Risendros® [Sodium Risedronate]

Pharmacological properties

Risedronate is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoblast-mediated bone resorption. at the same time, bone remodeling decreases, while the activity of osteoblasts and bone mineralization remain unchanged. in preclinical studies, a powerful anti-osteoclastic and antiresorptive activity of the drug and a dose-dependent increase in bone mass and biomechanical strength of the skeleton were demonstrated. the activity of risedronic acid is confirmed by the determination of the content of biochemical markers of bone remodeling during pharmacodynamic and clinical studies. in studies in which women participated in the postmenopausal period, a decrease in the content of biochemical markers of bone metabolism was noted within 1 month of use of the drug and reached a maximum after 3-6 months from the start of its use. a decrease in the content of biochemical markers of bone metabolism after 12 months from the start of the drug administration in the risedronic acid group at a dose of 35 mg once a week and in the risedronic acid group at a dose of 5 mg / day was similar.

In a study in which men with osteoporosis took part, a decrease in the content of biochemical markers of bone remodeling was noted no earlier than 3 months after the start of the drug, and was noted after 24 months of its use.

Treatment of postmenopausal osteoporosis. A number of risk factors are associated with postmenopausal osteoporosis, such as low bone mass in the body, low bone mineral density, early menopause, a history of smoking, and family history of osteoporosis. The clinical consequences of osteoporosis are fractures. The risk of fractures increases with the number of risk factors.

The data obtained indicate that in the group of elderly patients (over 80 years of age) less pronounced protection is noted. This is possible due to an increase in the importance of non-skeletal risk factors for femoral fracture with age.

In these studies, data that were analyzed as secondary endpoints showed a reduced risk of new vertebral fractures in patients with or without vertebral fractures at the initial level.

Reception of risedronate, which was prescribed at a dose of 5 mg / day for 3 years, increased bone mineral density (BMD) of the lumbar spine, femoral neck, trochantericum and wrist bones and maintained constant bone density in the middle part of the radius compared to control group.

Treatment of osteoporosis in men. The effectiveness of sodium risedronate, which was used at a dose of 35 mg once a week, in men with osteoporosis (age 36–84 years) was demonstrated. All patients were supplemented with calcium and vitamin D.

An increase in BMD was noted already 6 months after the start of treatment with sodium risedronate. The use of sodium risedronate at a dose of 35 mg once a week caused an average increase in BMD in the lumbar spine, neck of the femur, trochanter and femur as a whole compared with placebo after 2 years of treatment. The effectiveness of the drug to reduce the risk of fractures in this study has not been demonstrated.

The effect of sodium risedronate on bone tissue (an increase in BMD and a decrease in the content of markers of bone remodeling) in men and women was similar.

Children. All the results obtained do not support the use of sodium risedronate in children with imperfect osteogenesis.

Pharmacokinetics Absorption.The absorption of the drug after oral administration occurs rather quickly (maximum 1 hour) and does not depend on the dose of the drug (a single dose of 2.5–30 mg, multiple daily doses of 2.5–5 mg and a dose of up to 50 mg Once a week). Oral bioavailability is 0.63%, reduced in case of simultaneous administration of the drug with food.

Distribution. The average volume of distribution in equilibrium is 6.3 l / kg body weight. Plasma protein binding is about 24%.

Metabolism. There is no data on systemic metabolism of risedronate.

About half of the absorbed dose of the drug is excreted in the urine for 24 hours. The average renal clearance is 105 ml / min, the average total clearance is 122 ml / min, the rest of the drug accumulates in the bone tissue. Renal clearance does not depend on the concentration of the drug in the blood; there is a linear relationship between its renal clearance and creatinine clearance. An unabsorbed drug is excreted in the feces unchanged. After oral administration, the dynamics of changes in the concentration of the drug in blood plasma is characterized by the presence of three elimination phases with a final T_½ 480 h

Indications

Treatment of postmenopausal osteoporosis to reduce the risk of vertebral fractures; treatment of confirmed postmenopausal osteoporosis to reduce the risk of femoral fractures; treatment of osteoporosis in men with a high risk of fractures.

Application

The recommended dose for adults is inside 1 tablet per week. the tablet should be taken on the same day of the week. food is affected by the absorption of risedronate, therefore, to ensure proper absorption, patients should take Risendros 35 30 minutes before the first meal on this day, other medicines or drinks (except ordinary water).

Patients should be instructed that in case of a missed dose, you can take Risendros 35 tablet on the day when the patient remembers the drug. Then patients should return to taking the drug according to the scheme 1 tablet 1 time per week on the day when the drug was usually taken. On the same day, you can take 2 tablets.

