Alendronate 70mg tab 4 pcs vertex

Description

Composition
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; Colloidal silicon dioxide – 7.0 mg; calcium stearate – 3.5 mg; lactose monohydrate – sufficient quantity to yield a tablet weighing 350 mg.
Description:
Round Valium tablets white or nearly white with a facet and Valium. Slight marbling.
Product form:
4 tabletrb in blisters of PVC film and aluminum foil.
1 blisters 4 tablets together with instructions for use in a stack of cardboard.
Contraindications
– esophageal disease and other factors that retard emptying, for example, a stricture or achalasia;
– the patient’s inability to stand or sit upright for at least 30 minutes after dosing;
– hypersensitivity to alendronic acid or any auxiliary component of the drug;
– hypocalcemia, calcium malabsorption, severe hypoparathyroidism;
– violation of mineral metabolism;
– chronic renal failure (at least 35 ml QC / min increases the risk of cumulation alendronic acid);
– Children up to age 18 years (effectiveness and safety have been established);
– lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
– pregnancy;
– the period of breastfeeding.
Be wary – diseases of the gastrointestinal tract (GIT) in the acute phase (dysphagia, esophageal disease, esophagitis, gastritis, duodenitis, gastric ulcer and 12 duodenal ulcer);
– serious gastrointestinal diseases transferred during the previous 12 months, such as peptic ulcers, gastrointestinal bleeding, surgery on the upper gastrointestinal tract, except pyloroplasty;
– propensity to hypocalcemia (hypothyroidism, calcium malabsorption);
– deficiency of vitamin D.
Dosage
70 mg
Indications
– osteoporosis in postmenopausal women (prevention of bone fractures, including hip and spine);
– osteoporosis in men;
– Paget’s disease.
Interaction with other drugs
Calcium, antacids, some oral drugs, food, drinks, including mineral water, affect the absorption of alendronate. The interval between administration of the drug and other drugs and food additives should be at least 30 minutes.
Other clinically significant interactions with the drug is expected.
In clinical studies in patients taking estrogen drugs (intravaginally, transdermally or orally) simultaneously with alendronate showed no clinically significant interaction.
In clinical studies, alendronic acid in men and postmenopausal women patients taking steroids showed no clinically significant drug interaction on the effect on protein binding, metabolism and renal excretion.
In clinical studies, there was an increase in adverse reactions from the upper gastrointestinal patients taking more than 10 mg of alendronate per day simultaneously with drugs containing acetylsalicylic acid. However, this phenomenon was not observed when receiving alendronic acid at a dose of 70 mg once a week.
Alendronic acid may be administered to patients who take non-steroidal anti-inflammatory drugs (NSAIDs). The three-year controlled clinical trial (number of patients in 2027), during which the majority of patients taken as a concomitant therapy NSAID, the amount of adverse events relating to the upper GI, was similar in patients treated with alendronic acid at a dose of 5 and 10 mg per day, and patients receiving placebo. However, the use of NSAIDs is associated with irritation of gastrointestinal mucosa, so NSAID simultaneously with alendronic acid should be cautious.
Overdose
symptoms
Hypocalcemia, hypophosphatemia; adverse reaction from the upper gastrointestinal tract (abdominal pain, dyspepsia, dysphagia, heartburn, esophagitis, gastritis, ulcer).
Treatment
There is no specific treatment. Recommended intake of milk, antacids. To avoid irritation of the esophagus, do not induce vomiting, the patient should be given to a vertical position ( “standing” or “sitting”).
pharmachologic effect
Pharmacological group:
Bone resorption inhibitor – bisphosphonate.
Pharmacodynamics:
Alendronic acid – nonhormonal specific inhibitor of osteoclastic bone resorption (Group of aminobisphosphonates – synthetic analogues of pyrophosphate, hydroxyapatite binding, located in the bone), inhibits the activity of osteoclasts. Stimulates bone formation and restores a positive balance between bone resorption and bone repair, progressively increases bone mineral density (regulates calcium and phosphorus metabolism), promotes the formation of bone tissue with normal histology.
