Osteolate (Osteolate)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceStrontium ranelateStrontium ranelate
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    • Dosage form: & nbspPowder for suspension for oral administration
    Composition:
    1 sachet contains:
    active substance: strontium ranelate octahydrate 2,6144 g (in terms of strontium ranelate - 2.00 g);
    Excipients: aspartame 0.02 g, maltodextrin 0.4 g, mannitol 0.9656 g
    Description:
    Homogeneous powder from white to light yellow color.
    While stirring the contents of one sachet in 100 ml of water, a white to light yellow suspension forms.
    Pharmacotherapeutic group:Means for the treatment of osteoporosis
    ATX: & nbsp

    M.05.B.X   Other drugs affecting the mineralization of bones

    M.05.B.X.03   Strontium ranelate

    Pharmacodynamics:
    Osteoporosis
    In vitro studies of strontium ranelate:
    - stimulates bone formation in bone tissue culture, and also stimulates the replication of osteoblast precursors and the synthesis of collagen in bone cell culture;
    - reduces the resorption of bone tissue by suppressing the differentiation of osteoclasts, as well as their resorptive activity.
    As a result of actionstrontium ranelata, the balance between the formation and destruction of bone tissue changes in the direction of the processes of bone formation.
    In human bone tissue and experimental animals, who were prescribed the drug, strontium ranelate, was mainly absorbed on the surface of hydroxyapatite crystals and only slightly superseded calcium in these crystals in the newly formed bone tissue.
    Strontium ranelat does not change the characteristics of bone crystals. According to the data of the biopsy of the crest of the ilium, performed after the treatment with strontium ranelate at a dose of 2 g per day for up to 60 months in clinical studies, there was no adverse effect on bone quality or mineralization.
    Combined effects of distribution of strontium in bone tissue and increased absorption of X-rays by strontium in comparison with calcium lead to an increase in bone mineral density (BMD), which is measured by two-photon X-ray absorptiometry. The data obtained so far indicate that these factors account for approximately 50% of the increase in BMD after 3 years of treatment with strontium ranelate at a dose of 2 g per day.This feature should be taken into account when interpreting changes in the BMD index during treatment with strontium ranelate.
    In studies that confirmed the ability of strontium ranelate to reduce the risk of fractures, the measured mean BMD increased in the group of patients who received strontium ranelate in comparison with the initial value - for lumbar vertebrae by approximately 4% per year, and for the neck of the femur by 2% per year; after 3 years, the increase in BMD was 13-15% and 5-6%, respectively, according to various studies.
    Beginning with the third month of therapy and during 3 years of follow-up, there was an increase in biochemical markers of bone formation (bone fraction of alkaline phosphatase and C-terminal propeptide of procollagen type I) and a decrease in bone resorption markers (cross-linked C-terminal and N-terminal telopeptides in urine) compared with placebo.
    For strontium ranelate secondary effect in relation to the main pharmacological properties is a slight decrease in serum calcium and parathyroid hormone concentrations,as well as an increase in the concentration of phosphorus in the blood and the activity of total alkaline phosphatase, which, however, is not accompanied by any clinical effects.
    Treatment of postmenopausal osteoporosis
    Risk factors for postmenopausal osteoporosis include decreased bone mass, decreased BMD, early menopause, history of smoking, and familial osteoporosis burden.
    One of the most clinically significant complications of osteoporosis is the development of fractures, with the risk of fractures increasing with an increase in the number of risk factors.
    In clinical trials involving more than 6.5 thousand postmenopausal women with documented osteoporosis, the effect of strontium ranelate on the prevention of fractures was studied.
    It was shown that the use of strontium ranelate reduced the relative risk of new vertebral fractures by 41% after 3 years of therapy. This effect became reliable, beginning with the first year of therapy. The relative risk of vertebral fractures accompanied by clinical manifestations (defined as fractures with development of pain syndrome and / or a decrease in the patient's growth by at least 1 cm) decreased by 38%.Also, strontium ranelate therapy compared with placebo significantly reduced the number of patients whose growth decreased by 1 cm or more. The effectiveness of strontium ranelate application in reducing the risk of new vertebral fractures was confirmed, including in patients who did not have a history of fractures associated with osteoporosis.
    In a retrospective analysis, it was shown that in patients with a history of fractures and with an index of BMD of the lumbar vertebrae and / or femoral neck indicating osteopenia, the use of strontium ranelate for 3 years reduced the risk of a first vertebral fracture by 72%.
