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Active ingredients
Alendronic acid
Release form
Pills
Composition
1 tab. sodium alendronate monohydrate 81.2 mg, which corresponds to the content of alendronic acid 70 mg 1 caps. Alfacalcidol 1 mcg. Excipients: citric acid - 0.
Pharmacological 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 having a direct effect on the formation of new bone tissue. Having a tropism for hydroxyapatite bone, alendronic acid accumulates mainly in the areas of its active resorption. The mechanism of action is associated with the suppression of functional activity and the stimulation of osteoclast apoptosis. During 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, the precursor of the active metabolite of vitamin D3 - calcitriol. Increases the absorption of calcium and phosphorus in the intestines, increases their reabsorption in the kidneys, restores the positive calcium balance in the treatment of calcium malabsorption, reduces the concentration of parathyroid hormone in the blood. By acting on both parts of the bone remodeling process (resorption and synthesis), alfacalcidol not only increases the mineralization of bone tissue, but also increases its elasticity by stimulating the synthesis of proteins of bone matrix, bone morphogenetic proteins, and bone growth factors. In the treatment with alfacalcidol, a bone with a normal histological structure is formed, the bone tissue strength increases in all parts of the skeleton. Alendronic acid and alfacalcidol increase bone strength, while their effects are synergistic, thanks to various mechanisms of action. Inhibition of alendronic acid catabolic processes in the bones 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 reduces the potential risk of hypocalcemia, hypercalcemia and hypercalciuria.A significant reduction in the risk of fractures is achieved not only by increasing the strength of the bone, but also due to the extra-bone (pleiotropic) effect of alfacalcidol — an increase in muscle strength, and an acceleration of the speed of the muscle response.
Pharmacokinetics
Alendronic acid: Absorption: When ingested 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 is reduced by about 60%. The plasma concentration of alendronic acid after oral administration at a therapeutic dose is below the possible detection limit (less than 5 ng / ml). Distribution: The binding of alendronic acid to plasma proteins is about 78%. Alendronic acid is distributed in the 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. Displayed unchanged. The excretion 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: Absorption: After oral administration, alfacalcidol is rapidly absorbed from the gastrointestinal tract. Cmax is achieved in 8-12 hours after a single dose of alfacalcidol. Bioavailability when administered is about 100%. Metabolism: The pharmacological effects of alfacalcidol are realized after it is converted into calcitriol in the body. The conversion of alfacalcidol to calcitriol occurs in the liver by hydroxylation at 25 carbon atoms, and the hydroxylation process occurs very quickly (wears a substrate-dependent nature) 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 renal 1-alpha hydroxylase activity (renal pathology, old age). Withdrawal: Calcitriol is excreted by the kidneys and liver in approximately equal parts, T1 / 2 is about 35 hours.
Indications
- postmenopausal osteoporosis - osteoporosis caused by the use of GCS.
Contraindications
- conditions leading to a slowdown in the movement of food through the esophagus (includingstrictures or achalasia of the esophagus) - inability of the patient to stand or sit upright for at least 30 minutes - hypocalcemia - hypercalcemia - Burnett syndrome and / or milky-alkaline syndrome (plasma calcium concentration> 2.6 mmol / l, calcium phosphate> 3.7 mmol / l , pH> 7.44) - severe renal dysfunction (CC less than 35 ml / min) - patients on hemodialysis - hypervitaminosis D - hyperphosphatemia (except for hyperphosphatemia in hypoparathyroidism) - hypermagneemia - sucrase / isomaltase deficiency, intolerance fruk oses, malabsorption of glucose / galactose - childhood - pregnancy - lactation (breast-feeding) - Hypersensitivity to alendronic acid, alfacalcidol and other ingredients. Precautions should be prescribed the drug for gastrointestinal diseases in the acute phase, including dysphagia, esophagitis, gastritis, duodenitis, gastric ulcer and duodenal ulcer with hypoparathyroidism, hypovitaminosis D, calcium malabsorption, nephrolithiasis, atherosclerosis, impaired renal function (KK more than 35 ml / min), chronic heart failure, patients, patients with renal dysfunction including with leukemia, lymphoma, sarcoidosis, pulmonary tuberculosis (active form).
Use during pregnancy and lactation
In connection with insufficient data on the use of alendronic acid and / or with the risk of an overdose of alfacalcidol, Tevabon is contraindicated during pregnancy and during breastfeeding.
