Alendronovy acid

General characteristics. Structure:

Active ingredient: 70 mg of alendronovy acid (in the form of sodium of an alendronat).

Excipients: lactose anhydrous, cellulose microcrystallic (Е 460), croscarmellose sodium, magnesium stearate (Е 572).

Pharmacological properties:

Pharmacodynamics. Alendronat treats bisfosfonata - without exerting connections 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 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.

Prolonged treatment of osteoporosis alendronaty 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, 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 alendronovy acid. Also decrease in levels of markers of formation of a bone - osteocalcine and a kostespetsifichesky alkaline phosphatase is noted. Similar reduction in the rate of bone metabolism happens also at reception of alendronovy acid in a dose of 70 mg within one year once a week.

Treatment of osteoporosis. Post-menopausal osteoporosis. Influence on the mineral density of a bone tissue. Alendronovy acid at patients with post-menopausal 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. The general MPK also considerably increases, 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, alendronovy acid causes osteoporosis involution. Efficiency of alendronovy acid 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.

Cancellation of alendronovy acid after 1-2 years of reception is followed by gradual return of intensity of bone metabolism to reference values. Therefore therapy by alendronovy acid has to be carried out is long to provide gradual increase in bone weight.

In a research at women with post-menopausal osteoporosis it was shown that alendronovy acid in a dose of 70 mg therapeutic is equivalent once a week to alendronovy acid in a dose of 10 mg a day and also the alendronovy acid of 10 mg accepted daily is effective in decrease in frequency of changes, as well as. Extent of increase in MPK of lumbar department of a backbone and other sites of a bone skeleton is comparable between these therapeutic groups.

Influence on the frequency of development of fractures of bones. At women with post-menopausal osteoporosis at reception of alendronovy acid within 3 years, the risk of spinal fracture decreases almost twice.

Pharmacokinetics. Absorption. Bioavailability of alendronovy acid in a dose of 5 - 70 mg at intake on an empty stomach not later than 2 hours till a standard breakfast, makes 0,64% at women and men have 0,6%. At reception of alendronovy acid on an empty stomach in 1-1,5 hours prior to a standard breakfast bioavailability decreases approximately by 40%. At patients with osteoporosis and a bone disease Pedzheta alendronovy acid is effective at use on an empty stomach, not later than 30 minutes before the first meal or liquid.

Bioavailability of alendronovy acid is insignificant at its appointment along with meal or within two hours 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 3 times a day within 5 days, do not occur clinically significant change of bioavailability of an alendronat.

Distribution. The average volume of distribution 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 that alendronovy acid is exposed to metabolism in a human body or animals.

Removal. After single intravenous administration of alendronovy acid, marked carbon atoms 14C, about 50% of drug are removed with urine within 72 hours; removal of marked drug with a stake was insignificant or was not defined. After single intravenous administration of alendronovy acid in a dose of 10 mg its renal clearance makes 71 ml/min. In 6 hours after intravenous maintaining concentration in a blood plasma decreases more than by 95%. The final elimination half-life exceeds 10 years that reflects release of drug from a bone tissue. Alendronovy acid 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;

- prevention of development of changes, including fractures of a hip and compression spinal fractures.

Route of administration and doses:

Alendronovy acid needs to be accepted, at least, in 30 minutes 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 absorption of alendronovy acid.

The recommended dose makes: 1 tablet of 70 mg once a week.

For reduction of risk of emergence of irritation of a gullet, alendronovy acid should be accepted, carrying out the listed below 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 minutes after reception of alendronovy acid;

- alendronovy acid should not be accepted 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.

For elderly patients and patients with a slight and moderate renal failure (the clearance of creatinine (CC) from 35 to 60 ml/min.) of correction of doses it is not required. Patients are not recommended to appoint Alendronovy acid with a heavy renal failure (KK <35 ml/min.) due to the lack of experience of use for these patients.

Features of use:

Alendronovy acid, as well as other bisfosfonata, can cause local irritation of a mucous membrane of upper parts of digestive tract.

At the patients receiving treatment alendronaty 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 or demand hospitalization. In this regard, doctors have to be especially attentive to any signs or symptoms indicating possible disturbances from a gullet, and patients have to be warned about need to stop reception of alendronovy acid and to see a doctor in case of emergence at them 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 development of stomach ulcer and duodenum, sometimes heavy and complicated are known. However in these cases relationship of cause and effect is not established with administration of drug.

Patients should appoint Alendronovy acid 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 alendronovy acid to a mucous membrane of upper parts of digestive tract and deterioration in a current of a basic disease.

