Fosamax, 4 pcs., 70 mg, tablets
Fosamax, like other bisphosphonates, can cause local irritation of the mucous membrane of the upper gastrointestinal tract. Patients treated with Fosamax have experienced adverse reactions such as esophagitis, esophageal ulcers and esophageal erosions, rarely leading to esophageal strictures or perforation. In some cases, these adverse events can be severe and require hospitalization, so you should be especially careful to monitor any symptoms indicating possible problems with the esophagus. Patients should be warned to stop taking Fosamax and consult a doctor if dysphagia, pain when swallowing or behind the breastbone, or heartburn develops or worsens.
The risk of severe esophageal adverse events is higher in patients who do not follow the drug dosage recommendations and/or continue to take the drug when symptoms of esophageal irritation occur. It is especially important that the patient has recommendations for taking the drug, understands them, and is informed that the risk of developing damage to the esophagus increases if these recommendations are not followed.
There are rare cases of stomach and duodenal ulcers, sometimes severe and complicated (a cause-and-effect relationship with taking the drug has not been established).
Fosamax should be prescribed with caution to patients with exacerbations of diseases of the upper gastrointestinal tract, such as dysphagia, diseases of the esophagus, gastritis, duodenitis and ulcers due to the possible irritant effect of the drug on the mucous membrane of the upper gastrointestinal tract and worsening of the underlying disease.
There are cases of localized osteonecrosis of the jaw, associated mainly with previous tooth extraction and/or local infection (including osteomyelitis), often with slow recovery.
In most cases, bisphosphonate-associated osteonecrosis of the jaw occurs in cancer patients receiving IV bisphosphonates. Known risk factors for osteonecrosis of the jaw include cancer, concomitant therapies (eg, chemotherapy, radiation therapy, corticosteroids), poor oral hygiene and comorbidities (eg, periodontal and/or other dental diseases, anemia, coagulopathy, infection), and smoking. Patients who develop osteonecrosis of the jaw should receive specialized medical care from an oral and maxillofacial surgeon, and discontinuation of bisphosphonate therapy should be considered based on an individual assessment of the risk/benefit ratio. Dental surgery may worsen the condition. The management of any patient requiring invasive dental procedures (eg, tooth extraction, implantation), including bisphosphonate therapy, should be based on the clinical judgment of the treating physician and/or oral surgeon and an individualized risk/benefit assessment.
Bone, joint and/or muscle pain has been reported in patients receiving bisphosphonates. These symptoms are rarely severe and/or disabling. The time until symptoms appear varies from one day to several months from the start of therapy. In most patients, symptoms subside when therapy is stopped, but in some patients, symptoms reappear when the same drug or another bisphosphonate is restarted.
Pathologic (ie, low-force or spontaneous) subtrochanteric or proximal femoral shaft fractures have been reported in a small number of patients taking bisphosphonates. Some of the fractures were classified as stress fractures (also known as stress fractures, marching fractures, and Deutschlander fractures), which occur in the absence of trauma. Some patients have experienced prodromal pain in the affected area for weeks or months before the onset of a complete fracture, often associated with the characteristic radiographic appearance of a stress fracture. The number of reports has been very small, and stress fractures with similar clinical features occur in patients not taking bisphosphonates. Patients with stress fractures should be evaluated for known causes and risk factors (eg, vitamin D deficiency, malabsorption, corticosteroid use, history of stress fracture, arthritis or lower extremity fracture, excessive or increased exercise, diabetes mellitus, chronic alcoholism) and provide they receive proper orthopedic care. Pending evaluation results, consideration should be given to stopping bisphosphonates in patients with stress fractures based on a case-by-case assessment of the benefit/risk ratio.
Patients should be warned that if they accidentally miss a dose of Fosamax once a week, they should take one tablet in the morning of the next day. You should not take two doses on the same day, but subsequently you should return to taking the drug once a week on the day of the week that was chosen at the beginning of treatment.
Causes of osteoporosis other than estrogen deficiency, age, and glucocorticoid treatment should be considered.
In the presence of hypocalcemia, the level of calcium in the blood must be normalized before starting treatment with Fosamax. Other disorders of mineral metabolism (for example, vitamin D deficiency) should also be corrected. In patients with these disorders, it is necessary to monitor blood calcium levels and symptoms of hypocalcemia.
