapeutic is equivalent once a week to Fosamaks in a dose of 10 mg/days. So, average increase in MPK of lumbar department of a backbone on the first year of reception of Fosamaks in a dose of 70 mg and Fosamaksa in a dose of 10 mg of 1 times/days makes once a week 5.1% and 5.4% respectively. Extent of increase in MPK was also comparable between these therapeutic groups and for other sites of a bone skeleton. The obtained data support the point of view that Fosamaks® in a dose of 70 mg accepted once a week is also effective in decrease in frequency of changes, as well as Fosamaksa of 10 mg at daily reception.

Influence of a pas frequency of development of fractures of bones. It is established that among the women with postmenopauzny osteoporosis accepting Fosamaks® within 3 years statistically authentically the share of patients at whom occurred one or more spinal fractures decreases by 48% (3.2% against 6.2% at placebo reception). Moreover, at those patients who accepted Fosamaks® and had spinal fractures, reduction of growth was not as considerable, as in group of placebo (5.9 mm and 23.3 mm respectively) that was explained by reduction of quantity and weight of changes.

At Fosamaks's reception within 2-3 years in doses> 2.5 mg/days decrease in frequency of developing of extra vertebral fractures by 29% is observed (9.0% against 12.6% in group of placebo). Thus, Fosamaks® effectively reduces the frequency of changes, including a backbone and hip, that is sites of a skeleton, the most vulnerable for development of osteoporosis and its complications.

Histology of a bone tissue. At a histologic research at the women with postmenopauzny osteoporosis accepting Fosamaks® in doses from 1 to 20 mg/days within 1, 2 or 3 years it was revealed that the bone tissue has normal structure and a mineralization, and also reduction in the rate of bone metabolism in comparison with placebo is recorded.

Use for men. Though osteoporosis occurs at men not so often as at women in a postmenopause, a considerable part of the changes connected with osteoporosis are the share of men. Prevalence of the deformation of a backbone connected with osteoporosis is identical at men and women. Fosamaks's use in a dose of 10 mg of 1 times/days for men within 2 years reduces allocation with urine of the cross and connected N-telopeptidov of collagen I of type approximately by 60% and kostespetsifichesky ShchF approximately for 40%. Similar results are observed also at Fosamaks's reception in a dose of 70 mg during 1 year once a week. Increase in MPK in lumbar department of a backbone makes 5.3%, in a hip neck – 2.6%, in a big spit – 3.1%, the general MPK – 1.6% in comparison with placebo.

At Fosamaks's use 10 mg/days at men reduction of frequency of new spinal fractures which makes 0.8% in comparison with 7.1% at placebo reception is noted. Also decrease in size of reduction of growth which makes 0.6 mm at Fosamaks's reception in comparison with 2.4 mm at placebo reception is noted.

At Fosamaks's use in a dose of 70 mg once a week during 1 year there is an increase in MPK in lumbar department of a backbone for 2.8%, in a hip neck - for 1.9%, in a femur - for 2%, in other parts of a body - for 1.2% in comparison with placebo.

Фосамакс® it is effective at men irrespective of age, function of gonads and initial MPK in a neck of a hip and lumbar department of a backbone.

Prevention of osteoporosis at women in a postmenopause. At women at the age of 40-60 years which began to accept Fosamaks® in a dose of 5 mg/days at least in 6 months after approach of a menopause mean increment of MPK in comparison with an initial indicator in lumbar department of a backbone, a hip neck, a big spit and in general in skeleton bones in 2 years of therapy makes 3.46%; 1.27%; 2.98% and 0.67% respectively, in 3 years – 2.89%; 1.10%; 2.71% and 0.32% respectively. Besides, Fosamaks® in a dose of 5 mg/days reduces the speed of loss of bone weight in forearm bones approximately half in comparison with placebo and is effective irrespective of age, the period of a menopause, race and initial speed of bone metabolism.

In 3 years of administration of drug the histologic research reveals normal structure of a bone tissue.