Pharmacokinetics:
Suction
The bioavailability of alendronate orally at a dose of 5-70 mg in the morning fasting for 2 hours before a standard breakfast is 0.64% for women and 0.6% for men; in the fasting state for 0.5-1 hours before a standard breakfast reduced bioavailability to 0.46% and 0.39% respectively. The bioavailability of alendronate is significantly reduced when taking the drug in less than 30 minutes before meals or liquids is minimal bioavailability if administered with a meal or within two hours after a meal.
When simultaneous administration of alendronate with coffee or orange juice reduced bioavailability by approximately 60%.
Distribution
The average volume of distribution in the state of equilibrium concentration (except bone) a person not less than 28 liters. alendronic acid concentration in blood plasma after oral administration of a therapeutic dose is too low for analytical detection (
Metabolism
There is no evidence that the alendronic acid is metabolized in humans or animals.
breeding
Excreted unchanged. The process is characterized by a rapid decrease in excretion of alendronic acid concentration in blood plasma and extremely slow release from the bone. When administered intravenously through 6 hours under the plasma concentration is reduced by more than 95%. Absorbed, but not embedded in the bone alendronate is rapidly excreted by the kidneys. After a single intravenous administration of 10 mg of alendronic acid renal clearance of 71 mL / min, System – 200 ml / min.
After intravenous administration of a single dose of [14C] alendronic acid of approximately 50% of the radioactivity was excreted in the urine within 72 hours, and marginally or substantially excreted with feces.
Terminal half-life exceeds 10 years, reflecting release of alendronic acid from the bone.
Alendronic acid is not output from the acidic and basic transport system of the kidneys of rats; so we can expect that it does not violate the excretion of other drugs by those systems in humans.
In special patient groups
Floor
The bioavailability of alendronate is not significantly different in men and women.
Race
Pharmacokinetic differences due to race have not been studied.
Elderly patients
The bioavailability and elimination of alendronate are similar in elderly and younger patients.
Patients with impaired liver function
Patients with impaired hepatic function it is not necessary to adjust the dose of alendronate, since it is not metabolized and excreted in the bile.
Patients with impaired renal function
In healthy volunteers, alendronate, do not accumulate in bone is rapidly excreted in the urine. Controlled pharmacokinetic studies on the use of alendronic acid with no renal failure, but patients with severe renal impairment alendronic acid excretion will be reduced. We can therefore expect some greater accumulation of alendronate in bone in patients with impaired renal function.
If creatinine clearance (CC) from 35 to 60 ml / min the dose correction is not required.
Use alendronic acid in patients with CC less than 35 ml / min is not recommended due to lack of application experience.
Pregnancy and breast-feeding
Pregnancy
The use of alendronate during pregnancy is contraindicated.
There are no data on the use of alendronate in pregnant women.
Animal studies do not indicate a direct adverse effects during pregnancy, embryo-fetal development, or postnatal development. Alendronic acid was administered to rats during pregnancy, caused dystocia due to hypocalcemia.
Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over several years. The amount of the bisphosphonate,
incorporated into the bone tissue and women liberated from it into the systemic circulation, is directly related to the dose and duration of treatment. There is a theoretical risk of effects on the fetus (especially bone), if pregnancy occurs after a course terpanes bisphosphonates. No data on direct embryotoxic or teratogenic effect. The impact of such risks on the fetus,
as time between cessation of bisphosphonate therapy and the onset of pregnancy,
route of administration (intravenous, oral), has not been studied.
Breastfeeding
Information about the penetration into breast milk is not; receiving alendronate during lactation is contraindicated.
Conditions of supply of pharmacies
Prescription.
side effects
The annual study in women with osteoporotic postmenopausal common security profiles alendronic acid 70 mg once a week (n = 519) and 10 mg of alendronic acid per day (n = 370) were generally similar.