Because Fosamax increases bone mineral content, a small asymptomatic decrease in serum calcium and phosphate levels may occur, especially in Paget's disease of bone, with an initially significantly increased bone turnover rate, and in patients receiving glucocorticoids, which is accompanied by a possible decrease in absorption calcium. It is especially important to ensure adequate calcium and vitamin D intake in these patients.
In rare cases, hypocalcemia can be severe, usually in patients with a predisposition to this complication (hypoparathyroidism, vitamin D deficiency, calcium malabsorption).
Use in pediatrics
Fosamax has not been studied in children, so the drug should not be used in pediatrics.
Impact on the ability to drive vehicles and operate machinery
There is no evidence that Fosamax affects the ability to drive or operate machines.
Features of the use of bisphosphonates for osteoporosis
Bisphosphonates (bisphosphonates or diphosphonates) are pharmacological drugs that prevent bone loss and are used to treat osteoporosis and other related diseases.
Bisphosphonates have been known in pharmacology since the mid-19th century. Initially they were used to soften water in irrigation systems (agriculture). The main property of these substances, preventing the dissolution of hydroxyapatite (the main mineral that makes up bone tissue) and, consequently, slowing down the decline in bone mass, has attracted the attention of pharmacologists.
Only in 1990, the first drug based on bisphosphonates was introduced, which became firmly established in the complex of therapeutic treatment of diseases associated with bone loss. This group of drugs can be effectively used for deforming osteitis (Paget's disease), for metastases of bone tissue (due to hypercalcemia or without it), for multiple myeloma, for osteoporosis, for primary hyperparathyroidism, for osteogenesis imperfecta, etc. All of these diseases are characterized by fragility of bones and high risk of fractures.
Mechanism of action of bisphosphonate drugs
Bone tissue has the property of constantly being renewed and restored. The balance of bone structures is maintained with the help of osteoblasts, responsible for the formation of bone tissue, and osteoclasts, responsible for the destruction of bones. Bisphosphonate drugs inhibit the action of osteoclasts, thereby preventing the destruction of bone tissue, and in some cases trigger their self-destruction.
The mechanisms of action of bisphosphonates are based on their structural similarity to natural substances - pyrophosphates. They are part of the bone matrix and are active inhibitors of enzymes that utilize (naturally destroy) pyrophosphates. These substances bind to hydroxyapatite particles of bones, reducing their fragility, and lower the level of hydroxyproline and alkaline phosphatase in the blood.
Two phosphate molecules combine with calcium ions to accumulate in the layers of bone tissue and are then destroyed by osteoclasts. It is these pharmacological properties of bisphosphonates and the inhibition (suppression) of osteoblasts that underlie the slowdown in the destruction and fragility of skeletal bones. Moreover, some types of these compounds can reduce the synthesis of mevalonate, which acts as the basis for the formation of osteoblasts, and reduce the content of geranyl diphosphate, which is involved in the synthesis of certain protein compounds of osteoclasts.
A number of studies have confirmed the advisability of using bisphosphonates in the treatment of tumor diseases of varying quality. Thus, bisphosphonates inhibit the process of fusion of tumor cells with the bone matrix, thereby preventing the formation of metastases.
The high analgesic qualities of the drugs have also been clinically confirmed, and they are now actively used in the complex treatment of bone fractures caused by osteoporosis or other similar diseases. For example, bisphosphonates helped more than 50% of patients reduce back pain due to compression fractures of the spine, and completely relieve pain in 18%.
In some cases, drugs are prescribed to relieve pain and to treat spinal diseases such as herniated intervertebral discs, protrusion of intervertebral discs, etc.
Types of bisphosphonate drugs
To date, pharmacology has already developed the third generation of bisphosphonate drugs, but has not completely abandoned the use of the previous ones. All drugs based on bisphosphonates can be divided into two groups: nitrogen-containing and nitrogen-free compounds. They have different mechanisms of action on osteoclast cells during their destruction.
Nitrogen containing:
- Zoledronic acid (zoledronate) is a third generation bisphosphonate. It selectively affects bone tissue, suppressing the activity of osteoclasts, therefore it is widely used to treat osteoporosis. At the same time, no undesirable effects of the drug on the formation of the molecular lattice of bone structures, as well as on their mineralization or load-mechanical properties of bones were detected. The selective effect of the drug on the bone structure is based on its ultra-high affinity for the natural mineralized bone lattice, which ensures inhibition of osteoclasts. It has unique antitumor properties and prevents the formation of bone metastases.
