Alendronic acid, Alfacalcidol | Tevabon tablets 70 mg, 4 pcs. + capsules 1 mcg, 28 pcs.

Latin name

Tevabon

release form

capsules and tablets.

Pharmacological action

TEVABON - a combined drug for the treatment of osteoporosis.

Alendronic acid, being a bisphosphonate, inhibits the process of active bone resorption caused by osteoclasts, without directly affecting the formation of new bone tissue. Having tropism for bone hydroxyapatite, alendronic acid accumulates mainly in areas of its active resorption. The mechanism of action is associated with the suppression of functional activity and the stimulation of apoptosis of osteoclasts. Against the background of alendronic acid therapy, there is an increase in bone mineralization and an improvement in its quality characteristics.

Alfacalcidol - 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 also increases its elasticity by stimulating the synthesis of bone matrix proteins, bone morphogenetic proteins, and bone growth factors. In the treatment with alfacalcidol, a bone with a normal histological structure is formed, bone strength increases in all parts of the skeleton.

Alendronic acid and alfacalcidol increase bone strength, while their effects are synergistic due to various mechanisms of action. Inhibition of catabolic processes in bones by alendronic acid is supplemented 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 extra-bone (pleiotropic) effect of alfacalcidol - an increase in muscle strength, acceleration of the speed of muscle reaction.

Indications

- postmenopausal osteoporosis

- osteoporosis caused by the use of corticosteroids.

Contraindications

- conditions that slow down the movement of food through the esophagus (including strictures or achalasia of the esophagus)

- patient's inability to stand or sit straight for at least 30 min

- hypocalcemia

- hypercalcemia

- Burnett syndrome and / or milk-alkaline syndrome (plasma calcium concentration> 2.6 mmol / l, calcium phosphate> 3.7 mmol / L, pH> 7.44)

- severe renal impairment (CC
- patients undergoing hemodialysis

- hypervitaminosis D

- hyperphosphatemia (with the exception of hyperphosphatemia with hypoparathyroidism) srdlpkrd - - sucrose deficiency / from maltase, fructose intolerance, malabsorption of glucose / galactose

- childhood

- pregnancy

- lactation (breastfeeding)

- Hypersensitivity to alendronic acid, alfacalcidol and other components of the drug.

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 consult a doctor with the development of dysphagia, pain when swallowing, pain behind the sternum, the appearance or intensification of heartburn.

Due to the risk of irritation of the mucous membrane of the upper gastrointestinal tract, as well as aggravation of the underlying disease, caution is advised when prescribing the drug to patients with gastrointestinal diseases in the exacerbation phase, such as dysphagia, esophagitis, gastritis, duodenitis, gastric and duodenal ulcer, as well as recent (during the previous year) gastrointestinal diseases (gastric and duodenal ulcer , active bleeding from the gastrointestinal tract, surgery on the upper gastrointestinal tract, except for pyloroplasty).

There have been reports of cases of jaw osteonecrosis, usually associated with tooth extraction and / or local infection (including osteomyelitis), in cancer patients receiving treatment regimens that include bisphosphanates (primarily intravenous). Many of these patients also received chemotherapy and corticosteroids. There are also reports of jaw osteonecrosis in patients with osteoporosis, receiving oral bisphosphonates. Before using bisphosphonates, patients with concomitant risk factors (for example, cancer, chemotherapy, radiation therapy, GCS therapy, insufficient oral hygiene) must undergo a dental examination with appropriate preventive dentistry. Patients on bisphosphanate treatment should avoid invasive dental procedures whenever possible. In patients with jaw osteonecrosis undergoing bisphosphanate therapy, dental surgery may worsen the condition. If surgical interventions are necessary, it should be borne in mind that there is no data on the possibility of reducing the risk of jaw osteonecrosis after the abolition of bisphosphanates. The appointments and recommendations of the attending physician should be based on an individual assessment of the benefit / risk ratio for each patient.

The time of appearance of pain in the bones, joints and muscles of patients during bisphosphanate therapy ranged from 1 day to several months after the start of treatment. In most patients, after the cessation of treatment, a decrease in the severity of pain was noted, in some patients the pain reappeared with the resumption of therapy with the same or another bisphosphanate.

