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Active ingredients
Ibandronic acid
Release form
Pills
Composition
Active ingredient: Ibandronic acid (Ibandronic acid). Concentration of active ingredient (mg): 150
Pharmacological effect
Ibandronic acid is a highly active nitrogen-containing bisphosphonate inhibitor of bone resorption and osteoclast activity. Ibandronic acid prevents bone destruction caused by blockade of the function of the sex glands, retinoids, tumors and extracts of tumors in vivo. Does not violate the mineralization of bones when administered in doses greater than 5,000 times the dose for the treatment of osteoporosis. It does not affect the process of replenishing the osteoclast pool. The selective effect of ibandronic acid on bone tissue is due to its high affinity for hydroxyapatite, which constitutes the mineral matrix of bone. Ibandronic acid inhibits bone resorption in a dose-dependent manner and does not directly affect the formation of bone tissue. In women in menopause, it decreases the increased rate of bone tissue renewal to the level of reproductive age, which leads to a general progressive increase in bone mass, a decrease in splitting of bone collagen (concentration of deoxypyridinium and cross-linked C- and N-telopeptides of type I collagen) in urine and serum, fracture rates and increased bone mineral density (BMD). High activity and therapeutic range provide the possibility of a flexible dosing regimen and an intermittent administration of a drug with a long period of no treatment at relatively low doses. Efficiency. Bone mineral density (BMD): Taking Bonviva 150 mg once a month for one year increases the average BMD of the lumbar vertebrae, hip, femoral neck and skewer by 4.9%, 3.1%, 2.2% and 4.6. % Regardless of the duration of menopause and the degree of the initial loss of bone mass, the use of Bonviva leads to a significantly more pronounced change in BMD than placebo. The effect of treatment throughout the year, defined as an increase in BMD, is observed in 83.9% of patients. Biochemical markers of bone resorption: A decrease in the serum concentration of the C-terminal peptide of type I collagen (CTX) by 28% was noted 24 hours after the first dose of 150 mg of Bonviva, the maximum decrease is 68% after 6 days.After the third and fourth intake of Bonviva 150 mg, the maximum decrease in serum CTX by 74% was noted in 6 days. 28 days after the fourth dose, a decrease in the suppression of biochemical markers of bone resorption was noted to 56%. A clinically significant reduction in serum CTX was obtained after 3, 6, and 12 months of therapy. After a year of treatment with Bonviva 150 mg, the reduction is 76%. A decrease in CTX more than 50%) compared with the initial value was observed in 83.5% of patients who received Bonviva 150 mg 1 time in 28 days.
Pharmacokinetics
No direct dependence of the efficacy of ibandronic acid on the concentration of the substance in the blood plasma was revealed. Absorption: After oral administration, ibandronic acid is rapidly absorbed in the upper gastrointestinal tract. Plasma concentration increases in a dose-dependent manner as the dose is increased to 50 mg and much more with a further increase in the dose. The time to reach the maximum concentration of TStah 0.5-2 h (median - 1 h) after administration on an empty stomach, the absolute bioavailability of 0.6%. Simultaneous ingestion of food or drinks (except pure water) reduces the bioavailability of ibandronic acid by 90%. When taking ibandronic acid 60 minutes before a meal, a significant reduction in bioavailability is not observed. Eating food or liquids less than 60 minutes after ibandronic acid reduces its bioavailability and the resulting increase in BMD. Distribution: After entering the systemic circulation, ibandronic acid quickly binds to the bone tissue or is excreted in the urine. 40-50%) of the amount of the drug circulating in the blood penetrates well into the bone tissue and accumulates in it. The seeming final volume of distribution is 90 l. Communication with proteins of blood plasma 85%. Metabolism There is no evidence that ibandronic acid is metabolized. Excretion: 40-50% of the orally ingested dose absorbed into the bloodstream is bound in the bones, and the rest is excreted unchanged by the kidneys. An unabsorbed drug is excreted unchanged with feces. Terminal T1 / 2 10 - 72 h. The concentration of the drug in the blood decreases rapidly and is 10% of the maximum 8 hours after oral administration. The total clearance of ibandronic acid 84 - 160 ml / min. Renal clearance (60 ml / min in healthy menopausal women) is 50-60% of the total clearance and depends on