The combined use with estrogen/ZGT. When carrying out a combination therapy significant increase or a tendency to increase in MPK in a femur in general, and also in a neck of a hip and a big spit in comparison with the isolated ZGT is observed.

The osteoporosis caused by reception of glucocorticoids. Long reception of glucocorticoids is associated with development of osteoporosis and the subsequent fractures in men and women at any age. Фосамакс® reduces the level of biochemical markers of a bone resorption and causes significant increase in MPK in lumbar department of a backbone, a hip neck, a big spit of a hip irrespective of a dose and duration of reception of glucocorticoids. At use of drug in a dose to 10 mg of 1 times/days during 1 year the histologic research reveals a normal picture of a bone tissue.

Bone disease of Pedzhet. At a bone disease of Pedzhet of Fosamaks® reduces the speed of a resorption of a bone tissue that is followed by decrease in an osteogenesis. Use of drug in a dose of 40 mg of 1 times/days within 6 months causes considerable decrease in the ShchF level in serum which is an objective indicator of disease severity. Besides, Fosamaks's reception leads to formation of a normal splenial on site of the disorganized bone tissue, at the same time without breaking a bone mineralization. Histologic data confirm that under the influence of Fosamaks disturbances of a mineralization are not noted and the normal bone tissue forms.

Pharmacokinetics. Absorption. After intake in doses of 5-70 mg on an empty stomach not later than 2 h till a standard breakfast bioavailability of an alendronat makes 0.64% at women and 0.6% - at men.

After reception of an alendronat on an empty stomach for 1-1.5 h till a standard breakfast bioavailability decreases approximately by 40%.

At patients with osteoporosis and a bone disease of Pedzhet of Fosamaks® it is effective at use on an empty stomach not later than 30 min. before the first meal or liquid.

Bioavailability of an alendronat is insignificant at its appointment along with meal or during 2 h after meal. The concomitant use with coffee or orange juice reduces bioavailability of drug approximately by 60%.

At reception of Prednisolonum in a dose of 20 mg of 3 times/days within 5 days there is no clinically significant change of bioavailability of an alendronat.

Distribution. Average Vd of an alendronat in an equilibrium state (except for a bone tissue) makes at least 28 l. At reception in therapeutic doses concentration of drug in a blood plasma is insignificant (less than 5 ng/ml). Linkng of an alendronat with proteins of plasma makes about 78%.

Metabolism. There are no data on what алендронат is exposed to metabolism in a human body or animals.

Removal. After single in/in introductions of an alendronat, marked carbon atoms 14C, about 50% of drug are removed with urine during 72 h; removal of marked drug with a stake was insignificant or was not defined.

After single in/in introductions of an alendronat in a dose of 10 mg its renal clearance makes 71 ml/min. In 6 h later in/in maintaining concentration in a blood plasma decreases more, than by 95%. Final T1/2 exceeds 10 years that reflects release of drug from a bone tissue. Alendronat does not break removal of drugs through acid and main transport systems of kidneys.

A little bigger accumulation of drug in a bone tissue can be expected at patients with a renal failure.

Indications to use:

— treatment of osteoporosis at women in a postmenopause for the purpose of the prevention of development of changes, including fractures of a hip and compression spinal fractures;

— prevention of osteoporosis with risk of its development in women in a postmenopause for the purpose of decrease in probability of development of changes;

— treatment of osteoporosis at men for the purpose of prevention of developing of fractures;

— treatment and prevention of the osteoporosis induced by glucocorticoids at men and women;

— treatment of a bone disease of Pedzhet at men and women.

Route of administration and doses:

Фосамакс® it is necessary to accept, at least, in 30 min. prior to the first meal, liquid or medicines, washing down only with simple water. Other drinks (including mineral water), food and some drugs can reduce Fosamaks's absorption.

