Strommetta (Strometta)

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: & nbspDpellets for the preparation of a suspension for oral administration.
    Composition:

    One packet contains:

    active substance: strontium ranelate octahydrate 2.561 g in terms of strontium ranelate anhydrous - 2.00 g;

    Excipients: aspartame - 0.020 g, maltodextrin - 0.400 g, mannitol - up to 4,000 g.

    Description:

    The granules are white to light yellow in color. Available from white to light yellow powder.

    Pharmacotherapeutic group:osteoporosis treatment
    ATX: & nbsp

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

    M.05.B.X.03   Strontium ranelate

    Pharmacodynamics:

    In studies in vitro strontium ranelate:

    - stimulates the formation of bone in bone tissue culture, and also stimulates the replication of osteoblast precursors and the synthesis of collagen in bone cell culture;

    - reduces bone resorption by suppressing the differentiation of osteoclasts, as well as their resorptive activity. As a result of the drug, the balance between the formation and destruction of bone tissue changes toward bone formation processes.

    The strontium ranelate activity was studied in experiments using various preclinical models. In particular, in experiments on intact rats, the use of strontium ranelate led to an increase in the trabecular bone mass, the number of trabeculae and their thickness, as a result of which the mechanical properties of the bone improved.

    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the drug, strontium ranelate, was mainly absorbed on the surface of hydroxyapatite crystals and only slightly superseded calcium in these crystals in the newly formed bone. Strontium ranelate does not change the characteristics of bone tissue 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 received so far indicate that these factors are approximately 50% an increase in the BMD index after 3 years of treatment with strontium ranelate at a dose of 2 g / day. These data should be taken into account when interpreting changes in the BMD index during treatment with strontium ranelate.

    In clinical studies that confirmed the ability of strontium ranelate to reduce fracture risk, the 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 tissue formation (bone fraction of alkaline phosphatase (SHF) 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 onthe main pharmacological properties are 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.

    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.

    Treatment of postmenopausal osteoporosis

    In the course of studies involving more than 6.5 thousand postmenopausal women with documented osteoporosis, the effect of strontium ranelate 2 g / day 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 becomes reliable, beginning with the first year of therapy.The relative risk of vertebral fractures accompanied by clinical manifestations (defined as fractures with the development of the 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 has been confirmed with respect to reducing the risk of new vertebral fractures, 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 CO) at the age of more than 74 years, 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.

    In patients over the age of 80 years, according to combined research data, there was a decrease in the relative risk of new vertebral fractures by 32% in 3 years.

    Treatment of osteoporosis in men

    The effectiveness of strontium ranelate in the treatment of osteoporosis in men has been demonstrated in a two-year clinical trial involving 243 patients at high risk of fractures (mean age of the patients was 72.7 years, the mean T-score index lumbar spine BMD -2.6; 28 % with vertebral fractures in the anamnesis).

    In the course of 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 therapy, strontium ranelate showed a statistically significant increase in the average lumbar spine BMD (primary endpoint of 5.32%; p <0.001), similar values ​​were observed in studies on the effect 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, the organic part, due to which the required values ​​of molecular weight are achieved, favorable pharmacokinetic properties and good tolerance of the drug are provided. The pharmacokinetic properties of strontium and ranelic acid were evaluated in the group of healthy young men and healthy postmenopausal women, as well as during prolonged use of the drug in the postmenopausal women with osteoporosis, including elderly women.

    Due to the high polarity of ranelic acid, absorption, distribution and association with plasma proteins are low. Ranelic acid does not cumulate and does not show metabolic activity in the body of laboratory animals and humans. Absorbed woundelic acid is rapidly and unchanged removed from the human body by the kidneys.

    Suction

    Absolute bioavailability of strontium after taking 2 g of strontium ranelate is about 25% (from 19 to 27%). The maximum concentration in blood plasma is achieved 3-5 hours after taking the drug inside at a dose of 2 g. Equilibrium concentration is achieved after 2 weeks of therapy. The intake of strontium ranelate along with calcium, food and food additives reduces the bioavailability of strontium by about 60-70% in comparison with the indicators of bioavailability when taking the drug 3 hours after eating. Due to the relatively slow absorption of strontium, calcium and food intake should be avoided both before and after taking strontium ranelate. Preparations and nutritional supplements of vitamin A D do not have any effect on the absorption of strontium.

    Distribution

    The volume of distribution of strontium is about 1 l / kg. In humans, the relationship of strontium with plasma proteins is low (25%); strontium is characterized by a high affinity for bone tissue. Measurement of strontium concentration in the ileal biopsy specimens in patients who received strontium ranelate at a dose of 2 g / 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.There is no data on the removal of strontium from bone tissue after discontinuation of therapy.

