Alendronate - instructions for use, dosage, side effects, contraindications

active substance: alendronate sodium (in terms of alendronic acid) - 10.0 mg; Excipients: potato starch - 50.0 mg; povidone (low molecular weight polyvinylpyrrolidone) 5.0 mg; silicon dioxide colloid - 4.0 mg; calcium stearate - 2.0 mg; lactose monohydrate is sufficient to prepare a tablet weighing 200 mg.

Dosage of 70 mg

active substance: Alendronate sodium (in terms of alendronic acid) - 70.0 mg; Excipients: potato starch - 100.0 mg; povidone (polyvinylpyrrolidone low molecular weight) - 8.8 mg; silicon dioxide colloidal - 7.0 mg; calcium stearate - 3.5 mg; lactose monohydrate is sufficient to prepare a tablet weighing 350 mg.

Description:

Round flat cylindrical tablets of white or almost white color with a bevel (10 mg dosage) or with a facet and a risk (dosage of 70 mg). Allowed a slight marbling.

Pharmacotherapeutic group:Bone resorption inhibitor-bisphosphonate

ATX: & nbsp

M.05.B.A.04 Alendronic acid

Pharmacodynamics:

Alandronic acid - a non-hormonal specific inhibitor of osteoclastic bone resorption (from the group of aminobisphosphonates - synthetic analogues of pyrophosphate, binding hydroxyapatite, located in the bone), suppresses the activity of osteoclasts. Stimulates osteogenesis, restores a positive balance between resorption and bone restoration, progressively increases bone mineral density (regulates phosphorus-calcium metabolism), promotes the formation of bone tissue with a normal histological structure.

Treatment of osteoporosis in postmenopausal women

Osteoporosis is defined as a decrease in bone mineral density (BMD) of the spine or hip by 2.5 standard deviations (SD) compared with the average value in a population of healthy young men or as having a history of pathologic fracture irrespective of BMD.

The therapeutic equivalence of alendronate in a dose of 70 mg, taken once a day (n = 519), and alendronate in a dose of 10 mg, taken once a day (n = 370) was shown in the annual multicenter study in women with postmenopausal osteoporosis. The average increase in bone mineral density of lumbar vertebrae as compared with the initial value for one year was 5.1% in the group treated with 70 mg once a week, and 5.4% in the group treated with 10 mg once a day. The average increase in femoral neck BMD was 2.3% and 2.9%, femoral BMD - 2.9% and 3.1% in the group treated with 70 mg once a week, and in the group treated with 10 mg once a day , respectively. In both groups, there were similar values of BMD increase in other parts of the skeleton.

The effect of alendronate on bone mass and fracture rate in postmenopausal women was investigated in two studies initial efficiency equal design (n = 994), as well as in the study of fracture therapy (FIT: n = 6459).

In initial studies, the average BMD increase efficiency when alendronate 10 mg per day compared with placebo after three years was 8.8%, 5.9% and 7,8 % for the spine, cervix 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 receiving alendronate compared to patients receiving placebo. During the two-year extension period of these studies, the BMD values of the spine and trochanter continued to increase, and the BMD of the femoral neck and the entire body remained unchanged.

Study FIT consisted of two placebo-controlled studies using alendronate daily (5 mg daily for two years and 10 mg daily for one year or two years in addition):

- FIT 1: a three-year study in which 2027 patients were included c at least one initial vertebral fracture (compression). In this study, with a daily intake of alendronate, there was a decrease in the incidence of> 1 new vertebral fracture by 47% (7.9 % in the alendronate group compared with 15.0% in the placebo group). In addition, a statistically significant reduction in the incidence of hip fractures was found (1.1% compared with 2.2%, a decrease of 51%);

- FIT 2: A four-year study in which 4432 patients with low bone mass were included, but without an initial vertebral fracture. In this study, when analyzing a subgroup of women with osteoporosis (37 % of the total population with a condition that corresponds to the above definition of osteoporosis) There was a significant difference in the incidence of hip fractures (1.0% in the alendronate group compared with 2.2% in the placebo group, a decrease of 56%) and at a frequency> 1 fracture of the spine (2.9% compared with 5.8%, a decrease of 50%).

