Pharmacokinetics
Suction
Absorption of the drug after oral administration is relatively rapid, and is approximately 1 hour. The average bioavailability of the drug is 0.63%, and decreases with food intake.
Distribution and metabolism
Plasma protein binding - 24%. Volume of distribution - 6.3 l/kg. There are no data to support the systemic metabolism of risedronic acid.
Removal
Approximately half of the absorbed dose is excreted by the kidneys within 24 hours. The average renal clearance is 105 ml/min and the average total clearance is 122 ml/min. Renal clearance is independent of drug concentration; there is a linear relationship between renal clearance and creatinine clearance.
Unabsorbed risedronic acid is excreted through the intestines in unchanged form.
Pharmacological properties
Pharmacodynamics.
Risedronate is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoblast-mediated bone resorption. At the same time, bone tissue remodeling decreases, while osteoblast activity and bone mineralization remain unchanged. preclinical studies demonstrated powerful antiosteoclast and antiresorptive activity of the drug and a dose-dependent increase in bone mass and biomechanical strength of the skeleton. The activity of risedronic acid was confirmed by determining the content of biochemical markers of bone tissue remodeling during pharmacodynamic and clinical studies. in studies in which postmenopausal women took part, a decrease in the content of biochemical markers of bone tissue metabolism was observed within 1 month of using the drug and reached a maximum 3–6 months after the start of its use. the decrease in the content of biochemical markers of bone tissue metabolism 12 months after the start of drug use in the group taking risedronic acid at a dose of 35 mg once a week and in the group taking risedronic acid at a dose of 5 mg/day was similar. In a study of men with osteoporosis, a decrease in biochemical markers of bone tissue remodeling was observed no earlier than 3 months after starting the drug, and was observed after 24 months of its use.
Treatment of postmenopausal osteoporosis. A number of risk factors are associated with postmenopausal osteoporosis, such as low body bone mass, low bone mineral density, early menopause, 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 observed. This is possible due to the increasing importance of non-skeletal risk factors for femoral fracture with age.
In these studies, data analyzed as secondary endpoints suggested a reduction in the risk of new vertebral fractures in patients with or without vertebral fractures at baseline.
Risedronate 5 mg/day for 3 years increased bone mineral density (BMD) at the lumbar spine, femoral neck, trochanter and carpus and maintained bone density at the mid-radius compared with control group.
Treatment of osteoporosis in men. The effectiveness of risedronate sodium, administered at a dose of 35 mg once a week, has been demonstrated in men with osteoporosis (aged 36–84 years). All patients took additional calcium and vitamin D.
An increase in BMD was observed already 6 months after the start of treatment with risedronate sodium. Risedronate sodium 35 mg once weekly resulted in mean increases in BMD at the lumbar spine, femoral neck, trochanter, and total femur compared with placebo after 2 years of treatment. The effectiveness of the drug in reducing the risk of fractures was not demonstrated in this study.
The effect of risedronate sodium on bone tissue (increased BMD and decreased bone turnover markers) was similar in men and women.
Children. All findings do not support the use of risedronate sodium in children with osteogenesis imperfecta.
Pharmacokinetics. Absorption. Absorption of the drug after oral administration occurs quite quickly (maximum - 1 hour) and does not depend on the dose of the drug (single dose of 2.5-30 mg, repeated daily dose of 2.5-5 mg and dose of up to 50 mg 1 time per week). Bioavailability when taken orally is 0.63%, decreasing when the drug is taken simultaneously with food.
Distribution. The average volume of distribution at steady state is 6.3 l/kg body weight. Binding to plasma proteins is about 24%.
Metabolism. There are no data on the systemic metabolism of risedronate.
Excretion. About half of the absorbed dose of the drug is excreted in the urine within 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 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. The unabsorbed drug is excreted unchanged in the feces. After oral administration, the dynamics of changes in the concentration of the drug in the blood plasma is characterized by the presence of three phases of elimination with a final half-life of 480 hours.
Dosage regimen
For adults, the drug is prescribed at a dose of 35 mg once a week. The tablet must be taken on the same day of the week. The absorption of risedronic acid is dependent on food intake, therefore, to ensure adequate absorption, risedros® should be taken at least 30 minutes before the first meal, other drug or drink (other than water).
If a drug dose is missed, it must be taken on the day the patient remembers. Then you should return to taking 1 tablet once a week on the day of your usual intake. Do not take 2 tablets on the same day.
The tablet should be taken whole and not chewed, preferably standing and washed down with plain water (>120 ml). After taking the tablet, patients should not lie down for 30 minutes.