If the patient forgot to take the alendronic acid tablet, then it should be taken the next morning. Do not take 2 tab. in one day, you must continue to take 1 tab. 1 time per week on the day that was selected 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 metabolic disorders before treatment with alendronic acid. Due to the positive effect of alendronic acid on the bone mineral density during treatment, a slight asymptomatic decrease in the concentration of calcium and phosphorus in the blood serum may be observed. There are isolated 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 stress fractures of the proximal femur with prolonged treatment with alendronic acid (from 18 months to 10 years.)

Fractures occurred after minimal injury or without it. Some patients initially had pain in the proximal part of the thigh, which persisted for several weeks or even months before this symptom ended with a fracture of the femur. Often the fractures were bilateral, so when a patient fractures one femur, it is necessary to monitor the condition of the other femur.

In patients taking alendronic acid, especially with concomitant therapy with GCS, it is extremely important to ensure sufficient intake of calcium and vitamin D in food or in the form of medications.

The absorption of bisphosphonates is significantly reduced with food intake.

For the use of alfacalcidol

Alfacalcidol may enhance hypercalcemia and / or hypercalciuria when given to patients with the disease, associated with uncontrolled hyperproduction of calcitriol (for example, with leukemia, lymphoma, sarcoidosis), and can also enhance hyperphosphatemia. With a plasma calcium concentration of 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 concentration of calcium in the blood serum normalizes (2.2-2.6 mmol / l). Monitoring the concentration of calcium and phosphates in the blood is carried out before treatment with alfacalcidol and, if necessary, corrective therapy is carried out. In the treatment with alfacalcidol, the concentration of electrolytes at the beginning is determined once a week, when Cmax is reached and during the entire treatment period, every 3-5 weeks, and alkaline phosphatase activity is monitored (in case of impaired renal function (CC more than 35 ml / min) - weekly the control). 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 kit contains alfacalcidol capsules containing sorbitol.

Effect on the ability to drive vehicles and control mechanisms

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

Composition

Tablets

Sodium alendronate monohydrate

Excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate.

Capsules

Alfacalcidol

Excipients: citric acid, propyl gallate, -tocopherol, ethanol, peanut butter, gelatin, glycerol 85%, anidrisorb 85/70 (sorbitol, sorbitan, mannitol, higher polyols, water (E) di1, titanium , black ink A10379 (shellac, iron dye black oxide, denatured ethanol (methylated alcohol), isopropanol, 1-butanol, ethyl acetate).

Dosage and administration of

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

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

Alendronic acid

Assign inside 1 tablet. (70 mg) once a week, washed down with a glass of water, at least 30 minutes before the first meal, drinks or other medicines. It is washed down with plain water only, since other drinks (including mineral water), foodstuffs and certain medicines can reduce the bioavailability of alendronic acid. Do not chew or dissolve tablets.

After taking the pill, the patient should maintain an upright position (standing or sitting) for at least 30 minutes. You can not take the pill before bedtime or before the morning rise from bed.

Elderly patients do not require dose adjustment.

In case of impaired renal function, QC> 35 ml / min dose adjustment is not required.

Alfacalcidol

Assign inside 1 capsule. (1 mcg) 1 time / day in the evening daily. Capsules should be swallowed whole with a sufficient amount of liquid.

The drug Tevabon is intended for long-term use.

Side effects

Side effects are classified according to the following frequency: very often -? 10% often -? 1%, but <10% infrequently -? 0.1%, but <1% rarely -? 0.01%, but <0.1% very rarely - <0.01%, including isolated cases.

When using alendronic acid

From the digestive system: often - abdominal pain, dyspepsia, sour belching, diarrhea, dysphagia, flatulence, gastritis, gastric ulcer, ulceration of the esophageal mucosa infrequently - nausea, vomiting, constipation, gastritis, gastritis, gastritis, esophagus, melena rarely - stricture of the esophagus, ulceration of the mucous membrane of the oropharynx, perforation of the esophagus, bleeding from the upper gastrointestinal tract (connection with alendronic acid intake 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 were noted in patients undergoing treatment for osteoporosis with an unknown frequency - proximal stress fracture of the femur, associated or not associated with trauma.