Results of laboratory tests

In clinical studies, asymptomatic, small and temporary decreases in plasma calcium and phosphate concentrations were observed in approximately 18% and 10% of patients taking alendronate at a dose of 10 mg per day, compared with about 12% and 3% of patients taking placebo. However, the frequency of reduction in serum calcium concentration to <8.0 mg / dL (2.0 mmol / L) and serum phosphate to <2.0 mg / dl (0.65 mmol / L) was similar in both groups.

Use in children

The use of alendronate was studied in a small number of patients with imperfect osteogenesis at the age of 18 years. The results are Inadequate to justify the use of alendronate in children with imperfect osteogenesis.

Application in men

Although osteoporosis in men is not as common as in postmenopausal women, a significant proportion of fractures associated with osteoporosis are men. The prevalence of deformity of the spine associated with osteoporosis is the same in men and women. The use of alendronate in a dose of 10 mg once a day in men for 2 years reduced the excretion in the urine of cross-linked N-lopeptides of collagen I tin by approximately 60% and bone-specific alkaline phosphatase by approximately 40%. Similar results are observed when taking alendronate in a dose of 70 mg once a week for one year. In comparison with placebo, the increase in BMD in the lumbar spine is 5.3%, in the neck of the femur - 2.6%, in the large spit - 3.1%, the overall BMD - 1.6%.

When using alendronate 10 mg per day in men, there is a decrease in the incidence of new vertebral fractures, which is 0.8% compared with 7.1% when taking placebo. There is also a decrease in the amount of growth reduction, which is 0.6 mm with alendronate compared to 2.4 mm with placebo.

With the use of alendronate in a dose of 70 mg once a week for one year, the increase in BMD in the lumbar spine by 2.8%, in the neck of the femur by 1.9%, in the femur by 2.0%, in others body parts - by 1.2% compared with placebo.

Alendronate is effective in men irrespective of age, the function of the gonads and the initial MG1KT in the neck of the thigh and the lumbar spine.

Pharmacokinetics:

Suction

Bioavailability of alendronate at oral intake in a dose of 5-70 mg on an empty stomach in the morning for 2 hours before a standard breakfast is 0.64% in women and 0.6% in men; when taken on an empty stomach 0.5-1 hour before a standard breakfast, bioavailability is reduced to 0.46% and 0.39%, respectively. In studies it was shown that in the treatment of osteoporosis, alendronate is effective when taken at least 30 minutes before the first meal or drink during the day.

Bioavailability was insignificant when taking alendronate during a standard breakfast and within two hours after it.

With the simultaneous administration of alendronate with coffee or orange juice, bioavailability is reduced by approximately 60%.

In healthy volunteers with oraltaking prednisone (20 mg three times daily for five days) there were no clinically significant changes in the bioavailability of alendronate in oral administration (mean increase in the range of 20% to 44%).

Distribution

The average volume of distribution in a state of equilibrium concentration (excluding stagnant) in man is at least 28 liters. The concentration of the drug in the blood plasma after oral administration at a therapeutic dose is too low for analytical detection (<5 ng / ml). Binding to plasma proteins is approximately 78%.

Metabolism

There is no evidence that alendronate is metabolized in humans or animals.

Excretion

Outputs unchanged. The elimination process is characterized by a rapid decrease in the concentration of alendronic acid in the blood plasma and extremely slow release from the bones. When administered orally after 6 hours, the plasma concentration is reduced by more than 95 %. Absorbed, but not embedded in the bone Alendronate tissue is quickly excreted by the kidneys. After a single intravenous injection of 10 mg alendronate, the kidney clearance is 71 ml / min, the systemic clearance is 200 ml / min.

After a single intravenous dose of [¹⁴C] alendronate, approximately 50% of the radioactivity was excreted in the urine for 72 hours and was not significantly or virtually eliminated with feces.

The final half-life is more than 10 years, which reflects the release of alendronic acid from bone tissue.

Alendronate is not excreted through the acid and basic transport systems of the kidneys in rats; so you can expect that it does not violate the excretion of other drugs through these systems in humans.

Pharmacokinetics in specific patient groups

Floor

The bioavailability of alendronic acid does not differ significantly between men and women.

Race

Pharmacokinetic differences on the basis of race were not studied.

Elderly patients

Bioavailability and excretion of alendronic acid are similar in elderly and younger patients.