The tablet should be swallowed whole without absorbing or chewing it. To facilitate the entry of the pill into the stomach, Risendros 35 should be swallowed in a standing position with a glass of ordinary water (at least 120 ml). Patients should not take a lying position for 30 minutes after taking the pill (see SPECIAL INSTRUCTIONS).

The appropriateness of additional intake of calcium and vitamin D should be weighed if the intake of these substances with food is insufficient.

Elderly patients. In clinical trials, no differences were found in the efficacy or safety of risedronate depending on the age of the patient. Thus, elderly patients do not require dose adjustment. The same goes for women over the age of 75.

Patients with impaired renal function. For patients with mild or moderate renal failure, there is no need for dose adjustment.

In patients with severe renal failure (creatinine clearance 30 ml / min), the use of the drug is contraindicated (see CONTRAINDICATIONS).

The optimal duration of treatment for osteoporosis with bisphosphonates has not yet been determined. The need for further continued use of the Risendros 35 drug should be periodically reassessed, taking into account the benefits and potential risks of such treatment in a particular patient, especially after treatment lasting 5 years or more.

Contraindications

Known hypersensitivity to risedronate or any other component of the drug; hypocalcemia; severe renal failure (creatinine clearance 30 ml / min); During pregnancy and breastfeeding.

Side effects

The following adverse reactions were noted in clinical trials.side effects are given using such criteria for assessing the frequency: very often (≥1 / 10), often (≥1 / 100 to 1/10); infrequently (≥1 / 1000 1/100), rarely (from ≥1 / 10,000, 1/1000), very rarely (1/10 000).

From the nervous system: often - headache.

From the side of the organ of vision: infrequently - inflammation of the iris.

From the digestive tract: often - constipation, dyspepsia, nausea, abdominal pain, diarrhea; infrequently - gastritis, esophagitis, dysphagia, duodenitis, ulcers of the esophagus; rarely - glossitis, stricture of the esophagus.

From the musculoskeletal system and connective tissue: often - pain in the muscles, joints and bones.

Laboratory results: rarely - changes in liver function indicators.

Some patients experienced an early temporary asymptomatic mild decrease in plasma calcium and phosphate levels.

In the post-marketing period, the following additional adverse reactions were reported (frequency unknown):

on the part of the organ of vision: the frequency is unknown - inflammation of the iris, uveitis.

From the side of the musculoskeletal system and connective tissue: rarely - atypical inert and diaphyseal fractures of the femur; frequency unknown - osteonecrosis of the lower jaw.

On the part of the skin and subcutaneous tissue: the frequency is unknown - hypersensitivity reactions and skin reactions, including angioedema, generalized rash, urticaria, as well as bullous skin reactions and leukocytoclastic vasculitis (severe reactions were sometimes noted, including isolated cases of Stevens-Johnson syndrome and toxic epidermal necrolysis), hair loss.

From the immune system: the frequency is unknown - anaphylactic reactions.

From the hepatobiliary system: the frequency is unknown - serious liver disorders. In most cases, patients also received treatment with other drugs with a known ability to cause liver disorders.

special instructions

Food products, drinks (except ordinary water) and medicines containing polyvalent cations (such as calcium, magnesium, iron and aluminum) affect the absorption of bisphosphonates and cannot be taken simultaneously with Risendros 35 (see interaction). to achieve the intended effectiveness of treatment, you should clearly adhere to the recommendations on the dosage of the drug (see application).

The effectiveness of bisphosphonates in the treatment of postmenopausal osteoporosis has been confirmed in patients with low bone density and / or frequent fractures. Elderly age or the presence of clinical risk factors for fracture alone are not sufficient reasons to initiate treatment of osteoporosis with bisphosphonates. Evidence to support the effectiveness of bisphosphonates, including risedronic acid, in older women (over 80) is still limited (see PHARMACOLOGICAL PROPERTIES).

The use of certain bisphosphonates is associated with the occurrence of esophagitis, gastritis, gastrointestinal ulcers. In this regard, patients should pay special attention to instructions for the dosage of the drug (see APPLICATION).

Particular caution when using this medication must be observed in the following cases:

• in patients with a history of esophageal lesions who slow down the passage of food through the esophagus or its emptying, for example, stricture or achalasia;
• in patients who cannot remain upright for at least 30 minutes after taking the pill;
• in the case of risedronate in patients with active or recent lesions of the esophagus or upper gastrointestinal tract.