The two three-year studies with practically identical design in postmenopausal women (10 mg alendronic acid: n = 196; placebo: n = 397) security profiles alendronic acid 10 mg daily and placebo were generally similar.
Adverse reactions described in these studies as possible, probably, or definitely related to the reception of alendronic acid, are presented below.
Adverse reactions observed at> 1% of patients in each group receiving a one-year study. Y> 1%, taking alendronic acid 10 mg per day,
adverse reactions were observed more frequently than with placebo in three-year study.
Adverse reactions described in the clinical trials of alendronic acid
From the digestive system:
annual survey
1. 70 mg Alendronic acid (once per week, n ​​= 519)
– abdominal pain – 3.7%
– indigestion – 2.7%
– acid regurgitation – 1.9%
– nausea – 1.9%
– bloating – 1.0%
– constipation – 0.8%
– Diarrhea – 0.6%
– dysphagia – 0.4%
– flatulence – 0.4%
– Gastritis – 0.2%
2. Alendronic acid 10 mg (once daily, n = 370)
– abdominal pain – 3.0%
– dyspepsia – 2.2%
– brash – 2.4%
– nausea – 2.4%
– bloating – 1.4%
– constipation – 1.6%
– Diarrhea – 0.5%
– dysphagia – 0.5%
– flatulence – 1.6%
– Gastritis – 1.1%
– stomach ulcer – 1.1%
The three-year study
1. Alendronic acid 10 mg (once daily, n = 196)
– abdominal pain – 6.6%
– indigestion – 3.6%
– brash – 2.0%
– nausea – 3.6%
– bloating – 1.0%
– Constipation – 3.1%
– diarrhea – 3.1%
– dysphagia – 1.0%
– flatulence – 2.6%
– Gastritis – 0.5%
– esophageal ulcer – 1.5%
2. Placebo (n = 397),%
– abdominal pain – 4.8%
– indigestion – 3.5%
– brash – 4.3%
– nausea – 4.0%
– bloating – 0.8%
– Constipation – 1.8%
– diarrhea – 1.8%
– flatulence – 0.5%
– Gastritis – 1.3%
On the part of the musculoskeletal system:
annual survey
1. 70 mg Alendronic acid (once per week, n ​​= 519)
– musculoskeletal pain (bone, muscle or joint pain) – 2.9%
– muscle spasm – 0.2%
2. Alendronic acid 10 mg (once daily, n = 370)
– musculoskeletal pain (bone, muscle or joint pain) – 3.2%
– muscle spasm – 1.1%
The three-year study
1. 70 mg Alendronic acid (once per week, n ​​= 519)
– musculoskeletal pain (bone, muscle or joint pain) – 4.1%
2. Placebo (n = 397)
– musculoskeletal pain (bone, muscle or joint) – 2.5%
– muscle spasm – 1.0%
On the part of the central nervous system:
annual survey
1. 70 mg Alendronic acid (once per week, n ​​= 519)
– headache – 0.4%
2. Alendronic acid 10 mg (once daily, n = 370)
– headache – 0.3%
The three-year study
1. 70 mg Alendronic acid (once per week, n ​​= 519)
– headache – 2.6%
2. Alendronic acid 10 mg (once daily, n = 370)
– headache – 1.5%
Classification of the incidence of side effects according to the recommendations of the World Health Organization (WHO):
often> 1/10;
often by> 1/100 to
infrequently by> 1/1000 to
rarely from> 1/10000 to
very rarely
frequency is unknown – the available data establish the occurrence frequency is not possible.
Immune system:
rarely – hypersensitivity reactions including skin flushing, urticaria, angioneurotic edema (Quincke’s edema).
Laboratory findings:
rarely – a symptomatic hypocalcemia and hypophosphatemia (often against the background of predisposing risk factors) 1;
very rarely – transient asymptomatic hypophosphatemia.