    In the group of patients with a high risk of fracture (value of the T-criterion of the BMD index of the femoral neck within <3 ° C) over the age of 74, the intake of strontium ranelate for 3 years reduced the risk of fracture of the femur by 36% compared to the group of patients receiving placebo.
    Treatment of osteoporosis in men
    The efficacy of strontium ranelate for the treatment of osteoporosis in men was demonstrated in a two-year clinical trial involving 243 patients with a high risk of fracture (mean age of the patients
    was 72.7 years, the average value of the T-criterion of the MSCT of the lumbar spine was 2.6; 28% with vertebral fractures in the anamnesis).
    During the study, patients received calcium (1000 mg / day) and vitamin D (800 IU / day).
    A statistically significant increase in BMD was observed 6 months after initiation of therapy (compared with placebo).
    After 12 months of treatment with strontium ranelate, a statistically significant increase in the mean BMD of the lumbar spine was shown (the main efficacy criterion was 5.32%, p <0.001), similar values ​​were noted in studies on the effects of strontium ranelate on the prevention of fractures in postmenopausal women.
    A statistically significant increase in the BMD of the femoral neck and BMD index of the femur (p <0.001) was observed 12 months after the start of strontium therapy with ranelate.
    Pharmacokinetics:
    In the medicinal formula of strontium ranelate contains two stable strontium atoms and one molecule of ranelic acid (organic part, due to which the required values ​​of molecular weight are achieved, favorable pharmacokinetic properties and good drug tolerance are provided).Absorption, distribution and binding of ranelic acid with plasma proteins are sufficiently low, which is due to the high polarity of the molecule. Ranelic acid does not cumulate and does not show metabolic activity in the body. Absorbed woundelic acid is rapidly and unchanged in the form of kidneys.
    Suction
    Absolute bioavailability of strontium after taking 2 g of strontium ranelate is about 25%. After taking the drug inside a single dose of 2 g, the maximum concentration in the blood plasma is achieved in 3-5 hours. The equilibrium concentration is achieved after 2 weeks of therapy. The intake of strontium ranelate together with calcium preparations, food and food additives reduces the bioavailability of strontium by about 60-70% compared to bioavailability when taking the drug 3 hours after a meal. Considering the relatively slow absorption of strontium, you should not take food, dietary supplements and calcium preparations before or after taking strontium ranelate. The drugs and vitamin D supplements do not have any effect on the absorption of strontium.
    Distribution
    The volume of distribution of strontium is about 1 l / kg.The association of strontium with human plasma proteins is low and is 25%, with strontium characterized by a high affinity for bone tissue. Measurement of strontium concentration in patients with ileal biopsies who received strontium ranelate in a dose of 2 g per day for a long time (up to 60 months), indicates that the concentration of strontium in the bone tissue reaches a plateau after about 3 years of therapy. Data on removal of strontium from bone tissue after discontinuation of therapy are absent.
    Metabolism
    Representing a divalent cation, strontium is not metabolized in the human body. Strontium ranelate does not suppress the enzymes of the cytochrome P450 system.
    Excretion
    Excretion of strontium is time- and dose-dependent. The half-life of strontium is about 60 hours. Strontium is excreted by the kidneys and through the intestines. Plasma clearance of strontium is about 12 ml / min (CV 22%), renal clearance - about 7 ml / min (CV 28%).
    Pharmacokinetics in specific patient groups
    Elderly patients. Data on the pharmacokinetics in this target population indicate that there is no correlation between age and the determined strontium clearance.
    Patients with renal insufficiency. For renal insufficiency of mild and moderate severity (creatinine clearance 30-70 ml / min), the strontium clearance decreases with the decrease in creatinine clearance (by approximately 30% with creatinine clearance values ​​ranging from 30 to 70 ml / min), which leads to an increase plasma concentration of strontium. Correction of the dose of strontium ranelate in patients with mild and moderate severity of renal failure is not required. Data on pharmacokinetics of strontium ranelate in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) are absent.
    Patients with hepatic insufficiency. Data on the pharmacokinetics of strontium ranelate in patients with hepatic insufficiency are absent. However, given the pharmacokinetic properties of strontium, it can be assumed that they do not change in this group of patients.
    Indications:
    Treatment of severe osteoporosis in postmenopausal women with a high risk of vertebral and femoral fractures, including fracture of the femoral neck (with intolerance or contraindications to the use of other drugs for the treatment of osteoporosis).