- Ibandronate acid is a third generation bisphosphonate. It has been successfully used for therapeutic treatment and preventive measures in postmenopausal women susceptible to osteoporosis. The drug has also been approved for daily use by postmenopausal women as hormone replacement therapy with sex hormones. Men are not recommended to take the drug unless clinical studies are conducted. Ibandronate may be used to treat hypercalcemia (high levels of calcium in the blood).
- Alendronate sodium is the second generation of drugs. Non-hormonal specific corrector of bone tissue metabolism. By destroying osteoclasts, it inhibits osteoclastic bone resorption and effectively restores the structure and properties of bone tissue. It has a positive effect on the natural balance of destruction and restoration, regulates the process of restoring bone mineral density, and stimulates the formation of correct bone histology. Indicated for osteoporosis in women and men, Paget's disease.
- Sodium ibandronate (Boniva, Bonviva, Bondronate) is a third-generation drug. A nitrogen-containing drug that suppresses the activity of osteoclasts does not affect their number. While reducing the destruction of bone tissue, it does not have a direct effect on the formation of bone cells. Prescribed to postmenopausal women, which allows you to quickly increase the level of bone mass to the level characteristic of reproductive age. At the same time, normalization of the mineral density of skeletal bones is observed. Prescribed for postmenopausal osteoporosis to prevent bone fractures.
Nitrogen-free bisphosphonates:
- Sodium etidronate (didronel) is a first-generation bisphosphonate. Activates the restoration of bone tissue. It has a beneficial effect on the mineralization of bone tissue in postmenopausal women diagnosed with osteoporosis. Also prescribed for the treatment of Paget's disease, pathological ossification of the spinal column with spinal cord deformation, hypercalcemia.
- Clodronate (Bonefos, Loron) is the first generation of drugs. Prevents osteolysis and the development of hypercalcemia. Forming complex compounds with bone hydroxyapatite, it changes the crystal lattice and prevents the rupture of phosphate and calcium molecules. Effectively relieves pain in bone tissue metastases, slows their progression, and prevents the development of new formations.
- Sodium tiludronate (skelid) is the first generation of drugs. Reduces the process of destruction of bone tissue, promotes the accumulation of compounds of calcium and phosphate molecules in the bones, thereby increasing the strength of bones. Suppresses the active work of osteoclasts and stimulates the production and performance of osteoblast functions. Prescribed for Paget's disease, deforming osteodystrophy.
Side effects when taking bisphosphonate drugs
Undoubtedly, bisphosphonates show high therapeutic results in the treatment of osteoporosis, hypercalcemia, in reducing pain caused by diseases of the spine and cancerous formations in the skeletal bones, and stop the spread of metastases in bone tissue. In some cases, these substances are used in the treatment of complex fractures of a traumatic nature or those arising due to skeletal diseases and a decrease in their density.
It has also been clinically established that bisphosphonates can increase the implantation stability of endoprostheses after removal of one or more skeletal bones, reduce calcification of prosthetic heart valves, and increase the capabilities of the immune system.
But, like all drugs, bisphosphonates have a number of side effects:
- negative impact on kidney function, intoxication;
- hypocalcemia observed when the drug is administered intravenously;
- osteonecrosis of the jaw bones, which can occur during treatment with amino-containing bisphosphonates;
- an increased risk of hip fractures during therapy with zoledronate, which is caused by blocking the restoration of bone tissue when cancer cells develop in them;
- increased risk of atrial fibrillation;
- disturbances in the normal functioning of the digestive system (constipation, diarrhea), pain in the intestines, swallowing disorders;
- erosion of the esophagus, stomach;
- fever and muscle pain;
- feeling of general weakness and nausea;
- allergic and dermatological reactions (rashes of various types, erythema);
- disorders of the visual organs (conjunctivitis, visual disturbances, pain and stinging in the eyes).
Considering all of the above side effects, we can say that bisphosphonate therapy should only be carried out under the supervision of a physician.
In this case, a dosage corresponding to the disease must be prescribed specifically for each patient, and laboratory research monitoring of the condition of bone tissue, blood, urine, etc. must be periodically performed. Author: K.M.N., Academician of the Russian Academy of Medical Sciences M.A. Bobyr