For reduction of risk of emergence of irritation of a gullet of Fosamaks® it is necessary to accept, carrying out the following rules: to accept in the morning right after rise from a bed; to wash down with a full glass of water for simplification of receipt of a tablet in a stomach; not to chew a tablet and not to rassasyvat them in a mouth because of possible formation of ulcers in an oral cavity and a drink; patients should not lay down before the first meal which should be made at least in 30 min. after Fosamaks's reception; Фосамакс® it is not necessary to accept before going to bed or before rise from a bed.

Patients should accept in addition drugs of calcium and vitamin D if intake of these substances with food is not enough.

Treatment of osteoporosis at women in a postmenopause and men: the recommended dose - 1 таб. 70 mg once a week.

Prevention of osteoporosis at women in a postmenopause: 5 mg of 1 times/days.

Treatment and prevention of the osteoporosis caused by reception of glucocorticoids at men and women: 5 mg of 1 times/days.

At women in a postmenopause who do not receive estrogen the recommended dose makes 10 mg of 1 times/days.

Bone disease of Pedzhet at men and women: 40 mg of 1 times/days within 6 months.

The repeated course of treatment of a bone disease of Pedzhet can be carried out in 6 months after 1 course if at patients the exacerbation of a disease which diagnosis is based on increase in the ShchF level developed. The repeated course of treatment can be also carried out at patients at whom the ShchF level was not normalized after an initial course of therapy.

For patients of advanced age and patients with a renal failure easy and moderate severity (KK from 35 to 60 ml/min.) of dose adjustment is not required. Фосамакс patients are not recommended to appoint with a renal failure of heavy degree (KK <35 ml/min.) due to the lack of experience of use for these patients.

Features of use:

Use at pregnancy and feeding by a breast. Фосамакс® it is not necessary to appoint at pregnancy and in the period of a lactation (breastfeeding).

Use at renal failures. For patients of advanced age, patients with a renal failure easy or moderate severity (KK from 35 to 60 ml/min.) of dose adjustment is not required.

Fosamaks's use for patients with a renal failure of heavy degree (KK less than 35 ml/min.) is not recommended due to the lack of clinical observations.

Use for children. Fosamaks's researches at children were not conducted therefore drug should not be used in pediatrics.

Use for elderly patients. For patients of advanced age of dose adjustment it is not required.

Special instructions. Фосамакс®, as well as other bisfosfonata, the local irritation of a mucous membrane of upper parts of a GIT can cause. At the patients receiving treatment by Fosamaks such side reactions as an esophagitis, the ulcer of a gullet and erosion of a gullet which are occasionally leading to emergence of strictures or perforation of a gullet are noted. In certain cases these undesirable phenomena can be heavy and demand hospitalization therefore it is necessary to control especially attentively any symptoms indicating possible disturbances from a gullet. Patients should be warned about need to stop Fosamaks's reception and to see a doctor in case of a dysphagy, pain when swallowing or behind a breast, emergence or strengthening of heartburn.

The risk of emergence of the heavy undesirable phenomena from a gullet is higher at patients who violate recommendations about administration of drug and/or continue to accept it at emergence of symptoms of irritation of a gullet. It is especially important that the patient had recommendations about administration of drug, understood them and it was informed that the risk of development of damage of a gullet increases in a case of failure to follow these recommendations.

Exceptional cases of emergence of stomach ulcer and duodenum, sometimes heavy and complicated are known (relationship of cause and effect is not established with administration of drug).

Фосамакс patients should appoint with care with exacerbations of diseases of upper parts of digestive tract, such as dysphagy, gullet diseases, gastritis, duodenitis and ulcers because of possible irritant action of drug to a mucous membrane of upper parts of a GIT and deterioration in a current of a basic disease.

Cases of emergence of the local osteonecrosis of a jaw associated mainly with the previous extraction of tooth and/or a local infection are known (including osteomyelitis), it is frequent with a gradual return to health.