    Treatment of severe osteoporosis in men with an increased risk of fractures (with intolerance or the presence of contraindications to the use of other medications for the treatment of osteoporosis).
    Contraindications:
    Known hypersensitivity to strontium ranelate and / or to any other component of the drug.
    Pregnancy and the period of breastfeeding.
    Age to 18 years.
    Venous thromboembolism (VTE) or episodes of VTE in the anamnesis, including deep vein thrombosis and pulmonary embolism.
    Permanent or temporary immobilization (for example, when strictly confined to a post-operative period or for some other reason).
    The established diagnosis of coronary heart disease, obliterating peripheral arterial disease and / or cerebrovascular disease - or an indication of the presence of these diseases in history.
    Uncontrolled hypertension.
    Phenylketonuria.
    Severe renal insufficiency (creatinine clearance less than 30 ml / min).
    Carefully:
    In patients with an increased risk of VTE.
    Pregnancy and lactation:
    Pregnancy
    Strontium ranelate is intended only for the treatment of women in the postmenopausal period.
    Clinical data on the use of strontium ranelate during pregnancy are absent.The drug is contraindicated in pregnancy.
    In the case of pregnancy on the background of taking the drug, treatment should be immediately stopped.
    Breastfeeding period
    Strontium penetrates into breast milk. The drug is contraindicated in the period of breastfeeding.
    Dosing and Administration:
    The drug should be taken orally in the form of a suspension obtained after mixing the powder from the sachet in a 1 / 3-1 glass of water. Suspension is recommended to be consumed immediately after preparation.
    Due to the fact that food, preparations and calcium supplements, milk and dairy products can reduce the absorption of strontium ranelate, Osteolate is recommended to be taken between meals, preferably before going to bed, at least 2 hours after eating, drinking milk, dairy products, food additives or calcium preparations. You can take a horizontal position immediately after taking the drug.
    The recommended dose of Osteolate is 2 g (1 sachet content) per day. Due to the chronic nature of the disease, the drug is expected to be taken for a long time.
    Patients with osteoporosis taking Osteolate drug should additionally prescribe drugs and / or nutritional supplements of calcium and vitamin D if their intake is insufficient.
    Use in elderly patients
    The efficacy and safety of strontium ranelate in patients of a wide age group, including those with osteoporosis in the postmenopausal period (up to 100 years of age) have been established. Correction of the dose of the drug according to age is not required.
    Application for renal failure
    In patients with mild or moderate severity of renal failure (creatinine clearance 30-70 ml / min), dose adjustment is not required. In patients with severe renal failure (creatinine clearance less than 30 ml / min), the drug is not recommended (see the sections "Pharmacokinetics" and "Special instructions").
    Application for liver failure
    Because the strontium ranelate is not metabolized in the body, dose adjustment in patients with hepatic insufficiency is not required.
    Application in children and adolescents
    The effectiveness and safety of the use of strontium ranelate in children and adolescents under the age of 18 years has not been studied, and therefore, the drug should not be prescribed to patients of this age group.
    Side effects:
    The frequency of unwanted reactions is as follows: very often (≥1 / 10 cases), often (≥1 / 100 and <1/10 cases) infrequently (≥1 / 1000 and <1/100 cases), rarely (> 1 / 10000 and <1/1000 cases) and very rarely (<1/10000 cases, including individual messages). Undesirable reactions that were noted in the postmarketing period of application of strontium ranelate and the frequency of development of which can not be calculated from available data are labeled "frequency unknown."
    From the nervous system: often - headache, impaired consciousness, memory loss; infrequently - convulsions; frequency unknown - paresthesia, dizziness, vertigo.
    From the side of the vessels: often - venous thromboembolism.
    From the heart: often - myocardial infarction.
    From the gastrointestinal tract: often - nausea, diarrhea, unformed stool; frequency unknown - vomiting, abdominal pain, mucous membrane damage to the oral cavity, including stomatitis and / or ulceration of the oral mucosa, flatulence, constipation, dyspepsia, gastroesophageal reflux,dry mouth.
    From the side of metabolism and nutrition: often - hypercholesterolemia.
    From the skin and subcutaneous tissues: often - dermatitis, eczema; rarely - DRESS-syndrome (see section "Special instructions"); very rarely severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (see section "Special instructions"); frequency unknown - skin reactions of hypersensitivity, including rash, itching, hives, angioedema (see section "Special instructions"), alopecia.