On the part of the central nervous system:
often – headache, golovokruzhenie2;
infrequently – violation flavoring oschuscheniy2;
the frequency is unknown – irritability.
From a sight organ:
infrequently – inflammation of eye (uveitis, scleritis, episcleritis).
On the part of the ear and labyrinth disorders:
often – golovokruzhenie2 system.
On the part of the gastrointestinal tract:
often – abdominal pain, dyspepsia, constipation, diarrhea, ulcers pischevoda3, disfagiya3, bloating, acid regurgitation, flatulence;
infrequently – nausea, vomiting, gastritis, ezofagit3, erosion of the esophagus, stomach ulcer, including peptic ulcer complicated by hemorrhage (melena);
rarely – pischevoda3 stricture, ulceration pischevoda3, disorders of the upper gastrointestinal tract (perforation pischevoda1, rotoglotki1 ulcer, ulceration of the oral mucosa, krovotechenie1).
Skin and subcutaneous tissue disorders:
often – zud2, alopetsiya2;
seldom – a skin rash, erythema;
rarely – a photosensitivity rash, severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (toxic epidermal necrolysis) 4.
On the part of the musculoskeletal system:
very often – myalgia, bone pain, joint pain (sometimes strongly expressed) 1.2;
often – swelling sustavov2;
rarely – local jaw osteonecrosis associated mainly with the previous extraction of the tooth and / or local infection (including osteomyelitis), often slow vyzdorovleniem1,4, severe muscle spasms, abnormal diaphyseal fractures and subtrochanteric femur (adverse reaction bisphosphonate class of drugs) 5;
frequency is unknown – the external auditory canal cholesteatoma (focal osteonecrosis).
Other:
often – asteniya2, peripheral oteki2;
rarely – transient symptoms such as acute phase reaction (myalgia, malaise, rarely – fever) usually in connection with the beginning of lecheniya2.
1 cm. See “Cautions”
2 in clinical trials has a comparable rate to the drug group and the placebo group
3 cm. The sections “Dosage and Administration” and “Cautions”
4 This adverse reaction was set during post-marketing surveillance
5 is set at a post-registration application
special instructions
Wash down Alendronate tablets should only ordinary water, as other beverages (including mineral water, tea, coffee, fruit juices) degrade the drug absorption. Receiving alendronic acid before going to bed or in a horizontal position increases the risk of esophagitis.
Alendronic acid can cause local irritation of the mucosa of the upper gastrointestinal tract. When treating alendronic acid are known cases undesirable reactions of the esophagus (esophagitis, esophageal ulcer, or erosion) sometimes be severe and demanding patient treatment, and in rare cases complicated by stricture formation. It is necessary to monitor the possibility of the appearance of any signs of adverse reactions on the part of the esophagus. The patient should be informed of the need to stop taking the drug and contact your doctor if you develop dysphagia, pain on swallowing, chest pain or heartburn.
It should inform the patient about possible risks of damage esophageal mucosa non-compliance with instructions for use. The risk of severe adverse reactions on the part of the esophagus is higher in those patients who violate the guidelines for receiving the drug and / or continue to take it at the appearance of symptoms of irritation of the esophagus. It is particularly important to give the patient advice on receiving the drug, so that he knew that the risk of developing esophageal increases in case of failure of these recommendations.
Alendronate drug should be prescribed with extreme caution in patients with acute exacerbations of diseases of the upper gastrointestinal tract, such as dysphagia, oesophageal disease, gastritis, duodenitis, ulcers, as well as with active gastrointestinal bleeding, surgery on the upper sections of the gastrointestinal tract, except pyloroplasty, due the possible irritating effect of the preparation on the mucous membrane of upper gastrointestinal and deterioration of the underlying disease. For patients diagnosed with Barrett’s esophagus the appointment of alendronate should be decided individually on the basis of an estimate of the expected benefit to the possible risk.
