Expiration date: 11/2025
Clinico-pharmacological group
(A combination drug for the treatment of osteoporosis)
Release form, composition and packaging
A set of tablets and capsules:
1 tablet contains:
sodium alendronate monohydrate 81.2 mg,
that corresponds to the content Alendronic acid 70 mg
1 capsule contains:
alfacalcidol 1 mcg
Tablets white or almost white, round, flat, with facet, with engraving "T" on one side.
Excipients: cellulose microcrystalline - 113.8 mg croscarmellose sodium 3 mg magnesium stearate - 2 mg.
Capsules soft gelatine, oval, white or almost white, opaque, labeled "1.0" in black ink, the contents of capsules - pale yellow oily solution.
Auxiliary substances: citric acid - 0.015 mg propyl gallate - 0.02 mg, ?-tocopherol and 0.02 mg ethanol 1.144 mg, oil, peanut - 98.8 mg.
The composition of the shell capsules: gelatin - 48.27 mg, glycerol 85% - 11.78%, antiserb 85/70 (sorbitol 25-40%, sorbitan 20-30%, mannitol 0-6%, higher polyols 12.5-19%, water 15% to 17%) - 7.88 mg, titanium dioxide (E171) - 0.68 mg.
Composition of black ink A10379: shellac, dye iron oxide black, denatured ethanol (methylated alcohol), isopropanol, 1-butanol, ethyl acetate.
1 PCs. (tab.) - blisters (1) + 7. (caps.) - blisters (1) - cardboard envelope (4) - packs of cardboard.
1 PCs. (tab.) - blisters (1) + 7. (caps.) - blisters (1) - cardboard envelope (12) - packs of cardboard.
Pharmacological action
Combined preparation for the treatment of osteoporosis.Alendronic acid, as bisphosphonates, inhibits the active process of bone resorption caused by osteoclasts, without exerting direct influence on the formation of new bone tissue. Having an affinity to the hydroxyapatite of bone, Alendronic acid accumulates primarily in the areas of active resorption. The mechanism of action is associated with inhibition of functional activity and stimulation of apoptosis of osteoclasts. The therapy Alendronic acid is an increase in bone mineralization and to improve its quality characteristics.Alfacalcidol - regulator of calcium-phosphorus metabolism, precursor of the active metabolite of vitamin D3 - calcitriol. Increases the absorption of calcium and phosphorus in the gut, increases their reabsorbqiyu in the kidneys, restores a positive calcium balance in the treatment of calcium malabsorption syndrome, reduces the blood concentration of parathyroid hormone. Acting on both parts of the process of bone remodeling (resorption and synthesis), alfacalcidol not only increases the mineralization of bone tissue, but increases its elasticity by stimulating the synthesis of proteins of the bone matrix, bone morphogenetic proteins, growth factors, bone. During treatment with alfacalcidol is formed with a normal histological bone structure, bone strength is increased in all parts of the skeleton. Alendronic acid and alfacalcidol increases bone strength, and their synergistic effects through various mechanisms of action. Inhibition of Alendronic acid catabolic processes in bone supplemented with bone anabolic effects of alfacalcidol, which leads to the formation of normal bone structure. Due to the pharmacological effects of both substances, their use in combination allows to reduce the potential risk of developing hypocalcemia, hypercalciuria and hypercalcemia. A significant reduction in the risk of fractures is achieved not only by increasing bone strength, but also because vneconomy (pleiotropic) effect of alfacalcidol to increase muscular strength, accelerate the speed of muscle reactions.
Pharmacokinetics
Alendronic kislotalimonnaya ingestion on an empty stomach in the dose range of 5 to 70 mg directly 2 hours before Breakfast the bioavailability of Alendronic acid in women is 0.64%, in men - 0.6%. The bioavailability of Alendronic acid is reduced by 40% when taken on an empty stomach 1-1.5 hours before Breakfast. After drinking coffee and orange juice reduced bioavailability by approximately 60%. The concentration of Alendronic acid in the blood plasma after oral therapeutic dose is below the limit of determination (<5 ng/ml). Distributed alendronic acid with blood plasma proteins is approximately 78%. Alendronic acid is distributed in the soft tissues, then rapidly redistributed to bone, where it is fixing, or is excreted through the kidneys.Vyvedenie metabolism and biotransformation.Output 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.