Patients with hepatic impairment

In patients with impaired liver function, there is no need to adjust the dose of alendronic acid, since it is not metabolized and is not excreted with bile.

Patients with impaired renal function

In healthy volunteers alendronic acid, not accumulating in bone tissue, is quickly excreted in the urine.Controlled pharmacokinetic studies but the use of alendronic acid in renal failure is not, but in patients with severe renal dysfunction the excretion of alendronic acid will be reduced. Therefore, we can expect a somewhat greater accumulation of alendronic acid in bone tissue in patients with impaired renal function.

With the clearance of creatinine (CK) from 35 to 60 ml / min, dose adjustment is not required. Apply alendronic acid in patients with SC less than 35 mL / min is not recommended due to lack of experience.

Indications:

- osteoporosis in postmenopausal women (prevention of bone fractures, including hip and spine);

- osteoporosis in men;

- Paget's disease.

Contraindications:

- diseases of the esophagus and other factors that slow its emptying, for example, strictures or achalasia;

- inability to sit or stand upright for at least 30 minutes;

- hypersensitivity to alendronate or any auxiliary component of the drug;

- hypocalcemia;

- chronic renal failure (CC less than 35 ml / min);

- children under 18 years of age (efficacy and safety not established);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- pregnancy;

- the period of breastfeeding.

Carefully:

- diseases of the gastrointestinal tract (GIT) in the phase of exacerbation (dysphagia, esophagitis, gastritis, duodenitis, peptic ulcer and duodenal ulcer);

- serious gastrointestinal diseases transferred in the previous 12 months, for example, peptic ulcer, gastrointestinal bleeding, surgical intervention on the upper gastrointestinal tract, with the exception of pyloroplasty;

- predisposition to hypocalcemia (hypothyroidism, calcium malabsorption);

- disorders of mineral metabolism (eg, vitamin deficiency D);

- oncological diseases;

- concomitant therapy (eg, chemotherapy, radiation therapy, corticosteroids);

- poor hygiene of the oral cavity;

- concomitant pathologies (eg, periodontal disease and / or other dental diseases, anemia, coagulopathy, infection).

Pregnancy and lactation:

Pregnancy

There is no data on the use of alendronic acid in pregnant women.

Studies in animals do not indicate the presence of immediate adverse effects during pregnancy, embryo and fetus development, or postnatal development.Alendronate, administered to rats during pregnancy, caused dystocia caused by hypocalcemia.

The use of alendronic acid during pregnancy is contraindicated.

Breastfeeding period

There are no data on the penetration into breast milk; the intake of alendronic acid during breastfeeding is contraindicated.

Dosing and Administration:

Inside, for 2 hours (but not less than 30 minutes) before the first meal, water or other medicines. Drink only with normal water, as other beverages (including mineral water, coffee, tea, orange juice) reduce absorption. Tablets can not be chewed or rassasyvat.

The optimal duration of the drug is not established. The need for continuing bisphosphonate therapy should be evaluated on a regular basis, especially after 5 or more years of use.

The drug should be taken with the daily requirement of calcium and vitamin D.

When osteoporosis in postmenopausal women and osteoporosis in men - 70 mg once a week or 10 mg once a day.

When disease Paget - 40 mg once a day for 6 months.

Dose adjustments in elderly patients, in patients with impaired liver function, as well as in patients with mild and moderate renal failure (CK from 35 to 60 ml / min) is not required.

To reduce the irritant effect on the esophagus, the drug must be taken immediately after the morning ascent, with a full glass of water; after taking, you should not lie down for 30 minutes (it is dangerous to use in the case of the patient's inability to cost or sit upright for 30 minutes). Admission before bed or in the horizontal position increases the risk of esophagitis.

If you miss a dose of the drug once a week, you should take one pill in the morning of the next day. Do not take two tablets in one day, but in the future you should continue to take one tablet on the day of the week that was chosen for admission from the beginning of treatment.

Side effects:

In a one-year study in women with osteoporosis during the postmenopause, general safety profiles of alendronate 70 mg once a week (n = 519) and alendronate 10 mg per day (n = 370) were generally similar.