    Metabolism

    Representing a divalent cation, strontium is not metabolized in the human body. Strontium ranelate It does not suppress the isoenzymes of the cytochrome P450 system.

    Excretion

    The removal of strontium depends on the dose and time. Effectivenessthe 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 special clinical cases

    Elderly patients

    Data on pharmacokinetics in elderly patients indicate that there is no correlation between age and the determined strontium clearance.

    Patients with renal insufficiency

    In patients with mild to moderate renal insufficiency (creatinine clearance 30-70 ml / min), the strontium clearance decreases as creatinine clearance decreases (by approximately 30% for creatinine clearance values ​​ranging from 30 to 70 ml / min ), which leads to an increase in the concentration of strontium in the blood plasma.In clinical studies, in 85% of the patients, the creatinine clearance was 30-70 ml / min, and in 6% less than 30 ml / min at the time of enrollment, with a mean creatinine clearance of about 50 ml / min. Thus, no dose adjustment in patients with mild to moderate renal insufficiency is 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

    There are no data on the pharmacokinetics of the drug in patients with hepatic insufficiency. 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 fractures in order to reduce the 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 in order to reduce it (withintolerance or the presence of contraindications to the use of other drugs for the treatment of osteoporosis).

    The decision to prescribe the drug should be taken after a general risk assessment for the patient.

    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 venous thromboembolism (VTE); in patients with severe cardiovascular risk factorsdiseases (for example, arterial hypertension, hyperlipidemia, diabetes, smoking).

    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:

    Inside.

    Treatment with STROMETTA can be prescribed only by a doctor who has experience in the treatment of osteoporosis.

    The recommended daily dose is 2 g (the contents of one sachet) per day.

    Due to the fact that food, preparations and calcium supplements, milk and dairy products can reduce the absorption of strontium ranelate, it is necessary to take the drug in between meals, preferably at bedtime, at least 2 hours after eating.

    The preparation of STROMETTA should be taken in the form of a suspension, for the preparation of which the contents of one sachet should be mixed in one glass in at least 30 ml of water (about 1/3 of an ordinary glass).

    Suspension is recommended to be taken orally immediately after application.

    Due to the chronic nature of the disease, the drug STROMETTA is expected to be taken for a long time.

    Patients with osteoporosis taking the drug STROMETTA, it is necessary to additionally take drugs and / or nutritional supplements of calcium and vitamin D with insufficient intake of these substances with food.

    Use in elderly patients

    The effectiveness and safety of strontium ranelate in patients of a wide age group is established. Correction of the dose of the drug depending on the age is not required (see the sections "Pharmacokinetics" and "Special instructions").

    Application for renal failure

    In patients with mild or moderate renal insufficiency (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 STROMETTA 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.

    Children

    The safety and efficacy of strontium ranelate in children less than 18 years of age have not been studied, and therefore this drug should not be prescribed to patients of this age group.

    Side effects:

    The incidence of adverse 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 <1000 cases) 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, paresthesia, dizziness; infrequently, convulsions.

    From the side of the vessels: often - venous thromboembolism.

    From the heart: often myocardial infarction.

    From the gastrointestinal tract: often - nausea, diarrhea, unformed stool, vomiting, abdominal pain, flatulence,constipation, dyspepsia, gastroesophageal reflux; infrequent - damage to the oral mucosa, including stomatitis and / or ulceration of the oral mucosa, dry mouth.

    From the skin and subcutaneous tissues: very often - skin reactions of hypersensitivity, including rash, itching, hives, angioedema (see section "Special instructions"); often - eczema; infrequently - dermatitis, alopecia; rarely - DRESS-syndrome (see section "Special instructions"); very rarely - severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (see section "Special instructions").

    Laboratory and instrumental data: often transient acute increase in the activity of the muscle fraction of creatine phosphokinase (CK), more than 3 times higher than the upper limit of the norm (in most cases, it returned to normal on continuation of treatment with strontium ranelate without changing the therapy).

    From the side of musculoskeletal and connective tissue: very often - muscle spasm, myalgia, bone pain, arthralgia and pain in the extremities.

    Disorders of the psyche: often - insomnia; infrequently - confusion.

    From the liver and biliary tract: often-hepatitis; nechahundred - increased activity of "hepatic" transaminases (in connection with skin reactions of hypersensitivity).

    From the respiratory system, organs of the chest and mediastinum: often - hyperreactivity of the bronchi.

    On the part of the blood and lymphatic system: infrequently - lymphadenopathy (in connection with skin reactions of hypersensitivity); rarely - bone marrow failure, eosinophilia (due to skin reactions of hypersensitivity).

    Hearing disorders and labyrinthine disorders: often - Vertigo.

    Disorders from the metabolism and nutrition: often - hypercholesterolemia.

    General disorders: often - peripheral edema; infrequently - hyperthermia (due to skin reactions of hypersensitivity), malaise.