From the side of metabolism: rarely - symptomatic hypocalcemia, usually associated with predisposing conditions, hypophosphatemia.

From the side of the central nervous system: often - headache.

On the part of the sensory organs: rarely - uveitis, scleritis, episcleritis.

Allergic reactions: infrequently - rash, itching, erythema rarely - rash associated with photosensitization, urticaria, angioedema very rarely - severe skin reactions, including erythema multiforme exudative (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome).

Other: rarely, transient symptoms similar to those in the acute phase of the disease (myalgia, malaise, and fever), usually at the beginning of treatment.

When using alfacalcidol

From the side of metabolism: rarely - hypercalcemia is very rare - a slight increase in the concentration of HDL in the blood plasma. In patients with severe renal impairment, hyperphosphatemia, heterotopic calcifications in the cornea of ​​the eye and blood vessels are possible.

From the digestive system: infrequently - anorexia, vomiting, heartburn, abdominal pain, nausea, dry mouth, a feeling of 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 cardiovascular system: rarely - tachycardia.

From the musculoskeletal system: infrequently - moderate pain in the 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 the concentration of calcium in the blood serum, the use of a combination of these drugs avoids sharp fluctuations in the concentration of calcium in the serum.

Drug interaction

When taken with food, drinks containing calcium (including mineral water), food additives, antacids and other drugs for oral administration may impair absorption of alendronic acid. In this regard, the interval between taking alendronic acid and other oral drugs 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.

Intake of prednisolone is not accompanied by clinically significant changes in the bioavailability of alendronic acid.

corticosteroids increase the side effect of alendronic acid on the digestive tract.

With the simultaneous use of alfacalcidol with cardiac glycosides, the risk of developing arrhythmia increases.

Inducers of microsomal liver enzymes (including phenytoin and phenobarbital) reduce and inhibitors - increase the concentration of alfacalcidol in the plasma (a change in its effectiveness is possible).

Absorption of alfacalcidol is reduced when used together with mineral oil (for a long time), colestyramine, colestipol, sucralfate, antacids, and 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 hyperaluminemia. Retinol, tocopherol, ascorbic acid, pantothenic acid, thiamine, riboflavin weaken the toxic effect.

In perimenopausal women, the effects of alfacalcidol may be enhanced by estrogens. Calcitonin derivatives of ethidronic and pamidronic acids, plicamycin 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, due to increased absorption of calcium in the intestine, increase its reabsorption in the kidneys.

Against the background of therapy with alfacalcidol, other vitamin D drugs and its derivatives should not be prescribed because of the possible additive interaction and increased risk of developing hypercalcemia.

Overdose

Alendronic acid

Symptoms: hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis, erosive and ulcerative lesions of the gastrointestinal mucosa are possible.

Treatment: taking milk or antacid to bind alendronic acid. Due to the risk of irritation of the esophagus, vomiting should not be induced. The patient should be upright.

Alfacalcidol

Early symptoms of hypervitaminosis D (caused by hypercalcemia): diarrhea, constipation, nausea, vomiting, dry mouth, anorexia, metallic taste in the mouth, hypercalciuria, polyuria, polydipsia, pollakiuria / nicturia, weakness, mytomy, headache, bone pain.

Late symptoms of hypervitaminosis D: dizziness, confusion, drowsiness, cardiac arrhythmias, skin itching, increased blood pressure, conjunctival hyperemia, nephrolithiasis, weight loss, photophobia, pancreatitis, gastralgia rarely - changes 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: discontinue the drug. In the early stages of acute overdose, the use of mineral oil can have a positive effect (which helps to reduce absorption and increase the excretion of alfacalcidol with feces). In severe cases, hydration is carried out with the introduction of infusion saline solutions, loop diuretics, corticosteroids, bisphosphonates, calcitonin are prescribed, hemodialysis is performed using solutions with a low calcium content. It is necessary to control the content of electrolytes in the blood, kidney and heart function (according to ECG), especially in patients receiving digoxin. There is no specific antidote.

Storage Conditions

At a temperature not exceeding 25 РC.

Expiration

2.5 years

Active ingredient

Algeldrat, Benzocaine, Alfacalcidol set

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Teva Pharmaceutical Enterprises Co., Ltd. Israel