Tevabon set of tablets and capsules 1 + 70mkg / mg, No. 96

• postmenopausal osteoporosis;

• osteoporosis caused by the use of corticosteroids.

The drug Tevabon consists of two dosage forms: alendronic acid tablets and alfacalcidol capsules.

To ensure normal absorption and reduce the risk of adverse reactions, the recommendations for use and dosage should be strictly followed.

Alendronic acid

Assign inside 1 tab. (70 mg) 1 time per week with a glass of water, at least 30 minutes before the first meal, drinks or other medicines. Drink only with plain water, as other drinks (including mineral water), foods, and some medicines can reduce the bioavailability of alendronic acid.

The tablets should not be chewed or sucked. After taking the pill, the patient must maintain an upright position (standing or sitting) for at least 30 minutes. Do not take the pill at bedtime or before getting out of bed in the morning.

Elderly patients do not need dose adjustment. In case of impaired renal function, CC> 35 ml / min, dose adjustment is not required.

Alfacalcidol

Assign inside 1 caps. (1 mcg) 1 time / day in the evening every day. The capsules should be swallowed whole with plenty of liquid. The drug Tevabon is intended for long-term use.

A set of tablets and capsules:

The tablets are white or off-white, round, flat, beveled, with a 'T' engraved on one side.

1 tab. sodium alendronate monohydrate 81.2 mg,?

which corresponds to the content of alendronic acid 70 mg

Excipients: microcrystalline cellulose - 113.8 mg, croscarmellose sodium - 3 mg, magnesium stearate - 2 mg.

Capsules are soft gelatinous, oval, white or almost white, opaque, with the inscription '1.0' in black ink; the contents of the capsules are a pale yellow oily solution.

1 caps. alfacalcidol 1 mcg

Excipients: citric acid - 0.015 mg, propyl gallate - 0.02 mg, ?-tocopherol - 0.02 mg, ethanol - 1.144 mg, peanut oil - 98.8 mg.

• conditions leading to a slowdown in the movement of food through the esophagus (including strictures or achalasia of the esophagus);

• inability of the patient to stand or sit upright for at least 30 minutes;

• hypocalcemia; hypercalcemia;

• Burnett's syndrome and / or lactic-alkaline syndrome (plasma calcium concentrations> 2.6 mmol / L, calcium phosphate> 3.7 mmol / L, pH> 7.44);

• severe renal dysfunction (CC <35 ml / min);

• patients on hemodialysis;

• hypervitaminosis D;

• hyperphosphatemia (with the exception of hyperphosphatemia in hypoparathyroidism);

• hypermagnesemia;

• sucrase / isomaltase deficiency, fructose intolerance, glucose / galactose malabsorption;

• childhood;

• pregnancy;

• lactation period (breastfeeding);

• hypersensitivity to alendronic acid, alfacalcidol and other components of the drug.

• The drug should be prescribed with caution for gastrointestinal diseases in the acute phase, incl. dysphagia, esophagitis, gastritis, duodenitis, gastric ulcer and duodenal ulcer; with hypoparathyroidism, hypovitaminosis D, calcium malabsorption, nephrolithiasis, atherosclerosis, impaired renal function (CC more than 35 ml / min), chronic heart failure, patients with an increased risk of hypercalcemia, incl. with leukemia, lymphoma, sarcoidosis, pulmonary tuberculosis (active form).