While extensive clinical studies alendronate increased risk were observed in post-marketing reports of reports of rare cases of gastric and duodenal ulcers, sometimes severe and complicated.
Known cases of local appearance jaw osteonecrosis associated mainly with the previous extraction of the tooth and / or local infection (including osteomyelitis), often with slow recovery. In most cases, osteonecrosis of the jaw in patients receiving bisphosphonates occurs in cancer patients receiving intravenous bisphosphonates. Many of the patients were also receiving chemotherapy and corticosteroids. Also, there are cases of osteonecrosis of the jaw in patients with osteoporosis treated with bisphosphonates orally. In assessing individual risk of developing osteonecrosis of the jaw following risk factors should be considered: a bisphosphonate activity (the highest in the zoledronic acid), route of administration and total dose; cancer, chemotherapy, radiotherapy, corticosteroids intake, smoking; dental diseases in history, poor oral hygiene, periodontal disease, invasive dental procedures, poorly selected prosthesis. Before therapy with oral bisphosphonates in patients with poor dental status recommended dental examination and preventive therapeutic measures. During the course of bisphosphonates in these patients is recommended as far as possible, avoid invasive dental procedures. Если у пациента развился остеонекроз челюсти во время терапии бисфосфонатами, хирургическое стоматологическое лечение может ухудшить его состояние. Неизвестно, уменьшает ли прекращение приема бисфосфонатов риск развития остеонекроза челюсти у пациентов, которым требуются стоматологические процедуры. В каждом случае решение должен принимать лечащий врач на основании оценки отношения ожидаемой пользы к возможному риску для конкретного пациента. Во время терапии бисфосфонатами следует разъяснить пациентам важность правильной гигиены полости рта, профилактических осмотров, а также предупредить их о необходимости сообщения о любых симптомах со стороны полости рта, например подвижности зубов, боли или появлении припухлости.
It reported the occurrence of pain in the bones, joints and / or muscles in patients receiving bisphosphonates. These symptoms rarely are severe and / or lead to disability. Время появления симптомов варьирует от одного дня до нескольких месяцев от начала терапии. У большинства пациентов симптомы разрешались после прекращения лечения. У некоторых из них симптомы появлялись снова при возобновлении приема того же препарата или другого бисфосфоната.
При наличии гипокальциемии необходимо провести ее коррекцию до начала лечения. Другие нарушения минерального обмена (например, при дефиците витамина D) также должны быть устранены. Терапию следует сочетать с диетой, обогащенной солями кальция и витамином D. У пациентов с данными нарушениями необходимо контролировать содержание кальция в крови и симптомы гипокальциемии.
В процессе лечения возможно незначительное бессимптомное снижение концентрации кальция в сыворотке крови и фосфатов за счет положительного воздействия алендроновой кислоты на минеральную плотность костной ткани, что имеет особое значение для пациентов, получающих глюкокортикостероидные препараты, поскольку у них может наблюдаться сниженная абсорбция кальция.
In rare cases, severe hypocalcemia can be commonly in patients with predisposition to this complication (hypoparathyroidism, vitamin D, calcium malabsorption).
Сообщалось о возникновении патологических (то есть при воздействии незначительной силы или самопроизвольных) подвертельных переломов или переломов проксимальных отделов диафиза бедренной кости у небольшого количества пациентов, принимающих бисфосфонаты, главным образом у пациентов, получающих длительную терапию по поводу остеопороза. Некоторые из переломов относились к категории стрессовых (также известны под названием нагрузочный перелом, маршевый перелом, перелом Дойчлендера), возникающих в отсутствие травмы. Переломы часто бывают двусторонними, поэтому у пациентов с переломом бедра, принимающих бисфосфонаты, следует обследовать второе (контралатеральное) бедро. Известно, что данные переломы плохо срастаются. Some patients for weeks or months before the full fracture experienced prodromal pain in the affected area, often associated with a characteristic X-ray picture of a stress fracture.