    Laboratory and instrumental data: often - transient acute increase in activity of the muscle fraction of creatine phosphokinase (CK), more than 3 times higher than the upper limit of the norm, was noted with a frequency of 1.4% and 0.6% in the groups of patients who received strontium ranelate and placebo, respectively (in most cases, the activity of CK itself returned to normal with the continuation of treatment with strontium ranelate without changing the therapy).
    From the musculoskeletal and connective tissue: frequency unknown - muscle spasm, myalgia, bone pain, arthralgia and pain in the extremities.
    Disorders of the psyche: frequency unknown - confusion, insomnia.
    From the liver and biliary tract: frequency unknown - increased activity of "hepatic" transaminases (due to skin reactions of hypersensitivity), hepatitis.
    On the part of the respiratory system, the organs of the thorax and the mediastinum: frequency unknown - bronchial hyperreactivity.
    On the part of the blood and lymphatic system: frequency unknown - bone marrow failure, eosinophilia (due to skin reactions of hypersensitivity), lymphadenopathy (due to cutaneous hypersensitivity reactions).
    General disorders: the frequency is unknown - peripheral edema, hyperthermia (due to skin reactions of hypersensitivity), malaise.
    If any of the unwanted reactions specified in the manual is aggravated, or if you notice any other undesirable reactions not listed in the instructions, inform your doctor.
    Overdose:
    When applying strontium ranelate to 4 grams per day with a maximum duration of 147 days, no clinically significant adverse events were noted.
    In healthy volunteers, a single dose of the drug in doses up to 11 g did not lead to the development of any special symptoms.
    In cases of overdose, in order to reduce the absorption of the active substance in the gastrointestinal tract, it is recommended that milk or antacid preparations be taken.
    In case of a significant excess of the recommended dose, it is necessary to induce vomiting to remove the unabsorbed active substance.
    Interaction:
    Food products, in particular milk and dairy products, as well as medicines and nutritional supplements containing calcium, can reduce the bioavailability of strontium ranelate by about 60-70%. In this regard, between the reception of strontium ranelate and these substances should be observed interval of at least 2 hours.
    The appointment of aluminum and magnesium hydroxides both 2 hours before and simultaneously with the use of strontium ranelate causes a slight decrease in the absorption of strontium ranelate (a decrease in the area under the AUC curve by 20-25%), while in the appointment of an antacid preparation 2 hours after reception of strontium ranelate absorption practically does not change. Thus, antacid preparations should preferably be taken no earlier than 2 hours after taking strontium ranelate. However, in practice this scheme of taking medicines is inconvenient, since strontium ranelate it is recommended to take before bedtime.In this regard, concomitant administration of antacids and strontium ranelate is allowed.
    Since molecular complexes containing divalent cations interact in the gastrointestinal tract with antibiotics of tetracycline and
    quinolone series, simultaneous application of strontium ranelate and these drugs leads to a decrease in the absorption of these antibiotics. In this regard, it is not recommended to take these medicines at the same time. In order to prevent such interaction, in the administration of antibiotics from the group of tetracyclines or quinolones, strontium treatment with ranelate should be stopped.
    In the combined administration of strontium ranelate with food additives or vitamin D preparations, no interaction was established.
    There was no clinically significant interaction or an increase in the level of strontium ranelate in the blood with simultaneous application of strontium ranelate with the following medicines: non-steroidal anti-inflammatory drugs (including acetylsalicylic acid), anilides (for example, paracetamol), blockers H2-histamine receptors and proton pump inhibitors, diuretics, cardiac glycosides (including digoxin), organic nitrates and other vasodilators used in heart diseases, slow calcium channel blockers, beta adrenoblockers, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists , selective beta-2-adrenomimetics, oral anticoagulants, platelet aggregation inhibitors, statins, fibrates and benzodiazepine derivatives.
    Special instructions:
    Cardiac ischemic events
    In the pooled data of randomized placebo-controlled trials, there was a significant increase in the incidence of myocardial infarction in patients with postmenopausal osteoporosis taking strontium ranelate, compared with the placebo group.
    Treatment of patients with osteoporosis can be prescribed only by a doctor who has experience in the treatment of osteoporosis.
    Before the start of treatment and regularly in the future doctors are recommended to assess the risk of developing cardiovascular diseases.