pharmachologic effect

Combined drug for the treatment of osteoporosis. Alendronic acid, being a bisphosphonate, inhibits the process of active resorption of bone tissue caused by osteoclasts, without directly affecting the formation of new bone tissue. Having a tropism for bone hydroxyapatite, alendronic acid accumulates mainly in the zones of its active resorption. The mechanism of action is associated with suppression of functional activity and stimulation of osteoclast apoptosis. Against the background of therapy with alendronic acid, there is an increase in bone mineralization and an improvement in its quality characteristics. Alfacalcidol is a regulator of calcium-phosphorus metabolism, a precursor of the active metabolite of vitamin D3 - calcitriol. Increases the absorption of calcium and phosphorus in the intestine, increases their reabsorption in the kidneys,restores a positive calcium balance in the treatment of calcium malabsorption syndrome, reduces the concentration of parathyroid hormone in the blood. Acting on both parts of the bone remodeling process (resorption and synthesis), alfacalcidol not only increases bone mineralization, but increases its elasticity by stimulating the synthesis of bone matrix proteins, bone morphogenetic proteins, and bone growth factors. When treated with alfacalcidol, bone with a normal histological structure is formed, the strength of the bone tissue increases in all parts of the skeleton. Alendronic acid and alfacalcidol increase bone strength, while their effects are synergistic, due to different mechanisms of action. Inhibition of catabolic processes in bones by alendronic acid is complemented by the bone anabolic effect of alfacalcidol,which leads to the formation of a normal bone structure. Due to the pharmacological effects of both substances, their use in combination can reduce the potential risk of developing hypocalcemia, hypercalcemia and hypercalciuria. A significant reduction in the risk of fractures is achieved not only due to an increase in bone strength, but also due to the extraosseous (pleiotropic) effect of alfacalcidol - an increase in muscle strength, acceleration of the speed of muscle response.but also due to the extraosseous (pleiotropic) effect of alfacalcidol - an increase in muscle strength, acceleration of the speed of muscle reaction.but also due to the extraosseous (pleiotropic) effect of alfacalcidol - an increase in muscle strength, acceleration of the speed of muscle reaction.

Pharmacokinetics

Alendronic acid

Suction

When taken orally on an empty stomach in the dose range from 5 to 70 mg immediately 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, bioavailability decreases by about 60%. The concentration of alendronic acid in blood plasma after oral administration in a therapeutic dose is below the possible detection limit (less than 5 ng / ml). Distribution The binding of alendronic acid to blood plasma proteins is about 78%. Alendronic acid is distributed in soft tissues, and then quickly redistributed to the bone, where it is fixed, or excreted through the kidneys. Metabolism and excretion Does not undergo biotransformation. It is displayed unchanged.The elimination process is characterized by a rapid decrease in the concentration of alendronic acid in the blood plasma and an extremely slow release from the bones.

Alfacalcidol

Suction

After oral administration, alfacalcidol is rapidly absorbed from the gastrointestinal tract. Cmax is achieved 8-12 hours after a single dose of alfacalcidol. Oral bioavailability is about 100%.

Metabolism

The pharmacological effects of alfacalcidol are realized after its transformation in the body into calcitriol. The conversion of alfacalcidol to calcitriol occurs in the liver by hydroxylation at the 25 carbon atom, and the hydroxylation process occurs very quickly (it is substrate-dependent) and does not depend on the functional state of the liver. The maximum concentration of calcitriol in the body is reached 8-12 hours after a single dose of alfacalcidol. Unlike native vitamin D, alfacalcidol does not need hydroxylation in the kidneys, therefore it is effective even in patients with reduced activity of renal 1-alpha-hydroxylase (kidney pathology, old age).

Withdrawal

Calcitriol is excreted by the kidneys and liver in approximately equal proportions, T1 / 2 is about 35 hours.