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

The undesirable reactions described in these studies as possible, probably or definitely related to the use of alendronate, are presented in the table. Undesirable reactions were observed in ≥1% of patients in each admission group in a one-year study. Y ≥ 1 %, who took alendronate 10 mg per day, adverse reactions were observed with a greater frequency than in the placebo group in the triennium study.

Table

The adverse reactions described in the clinical studies of alendronate

	Annual study		Three-year study
	Alendronate 70 mg (once a week, n = 519), %	Alendronate 10 mg (once daily, n = 370), %	Alendronate 10 mg (once daily, n = 196), %	Placebo (n = 397), %
From the side digestive system: - abdominal pain	3,7	3,0	6,6	4,8
- indigestion	2,7	2,2	3,6	3,5
- sour belch	1,9	2,4	2,0	4,3
- nausea	1,9	2,4	3.6	4.0
- bloating	1,0	1,4	1,0	0,8
- constipation	0,8	1,6	3,1	1,8
- diarrhea	0,6	0,5	3,1	1,8
- dysphagia	0,4	0,5	1,0	0,0
- Flatulence	0,4	1,6	2,6	0,5
- gastritis	0,2	U	0,5	1,3
- Stomach ulcer	0,0	U	0,0	0,0
- an ulcer of the esophagus	0,0	0,0	1,5	0,0
From the musculoskeletal system: - musculoskeletal pain	2,9	3,2	4,1	2,5
(in bones, muscles or joints) - Muscle spasm	0,2	1,1	0,0	1,0
From the central nervous system: - headache	0,4	0,3	2,6	1,5

Classification of the frequency of development of adverse reactions according to the recommendations

World Health Organization (WHO):

very often ≥1 / 10;

often from ≥ 1/100 to <1/10;

infrequently from ≥ 1/1000 to <1/100;

rarely from ≥1 / 10,000 to <1/1000;

very rarely <1/10 000, including individual reports;

frequency is unknown - according to available data, establish the incidence does not seem possible.

Allergic reactions:

rarely - hypersensitivity reactions, including flushing of skin, hives, angioedema.

Laboratory indicators:

rarely symptomatic hypocalcemia and hypophosphataemia (especially in the presence of risk factors)¹.

From the central nervous system: often - headache, dizziness²; infrequent - a violation of taste²; frequency unknown - irritability.

From the side of the organ of vision:

infrequently - inflammation of the organs of vision (uveitis, scleritis, episcleritis).

From the organs of hearing and balance: often - systemic dizziness ".

From the digestive system:

often - abdominal pain, indigestion, constipation, diarrhea, ulcer of the esophagus³, dysphagia³bloating, sour belch, flatulence;

infrequently-nausea, vomiting, gastritis, melena², esophagitis³, erosion of the esophagus;

rarely - stricture of the esophagus³, ulceration of the esophagus³, perforation¹, ulcer¹, bleeding from the upper digestive tract¹.

From the skin: often itching², alopecia²; infrequently - skin rash, erythema;

rarely skin rash with photosensitivity, severe skin reactions, including Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis)⁴.

From the musculoskeletal system:

very often - myalgia, pain in the bones, pain in the joints (sometimes - heavy flow)

often swelling of the joints²;

rarely - local osteonecrosis of the jaw, associated mainly with previous tooth extraction and / or local infection (including osteomyelitis), often with slow recovery¹'⁴, atypical susceptible and diaphyseal fractures of the femur (an undesirable reaction of preparations of the bisphosphonate class)⁵.

Other:

often - asthenia², peripheral edema²;

infrequent - transient symptoms as an acute phase reaction at the beginning of treatment (myalgia, malaise, less often fever), usually in connection with the onset of treatment².

¹ see section "Special instructions"

² in clinical trials, the frequency was comparable for the drug group and the placebo group

³see the sections "Dosage and administration" and "Special instructions"

⁴this undesirable reaction was established during post-registration observation

⁵is established at postgistratsionnom application.

Overdose:

Symptoms

Hypocalcemia, hypophosphatemia; undesirable reactions from the upper parts of the LC1G (abdominal pain, dyspepsia, dysphagia, heartburn, esophagitis, gastritis, ulcer).

Treatment

Specific treatment is not. It is recommended to take milk, antacids. To avoid irritation of the esophagus can not be caused by vomiting, the patient should be given a vertical position ("standing" or "sitting").