Dosage and administration
The drug Tevabon consists of two dosage forms: alendronic acid pills and alfacalcidol capsules. To ensure normal absorption and reduce the risk of adverse reactions should strictly follow the recommendations for use and dosing. Alendronic acid Appoint inside on 1 tab. (70 mg) once a week with a glass of water, at least 30 minutes before the first meal, drink or other medicines. They wash down only with ordinary water, since other beverages (including mineral water), food products, and some drugs may decrease the bioavailability of alendronic acid. Tablets can not be chewed or rassasyvat.After taking the pill, the patient must maintain a vertical position (standing or sitting) for at least 30 minutes. You can not take a pill before bedtime or until the morning rise from the bed. Dose adjustment is not required to elderly patients. With impaired renal function QC> 35 ml / min dose adjustment is not required. Alfacalcidol Assign inside 1 caps. (1 mcg) 1 time per day in the evening daily. Capsules should be swallowed whole, washed down with a sufficient amount of liquid. The drug Tevabon intended for prolonged use.
Side effects
Side effects are classified according to the following frequency: very often (10%); often (1%, but less than 10%); infrequently (0.1%, but less than 1%); rarely (0.01%, but less than 0.1%); very rarely (less than 0.01%, including isolated cases). When using alendronic acid On the part of the digestive system: often - abdominal pain, dyspepsia, sour belching, diarrhea, dysphagia, flatulence, gastritis, gastric ulcer, ulceration of the mucous membrane of the esophagus; infrequently - nausea, vomiting, constipation, gastritis, esophagitis, erosion of the esophageal mucosa, melena; rarely, a stricture of the esophagus, ulceration of the mucous membrane of the oropharynx, perforation of the esophagus, bleeding from the upper GI tract (connection with the administration of alendronic acid has not been established). From the musculoskeletal system: often - pain in the bones, muscles, joints, muscle cramps; rarely, osteonecrosis of the jaw, mainly in oncological patients treated with bisphosphonates, however, similar cases were observed in patients undergoing therapy for osteoporosis; unknown frequency - stress fracture of the proximal femur, associated or not associated with injury. On the part of the metabolism: rarely - symptomatic hypocalcemia, usually associated with predisposing conditions, hypophosphatemia. From the side of the central nervous system: often - a headache. From the senses: rarely - uveitis, scleritis, episcleritis. Allergic reactions: rarely - rash, itching, erythema; rarely, photosensitization rash, 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 Metabolism: rarely - hypercalcemia; very rarely - a slight increase in the concentration of HDL in the blood plasma.In patients with severe impaired renal function, hyperphosphatemia may develop, heterotopic calcifications in the cornea and blood vessels. On the part of the digestive system: rarely - anorexia, vomiting, heartburn, abdominal pain, nausea, dry mouth, feeling of discomfort in the epigastric region, constipation, diarrhea; rarely, a slight increase in liver enzyme activity in plasma (ALT, AST). From the side of the central nervous system: rarely - weakness, fatigue, dizziness, drowsiness. Since 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 effects of alendronic acid and alfacalcidol on serum calcium concentration, the use of a combination of these drugs avoids sharp fluctuations in serum calcium concentration.
Overdose
Alendronic acid Symptoms: hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis, erosive-ulcerative lesions of the gastrointestinal tract mucosa are possible. Treatment: taking milk or antacid to bind alendronic acid. Due to the risk of irritation of the esophagus should not induce vomiting. The patient should be upright. Alfacalcidol Early hypervitaminosis symptoms 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, pain in the bones. Late symptoms of hypervitaminosis D: dizziness, confusion, drowsiness, abnormal heart rhythm, pruritus, increased blood pressure, conjunctival hyperemia, nephrolithiasis, weight loss, photophobia, pancreatitis, gastralgia; rarely - a change in psyche and mood. Symptoms of chronic intoxication with vitamin D: calcification of soft tissues, blood vessels and internal organs (kidneys, lungs), renal failure, cardiovascular insufficiency, growth disorder in children. Treatment: cancel the drug.In the early stages of acute overdose, the appointment of mineral oil may have a positive effect (which helps to reduce absorption and increase excretion of alfacalcidol with feces). In severe cases, carry out the hydration with the introduction of infusion of saline solutions, prescribed "loop" diuretics, GCS, bisphosphonates, calcitonin, conduct hemodialysis using solutions with a low calcium content. Blood levels of electrolytes, renal and cardiac function (according to ECG data) should be monitored, especially in patients receiving digoxin. There is no specific antidote.