creatinine clearance. The difference between total and renal clearance reflects the seizure of a substance in the bone tissue. Pharmacokinetics in special groups of patients: The pharmacokinetics of ibandronic acid does not depend on gender.There were no clinically significant interracial differences in the distribution of ibandronic acid in individuals of the South European and Asian races. Relatively Negroid race data is not enough. Patients with impaired renal function: In patients with impaired renal function, renal clearance of ibandronic acid is linearly dependent on creatinine clearance (CK). For patients with impaired renal mild or moderate severity (CC greater than 30 ml / min), dose adjustment is not required. In patients with severe impaired renal function (CC less than 30 ml / min) who received the drug at a dose of 10 mg orally for 21 days, the concentration of ibandronic acid in plasma is 2-3 times higher than in people with normal renal function (total clearance 129 ml / min.) In severe renal impairment, the total clearance of ibandronic acid is reduced to 44 ml / min. However, an increase in systemic concentration does not impair the tolerability of the drug. Patients with impaired liver function: There are no data on the pharmacokinetics of ibandronic acid in patients with impaired liver function. The liver does not play a significant role in the clearance of ibandronic acid, which is not metabolized, but is excreted through the kidneys and by trapping in bone tissue. Therefore, for patients with impaired liver function dose adjustment is not required. Since, at therapeutic concentrations, ibandronic acid is poorly bound to plasma proteins (85%), it is likely that hypoproteinemia in severe liver diseases does not lead to a clinically significant increase in the concentration of free substance in the blood. By residential age: The studied pharmacokinetic parameters do not depend on age. Consideration should be given to a possible reduction in renal function in elderly patients (see the section “Patients with impaired renal function” above). Children: Data on the use of Bonviva in persons under the age of 18 are not available.
Indications
Postmenopausal osteoporosis to prevent fractures.
Contraindications
Hypocalcemia. lesions of the esophagus, leading to a delay in its emptying, such as stricture or achalasia. inability to sit or stand for 60 minutes after taking the drug. hereditary intolerance to galactose, lactase deficiency or glucose-galactose malabsorption. severe renal impairment (creatinine clearance less than 30 mlmin).children's age (safety and efficacy in persons younger than 18 years old has not been established). Hypersensitivity to ibandronic acid or other components of the drug.
Precautionary measures
In cases where the drug is injected into an existing intravenous infusion system, the infusate must contain either an isotonic solution, or 50 mg / ml (5%) glucose solution. This also applies to solutions used to flush a butterfly infusion catheter and other devices. Any unused solutions, syringes and needles for injections must be disposed of according to local requirements. The release of pharmaceuticals into the environment should be minimized.
Use during pregnancy and lactation
Category C. Pregnancy: In rats and rabbits given oral ibandronic acid, no signs of direct embryotoxic or teratogenic effects were found; with a dose exceeding the dose for a human, at least 35 times, no adverse effect on the development of the offspring in B1 rats was detected. The adverse effects of ibandronic acid in reproductive toxicity studies in rats were the same as in all bisphosphonates - a decrease in the number of embryos, a disruption of the labor process, an increase in the frequency of visceral abnormalities (syndrome of contraction of the pelvic-ureter segment). Experience of clinical use of the drug Bonviva in pregnant women do not. Breastfeeding period: Excreted in milk in rats. After 24 h, the concentration of ibandronic acid in the blood plasma and milk is the same and corresponds to 5% of the maximum. It is not known whether ibandronic acid is excreted in breast milk in women.
Dosage and administration
The drug is administered orally 150 mg (1 tab.) 1 size (preferably on the same day of each month), 60 minutes before the first meal of a given day, liquid (except water) or other medicines and food additives. Tablets should be swallowed whole, with a glass (180-240 ml) of pure water, sitting or standing. You should not go to bed within 60 minutes after taking the drug. Tablets can not be chewed or dissolve due to possible ulceration of the upper GI tract. Do not use high calcium mineral water.