Alphagalactosidase oral alfacalcidol is rapidly absorbed from the gastrointestinal tract. Cmax is reached after 8-12 hours after a single dose of alfacalcidol. The oral bioavailability is approximately 100%. Metabolicmetabolic effects of alfacalcidol are implemented after its conversion in the body into calcitriol. The transformation of alfacalcidol to calcitriol occurs in the liver by hydroxylation at the 25 carbon atom, and the process of hydroxylation occurs very quickly (is substrate-dependent manner) and does not depend on the functional state of the liver. The maximum concentration of calcitriol in the body is achieved after 8-12 hours after a single dose of alfacalcidol. In contrast to native vitamin D, alfacalcidol does not need hydroxylation in the kidney, therefore, is effective even in patients with reduced activity of renal 1-alpha hydroxylase (kidney disease, elderly age).Wavegeneration excreted by the kidneys and liver in approximately equal proportions, T1/2 is about 35 hours Dozirovocnami Tevabon consists of two dosage forms: tablets Alendronic acid and alfacalcidol capsules.For proper absorption and decrease the risk of adverse reactions should strictly observe the recommendations for use and dosing.
Alendronic acid inside of 1 tab. (70 mg) 1 times a week with a glass of water at least 30 minutes before the first food, beverage, or other drugs. Drink only plain water, as other beverages (including mineral water), food and some medicinal products can reduce the bioavailability of Alendronic acid. The tablets should not be chewed or dissolve in the mouth.After taking the tablet the patient should remain fully upright (standing or sitting) for at least 30 minutes. you Cannot take the tablet before bedtime or before the morning rising from bed.
Elderly patients dose adjustment is not required.When kidney functions CC >,, 35 ml/min dose adjustment is not required.
Alfakalzidola inside 1 capsule. (1 mg) 1 times/day in the evening daily. Capsules should be swallowed whole, squeezed enough liquid. Drug Tevabon designed for prolonged use.
Overdose
Alendronic acid: possible hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis, erosivno-azwenne defeat mucous membrane of the gastrointestinal tract.Treatment: administration of milk or antacids to bind Alendronic acid. Due to the risk of esophageal irritation, should not cause vomiting. The patient should be kept in a vertical position.
Alfakalzidola symptoms of hypervitaminosis D (hypercalcemia due to): diarrhea, constipation, nausea, vomiting, dry mouth, anorexia, metallic taste in the mouth, hypercalciuria, polyuria, polydipsia, pollakiuria/nocturia, headache, fatigue, weakness, myalgia, bone pain.Late symptoms of hypervitaminosis D are: dizziness, confusion, drowsiness, abnormal heart rhythm, skin itching, the AD, hyperemia of conjunctiva, stone, reducing body weight, photophobia, pancreatitis, gastralgia, rarely the change of mentality and mood.Symptoms of chronic intoxication with vitamin D: calcification of soft tissues, blood vessels and internal organs (kidneys, lungs), renal failure, cardiovascular failure, impaired growth in children.Treatment: cancel the drug. In the early stages of acute overdose can have a positive effect the appointment of mineral oil (which promotes absorption decrease and increase of excretion of alfacalcidol with feces). In severe cases the hydration is carried out with the introduction of intravenous saline solutions, prescribed loop diuretics, corticosteroids, bisphosphonates, calcitonin, and hemodialysis with the use of solutions with low calcium content. You should control the content of electrolytes in the blood, the kidneys and heart (according to ECG), especially in patients receiving digoxin. There is no specific antidote.Medicinal vzaimodeistviyami simultaneous reception with food, beverage containing calcium (including mineral water), food additives, antacids and other medications for oral administration may malabsorption of Alendronic acid. In this regard, the interval between the reception Alendronic acid and other oral drugs should be at least 30 min. Combined application of Alendronic acid (but not simultaneous treatment) with drugs of estrogen is accompanied by changes in their actions and side effects.The taking prednisone inside is not accompanied by clinically significant changes in the bioavailability of Alendronic acid.GCS enhance the side effects of Alendronic acid on the gastrointestinal tract.While the application of alfacalcidol with cardiac glycosides increases the risk of arrhythmia.Inductors of microsomal liver enzymes (including phenytoin and phenobarbital) decrease, and inhibitors of increase the concentration of alfacalcidol in plasma (you can change its effectiveness).The absorption of alfacalcidol decreases with its joint application with mineral oil (for long time), colestyramine, colestipol, sucralfate, antacids, drugs based on albumin.In this regard, we should not take the capsules of alfacalcidol at the same time with antacids containing aluminum, the interval between administration of these drugs should be at least 2 hours of antacids increases the risk of gipermagniemii and hyperalbuminemia. Toxic effects of impaired retinol, tocopherol, ascorbic acid, Pantothenic acid, thiamine, Riboflavin.Women in perimenopause effect of alfacalcidol may increase estrogen. Calcitonin, derivatives etidronate and pamidronate acids, plicamycin and corticosteroids reduce the effect of alfacalcidol.Alfacalcidol increases the absorption of phosphorus-containing drugs and the risk of hyperphosphataemia.Coadministration of alfacalcidol with calcium supplementation, thiazide diuretics may cause hypercalcemia by increasing calcium absorption in the intestine, increasing its reabsorption in the kidneys.On the background of therapy with alfacalcidol should not be administered other drugs vitamin D and its derivatives because of possible additive interaction and increased risk of hypercalcaemia.