Interaction with other drugs
When taken simultaneously with food, drinks containing calcium (including mineral water), food additives, antacids and other drugs for oral administration, absorption of alendronic acid may be impaired. 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 intake) with estrogen preparations is not accompanied by a change in their action and the development of side effects. Oral intake of prednisolone 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 increases the risk of arrhythmias. Inductors of liver microsomal enzymes (including phenytoin and phenobarbital) reduce, and inhibitors increase the concentration of alfacalcidol in plasma (possibly changing its effectiveness). The absorption of alfacalcidol is reduced when it is combined with mineral oil (for a long time), Kolestiramine, Colestipol, sucralfate, antacids, and albumin-based preparations. In this regard, do not take Alfacalcidol capsules simultaneously with antacids containing aluminum, the interval between taking these medicines should be at least 2 hours. Taking antacids increases the risk of developing hypermagneemia and hyperaluminemia. Toxic effect weaken retinol, tocopherol, ascorbic acid, pantothenic acid, thiamine, riboflavin.In women in perimenopause, the effect of alfacalcidol may be enhanced by estrogen. Calcitonin, derivatives of etidronic and pamidronic acids, plicamycin and corticosteroids 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. During therapy with alfacalcidol, it is not necessary to prescribe other drugs of vitamin D and its derivatives due to the possible additive interaction and an increased risk of hypercalcemia.
special instructions
For the use of alendronic acid. Special attention should be paid to any signs of the occurrence of adverse reactions in the esophagus. The patient should be informed about the need to discontinue the drug and see a doctor when developing dysphagia, pain when swallowing, pain behind the sternum, the appearance or strengthening of heartburn. In connection with the existing risk of irritation of the mucous membrane of the upper GI tract, as well as aggravation 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, peptic ulcer and duodenal ulcer) and also recently transferred (during the previous year) diseases of the gastrointestinal tract (peptic ulcer of the stomach and duodenum, active bleeding from the gastrointestinal tract, surgical intervention Khnemu gastrointestinal except pyloroplasty). There are reports of cases of osteonecrosis of the jaw, usually associated with tooth extraction and / or local infection (including osteomyelitis) in cancer patients receiving treatment regimens that include bisphosphonates (primarily in iv). Many of these patients also received chemotherapy and SCS. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates. Before the use of 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 dental treatment. Patients undergoing treatment with bisphosphonates should, if possible, avoid invasive dental procedures.In patients with osteonecrosis of the jaw, being treated with bisphosphonates, dental surgery can lead to deterioration. If necessary, surgical interventions should be borne in mind that data on the possibility of reducing the risk of osteonecrosis of the jaw after the abolition of bisphosphonates are not available. 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 bones, joints and muscles in patients during bisphosphonate therapy varied from 1 day to several months after the start of treatment. In the majority of patients, after the cessation of treatment, a reduction in pain was noted, in some patients, pain reappeared when therapy with the same or another bisphosphonate was resumed. If the patient has forgotten to take a pill of alendronic acid, then it should be taken the next morning. Do not take 2 tab. on one day, you must continue to take 1 tab. Once a 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 of disorders of mineral metabolism prior to the start of treatment with alendronic acid. Due to the positive effects of alendronic acid on bone mineral density during treatment, a slight asymptomatic decrease in serum calcium and phosphorus concentrations may be observed. There are isolated reports of symptomatic hypocalcemia, sometimes severe, usually in patients with a predisposition to it (for example, in 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 with or without minimal injury. Some patients first had pain in the proximal femur, which persisted for several weeks or even months before this symptom ended with 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 therapy of corticosteroids, it is extremely important to ensure adequate intake of calcium and vitamin D with food or in the form of drugs. The absorption of bisphosphonates is significantly reduced with simultaneous ingestion of food. For the use of alfacalcidol Alfacalcidol may increase hypercalcemia and / or hypercalciuria when it is prescribed to patients with a disease associated with uncontrolled calcitriol hyperproduction (for example, with leukemia, lymphoma, sarcoidosis), and may also enhance hyperphosphatemia. When plasma calcium concentration is more than 2.6 mmol / l, it is necessary to exclude the use of other calcium-containing drugs. If there is no effect, stop taking alfacalcidol capsules until normalization of serum calcium concentration (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, carry out corrective therapy. 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 the activity of alkaline phosphatase is monitored (in case of impaired renal function (CC more than 35 ml / min) - weekly control ). Peanut butter in rare cases can cause severe allergic reactions. Patients with hereditary fructose intolerance or fructose malabsorption should not be given the drug Tevabon, since the kit includes alfacalcidol capsules containing sorbitol. Impact on the ability to drive vehicles and control mechanisms In connection with 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 other potentially dangerous activities that require increased concentration and psychomotor reactions.