Interaction:

Calcium, antacids, some oral preparations, food, drinks, including mineral water, affect the absorption of alendronic acid. The interval between taking the drug and other medications and food supplements should be at least 30 minutes.

Other clinically significant interactions with drugs are not expected.

In clinical studies in patients taking estrogen preparations (intravaginally, transdermally, orally) concomitantly with alendronate, there was no clinically significant interaction.

In clinical studies of alendronic acid in men, postmenopausal women and patients,taking glucocorticosteroids, there was no clinically significant drug interaction with respect to effects on protein binding, renal excretion, and metabolism.

In clinical studies, there was an increase in the incidence of adverse reactions from the upper gastrointestinal tract in patients taking more than 10 mg of alendronate per day simultaneously with drugs containing acetylsalicylic acid. However, this phenomenon was not observed when taking alendronic acid in a dose of 70 mg once a week.

Alendronate can be given to patients taking non-steroidal anti-inflammatory drugs (NSAIDs). In a three-year controlled clinical trial (the number of patients 2027), during which the majority of patients took concomitant therapy with NSAIDs, the incidence of adverse events related to the upper GI tract was similar in patients receiving alendronate at a dose of 5 and 10 mg per day, and in patients receiving placebo. However, the use of NSAIDs is associated with irritation of the gastrointestinal mucosa, so the use of NSAIDs simultaneously with alendronic acid should be cautious.

Special instructions:

Alendronate should be taken with ordinary water only, as other beverages (including mineral water, tea, coffee, fruit juices) impair the absorption of the drug. Taking alendronic acid before bedtime or in a horizontal position increases the risk of esophagitis.

Alendronate can cause local irritation of the mucous membrane of the upper parts of the gastrointestinal tract. In the treatment of alendronate, cases of unwanted reactions from the side of the esophagus (esophagitis, ulcer or erosion of the esophagus), sometimes occurring in severe form and requiring hospital treatment, are known, and in rare cases complicated by the formation of stricture. It is necessary to control the possibility of the appearance of any signs of the occurrence of undesirable reactions from the side of the esophagus. The patient should be informed of the need to stop taking the drug and contact a doctor when developing dysphagia, pain when swallowing, chest pain, or heartburn.

It is necessary to inform the patient about the possible risk of damage to the mucous membrane of the esophagus if the instructions for use are not observed. The risk of severe adverse reactions from the esophagus is higher in those patients,which violate the recommendations for taking the drug and / or continue to take it when symptoms of esophageal irritation appear. It is especially important to give the patient recommendations for taking the drug so that he understands that the risk of developing an esophageal lesion increases if these recommendations are not implemented.

Alendronate should be administered with extreme caution to patients with exacerbations of upper gastrointestinal disorders such as dysphagia, esophageal diseases, gastritis, duodenitis, ulcers, as well as with active gastrointestinal bleeding, surgery on the upper gastrointestinal tract, with the exception of pyloroplasty, for the possible irritant effect of the drug on the mucous membrane of the upper gastrointestinal tract and worsening of the course of the underlying disease. For patients with a diagnosed Barrett's esophagus, the question of the appointment of alendronate should be decided on an individual basis by assessing the relationship between the expected benefit and the potential risk.

Although there was no increased risk in the extended clinical trials of alendronate, post-marketing reports reported rare cases of stomach and duodenum ulcers, sometimes severe and complicated.

There are cases of local osteonecrosis of the jaw associated mainly with the previous extraction of the tooth and / or a local infection (including osteomyelitis), often with a slow recovery. In most cases, the osteonecrosis of the jaw against the background of bisphosphonate administration occurs in cancer patients receiving intravenous bisphosphonates. Many of the patients also received chemotherapy and glucocorticosteroids. There are also cases of osteonecrosis of the jaw in patients with osteoporosis who took bisphosphonates orally. When assessing the individual risk of osteonecrosis of the jaw, the following risk factors should be considered: bisphosphonate activity (highest in zoledronic acid), route of administration and total dose; oncological diseases, chemotherapy, radiotherapy, glucocorticosteroids, smoking; dental disease in the history, poor oral hygiene, periodontal disease, invasive dental procedures, poorly selected dentures. Before starting oral bisphosphonate therapy, patients with unsatisfactory dental status are recommended to have a dental examination and preventive medical measures.During the course of bisphosphonates, it is recommended that such patients avoid invasive dental procedures whenever possible. If a patient develops an osteonecrosis of the jaw during therapy with bisphosphonates, surgical dental treatment may worsen his condition. It is not known whether the discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw in patients who require dental procedures. In each case, the decision should be made by the attending physician on the basis of an estimate of the relationship between the expected benefit and the possible risk for the particular patient. During therapy with bisphosphonates, the importance of proper oral hygiene, preventive examinations, and warnings about the need to report any symptoms from the oral cavity, such as mobility of the teeth, pain or swelling, should be explained to patients.