    Patients with severe risk factors for cardiovascular disease(eg, hypertension, hyperlipidemia, diabetes, smoking) can be prescribed strontium ranelate Only after careful consideration of the ratio of benefit and risk.
    Treatment with Osteolate should be discontinued if the patient develops ischemic heart disease, peripheral arterial disease, cerebrovascular disease, or if the arterial hypertension becomes uncontrolled.
    Patients with renal insufficiency
    In patients with chronic renal failure, it is recommended to monitor kidney function. In view of the lack of sufficient data, the use of Osteopath in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) is not recommended (see section "Pharmacokinetics"),
    Patients with VTE
    In clinical studies, there was an increase in the incidence of VTE, including thromboembolism of the pulmonary artery. The reason for this phenomenon is not currently fixed.
    Care should be taken when treating patients with an increased risk of developing VTE.
    When treating patients older than 80 years with an increased risk of developing VTE, the doctor is recommended to re-evaluate the need to continue treatment with Osteopath.
    In the treatment of patients at risk of VTE or patients with a possible increase in the risk of VTE, special attention should be paid to identifying possible symptoms of this complication, as well as to carrying out its adequate prevention. It should be borne in mind that the risk of venous thrombosis is elevated in patients on bed rest and / or in preparation for surgery. In conditions that lead to immobilization, treatment with Osteopath should be stopped immediately. The decision to resume therapy is possible in the event of a complete recovery of the patient's motor activity. When developing symptoms of VTE, treatment with Osteopath should also be stopped immediately.
    Skin Reactions
    Against the background of the use of strontium ranelate, cases of development of severe, life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis and drug rash in combination with eosinophilia and systemic symptoms (DRESS-syndrome) were noted.
    Patients should be informed of the signs and symptoms of skin reactions. The maximum risk of developing Stevens-Johnson syndrome was noted during the first weeks of treatment, the time from the start of taking strontium ranelate until the development of the DRESS syndrome was usually 3-6 weeks.
    In case of signs or symptoms of Stevens-Johnson syndrome or toxic epidermal necrosis (for example, a spreading skin rash, often with blisters or lesions of the mucous membranes) or DRESS syndrome (rash, fever, eosinophilia and systemic symptoms such as adenopathy, hepatitis, interstitial nephropathy, interstitial lung disease), the use of Osteopath must be stopped immediately.
    The best results in the treatment of the described skin reactions are achieved with the early diagnosis and immediate cessation of the use of any suspicious drug.
    In most cases, DRESS-syndrome was resolved after drug withdrawal and the beginning of glucocorticosteroid therapy. The process of resolving this side effect could be long. There were cases of recurrence of DRESS-syndrome with the abolition of glucocorticosteroids.
    Patients who stopped taking strontium ranelate due to the development of hypersensitivity reactions should not resume therapy with strontium ranelate.
    Reports of severe cases of hypersensitivity reactions, including skin rash, Stevens-Johnson syndrome or toxic epidermal necrolysis,patients in Asian countries are more likely to be diagnosed, although in general they are rare.
    Laboratory Tests
    Strontium affects the results of colorimetric methods for estimating the concentration of calcium in the blood and urine. To more accurately assess the concentration of calcium in the blood, it is necessary to use methods such as atomic emission spectrometry with inductively coupled plasma or atomic absorption spectrometry.
    Excipients
    The composition of auxiliary substances of the drug Osteolat is aspartame, which can cause an undesirable reaction in patients with phenylketonuria (a rare metabolic disorder).
    Effect on the ability to drive transp. cf. and fur:
    Strontium ranelat does not affect the ability to drive vehicles and perform work that requires increased attention and speed of psychomotor reactions. Nevertheless, it is necessary to take into account the possibility of developing unwanted reactions during the use of the drug (headache, impaired consciousness, convulsions, dizziness, vertigo) and to use caution when operating vehicles and mechanisms.
    Form release / dosage:
    Powder for suspension for oral administration, 2 g.
    Packaging:
    4 grams of powder in a sachet of a combination film material or from a combined multilayered material, or from a foil laminated packaging.
    For 7, 14, 28, 56, 84, 100 sachets with instructions for medical use are placed in a pack of cardboard.
    Storage conditions:
    Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
    Shelf life:
    2 years.
    Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-002645
    Date of registration:08.10.2014 / 11.12.2015
    Expiration Date:08.10.2019
    The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia
    Manufacturer: & nbsp
    Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia
    Information update date: & nbsp15.06.2017
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