    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 the drug STROMETTA and the specified 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 absorption of strontium ranelate (a decrease in the area under the curve AUC on 20-25%), while with the appointment of an antacid drug 2 hours after taking 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 drug administration is inconvenient, since strontium ranelate it is recommended to take before bedtime. In this regard, simultaneous administration of antacid preparations and strontium ranelate is allowed.

    Since molecular complexes containing divalent cations interact in the gastrointestinal tract with antibiotics of tetracycline (for example, doxycycline) and quinolone (e.g., ciprofloxacin) series, the simultaneous use 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 with the oral administration of antibiotics from the group of tetracyclines or quinolones, strontium treatment with ranelate should be stopped.

    With the combined administration of strontium ranelate with nutritional supplements or vitamin preparations D no interaction was established.

    There was no clinically significant interaction or increase in the concentration of strontium ranelate in the blood with concomitant use of strontium ranelate with the following medicines: non-steroidal anti-inflammatory drugs (including acetylsalicylic acid), anilides (for example, paracetamol), blockers H2-gistaminovyh receptors and proton pump inhibitors, diuretics, cardiac glycosides (including digoxin), organic nitrates and other vasodilators used in heart diseases; blockers of "slow" calcium channels, beta-adrenoblockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, selective beta2adrenomimetics, oral anticoagulants, inhibitors of platelet aggregation, statins, fibrates and benzodiazepine derivatives.

    Special instructions:

    After dissolving the drug in water, the suspension is stable for 24 hours. Nevertheless, the suspension should be consumed immediately after preparation.

    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 beginning of treatment and regularly in the future (every 6-12 months) doctors are recommended to assess the risk of developing cardiovascular diseases.

    Patients with severe risk factors for developing cardiovascular diseases (eg, hypertension, hyperlipidemia, diabetes, smoking) strontium ranelate can be appointed only after careful consideration of the ratio of benefit and risk.

    Treatment with STROMETT should be discontinued if the patient develops ischemic heart disease, peripheral arterial disease, cerebrovascular disease, or if the arterial hypertension becomes uncontrolled.

    Venous thromboembolism

    In clinical placebo-controlled studies, there was an increase in the incidence of VTE, including pulmonary embolism. The reason for this phenomenon is not currently fixed. The use of the drug STROMETTA is contraindicated in patients with VTE in the anamnesis (see the section "Contraindications").

    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, a doctor is recommended to re-evaluate the need to continue treatment with STROMETTA.

    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 STROMETT 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 STROMETTA should also be stopped immediately.

    Patients with renal insufficiency

    In patients with chronic renal failure, it is recommended to monitor kidney function. In the absence of sufficient data, the use of STROMETTA in patients with severe renal failure (creatinine clearance less than 30 ml / min) is not recommended (see section "Pharmacokinetics").

    Skin Reactions

    Against the background of the application of strontium ranelate, cases of development of severe, life-threatening skin reactions (Stevens-Johnson syndrome,toxic epidermal necrolysis, drug rash in combination with eosinophilia and systemic symptoms (DRESS-syndrome)).

    Patients should be informed of the signs and symptoms of skin reactions. The maximum risk of development of Stevens-Johnson syndrome and toxic epidermal necrolysis was noted during the first weeks of treatment, the time from the start of taking strontium ranelate to development DRESS-syndrome, as a rule, was 3-6 weeks.

    In case of signs or symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis (for example, a spreading skin rash, often with blisters or lesions of mucous membranes) or DRESS-Syndrome (skin rash, fever, eosinophilia and systemic symptoms such as adenopathy, hepatitis, interstitial nephropathy, interstitial lung disease) The use of STROMETT should be immediately discontinued.

    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 the drug was discontinued and glucocorticosteroid therapy was started. The process of resolving this side effect could be long. There were cases of relapse DRESS-Syndrome for 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, have been observed in patients in Asian countries at a higher frequency, although, in general, rarely.

    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 excipients of the drug STROMETTA includes 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 side effects when using the drug (headache, impaired consciousness, convulsions, dizziness, vertigo) and take care when driving vehicles and mechanisms.

    Form release / dosage:

    Granules for oral suspension, 2 g.

    Packaging:

    By 4.0 g of the drug in multi-layered laminated bags.

    For 14, 28, 56, 84 or 100 bags together with the instruction for use are placed in a cardboard box.

    Storage conditions:

    Store at a temperature not exceeding 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003469
    Date of registration:26.02.2016
    Expiration Date:26.02.2021
    The owner of the registration certificate:K.O. Ромфарм Компани С.Р.Л.K.O. Ромфарм Компани С.Р.Л. Romania
    Manufacturer: & nbsp
    Representation: & nbspРомфарма ОООРомфарма ООО
    Information update date: & nbsp26.07.2016
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