Side effect

Side effects are classified according to the following frequency: very common (? 10%); often (? 1%, but <10%); infrequently (? 0.1%, but <1%); rarely (? 0.01%, but <0.1%); very rare (<0.01%, including isolated cases). When using alendronic acid From the digestive system: often - abdominal pain, dyspepsia, acid belching, diarrhea, dysphagia, flatulence, gastritis, stomach ulcer, ulceration of the esophageal mucosa; infrequently - nausea, vomiting, constipation, gastritis, esophagitis, erosion of the esophageal mucosa, melena; rarely - stricture of the esophagus, ulceration of the mucous membrane of the oropharynx, perforation of the esophagus, bleeding from the upper gastrointestinal tract (the connection with the intake of alendronic acid has not been established). From the musculoskeletal system: often - pain in bones, muscles, joints, muscle cramps; rarely - osteonecrosis of the jaw,mainly in cancer patients taking bisphosphonates, however, similar cases have been observed in patients undergoing therapy for osteoporosis; unknown frequency - proximal femur stress fracture, with or without injury. From the side of metabolism: rarely - symptomatic hypocalcemia, usually associated with predisposing conditions, hypophosphatemia. From the side of the central nervous system: often - headache. From the senses: rarely - uveitis, scleritis, episcleritis. Allergic reactions: infrequently - rash, itching, erythema; rarely - a rash associated with photosensitivity, urticaria, angioedema; very rarely - severe skin reactions, including erythema multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome). Others: rarely - transient symptoms,similar to symptoms in the acute phase of the disease (myalgia, malaise and fever), usually at the beginning of treatment. When using alfacalcidol Metabolic: rarely - hypercalcemia; very rarely - a slight increase in the concentration of HDL in the blood plasma. Patients with severe renal impairment may develop hyperphosphatemia, heterotopic calcifications in the cornea and blood vessels. From the digestive system: infrequently - anorexia, vomiting, heartburn, abdominal pain, nausea, dry mouth, discomfort in the epigastric region, constipation, diarrhea; rarely - a slight increase in the activity of liver enzymes in plasma (ALT, AST). From the side of the central nervous system: rarely - weakness, fatigue, dizziness, drowsiness. From the side of the cardiovascular system: rarely - tachycardia.From the musculoskeletal system: infrequently - moderate pain in muscles, bones, joints. Allergic reactions: rarely - skin rash, itching; very rarely - anaphylactic shock associated with peanut butter. Due to the multidirectional effect of alendronic acid and alfacalcidol on serum calcium concentration, the use of a combination of these drugs avoids sharp fluctuations in serum calcium concentration.

Application during pregnancy and lactation

Due to insufficient data on the use of alendronic acid and / or with the risk of an overdose of alfacalcidol, Tevabon is contraindicated in pregnancy and during breastfeeding.

Application for impaired renal function

In case of impaired renal function, CC> 35 ml / min, dose adjustment is not required. Contraindication: severe renal impairment (CC <35 ml / min); patients on hemodialysis

Application in children

Contraindication: childhood.

Use in elderly patients

Elderly patients do not need dose adjustment.