Pregnancy and lactation
Due to insufficient data on the use of Alendronic acid and/or a risk of overdose of alfacalcidol drug Tevabon contraindicated in pregnancy and during breastfeeding.
Side effects
Side effects classified in accordance with the following frequency: very common - ? 10%, often - ? 1% but <,, 10="" -="" 0="" 1="" 01="" p="">,
In the application of Alendronic acid
From the digestive system: often - abdominal pain, dyspepsia, sour belching, diarrhoea, dysphagia, flatulence, gastritis, gastric ulcer, ulceration of esophageal mucosa, rarely - nausea, vomiting, constipation, gastritis, esophagitis, erosion of the mucous membrane of the esophagus, melena, rarely esophageal stricture, ulceration of the mucous membrane of the fauces, perforation of the esophagus, bleeding from the upper gastrointestinal tract (the connection with the reception Alendronic acid is not established).
From the side of musculoskeletal system: often - pain in bones, muscles, joints, cramps in muscles, rarely - osteonecrosis of the jaw mainly in cancer patients taking bisphosphonates, however, such cases were noted in patients on therapy for osteoporosis, unspecified frequency, stress fracture of the proximal femur associated or not associated with trauma.
From the metabolic: rarely, symptomatic hypocalcemia, usually associated with predisposing conditions hypophosphatemia.
CNS: frequently - headache.
From the senses: rarely uveitis, scleritis, episcleritis.
Allergic reactions: infrequently - rash, itching, erythema, rarely - rash, associated with photosensitivity, urticaria, angioneurotic oedema, very rarely - severe skin reactions, including erythema exudative multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome).
Other: rare - transient symptoms, similar to symptoms in the acute phase of the disease (myalgia, malaise and fever), usually at the beginning of treatment.
While the application of alfacalcidol
From a metabolism: rarely - hypercalcemia; very rarely a slight increase in the concentration of HDL in plasma. In patients with the expressed violation of the kidney may develop giperfosfatemii, heterotopic calcification in the cornea and blood vessels.
From the digestive system: rarely - anorexia, vomiting, heartburn, abdominal pain, nausea, dry mouth, discomfort in epigastrium, constipation, diarrhea, rarely - a slight increase in liver enzymes in plasma (ALT, AST).
CNS: rarely - weakness, fatigue, dizziness, drowsiness.
Of the cardiovascular system: rarely- tachycardia.
From the side of musculoskeletal system: rarely - moderate pain in the muscles, bones and joints.
Allergic reactions: rarely - skin rash, itching, rarely - anaphylactic shock, which has a relationship with peanut butter.
In connection with the multidirectional influence of Alendronic acid and alfacalcidol on the concentrations of calcium in blood serum, the use of a combination of these drugs allows to avoid sharp fluctuations in the concentration of calcium in serum.
Terms and conditions storage
The drug should be stored out of reach of children at temperature not exceeding 25°C. shelf Life - 3 years.
Testimony
— postmenopausal osteoporosis
— osteoporosis caused by the use of corticosteroids.
Contraindications
— States, leading to slower movement of food through the esophagus (including stricture or achalasia of the esophagus),
— inability of patient to stand or sit upright for at least 30 minutes,
— hypocalcemia,
— hypercalcemia,
— syndrome of Burnett and/or milk-alkali syndrome (calcium concentrations in plasma of >,, 2.6 mmol/l, calcium phosphate >,, 3.7 mmol/l, pH >, and 7.44),
— impaired renal function, severe (CC <,, 35="" p="">,
— patients on hemodialysis,
— hypervitaminosis D
— hyperphosphatemia (except hyperphosphatemia when hypoparathyroidism),
— hypermagnesemia,
— deficiency of sucrase/isomaltase, fructose intolerance, malabsorption of glucose/galactose,
— children's age,
— pregnancy,
— lactation (breast-feeding),
— hypersensitivity to Alendronic acid, alfacalcidol, and other components of the drug.
With caution should designate product in diseases of the gastrointestinal tract in acute phase, including dysphagia, esophagitis, gastritis, duodenitis, gastric ulcer and duodenal ulcers, with the hypoparathyroidism, vitamin D deficiency, malabsorption of calcium, kidney stones, atherosclerosis, impaired renal function (QC over 35 ml/min), chronic heart failure, patients with increased risk of hypercalcaemia, including leukemia, lymphoma, sarcoidosis, pulmonary tuberculosis (active form).
Special instructions
For the application of Alendronic acid
You should pay special attention to any signs of adverse reactions occurrence in the oesophagus. The patient should be informed about the necessity of discontinuation of the drug and seeking medical attention with the development of dysphagia, pain when swallowing, pain behind the breastbone, the emergence or strengthening of heartburn.
