Pharmacodynamics
Sodium alendronate is a bisphosphonate, a synthetic analogue of pyrophosphate, which binds bone hydroxyapatite. Being a non-hormonal specific inhibitor of osteoclast activity, it prevents bone tissue resorption. Does not affect the processes of bone tissue formation. Stimulates osteogenesis, restores a positive balance between bone resorption and restoration. Progressively increases bone mineral density (regulates phosphorus-calcium metabolism), promotes the formation of bone tissue of normal composition and structure.
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
Osteoresorption blocker for osteoporosis . The active substance is a bisphosphonate, an artificial analogue of the bone hydroxyapatite- organizing .
Being a specific non-hormonal inhibitor of osteoclasts , it inhibits the resorption of bone tissue, but does not affect its formation. Stimulates osteogenesis , normalizes the positive balance of bone resorption and repair. Increases the mineral density of bone tissue, promotes the formation of its normal structure and composition.
Pharmacokinetics
After taking the drug once orally on an empty stomach in the morning, absorption reaches 0.64%; with a break between the use of the drug and food of less than 2 hours - 0.45-0.4%. However, such a weakening of absorption does not significantly affect the effect of the drug. Taking orange juice or coffee together reduces bioavailability by 60%.
The active substance first penetrates the soft tissues and then is actively incorporated into the bone tissue. Reaction with blood is 78%. Not metabolized. The substance that is not integrated into the bone is quickly excreted by the kidneys.
Pharmacokinetics
Absorption after a single dose of 35 or 70 mg in the morning on an empty stomach, 2 hours before breakfast, is 0.64%. With a shortened interval between taking the drug and food - 0.46–0.39%. Such a decrease in absorption does not significantly affect the effectiveness of the drug. Simultaneous intake of coffee or orange juice reduces bioavailability by 60%.
Distribution: after oral administration, it is temporarily distributed in soft tissues, then quickly incorporated into bone tissue. Plasma protein binding - 78%.
Metabolism: There is no data confirming the metabolism of alendronate in humans.
Excretion: Absorbed but not incorporated into bone tissue, alendronate is rapidly excreted by the kidneys. The maximum saturating capacity of bone tissue in animals could not be established with intravenous administration of a cumulative daily dose of 35 mg/kg. Although there is no evidence, decreased excretion of alendronate with increased accumulation in bone tissue is likely in kidney disease.
Pharmacological properties of the drug Ostalon
The active substance, alendronate, is a bisphosphonate (a synthetic analogue of natural pyrophosphate). By blocking the activity of osteoclasts, it prevents bone resorption by osteoclasts, does not affect the processes of bone tissue formation, the local growth of osteoclasts and interaction with the bone surface. When treated with alendronate, bone tissue of normal composition and structure is formed. Absorption after a single dose of 35 or 70 mg of the drug in the morning on an empty stomach, 2 hours before breakfast, is 0.64%. If the interval between taking the drug and food is too short (1 hour or 30 minutes), absorption is 0.46–0.39%. Such a decrease in absorption does not significantly affect the effectiveness of the drug. Simultaneous intake of coffee or orange juice reduces bioavailability by 60%. Administration of prednisone to healthy volunteers for 5 days (20 mg 3 times daily) did not affect the bioavailability of alendronate to a clinically significant extent (20–44% average increase). After oral administration, it is temporarily distributed in soft tissues, then quickly incorporated into bone tissue and excreted in the urine. Communication with blood plasma proteins is about 78%. There is no data confirming the metabolism of alendronate in humans. When administered orally, after 6 hours the plasma concentration is reduced by more than 95%. The half-life is approximately 10 years, indicating that alendronate is excreted from bone tissue. It is not excreted by either the acid or alkaline transport systems of the kidneys (alendronate probably does not affect the excretion of drugs by the above systems). Alendronate, which is absorbed but not incorporated into bone tissue, is quickly excreted in the urine. Although there is no evidence, decreased alendronate excretion with subsequent increased bone deposition may occur in kidney disease.
Contraindications
hypersensitivity to any of the components of the drug;
abnormalities of the esophagus and other factors that impede the patency of the esophagus (achalasia, stricture, etc.);
the patient’s inability to remain in an upright position, even sitting, for 30 minutes;
hypocalcemia;
chronic renal failure (Cl creatinine <35 ml/min);
pregnancy;
breastfeeding period;
childhood;
vitamin D deficiency;
severe disturbances of mineral metabolism.
With caution - diseases of the digestive tract in the acute phase (dysphagia, diseases of the esophagus, gastritis, duodenitis, ulcers, serious gastrointestinal disease in the previous 12 months, for example peptic ulcer, gastrointestinal bleeding, surgery, with the exception of operations on the spastic pylorus of the stomach).
Ostalon - alendronic acid drug for the treatment of osteoporosis
Along with this, the social significance of AP and associated bone fractures is great. This disease ranks 4th in the world among all non-infectious diseases as a cause of disability and mortality, which is determined primarily by its consequences in the form of fractures of the vertebrae and bones of the peripheral skeleton. The most severe outcomes are fractures of the proximal femur. Mortality during the first year after a fracture in various cities of Russia, according to studies, ranged from 30.8 to 35.1%, and of those who survived, 78% a year later and 65.5% after two years required constant care [7]. The main goal of osteoporosis treatment is to prevent bone fractures. Currently, the main criterion for the effectiveness of a drug used to treat AP is a reduction in the incidence of new fractures, both vertebral and non-vertebral, including fractures of the proximal femur, during a 5-year follow-up. In addition, when assessing the effectiveness of the drug, the dynamics of bone mineral density according to DXA, as well as the effect on markers of bone metabolism, including markers of bone formation and bone resorption, are assessed. Current clinical studies are examining the effect of a pharmacological agent on bone quality, including assessment of mineralization. The necessary data are obtained by conducting a histological examination of the bone biopsy. Pharmacological agents used to treat AP are different, and according to the main mechanism of action they are divided into three groups. Firstly, these are drugs that primarily suppress bone resorption (bisphosphonates, salmon calcitonin, HRT, SERM); secondly, drugs that primarily stimulate bone formation (teriparatide); thirdly, drugs with multidirectional effects (strontium ranelate, active metabolites of vitamin D). In a number of national clinical guidelines, nitro-containing bisphosphonates are considered first-line drugs for the prevention and treatment of AP. They are the drugs of choice because they have proven effectiveness in reducing the risk of fractures and an acceptable safety profile. Since the treatment of AP involves a long course of medication (3–5 years of continuous use of the drug), it is limited by the patient’s low adherence to taking medications. This requires the creation of dosage forms with convenient, preferably infrequent, administration. Bisphosphonates (BPs) are considered today as first-line drugs in the treatment of AP [8]. They are able to selectively bind to bone mineral, which is a significant advantage in the treatment of bone diseases. Early studies showed multiple effects of BF on hydroxyapatite (a bone mineral): preventing the precipitation of calcium phosphate, slowing down the transformation of amorphous hydroxyapatite into crystalline hydroxyapatite, suppressing aggregation and dissolution of crystals [9,10]. The main target cell for the action of BP is the osteoclast. During bone resorption, an acidic environment is created, which significantly increases the dissociation of BP from hydroxyapatite. The osteoclast captures BP, after which it blocks the enzyme farnesyl pyrophosphate synthase, which leads to a deterioration in osteoclast function and a decrease in bone destruction; subsequently, the osteoclast undergoes apoptosis [9]. In addition, there is evidence of the ability of BP to increase osteocyte survival, which helps reduce the frequency of activation and prevent bone loss in postmenopausal women [11]. Thus, the pathogenetic mechanism of action determines the high efficiency of nitrogen-containing BPs. Alendronic acid is the most studied BP, registered for the treatment of postmenopausal osteoporosis since 1995. In order to prove the effectiveness of this drug as a treatment for osteoporosis, several large randomized, double-blind, multicenter, placebo-controlled studies were conducted over a period of 3–5 years. The largest was the FOSIT study, which included 34 countries and 1908 postmenopausal women with AP who received daily therapy for 12 months. 10 mg alendronate, and the FIT study (11 US centers and 2027 postmenopausal women receiving 5 mg and 10 mg alendronate for 3 years). Alendronate has been shown to be clinically effective in preventing bone loss when taken at a prophylactic dose of 5 mg daily in postmenopausal women without AP [12], as well as increasing bone mineral density (BMD) at doses of 5 and 10 mg in patients suffering from postmenopausal AP. [13,14]. Alendronic acid significantly reduces the risk of vertebral fractures [13,14] and non-vertebral fractures [14] in women with and without a history of AP and fractures [15]. Effectiveness against fractures is maintained even in women at very high risk (patients with severe bone loss or older women) [16]. The large clinical trial FIT (Fracture Intervention Trial) showed an improvement in quality of life in patients receiving alendronate due to a decrease in the number of days spent in bed and days with limited physical activity [17]. Most clinical studies evaluate the drug's effectiveness in reducing the risk of fractures over 3 to 4 years, but patients receiving alendronic acid were followed for 10 years or more. Treatment contributed to an increase in BMD during the entire period of drug administration (+13.7% in the lumbar spine and 6.7% in the hip) [18]. In patients who stopped treatment, BMD gradually decreased. However, in patients who took alendronic acid continuously for 5 years and then stopped treatment, the decrease in markers of bone breakdown persisted for another 5 years, and in only a quarter of the patients, markers of bone turnover increased slightly 1 year after discontinuation, and these changes corresponded to the decrease IPC [19]. However, no statistically significant differences in the risk of new fractures were found between the groups of patients receiving alendronic acid for 10 years and only for 5 years with an additional 5 years of follow-up. A histological study of bone biopsies from patients taking alendronate for 10 years revealed suppression of bone turnover without signs of impaired bone mineralization [20]. At the same time, certain difficulties in taking the drug (you must take the tablet strictly on an empty stomach, wash it down with a full glass of water, do not eat for 30 minutes and be in an upright position) led to a rather low adherence of patients to treatment and the development of side effects from the gastrointestinal tract. This served as an incentive for further research and the creation of a modern dosage form of the drug - 70 mg tablets taken once a week. The use of alendronic acid at the above dose was as effective in increasing BMD as the previously tested dosage of 10 mg 1 time/day. [21]. Thus, the effectiveness of alendronic acid at a dose of 70 mg once a week corresponds to a daily intake of 10 mg of alendronic acid. However, the range of indications for the use of alendronic acid is much wider. Controlled clinical studies of the effectiveness of the drug in men and in patients with glucocorticoid AP were conducted. There is also evidence of the effectiveness of alendronic acid at a dose of 35 mg to increase BMD in postmenopausal women with AP and subclinical thyrotoxicosis while achieving euthyroidism [22]. Studies with a half dose of the drug (35 mg) showed its effectiveness in increasing BMD in postmenopausal women with osteopenia [23]. According to the results of studies conducted in men with a T-score of -2.0 SD or lower in the femoral neck and the presence of low-traumatic fractures, taking alendronate for 24 months. led to an increase in BMD in the lumbar spine by 7.1% compared to 1.8% in the group of patients receiving only calcium and vitamin D. In addition, its use reduced the risk of vertebral fractures determined by X-ray morphometry of the spine [8,24 ]. Moreover, the effectiveness of alendronate therapy did not depend on the level of sex hormones. Similar data were obtained when comparing the effectiveness of alendronate and alfacalcidol in an open 3-year study [25]. Alendronate is effective in both men and women for the prevention and treatment of glucocorticoid osteoporosis, both in terms of increasing BMD and reducing the risk of fractures. The principal evidence for the effectiveness of alendronate comes from a randomized, placebo-controlled clinical trial in which men and women (n=477) received either newly prescribed glucocorticoids (34% of patients) or glucocorticosteroid therapy lasting more than 4 months. (66% of patients) were followed up for more than 48 weeks. Positive effects of treatment for 12 months. on BMD were statistically significant in the lumbar spine and femoral neck. It was noted that in the alendronate group, fewer new vertebral fractures occurred during the observation period than in the placebo group (2.3 and 3.7%, respectively, p>0.05). Follow-up of 208 patients demonstrated the effectiveness of alendronate therapy during the second year and demonstrated a significant reduction in the number of new vertebral fractures in the alendronate group (0.7%) compared with the placebo group (6.8%; p = 0.026) [8, 26]. Contraindications for alendronate therapy include hypersensitivity to the drug, hypocalcemia, and the presence of esophageal diseases (for example, achalasia or stricture). A 3-month study assessed the safety of alendronate (70 mg/week) compared with placebo in patients taking concomitant NSAID therapy. The incidence of upper gastrointestinal adverse events was similar in both groups (9.3 and 10.8%, respectively, p = 0.744) [27]. Alendronate is relatively contraindicated in patients with acute diseases of the upper gastrointestinal tract, and the incidence of side effects is significantly lower when using 70 mg of the drug once a week. Hypocalcemia and other disorders of mineral metabolism should be corrected before treatment with alendronate. In patients with mild to moderate renal failure (with creatinine clearance above 35 ml/min.), no dose adjustment is required, if clearance decreases below 35 ml/min. the drug should be prescribed with caution [28]. Alendronate should be taken 30 minutes before. before meals or 2 hours after breakfast, with a full glass of plain water. It is necessary to maintain an upright body position for half an hour after administration to prevent gastroesophageal reflux, which can lead to esophagitis. Therefore, prescribing alendronate to patients on bed rest is inappropriate. Taking alendronate should not be combined with other medications. Thus, according to Russian clinical guidelines for AP [8], the following has been proven for alendronate. 1. Alendronate, along with other nitrogen-containing bisphosphonates, is a first-line drug for the treatment of women with postmenopausal osteoporosis (A). 2. Nitrogen-containing bisphosphonates are prescribed for 3–5 years, but women at high risk of fractures should continue treatment beyond 5 years (B). 3. For postmenopausal women, alendronate can be prescribed at half the dose (70 mg once every 2 weeks) to prevent primary osteoporosis (D). 4. Along with bisphosphonates, it is necessary to prescribe a constant intake of calcium 500–1000 mg per day (with food or additionally) and vitamin D 800 IU per day (A). The drug Ostalon®, which is alendronate sodium trihydrate, produced in Hungary, is currently registered in Russia. One tablet of Ostalon® contains 70 mg of alendronic acid for administration once a week, a package of Ostalon® contains 4 tablets and is designed for a month of treatment. A post-marketing phase IV study, which included 3789 women and 464 men from 294 centers in Hungary, to study the effectiveness and tolerability of Ostalon® for 12 months. therapy for patients with AP demonstrated a positive effect on BMD of the spine and proximal femur in both women and men. Thus, in 72% of patients, the increase in BMD in the spine was more than 5%, and only 2.83% of people had a decrease in BMD by more than 5%. During treatment with Ostalon®, men showed a significant decrease in the level of bone-specific alkaline phosphatase, a marker of bone formation, and a more significant decrease in the level of type I collagen C-telopeptide, a marker of bone resorption. Ostalon® was well tolerated. Registered adverse events associated with the effect on the gastrointestinal tract (loss of appetite, flatulence, abdominal discomfort and pain, gastritis, esophagitis, stomach ulcers, heartburn) were quite rare. When surveyed after 6 and 12 months. treatment, 88.3 and 77.1% of people, respectively, noted the tolerability of the drug as excellent and only 0.7 and 0.2%, respectively, as poor [29]. Thus, the study showed that the alendronic acid drug Ostalon® is bioequivalent to the original drug and can be used in daily clinical practice. Literature 1. Mikhailov E.E., Benevolenskaya L.I., Mylov N.M. Prevalence of spinal fractures in a population sample of people 50 years and older // Bulletin of Traumatology and Orthopedics named after. N.N. Priorova, 1997; No. 3: 20–27. 2. Komissarov A.N., Palshin G.A., Rodionova S.S. Frequency of fractures of the proximal femur among residents of the city of Yakutsk. // Osteoporosis and osteopathy, 2004; No. 1: 2–3. 3. Ahmed AIH, Blake GM, Rymer JM, Fogelman I. Screening for osteopenia and osteoporosis: Do accepted normal ranges lead too overdiagnosis? // Osteoporosis Int. 1997; 7:432–438. 4. Bauer DC, Gluer CC, Cauley JA, et al. Broadband ultrasound attention predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group.// Arch .Inter. Med. 1997; 157:629–634. 5. Ahmed AIH, Blake GM, Rymer JM, Fogelman I. Screening for osteopenia and osteoporosis: Do accepted normal ranges lead too overdiagnosis? // Osteoporosis Int. 1997; 7:432–438. 6. Bauer DC, Gluer CC, Cauley JA, et al. Broadband ultrasound attention predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group.// Arch .Inter. Med. 1997; 157:629–634. 7. Menshikova L.V., Khramtsova N.A., Ershova O.B., Lesnyak O.M., Kuzmina L.I., Anikin S.G., Mikhailov E.E., Benevolenskaya L.I., Otteva E.N. Short-term and long-term outcomes of fractures of the proximal femur in elderly people and their medical and social consequences (according to a multicenter study). // Osteoporosis and osteopathy, 2002; No. 1: 8–11. 8. Lesnyak O.M., Benevolenskaya L.I. (ed). Osteoporosis. Diagnosis, prevention and treatment. M.: GEOTAR-Media, 2008. – 270 pp. 9. Russell RGG, Watts NB, Ebetino FH, Rogers MJ.: Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. // Osteoporosis International, 2008 , Vol. 19, pp. 733–759. 10. Belaya Zh.E., Rozhinskaya L.Ya., Sosunova N.V. The role of risk factors in diagnosing osteoporosis and making decisions about prescribing therapy. The effectiveness of bisphosphonates in the treatment of osteoporosis.// RMZh., 2009, 17, no. 10. 11. Plotkin LI, Manolagas SC, Bellido T.: Dissociation of the pro–apoptotic effects of bisphosphonates on osteoclast from their anti–apoptotic effects on osteoblasts/ osteocytes with novel analogs.// J. Bone, 2006, Vol. 39, pp. 443–452. 12. McClung M, et.al.: Alendronate prevents postmenopausal bone loss in women without osteoporosis. // Annual Internal Medicine, 1998, Vol. 128, pp. 253–261. 13. Liberman UA, et.al.: Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. // New England J. Medicine, 1995, Vol. 333, pp. 1437–1443. 14. Black DM, et al.: Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures.// J. Lancet, 1996, Vol. 348, pp. 1535–1541. 15. Cummings SR, et.al.: Effect of alendronate on the risk of fracture in women with low bone mineral density but without vertebral fractures.// JAMA, 1998, Vol. 208, pp. 2077–2082. 16. Ensrud KE, et.al.: Treatment with alendronate prevents fractures in women at highest risk. // Arch Int Med, 1997, Vol. 157, pp. 2617–2624. 17. Nevitt MC, et al.: Effect of alendronate on limited–activity days and bed–disability days caused by back pain in postmenopausal women with existing vertebral fractures// J. Arch Int Med, 2000, Vol. 160, pp. 77–85. 18. Bone HG, et.al.: Ten years of experience with alendronate for osteoporosis in postmenopausal women. // New England J. Medicine, 2004, Vol. 350, pp. 1189–1199. 19. Bauer DC, et.al.: Increased bone turnover after discontinuing alendronate predicts bone loss over 5 years, the FLEX study. // J Bone Mineral Research, 2005, Vol. 20, suppl. 1, s 95. 20. Recker RR, et.al.: Normal bone histomorphometry and 3D microarchitecture after 10 years of alendronate treatment of postmenopausal women. // J. Bone Mineral Res, 19 Suppl 1, s 45. 21. Rizzoli R , et.al.: Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis.// J. Bone Miner. Res., 2002, Vol. 17, pp. 1988–1996. 22. Belaya Zh.E., Rozhinskaya L.Ya., Kolesnikova G.S., Ilyin A.V., Sazonova N.I., Chernova T.O., Alekseeva T.M., Dorofeeva O.K., Goldman E.I., Pimenova S.I., Melnichenko G.A.: Experience with the use of a prophylactic dose of alendronate (Fosamax 35 mg) for the treatment of osteoporosis in postmenopausal women with subclinical thyrotoxicosis J. Osteoporosis and Osteopathy, 2007, No. 1, pp. 12–19. 23. Luckey MM, Gilchrist N, Bone HG, Davie MW, de Villiers TJ, Wu M, Daifotis AG, Santora AC, Orloff JJ.: Therapeutic equivalence of alendronate 35 milligrams once weekly and 5 milligrams daily in the prevention of postmenopausal osteoporosis Obstet Gynecol. 2003 101:711–21. 24. Olszynski WP, Davison KS, Ioannidis G et al. Effectiveness of alendronate and etidronate in the treatment of osteoporosis in men: a prospective observational study. Osteoporos Int. 2006;17(2):217–24. 25. Ringe JD, Dorst A., Faber H., Ibach K. Alendronate treatment of established primary osteoporosis in men: 3–year results of a prospective? Comparative? Two-arm study. Rheumatol Int 2004;24:110–113. 26. Adachi JD, Saag KG, Delmas PD, Liberman UA, Emkey RD, Seeman E. Two–year effects of alendronate on bone mineral density and vertebral frac¬ture in patients receiving glucocorticoids: a randomized, double–blind, placebo–controlled extension trial. Arthritis Rheum 2001;44:202–11. 27. Cryer B, Miller P, Petruschke RA, Chen E, Geba GP, Papp AE. Upper gastrointestinal tolerance of once weekly alendronate 70 mg with concomitant non–steroidal anti–inflammatory drug use. Aliment Pharmacol Ther. 2005 Mar 1;21(5):599–607. 28. American association of endocrinologists (AACE) medical guidelines for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003 // Endocrine Practice, 2003, vol. 9, No. 6, p. 544–564 29. Geza B. Vizsgalatok a genericus alendronat natriummal, a Sedronnal. Praxis 2008;17:731–741.
Side effects
The following side effects are possible:
Often (≥1/100, <1/10):
from the digestive system: abdominal pain, dyspepsia, constipation, diarrhea, flatulence, esophageal ulcer, dysphagia, bloating, heartburn;
from the musculoskeletal system: ossalgia, arthralgia, myalgia;
from the nervous system: headache, irritability.
Sometimes (≥1/1000, <1/100):
general: itching, rash, skin hyperemia;
from the digestive system: nausea, vomiting, gastritis, esophagitis, esophageal erosion, melena.
Rarely (≥1/10000, <1/1000):
general: allergic reactions (urticaria, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis); transient symptoms resembling the acute reaction phase (myalgia, weakness, poor health, rarely high body temperature) most often develop at the beginning of treatment; rash; photosensitivity; hypocalcemia;
from the digestive system: narrowing of the esophagus, oropharyngeal ulcer, perforation of the upper gastrointestinal tract, ulcer, bleeding (however, the connection with treatment is not always clear);
from the senses: uveitis, scleritis;
laboratory indicators: temporary, mild asymptomatic hypocalcemia and hypophosphatemia.
Analogs
Level 4 ATC code matches:
Tevanat
Alendronic acid
Rizendros
Zolerix
Aklasta
Forosa
Bonviva
Xydiphone
Zometa
Ibandronic acid
Fosamax
Alendronate
Alendronat, Alendrokern, Alendronat Pliva, Lindron, Alenthal, Ostealen, Strongos, Osterepar, Forosa, Tevanat, Fosamax.
Interaction
Calcium, antacids, some oral medications, food, drinks, incl. mineral waters affect the absorption of alendronate; The drug can be taken orally no earlier than 1 hour after taking alendronate.
Other interactions, with the exception of changes in absorption, are unlikely.
Ranitidine increases bioavailability (clinical significance unknown).
NSAIDs increase the adverse effects of alendronic acid.
No specific studies on drug interactions were conducted, however, studies with alendronate included patients who were simultaneously taking other oral drugs.
At the same time, they did not experience any side effects associated with the simultaneous use of other drugs.
Drug interactions Ostalon
Calcium preparations, antacids, food, drinks, including mineral waters affect the absorption of alendronate, so they can be taken orally no earlier than half an hour after taking it. Other interactions, with the exception of changes in absorption, are unlikely. No specific drug interaction studies have been conducted, but trials with alendronate included patients taking other oral medications at the same time. There were no side effects associated with the simultaneous use of other drugs.
Directions for use and doses
Inside. The recommended dose is 70 mg once a week. To ensure optimal absorption, the drug should be taken in the morning on an empty stomach, 2 hours (at least 30 minutes) before the first meal or liquid, washed down with plain drinking water. Other drinks, incl. mineral waters, food, and a number of drugs can impair the absorption of alendronate.
To avoid local irritation of the oral mucosa and esophagus in the morning, immediately after getting out of bed, you should drink at least 200 ml of plain water, then take the tablet without chewing or allowing it to dissolve in the mouth; for the next 30 minutes you should not take a horizontal position , after this period you should take breakfast. You should not take the pill in the morning, before getting out of bed, or in the evening, after going to bed.
Treatment with alendronate should be supplemented with calcium and vitamin D.
Elderly patients: no dose adjustment is required.
Renal impairment: If renal filtration is >35 mL/min, no dose adjustment is required; in more severe stages of renal failure, prescribing the drug is not recommended due to the lack of clinical experience.
Children's age: due to the lack of clinical data, the drug is not prescribed to children.
Ostalon® calcium-d
For alendronic acid
To reduce the irritating effect on the esophagus, it should be taken immediately after getting up in the morning with a full glass of water; after taking it, you should not lie down for 30 minutes (it is dangerous to use if the patient is unable to stand or sit straight for 30 minutes). Taking before bed or in a horizontal position increases the risk of developing esophagitis.
In patients with hypocalcemia, before starting treatment with alendronic acid, it is necessary to carry out corrective therapy for disorders of mineral metabolism, incl. hypovitaminosis D and hypoparathyroidism.
During treatment, due to the positive effect of alendronic acid on bone mineral density, a slight asymptomatic decrease in the concentration of calcium and phosphate in the blood serum may be observed. When taking bisphosphonates (especially with concomitant therapy with corticosteroids), it is necessary to ensure adequate intake of calcium and vitamin D from food or in the form of medications.
There are reports of osteonecrosis of the jaw, usually associated with tooth extraction and/or local infection (including osteomyelitis) in cancer patients treated primarily with IV bisphosphonates. Many of these patients also received chemotherapy and corticosteroids. There have also been reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral bisphosphonates.
Before prescribing bisphosphonate therapy, patients with associated risk factors (eg, cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene) should undergo a dental examination with appropriate preventive dental treatment.
Patients being treated with bisphosphonates should avoid invasive dental procedures whenever possible. In patients on bisphosphonate therapy who have developed osteonecrosis of the jaw, dental surgery may worsen the condition. If surgical interventions are necessary, it should be taken into account that there is no data on the possibility of reducing the risk of developing osteonecrosis of the jaw after discontinuation of a bisphosphonate.
For the combination of colecalciferol + calcium carbonate
To avoid overdose, additional vitamin D intake from other sources must be taken into account.
Eating foods containing oxalates (sorrel, spinach) and phytin (cereals) reduces calcium absorption, so you should not take colecalciferol + calcium carbonate within 2 hours after eating sorrel, spinach, cereals.
Impact on the ability to drive vehicles and operate machinery
There have been no reports of adverse effects of drugs on the ability to drive vehicles or engage in other activities that require concentration and speed of psychomotor reactions.
special instructions
Alendronate may cause local irritation of the gastrointestinal mucosa. The course of diseases of the upper tract may worsen during treatment with alendronate.
There are known cases of adverse reactions from the esophagus (esophagitis, ulcer or erosion of the esophagus), sometimes severe, requiring hospital treatment, and complicated by the formation of a stricture. Patients should especially pay attention to the fact that if signs of esophageal irritation appear (dysphagia, chest pain when swallowing, the appearance or worsening of heartburn attacks), the drug should be stopped and consult a doctor. The risk of esophageal damage is higher in patients who do not comply with the rules for taking the drug, or who continue treatment despite the appearance of signs of esophageal irritation. It is extremely important to promptly inform patients about the importance of following the rules for taking the drug and make sure that the patient understands this.
Patients should be warned that if they miss another dose of the drug, the missed tablet should be taken the next morning; In no case should you take 2 tablets. one day.
Treatment can begin only after elimination of hypocalcemia, disorders of mineral and vitamin metabolism (for example, vitamin D deficiency). Taking alendronate leads to an increase in the content of mineral salts in bone tissue, a process that may be accompanied by asymptomatic changes in the levels of calcium and phosphorus. Ensuring adequate calcium and vitamin D intake is especially important when treating a patient with GCS.
Treatment should be combined with a diet enriched with calcium salts.
The drug does not affect the ability to drive a car and perform work associated with a high risk of injury, however, in the presence of adverse reactions from the organ of vision, driving a car and operating machinery is contraindicated until the adverse reactions completely disappear.
Instructions for use OSTALON
Ostalon may cause local irritation of the mucous membrane of the upper gastrointestinal tract. Due to the possibility of worsening the condition, the drug should be used with caution in patients with exacerbations of gastrointestinal diseases, such as dysphagia, esophageal diseases, gastritis, duodenitis, ulcers, as well as in patients who have recently (within the previous year) suffered severe gastrointestinal diseases, for example, peptic ulcer, gastrointestinal bleeding, upper gastrointestinal surgery other than pyloroplasty.
Esophageal reactions (sometimes severe, requiring hospitalization) such as esophagitis, ulcers and erosions of the esophagus, in rare cases complicated by esophageal strictures, have been reported in patients taking alendronate. Therefore, doctors should pay attention to the appearance of the first signs of possible complications from the esophagus in the patient. Patients should be taught that if they experience signs of esophageal irritation (dysphagia, pain when swallowing, chest pain, new or worsening heartburn), they should immediately stop taking the drug and seek medical help.
The risk of developing severe complications from the esophagus is higher in patients who neglect the recommendations for taking alendronate, as well as in those who continue to take the drug despite symptoms of esophageal irritation. It is very important that complete information on dosing and methods of taking the drug is accessible and understandable to patients. Patients should be informed that non-compliance with recommendations for use of the drug may increase the risk of complications from the esophagus.
Although large (post-marketing) clinical studies did not show an increase in risk, patients during drug therapy in rare cases experienced the development of gastric and duodenal ulcers, incl. severe forms and complications. It is not possible to exclude a causal relationship with the drug.
In patients with cancer who received treatment regimens containing IV bisphosphonates, cases of osteonecrosis of the jaw, more often associated with tooth extraction and/or local infection (including osteomyelitis), have been reported. A large number of these patients also received chemotherapy and corticosteroids. Cases of osteonecrosis of the jaw have also been observed in patients with osteoporosis receiving oral bisphosphonates.
Before starting bisphosphonate therapy, patients at risk (cancer patients receiving chemotherapy, radiation therapy, corticosteroids, patients with poor oral hygiene) should be examined by a dentist and the oral cavity should be sanitized.
During treatment with the drug, invasive dental interventions should be avoided if possible. In patients with osteonecrosis of the jaw, dental surgery may worsen the condition during treatment with bisphosphonates. For patients requiring dental care, it is unclear whether early discontinuation of bisphosphonate therapy reduces the risk of osteonecrosis of the jaw.
Therapeutic tactics should be determined for each individual patient, based on an individual assessment of the risk/benefit profile.
Pain in bones, joints and/or muscles has been described in patients taking bisphosphonates. In post-marketing studies, these symptoms were rarely severe and/or reduced the ability of patients to work. The time of onset of symptoms varied from one day to several months from the start of treatment. After discontinuation of the drug, in most cases, the undesirable effects were stopped. In some patients, after resuming the drug or replacing it with another bisphosphonate, a return of the described symptoms was noted.
Long-term use of alendronate may result in the development of atypical stress fractures of the proximal femoral diaphysis.
Patients should be instructed that if a dose of Ostalon is missed, they should take one tablet of the drug in the morning after they remembered the omission. You should not take two tablets of the drug in one day; You must return to your weekly dose of the drug on the day you have chosen.
Alendronate is not recommended for use in patients with renal failure and GFR less than 35 ml/min.
Causes of osteoporosis other than estrogen deficiency and age-related changes should always be considered.
Correction of hypocalcemia is necessary before starting alendronate treatment. In addition, correction of other conditions in which there are disturbances in mineral metabolism (for example, vitamin D deficiency and hypoparathyroidism) is required. In this category of patients, during treatment with Ostalon, close monitoring of serum calcium levels and symptoms of hypocalcemia is necessary.
Due to increased bone mineralization, patients may experience decreased serum calcium and phosphorus while taking alendronate. Usually this decrease is unexpressed and clinically insignificant, although in rare cases, especially in patients with predisposing factors (hypoparathyroidism, vitamin B deficiency, calcium malabsorption), severe hypocalcemia has been observed.
It is extremely important for patients receiving corticosteroids to ensure adequate intake of calcium and vitamin D.
Impact on the ability to drive vehicles and operate machinery
There was no effect of the drug on the ability to drive a car or use other mechanical means.
Experimental results
In preclinical studies for chronic toxicity, genotoxicity and carcinogenicity, no specific risk to the human body was identified.