The prescribing physician should advise patients of the importance of carefully following the dosage instructions for the drug and monitoring any signs or symptoms of a possible reaction from the esophagus.Patients should be instructed to seek timely medical attention in case of development of symptoms of irritation of the esophagus, such as dysphagia, pain when swallowing, pain behind the sternum or the appearance / worsening of heartburn.

Hypocalcemia should be treated before starting therapy with Risendros 35. Other disorders of the bone tissue and metabolism of minerals (such as parathyroid dysfunction, hypovitaminosis D) should be treated simultaneously with the start of therapy with Risendros 35.

In cancer patients receiving treatment, which included mainly the administration of bisphosphonates, there were cases of osteonecrosis of the lower jaw, usually associated with tooth extraction and / or local infection (including osteomyelitis). Many of these patients also received chemotherapy and corticosteroids. Cases of osteonecrosis of the lower jaw have also been reported in patients with osteoporosis who received oral bisphosphonates.

In patients with concomitant risk factors (for example, cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene), the feasibility of a dental examination should be weighed against bisphosphonates with the necessary preventive dental procedures.

During treatment, such patients should avoid invasive dental procedures whenever possible. In patients who develop osteonecrosis of the lower jaw during bisphosphonate therapy, dental surgery may exacerbate this condition. Data on whether canceling bisphosphonate therapy can reduce the risk of developing osteonecrosis of the lower jaw in patients requiring dental procedures is not yet available.

The management plan for each individual patient should be based on an individual assessment of the benefit / risk ratio according to the clinical opinions of the attending physician.

Atypical femoral fractures. Against the background of bisphosphonate therapy, atypical underwent and diaphyseal fractures of the femur can be noted - mainly in patients receiving long-term treatment for osteoporosis. These transverse or oblique fractures can be detected in any part of the femur - from the place directly under the small trochanter to the place directly above the supracondylar thickening. These fractures occur after minimal trauma or in the absence of trauma, in some patients pain in the thigh or in the inguinal region is noted, which is often accompanied by signs of a stress fracture according to the results of visualization diagnostic methods, which appear several weeks or months before a complete fracture of the femur. Such fractures are often bilateral; in this regard, in patients receiving bisphosphonates, in the event of a diaphyseal fracture of the femur, the contralateral femur should also be examined. Poor healing of these fractures has also been reported. The appropriateness of discontinuing bisphosphonate therapy in patients in whom an atypical femoral fracture is suspected should be considered, given the results of an individual assessment of the benefit / risk ratio in a particular patient.

During treatment with bisphosphonates, patients should be advised to report any cases of pain in the femoral or inguinal region, and any patient who complains of such symptoms should be examined for the presence of an incomplete fracture of the femur.

Use during pregnancy and lactation. Appropriate data on the use of risedronate in pregnant women are not yet available. The potential risk to humans is unknown. Risedronate should not be used during pregnancy and lactation.

Children.Since data on the safety and efficacy of risendronate in children under the age of 18 are insufficient, the drug is not used in this patient population.

The ability to influence the reaction rate when driving a vehicle or working with machinery. Although there is no direct effect of the drug on the reaction rate when driving vehicles or other mechanisms, it must be borne in mind that when taking the drug, side reactions from the organ of vision are possible, which may be accompanied by a deterioration in visual acuity and photophobia (see ADVERSE EFFECTS).

Interactions

No clinically significant interactions with other drugs have been identified.

Among patients taking acetylsalicylic acid or NSAIDs regularly (3 or more days per week), the incidence of side effects from the upper gastrointestinal tract in the risedronate group was similar to that in the control group.

Risedronate can be used simultaneously with estrogen drugs, if such a combination is considered appropriate.

Food products, beverages (excluding plain water), and medicines containing polyvalent cations (such as calcium, magnesium, iron, and aluminum) can affect the absorption of risedronate and should not be taken concomitantly with Rizendros 35. To achieve the intended treatment effectiveness you should clearly adhere to the recommendations on the dosage of the drug (see APPLICATION).

Risedronate is not amenable to systemic metabolism, does not induce enzymes of the cytochrome P450 group, and to a small extent binds to blood plasma proteins.

Overdose

Information on any specific treatment for acute overdose of risedronate is not yet available.

After a significant overdose of the drug, a decrease in plasma calcium levels may be noted. Signs and symptoms of hypocalcemia also occur in some patients.

The patient should be given milk or antacids containing magnesium, calcium or aluminum to bind risedronate and reduce its absorption. In case of a significant overdose of the drug, it is advisable to rinse the stomach to remove risedronate, which has not yet been absorbed.

Storage conditions

It does not require special storage conditions.