In most cases the jaw osteonecrosis against the background of reception of bisfosfonat arises at the oncological patients receiving bisfosfonata in / century. The known risk factors of an osteonecrosis of a jaw include an oncological disease, the accompanying therapy (for example, chemotherapy, radiation therapy, corticosteroids), bad hygiene of an oral cavity and the accompanying pathologies (for example, diseases of a periodontium and/or other diseases of teeth, anemia, a coagulopathy, an infection) and smoking. Specialized medical care by the maxillofacial surgeon has to be provided to patients at whom the jaw osteonecrosis develops, and the question of cancellation of therapy of a bisfosfonatama has to be considered, proceeding from individual assessment of a ratio risk/advantage. Dental surgical intervention can lead to an aggravation of symptoms.
Tactics of treatment of each patient which needs invasive dental intervention (for example, an odontectomy, implantation) including therapy of a bisfosfonatama, has to be based on clinical judgment of the attending physician and/or maxillofacial surgeon and individual assessment of a ratio risk/advantage.

It was reported about emergence of ostealgias, joints and/or muscles at the patients receiving bisfosfonata. These symptoms seldom have difficult character and/or lead to disability. Time before emergence of symptoms varies from one day to several months from the beginning of therapy. At most of patients after the therapy termination symptoms recede, but at some patients appear after resuming of reception of the same drug or other bisfosfonat again.

It was reported about emergence pathological (i.e. at influence of insignificant force or spontaneous) subtrochanterian fractures or changes of proximal departments of a diaphysis of a femur at a small amount of the patients accepting bisfosfonata. Some of changes belonged to the category stressful (the load change, a mid-flight change, Doychlender's change are also known under names), arising in the absence of an injury. Some patients one weeks or months prior to emergence of a complete fracture felt the prodromal pains in the struck area which are often connected with a characteristic X-ray pattern of a stressful change. The number of messages was very small, besides, stressful changes with similar clinical features arise also at the patients who are not accepting a bisfosfonata. Patients with stressful changes need to be inspected with assessment of the known reasons and risk factors (for example, deficit of vitamin D, absorption disturbance, use of corticosteroids, a stressful change in the anamnesis, arthritis or a fracture of the lower extremity, the excessive or increased loadings, a diabetes mellitus, an alcoholism) and to provide them the appropriate orthopedic assistance. Before obtaining results of inspection it is necessary to consider a question of suspension of reception of bisfosfonat at patients with stressful changes, proceeding from ratio assessment advantage/risk in each case.

Patients should be warned that at the accidental admission of administration of drug of Fosamaks® once a week, they have to take one pill in the morning of the next day. It is not necessary to accept two doses in one day, but in the subsequent it is necessary to return to administration of drug once a week to that day of the week which was chosen in an initiation of treatment.

It is necessary to take into account and other reasons of osteoporosis, in addition to deficit of estrogen, age and treatment by glucocorticoids.

In the presence of a hypocalcemia calcium level in blood needs to be normalized prior to treatment by Fosamaks. Other disturbances of mineral exchange (for example, deficit of vitamin D) also have to be eliminated. At patients with these disturbances it is necessary to control the content of calcium in blood and symptoms of a hypocalcemia.

As Fosamaks® increases the content of mineral substances in bones, small asymptomatic decrease in level of calcium and phosphates in blood serum can be observed, especially at a bone disease of Pedzhet, with initially considerably the increased speed of metabolism of a bone tissue, and also at the patients receiving glucocorticoids that is followed by possible reduction of absorption of calcium. It is especially important to provide adequate receipt in an organism of calcium and vitamin D at these patients.

In rare instances the hypocalcemia can be heavy, usually at patients with predisposition to this complication (a hypoparathyroidism, deficit of vitamin D, calcium malabsorption).

Use in pediatrics. Fosamaks's researches at children were not conducted therefore drug should not be used in pediatrics.

Influence on ability to driving of motor transport and to control of mechanisms. There are no data that Fosamaks influences ability to drive the car or to work with mechanisms.

Side effects:

In clinical trials the following side effects met frequency of 1%.