There have been reports of pain in the bones, joints and / or muscles in patients receiving bisphosphonates. These symptoms are rarely severe and / or lead to disability. The time of onset of symptoms varies from one day to several months from the start of therapy.In most patients, symptoms were resolved after discontinuation of treatment. In some of them, the symptoms appeared again with the resumption of the same drug or other bisphosphonate.

In the presence of hypocalcemia, it is necessary to correct it before treatment. Other disorders of mineral metabolism (eg, vitamin deficiency D) should also be eliminated. Therapy should be combined with a diet enriched with calcium salts and vitamin D. In patients with these disorders it is necessary to monitor the calcium content in the blood and the symptoms of hypocalcemia.

In the process of treatment, a slight asymptomatic decrease in the concentration of calcium in blood serum and phosphates is possible due to the positive effect of alendronic acid on the bone mineral density, which is of particular importance for patients receiving glucocorticosteroid preparations, since they may have a decreased absorption of calcium.

In rare cases, hypocalcemia can be severe, usually in patients with a predisposition to this complication (hypoparathyroidism, vitamin deficiency D, malabsorption of calcium).

There have been reports of the emergence of pathological fractures or fractures of proximal femoral diaphysis fractures in a small number of patients taking bisphosphonates, mainly in patients receiving long-term therapy for osteoporosis. Some of the fractures belonged to the category of stress (also known as stress fracture, march fracture, fracture of Deutschlander) arising in the absence of trauma. Fractures are often bilateral, so in patients with a hip fracture, taking bisphosphonates, the second (contralateral) thigh should be examined. It is known that these fractures are poorly fused. Some patients experienced prodromal pains in the affected area weeks or months before the onset of a complete fracture, often associated with a characteristic radiographic picture of a stress fracture.

The number of reports was very small, in addition, stress fractures with similar clinical features occur in patients who do not take bisphosphonates.Patients with stress fractures should be examined with an assessment of known causes and risk factors (eg, vitamin deficiency D, impaired absorption, the use of glucocorticosteroids, stress fracture in the history, arthritis or fracture of the lower limbs, excessive or increased loads, diabetes, chronic alcoholism) and provide them with proper orthopedic care. Prior to receiving the results of the survey, consideration should be given to stopping the use of bisphosphonates in patients with stress fractures, based on an assessment of the benefit / risk ratio in each specific case. During therapy with bisphosphonates, patients should be advised to report any pain in the thigh or inguinal area. All patients who have received such complaints should be examined for incomplete fracture of the femur.

During post-marketing use, rare reports of severe skin reactions have been reported, including Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis).

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

Patients should be warned that if you miss an Alendronate once a week, they should take one pill in the morning of the next day. Do not take two doses of the drug on the same day, but in the future you should return to taking the drug once a week on the day of the week that was chosen at the beginning of the treatment.

Effect on the ability to drive transp. cf. and fur:

There is no evidence of the effect of the drug on the ability to drive and other mechanisms. However, some of the undesirable reactions observed after the administration of alendronic acid may in some patients impair the ability to drive vehicles and mechanisms.

Form release / dosage:

Tablets 10 mg and 70 mg.

Packaging:

For a dosage of 10 mg

10 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil. 1 or 3 contour squeezed packs together with instructions but in a pack of cardboard.

For dosage of 70 mg

4 Look for 10 tablets in a planar cell box made of a polyvinylchloride film and aluminum foil. 1, 2 or 3 contourcell packs of 4 tablets or

1 circuit cell pack of 10 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001646

Date of registration:12.04.2012

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp16.09.2015

Illustrated instructions

Instructions

Alendronate (Alendronate)