Cases of emergence of the local osteonecrosis of a jaw (ONCh) 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 ONCh against the background of reception of bisfosfonat arises at the oncological patients receiving bisfosfonata intravenously. The known risk factors of ONCh 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 ONCh 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 mice at the patients receiving biphosphonates. 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 biphosphonate 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 patients, it is long accepting bisfosfonata (in most cases duration of reception of an alendronat made from 18 months to 10 years). 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. Changes often were bilateral in this connection at patients with a femur fracture against the background of biphosphonates it is necessary to conduct examination of a contralateral femur. These changes were characterized by bad accretion. The number of messages was very small, besides, stressful changes with similar clinical features arise at the patients who are not accepting biphosphonates. Patients with stressful changes need to be inspected with assessment of the known reasons and risk factors (for example, deficit of vitamin D, disturbance absorption, 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 biphosphonates at patients with stressful changes, proceeding from ratio assessment risk/advantage in each case.

Patients should be warned that at the accidental admission of administration of drug alendronovy acid once a week, they have to take 1 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.

Alendronovy acid is not recommended to patients with KK <35 ml/min.

It is necessary to take into account and other reasons of osteoporosis, in addition to deficit of estrogen, age and use of glucocorticosteroids.

In the presence of a hypocalcemia calcium level in blood needs to be normalized prior to treatment by alendronovy acid. 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 watch the content of calcium in blood and hypocalcemia symptoms.

As alendronovy acid 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 glucocorticosteroids at which absorption of calcium can be reduced. 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 during pregnancy of N of breastfeeding. Alendronovy acid should not be applied to women at pregnancy and a lactation.

Children's age. Researches of alendronovy acid at children were not conducted therefore drug should not be used at children's age.

Influence on ability to driving of motor transport and to control of potentially dangerous mechanisms. There are no data that alendronovy acid influences ability to manage motor transport and potentially dangerous mechanisms.

Side effects:

Alendronovy acid in general is well transferred, side effects usually easy and do not demand drug withdrawal.

In clinical trials the following side effects met frequency> 1%:

Digestive tract: 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).

Musculoskeletal system: mialgiya, ostealgias, joints, muscular spasms. Nervous system: headache.

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

Digestive tract: erosion or ulcers of a gullet, nausea, vomiting, gastritis, a melena, an esophagitis, a gullet stricture, perforation, a stomatopharynx ulcer, it is rare - 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 an itch and/or a local infection (including osteomyelitis), it is frequent with a gradual return to health.

Musculoskeletal system: a mialgiya, ostealgias, joint pains, it is rare - heavy, a swelling of joints, low-energy changes of a shaft of the femur. There is a risk of stressful changes of a proximal part of a femur. The following symptoms can precede a change: meralgia, weakness or discomfort.

Skin reactions seldom: skin rash, erythema.

Organism in general: hypersensitivity reactions, including a small tortoiseshell and it is rare - a Quincke's disease, passing symptoms of reaction of an acute phase in an initiation of treatment (a mialgiya, an indisposition, an adynamy, it is rare - fever), a hypocalcemia. Seldom - peripheral hypostases.

Skin reactions: rash, a photosensitization, an itch, an alopecia, it is rare - heavy skin reactions, including Stephens-Johnson's syndrome and a toxic epidermal necrolysis.

Sense bodys: seldom - a uveitis, a sclerite, an episcleritis.

Nervous system: dizziness, rotatory vertigo, disturbance of flavoring feelings.

Laboratory indicators. Decrease in level of calcium and phosphates in blood serum (usually easy, asymptomatic and tranzitorny) for 18% and 10%, respectively.

Interaction with other medicines:

Absorption of alendronovy acid can be broken if drug is accepted along with calcium drugs, antacids and other peroral drugs. In this regard the interval between reception of an alendronat and other medicines accepted inside has to make not less than 30 minutes.

When sharing alendronovy acid with gormonozamestitelny therapy (estrogen ± progestin) safety and portability of a combination therapy correspond to that at use of each of these drugs separately.

In clinical trials of alendronovy acid at men, women in a postmenopause and the patients accepting glucocorticosteroids clinically significant medicinal interactions influencing linkng with proteins, renal excretion and metabolism were not revealed. Frequency of the undesirable phenomena from an upper part of digestive tract increases at a combination of alendronovy acid in a dose more than 10 mg a day with the drugs containing acetylsalicylic acid. However this effect was not observed at reception of alendronovy acid in a dose of 70 mg once a 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 minutes;

- hypersensitivity to any component of drug;

- hypocalcemia.

With care:

- at an exacerbation of diseases of upper parts of digestive tract, such as dysphagy, gullet diseases, gastritis, duodenitis or stomach ulcer;

- patients are not recommended to appoint alendronovy acid with an impaired renal function at KK <35 ml/min.;

- at 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 digestive tract, including a gastric disturbance, heartburn, an esophagitis, gastritis, stomach ulcer and a gullet.

Treatment: specific information is absent. 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.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 4 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. One planimetric packaging together with the application instruction is placed in a pack from a cardboard.