Side effects
hypersensitivity reactions, headache, dizziness, esophagitis, gastritis, gastroesophageal reflux disease, dyspepsia, diarrhea, abdominal pain, nausea, rash, vomiting, flatulence, duodenitis, facial swelling, rash, arthralgia, myalgia, musculoskeletal pain, muscle cramps , musculoskeletal stiffness, back pain, flu-like syndrome, fatigue.
Overdose
Possible symptoms. Dyspepsia, heartburn, esophagitis, gastritis, ulcer, hypocalcemia. Treatment. No special information available. Milk or antacids are used to bind Bonviva. Due to the risk of irritation of the esophagus, one should not induce vomiting and should remain in a straight posture.
Interaction with other drugs
Products containing calcium and other polyvalent cations (for example, aluminum, magnesium, iron), including milk and solid food, can interfere with the absorption of the drug, they should be consumed no earlier than 60 minutes after the non-oral intake of Bonviva. Calcium supplements, antacids and drugs containing polyvalent cations (for example, aluminum, magnesium, iron) can interfere with the absorption of ibandronic acid, so they should be taken no earlier than 60 minutes after taking Bonviva. Bisphosphonates and nonsteroidal anti-inflammatory drugs (NSAIDs) can cause irritation of the gastrointestinal tract. Special care should be taken when using NSAIDs at the same time as Bonviva. With the simultaneous use of aspirin or NSAIDs and Bonviva drug for 1 year, the frequency of side effects from the upper GI tract was the same. Ranitidine IV increases the bioavailability of ibandronic acid by 20%. Dose adjustment of ibandronic acid with simultaneous use of histamine receptors with H2-blockers or other drugs that increase the pH in the stomach is not required. Ibandronic acid does not affect the activity of the main isoenzymes of the cytochrome P450 system. At therapeutic concentrations, ibandronic acid weakly binds to plasma proteins, and therefore, it is unlikely that it will displace other drugs from protein binding sites. Ibandronic acid is derived only through the kidneys and is not subjected to any biotransformation.Apparently, the route of ibandronic acid elimination does not include any transport systems involved in the elimination of other drugs.
special instructions
Osteoporosis can be confirmed by detecting a low BMD (T index less than -2.0 SD [Standard deviation]) and a fracture (incl. In history) or low bone mineral density (T index less than -2.5 SD ) in the absence of a confirmed fracture. Before starting Bonviva, hypocalcemia and other disorders of bone tissue metabolism and electrolyte balance should be corrected. Patients should consume enough calcium and vitamin D. If the patient is not getting enough calcium and vitamin D from food, they should be taken as supplements. Side effects of the drug is usually mild or moderate. Transient flu-like syndrome occurs after taking the first dose and resolves on its own without correction of therapy. There was no increase in the incidence of adverse effects from the upper GI tract in patients with gastrointestinal diseases (including peptic ulcer without bleeding and hospitalization, dyspepsia or reflux disease). The use of oral bisphosphonates is often accompanied by a violation of swallowing, esophagitis and the formation of ulcers of the esophagus and stomach, so you need to pay special attention to the implementation of recommendations for taking the drug (sitting or standing for 60 minutes after administration). If signs and symptoms of a possible esophageal lesion appear (appearance or aggravation of swallowing, pain when swallowing, chest pain, heartburn), you should stop taking Bonviva and consult a doctor. The postmarketing experience with Bonviva is limited. Osteonecrosis of the jaw was observed when prescribing bisphosphonates. Most cases were registered in cancer patients during dental procedures, a few cases in patients with postmenopausal osteoporosis or other diseases. Risk factors for osteonecrosis of the jaw include an established diagnosis of cancer, concomitant therapy (chemotherapy, radiation therapy, corticosteroids) and other disorders (anemia, coagulopathy, infection, gum disease).The majority of cases were observed with the on / in the appointment of bisphosphonates, but individual cases were observed in patients who received drugs orally. Surgical dental intervention with bisphosphonate therapy may enhance osteonecrosis of the jaw. It is not known whether the risk of osteonecrosis reduces the removal of bisphosphonates. The decision to conduct treatment must be made for each patient individually after evaluating the risk / benefit ratio.