During treatment, it is recommended to follow an adequate diet with sufficient calcium and vitamin D. If necessary, additional prescription of calcium and vitamin D supplements is possible.
Note!
Description of the drug Rizendros 35 tablets. p/o 35 mg No. 4 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
Contraindications to the use of the drug RISENDROS®
- hypersensitivity to the components of the drug;
- hypocalcemia;
- severe renal impairment (creatine clearance less than 30 ml/min);
- pregnancy and breastfeeding (lactation);
- children under 18 years of age;
Carefully:
- with erosive and ulcerative lesions of the mucous membrane of the gastrointestinal tract (including a history), in patients with a history of dysfunction of the esophagus (such as stricture or achlasia);
- if it is impossible to remain in an upright position for at least 30 minutes after taking the tablet.
Side effects
The following adverse reactions were noted in clinical studies. side effects are given using the following frequency assessment criteria: very often (≥1/10), often (≥1/100 to 1/10); uncommon (≥1/1000 1/100), rare (from ≥1/10,000, 1/1000), very rare (1/10,000).
From the nervous system: often - headache.
From the side of the organ of vision: infrequently - inflammation of the iris.
From the gastrointestinal tract: often - constipation, dyspepsia, nausea, abdominal pain, diarrhea; uncommon - gastritis, esophagitis, dysphagia, duodenitis, esophageal ulcers; rarely - glossitis, esophageal stricture.
From the musculoskeletal system and connective tissue: often - pain in muscles, joints and bones.
Laboratory test results: rarely - changes in liver function tests.
Some patients experienced early, temporary, asymptomatic, mild decreases in plasma calcium and phosphate levels.
During post-marketing use, the following additional adverse reactions have been reported (frequency unknown):
from the organ of vision: frequency unknown - inflammation of the iris, uveitis.
From the musculoskeletal system and connective tissue: rarely - atypical subtrochanteric and diaphyseal fractures of the femur; frequency unknown - osteonecrosis of the lower jaw.
From the skin and subcutaneous tissue: frequency unknown - hypersensitivity reactions and skin reactions, including angioedema, generalized rash, urticaria, as well as bullous skin reactions and leukocytoclastic vasculitis (sometimes severe reactions were observed, including isolated cases of Stevens-Johnson syndrome and toxic epidermal necrolysis), hair loss.
From the immune system: frequency unknown - anaphylactic reactions.
From the hepatobiliary system: frequency unknown - serious liver disorders. In most cases, patients were also treated with other drugs known to cause liver problems.
special instructions
Before starting drug therapy, it is necessary to correct hypocalcemia, as well as other pathologies that affect bone and mineral metabolism (for example, dysfunction of the parathyroid glands, vitamin D deficiency). If the dietary intake of calcium and vitamin D is insufficient, their additional intake is necessary.
The use of a number of bisphosphonates is accompanied by esophagitis and ulcerative lesions of the esophagus. Therefore, patients must strictly follow the instructions for dosage and method of administration (see section “Dosage and Administration”). Recommendations for taking the drug are of particular importance for patients with diseases of the esophagus such as stricture and achalasia. In patients who are unable to remain upright for 30 minutes after taking the drug, risedronate sodium should be used with extreme caution due to limited clinical experience with its use in such patients.
Cases of osteonecrosis of the jaw following tooth extraction and/or local infection (including osteomyelitis) have been reported in cancer patients. Before initiating bisphosphonate treatment, patients with concomitant risk factors (eg, cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene) should undergo a dental examination with appropriate therapeutic dental treatment. During treatment, these patients should avoid invasive dental procedures whenever possible. Foods, drinks (except plain water), and medications containing polyvalent cations (such as calcium, magnesium, iron, and aluminum) interfere with the absorption of bisphosphonates and should not be taken at the same time as risedronate sodium.
Overdose
Information on any specific treatment for acute risedronate overdose is not yet available.
After a significant overdose of the drug, a decrease in the level of calcium in the blood plasma may be observed. Some patients also experience signs and symptoms of hypocalcemia.
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 lavage the stomach to remove risedronate, which has not yet been absorbed.
Drug interactions
Medicines containing polyvalent cations such as calcium, magnesium, iron and aluminum may reduce the absorption of the drug.
There are no clinically significant interactions with NSAIDs (including acetylsalicylic acid), H2-histamine receptor blockers, proton pump inhibitors, antacid drugs, slow calcium channel blockers, beta-blockers, thiazide diuretics, glucocorticosteroids, anticoagulants, anticonvulsants, cardiac glycosides.
The drug is compatible with drugs for HRT.