special instructions

For the use of alendronic acid

Special attention should be paid to any signs of adverse reactions in the esophagus. The patient should be informed about the need to stop taking the drug and see a doctor if dysphagia develops, pain when swallowing, chest pain, appearance or intensification of heartburn. Due to the existing risk of irritation of the mucous membrane of the upper gastrointestinal tract, as well as aggravation of the course of the underlying disease, it is recommended to be careful when prescribing the drug to patients with gastrointestinal diseases in the acute phase (such as dysphagia, esophagitis, gastritis, duodenitis, gastric ulcer and duodenal ulcer) , as well as recently transferred (during the previous year) diseases of the gastrointestinal tract (gastric ulcer and duodenal ulcer, active bleeding from the gastrointestinal tract, surgery in the upper gastrointestinal tract,except pyloroplasty). There are reports of cases of osteonecrosis of the jaw, usually associated with tooth extraction and / or local infection (including osteomyelitis), in patients with cancer receiving treatment regimens that include bisphosphonates (primarily iv). Many of these patients also received chemotherapy and corticosteroids. There are also reports of osteonecrosis of the jaw in osteoporotic patients receiving oral bisphosphonates. Before using bisphosphonates, patients with concomitant risk factors (eg, cancer, chemotherapy, radiation therapy, GCS therapy, poor oral hygiene) should undergo a dental examination with appropriate preventive dental treatment. Patients on bisphosphonate therapy should avoid invasive dental procedures whenever possible.In patients with osteonecrosis of the jaw on bisphosphonate therapy, dental surgery can worsen the condition. If it is necessary to carry out surgical interventions, it should be borne in mind that there are no data on the possibility of reducing the risk of developing osteonecrosis of the jaw after discontinuation of bisphosphonates. Prescriptions and recommendations of the attending physician should be based on an individual assessment of the benefit / risk ratio for each patient. The time of onset of pain in bones, joints and muscles in patients during bisphosphonate therapy varied from 1 day to several months after the start of treatment. In most patients, after discontinuation of treatment, there was a decrease in the severity of pain, in some patients, pain reappeared when therapy was resumed with the same or a different bisphosphonate.If the patient has forgotten to take an alendronic acid tablet, it should be taken the next morning. Do not take 2 tablets. in one day, you must continue to take 1 tab. 1 time per week on the day that was chosen for admission from the very beginning of treatment. In patients with hypocalcemia, hypovitaminosis D and hypoparathyroidism, it is necessary to carry out corrective therapy for mineral metabolism disorders before starting treatment with alendronic acid. Due to the positive effect of alendronic acid on bone mineral density, a slight asymptomatic decrease in serum calcium and phosphorus concentration may be observed during treatment. There are sporadic reports of symptomatic hypocalcemia, sometimes severe, usually in patients with a predisposition to it (for example, with hypoparathyroidism, vitamin D deficiency,calcium malabsorption). There are reports of the occurrence of stress fractures of the proximal femur with prolonged treatment with alendronic acid (from 18 months to 10 years). Fractures occurred after minimal or no trauma. Some patients initially developed pain in the proximal femur, which persisted for several weeks or even months before the symptom resulted in a fracture of the femur. Often the fractures were bilateral, therefore, in the event of a fracture of one femur in a patient, it is necessary to monitor the condition of the other femur. In patients taking alendronic acid, especially with concomitant GCS therapy, it is extremely important to ensure a sufficient intake of calcium and vitamin D in the body with food or in the form of drugs.The absorption of bisphosphonates is greatly reduced with concomitant food intake.

For the use of alfacalcidol

Alfacalcidol may exacerbate hypercalcemia and / or hypercalciuria when administered to patients with a disease associated with uncontrolled overproduction of calcitriol (eg, leukemia, lymphoma, sarcoidosis), and may also exacerbate hyperphosphatemia. If the plasma calcium concentration is more than 2.6 mmol / l, it is necessary to exclude the intake of other calcium-containing preparations. If there is no effect, you should stop taking alfacalcidol capsules until the serum calcium concentration normalizes (2.2-2.6 mmol / l). Control of the concentration of calcium and phosphate in the blood is carried out before treatment with alfacalcidol and, if necessary, corrective therapy is carried out. When treating with alfacalcidol, the concentration of electrolytes is determined at the beginning once a week, upon reaching Cmax and during the entire period of treatment - every 3-5 weeks,and also control the activity of alkaline phosphatase (in case of impaired renal function (CC more than 35 ml / min) - weekly control). Peanut butter on rare occasions can cause severe allergic reactions. Patients with hereditary fructose intolerance or fructose malabsorption should not be prescribed Tevabon, since the set includes alfacalcidol capsules containing sorbitol.

Influence on the ability to drive vehicles and use mechanisms

Due to the possibility of side effects from the central nervous system during the period of treatment, care must be taken when driving vehicles, as well as in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Alendronic acid

Symptoms: possible hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis, erosive and ulcerative lesions of the gastrointestinal mucosa. Treatment: taking milk or an antacid to bind alendronic acid. Due to the risk of esophageal irritation, do not induce vomiting. The patient must be in an upright position.