The number of messages is very small, moreover, stress fractures with similar clinical features occur in patients not taking bisphosphonates. Пациентов со стрессовыми переломами необходимо обследовать с оценкой известных причин и факторов риска (например, дефицит витамина D, нарушения всасывания, применение глюкокортикостероидов, стрессовый перелом в анамнезе, артрит или перелом нижних конечностей, чрезмерные или увеличенные нагрузки, сахарный диабет, хронический алкоголизм) и предоставить им надлежащую ортопедическую помощь. Pending the results of the survey should consider the suspension of bisphosphonates in patients with stress fractures, based on an assessment of the benefit / risk in each case. Во время терапии бисфосфонатами следует рекомендовать пациентам сообщать о любых болях в бедре или паховой области. Всех пациентов, поступивших с такими жалобами, необходимо осматривать на предмет неполного перелома бедренной кости.
Во время пострегистрационного применения поступали редкие сообщения о тяжелых кожных реакциях, включая синдром Стивенса-Джонсона и синдром Лайелла (токсический эпидермальный некролиз).
Сообщалось о таком нежелательном явлении, как остеонекроз наружного слухового канала, который был преимущественно ассоциирован с длительным применением алендроновой кислоты. Возможные факторы риска развития остеонекроза наружного слухового канала включают применение стероидов, химиотерапию, травмы.
Следует принимать во внимание и другие причины остеопороза, помимо дефицита эстрогенов и возраста.
Пациентов следует предупредить, что при случайном пропуске приема препарата Алендронат один раз в неделю, они должны принять одну таблетку утром ближайшего дня. Не следует принимать две дозы препарата в один день, но в последующем надо вернуться к приему препарата один раз в неделю в тот день недели, который был выбран в начале лечения.
Effects on ability to drive vehicles and mechanisms
Исследований по влиянию алендроновой кислоты на способность управлять транспортными средствами и работу с точными механизмами не проводилось. Однако, учитывая возможность развития побочных реакций, (головокружение и других), следует соблюдать осторожность при управлении транспортными средствами, точными механизмами и воздерживаться от выполнения указанных видов деятельности в случае развития побочных эффектов.
Storage conditions
Хранить в защищенном от света месте при температуре не выше 25 градусов.
Keep out of the reach of children.
Dosing and Administration
Внутрь, за 2 часа (но не менее чем за 30 минут) до первого приема пищи, воды или других лекарственных средств. Для уменьшения раздражающего влияния на пищевод препарат необходимо принимать сразу после утреннего подъема, после приема не следует ложиться на протяжении 30 минут (опасно применять в случае неспособности пациента стоять или сидеть прямо в течение 30 минут). Прием перед сном или в горизонтальном положении увеличивает риск развития эзофагита.
Запивать только обычной водой (полный стакан – не менее 200 мл), поскольку другие напитки (включая минеральную воду, кофе, чай, апельсиновый сок) снижают абсорбцию.
Таблетки нельзя разжевывать или рассасывать.
The optimal duration of use of the drug has not been established. Необходимость продолжения терапии бисфосфонатами должна оцениваться лечащим врачом на регулярной основе, особенно после 5 или более лет применения.
Препарат следует принимать при обеспечении суточной потребности кальция и витамина D.
При остеопорозе у женщин в постменопаузе и остеопорозе у мужчин – 70 мг один раз в неделю или 10 мг один раз в сутки.
При болезни Педжета – 40 мг один раз в сутки в течение 6 месяцев.
Коррекции дозы у пациентов пожилого возраста, у пациентов с нарушением функции печени, а также у пациентов с легкой и умеренной почечной недостаточностью (КК от 35 до 60 мл/мин) не требуется.
При случайном пропуске приема препарата в дозировке один раз в неделю необходимо принять одну таблетку утром ближайшего дня. Не следует принимать две таблетки в один день, но в последующем надо продолжать принимать по одной таблетке в тот день недели,
который был выбран для приема с самого начала лечения.
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist