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.
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).
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.
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.