Alfacalcidol

Early symptoms of hypervitaminosis D (due to hypercalcemia): diarrhea, constipation, nausea, vomiting, dry mouth, anorexia, metallic taste in the mouth, hypercalciuria, polyuria, polydipsia, pollakiuria / nocturia, headache, fatigue, weakness, myalgia bones. Late symptoms of hypervitaminosis D: dizziness, confusion, drowsiness, heart rhythm disturbances, pruritus, increased blood pressure, conjunctival hyperemia, nephrolithiasis, weight loss, photophobia, pancreatitis, gastralgia; rarely - a change in the psyche and mood. Symptoms of chronic vitamin D intoxication: 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, the appointment of mineral oil can have a positive effect (which helps to reduce absorption and increase the excretion of alfacalcidol in the feces). In severe cases, hydration is carried out with the introduction of infusion saline solutions, loop diuretics, GCS, bisphosphonates, calcitonin are prescribed, hemodialysis is performed using solutions with a low calcium content. It is necessary to monitor the content of electrolytes in the blood, kidney and heart function (according to the ECG), especially in patients receiving digoxin. There is no specific antidote.bisphosphonates, calcitonin, hemodialysis is performed using solutions with a low calcium content. It is necessary to monitor the content of electrolytes in the blood, kidney and heart function (according to the ECG), especially in patients receiving digoxin. There is no specific antidote.bisphosphonates, calcitonin, hemodialysis is performed using solutions with a low calcium content. It is necessary to monitor the content of electrolytes in the blood, kidney and heart function (according to the ECG), especially in patients receiving digoxin. There is no specific antidote.

Drug interactions

When taken simultaneously with food, beverages containing calcium (including mineral water), food additives, antacids and other medicinal products for oral administration, malabsorption of alendronic acid may occur. In this regard, the interval between taking alendronic acid and other oral medications should be at least 30 minutes. The combined use of alendronic acid (but not simultaneous administration) with estrogen preparations is not accompanied by a change in their action and the development of side effects. Oral prednisolone intake 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. With the simultaneous use of alfacalcidol with cardiac glycosides, the risk of arrhythmia increases. Inducers of microsomal liver enzymes (incl.including phenytoin and phenobarbital) reduce, and inhibitors - increase the concentration of alfacalcidol in plasma (a change in its effectiveness is possible). The absorption of alfacalcidol decreases when it is used together with mineral oil (for a long time), cholestyramine, colestipol, sucralfate, antacids, albumin-based preparations. In this regard, alfacalcidol capsules should not be taken simultaneously with antacids containing aluminum, the interval between taking these drugs should be at least 2 hours. Taking antacids increases the risk of developing hypermagnesemia and hyperaluminaemia. The toxic effect is weakened by retinol, tocopherol, ascorbic acid, pantothenic acid, thiamine, riboflavin. In perimenopausal women, the effect of alfacalcidol may be enhanced by estrogens. Calcitonin,derivatives of etidronic and pamidronic acids, plikamycin and GCS reduce the effect of alfacalcidol. Alfacalcidol increases the absorption of phosphorus-containing drugs and the risk of hyperphosphatemia. The simultaneous use of alfacalcidol with calcium preparations, thiazide diuretics can cause hypercalcemia by increasing the absorption of calcium in the intestine, increasing its reabsorption in the kidneys. Against the background of therapy with alfacalcidol, other drugs of vitamin D and its derivatives should not be prescribed due to possible additive interactions and an increased risk of hypercalcemia.thiazide diuretics can cause hypercalcemia, by increasing the absorption of calcium in the intestine, increasing its reabsorption in the kidneys. During therapy with alfacalcidol, other drugs of vitamin D and its derivatives should not be prescribed due to possible additive interactions and an increased risk of hypercalcemia.thiazide diuretics can cause hypercalcemia, by increasing the absorption of calcium in the intestine, increasing its reabsorption in the kidneys. Against the background of therapy with alfacalcidol, other drugs of vitamin D and its derivatives should not be prescribed due to possible additive interactions and an increased risk of hypercalcemia.