From the alimentary system: abdominal pains, dyspepsia, a gullet ulcer, a dysphagy, a meteorism, a lock, diarrhea, an acid eructation, nausea, gastritis, stomach ulcer, including the peptic ulcer of a stomach complicated by bleeding (melena).

From a musculoskeletal system: mialgiya, ostealgias, joints, muscular spasms.

From TsNS: headache.

In broad clinical practice it was reported about the following side effects:

From the alimentary system: erosion or ulcers of a gullet, nausea, vomiting, gastritis, melena, esophagitis, gullet stricture, perforation, stomatopharynx ulcer; seldom – stomach ulcer and a duodenum (though connection with drug is not established), the local osteonecrosis of a jaw associated mainly with the previous extraction of tooth and/or a local infection (including osteomyelitis), it is frequent with a gradual return to health.

From a musculoskeletal system: a mialgiya, ostealgias, joint pains (it is rare – a heavy current), a swelling of joints, low-energy changes of a shaft of the femur.

Dermatological reactions: skin rash, erythema, photosensitization, itch, alopecia; seldom - heavy skin reactions, including Stephens-Johnson's syndrome and a toxic epidermal necrolysis.

Allergic reactions: small tortoiseshell; seldom - a Quincke's disease.

From an organism in general: passing symptoms of reaction of an acute phase in an initiation of treatment (the mialgiya, an indisposition, an adynamy, is more rare - fever), a hypocalcemia; seldom - peripheral hypostases.

From sense bodys: seldom - a uveitis, a sclerite, an episcleritis.

From TsNS: dizziness, rotatory vertigo, disturbance of flavoring feelings.

From laboratory indicators: decrease in level of calcium and phosphates in blood serum (usually easy, asymptomatic and tranzitorny) for 18% and 10% respectively.

Фосамакс® in general it is well transferred, side effects usually easy and do not demand drug withdrawal.

Interaction with other medicines:

At simultaneous use with calcium drugs, antacids and other means for intake possible disturbance of absorption of an alendronat. In this regard the interval between Fosamaks's reception and other medicines accepted inside has to make not less than 30 min.

At combined use of Fosamaks and ZGT (estrogen ± progestin) safety and portability of a combination therapy correspond to that at use of each of these drugs separately. In clinical trials of Fosamaks at men, women in a postmenopause and the patients accepting glucocorticoids clinically significant medicinal interaction concerning influence on linkng with proteins, renal excretion and metabolism was not revealed. Frequency of the undesirable phenomena from an upper part of a GIT increases at Fosamaks's combination in a dose more than 10 mg/days with the drugs containing acetylsalicylic acid. However this effect was not observed at Fosamaks's reception in a dose of 70 mg of 1 time/week.

Contraindications:

— the gullet diseases which are slowing down its emptying (for example, strictures or an achalasia);

— inability to sit or stand directly within 30 min.;

— hypocalcemia;

— hypersensitivity to drug components.

With care apply at an exacerbation of diseases of upper parts of a GIT, such as dysphagy, gullet diseases, gastritis, duodenitis or peptic ulcer of a stomach. Фосамакс patients are not recommended to appoint with renal failures at KK <35 ml/min.; in case of predisposition to a hypocalcemia (a hypoparathyroidism, deficit of vitamin D, calcium malabsorption).

Overdose:

Symptoms: a hypocalcemia, a hypophosphatemia, the undesirable phenomena from an upper part of a GIT, including a dipepsiya, heartburn, an esophagitis, gastritis, stomach ulcer and a gullet.

Treatment: the patient should accept milk or antacids for binding of an alendronat. For prevention of irritation of a gullet it is not necessary to cause vomiting. Patients have to keep vertical position. Data on specific therapy are not available.

Storage conditions:

Drug should be stored in the place, unavailable to children, at the room temperature from 15 °C to 30 °C, in original packaging. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

4 pieces - blisters (1) - covers cardboard (1) - packs cardboard.