In connection with the existing risk of irritation of the mucous membrane of the upper digestive tract, and worsening of the course of the underlying disease, caution should be used when prescribing the drug to patients with diseases of the gastrointestinal tract in the acute phase (dysphagia, esophagitis, gastritis, duodenitis, ulcers disease stomach and duodenal ulcers), and recent (within previous year) diseases of the gastrointestinal tract (stomach ulcer and duodenal ulcer, active bleeding from the gastrointestinal tract, surgical intervention in the upper gastrointestinal tract, excluding pyloroplasty).
There are reports on cases of osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) in patients with cancer receiving treatment regimens including bisphosphonates (primarily, in/in). Many of these patients also received chemotherapy and corticosteroids. There are also reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral bisphosphonates. Before the use of bisphosphonates to patients with concomitant risk factors (e.g. cancer, chemotherapy, radiation therapy, corticosteroids, inadequate oral hygiene) must undergo a dental examination with appropriate preventive dentistry. Patients undergoing treatment bisphosphonates should avoid invasive dental procedures. In patients with osteonecrosis of the jaw, located on the bisphosphonates treatment, dental surgical intervention may lead to worsening of the condition. If necessary, surgical interventions should be considered that the data on the possibility of reducing the risk of developing osteonecrosis of the jaw after the abolition of bisphosphonates are lacking. Appointments and recommendations of the attending physician must be based on individual assessment of the benefit/risk for each patient.
The time of appearance of pain in the bones, joints and muscles in patients during treatment bisphosphonates ranged from 1 day to several months after starting treatment. In the majority of patients after cessation of treatment was a decrease in the severity of pain in some patients, the pain reappeared with the resumption of therapy with the same or another bisphosphonate.
If the patient forgets to take the pill Alendronic acid, it should be taken in the morning of the next day. You should not take 2 tab. one day, you must continue to take on 1 tab. 1 time in a week that day, which was selected to be used from the start of treatment.
In patients with hypocalcemia, hypovitaminosis D and hypoparathyroidism it is necessary to conduct corrective therapy of mineral exchange violations prior to treatment Alendronic acid. Due to the positive effects of Alendronic acid on mineral bone density during treatment, there may be a slight asymptomatic reduction in the concentration of calcium and phosphorus in the blood serum. There are few reports of symptomatic hypocalcaemia, occasionally severe, usually patients with a predisposition to it (for example, hypoparathyroidism, vitamin D deficiency, malabsorption of calcium).
There are reports on the occurrence of stress fractures of the proximal femur with prolonged treatment Alendronic acid (from 18 months to 10 years).
The fractures occurred after minimal trauma. Some patients at first there is pain in the proximal thigh, which persisted for several weeks or even months before this symptom was ended by a fractured femur. Often the fractures were bilateral, therefore, the fracture of one femur of the patient is necessary to monitor the status of the other thigh.
In patients receiving Alendronic acid, especially when concomitant medication GCS, it is essential to ensure sufficient intake of calcium and vitamin D from food or drugs.
Absorption of bisphosphonates significantly reduces simultaneous food intake.
For use of alfacalcidol
Alfacalcidol may increase hypercalcemia and/or hypercalciuria when administered to patients with disease associated with uncontrolled overproduction of calcitriol (e.g., in leukemia, lymphoma, sarcoidosis), and can enhance giperfosfatemii. When the concentration of calcium in the plasma of more than 2.6 mmol/l is necessary to exclude the intake of other calcium-containing preparations. In the absence of effect should stop taking the capsules of alfacalcidol to normalise the calcium concentration in the serum (2.2-2.6 mmol/l). Monitoring of the concentration of calcium and phosphate in the blood is carried to the treatment with alfacalcidol and if necessary, carry out corrective therapy.
During treatment with alfacalcidol, the concentration of electrolytes in the early determine 1 time per week, upon reaching Cmax, and during the entire treatment period is every 3-5 weeks, and also control the activity of alkaline phosphatase (in violation of the kidney (QC over 35 ml/min) - weekly monitoring).
Peanut butter in rare cases can cause severe allergic reactions.
Patients with hereditary fructose intolerance or fructose malabsorption should not be prescribed the drug Tevabon, since the set consists of alfacalcidol capsule containing sorbitol.
Effects on ability to drive vehicles and management mechanisms
In connection with possibility of development of side effects in the Central nervous system during treatment use caution when driving and other potentially hazardous activities, require high concentration and psychomotor speed reactions.
Use in impaired renal function
When kidney functions CC >,, 35 ml/min dose adjustment is not required.
Contraindications: impaired renal function, severe (CC <,, 35="" p="">,
