Strometta, 2 g 28 pcs

In in vitro studies strontium ranelate:

• stimulates bone formation in bone tissue culture and stimulates the replication of osteoblast precursors and collagen synthesis in bone cell culture;
• reduces bone resorption by inhibiting osteoclast differentiation as well as their resorptive activity. As a result of the drug action the balance between the formation and destruction of bone tissue changes in the direction of the processes of bone formation.

The activity of strontium ranelate has been studied in experiments using different preclinical models. In particular, in experiments on intact rats the use of strontium ranelate resulted in the increase of trabecular bone mass, the number of trabeculae and their thickness, resulting in the improvement of bone mechanical properties.

In the bone tissue of humans and experimental animals to which the drug was administered, strontium ranelate was mainly absorbed on the surface of hydroxyappatite crystals and only marginally replaced the calcium in these crystals in the newly formed bone.

Strontium ranelate does not change the characteristics of bone crystals. No adverse effects on bone quality or mineralization were found in clinical studies according to iliac crest biopsies performed after therapy with strontium ranelate at a dose of 2 g per day for up to 60 months.

The combined effects of strontium distribution in bone tissue and increased X-ray absorption by strontium compared to calcium result in increased bone mineral density (BMD) as measured by two-photon X-ray absorptiometry.

The data to date 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/day. These data should be considered when interpreting the change in BMI during treatment with strontium ranelate.

In clinical studies confirming the ability of strontium ranelate to reduce the risk of fractures, the mean BMI increased in the group of patients treated with strontium ranelate compared to baseline – for the lumbar vertebrae by approximately 4% per year and for the femoral neck by 2% per year; after 3 years the increase in BMI was 13-15% and 5-6% respectively (according to various studies).

From the third month of therapy and over 3 years of follow-up, there was an increase in biochemical markers of bone formation (bone alkaline phosphatase (ALP) fraction and C-terminal procollagen type I propeptide) and a decrease in bone resorption markers (C-terminal and N-terminal telopeptide cross-linked in urine) compared to placebo.

For strontium ranelate, a secondary effect to the main pharmacological properties is a slight decrease in serum concentrations of calcium and parathyroid hormone, as well as an increase in blood phosphorus concentration and total alkaline phosphatase activity, which, however, is not accompanied by any clinical effects.

The risk factors for postmenopausal osteoporosis include decreased bone mass, reduced BMD, early menopause, a history of smoking, and a family history of osteoporosis.

One of the most clinically significant complications of osteoporosis is the development of fractures, and the risk of fracture increases with the number of risk factors.

The treatment of postmenopausal osteoporosis

In studies involving more than 6,500 postmenopausal women with documented osteoporosis, the effects of strontium ranelate 2 g/day on fracture prevention were studied. Use of strontium ranelate was shown to reduce the relative risk of new vertebral fractures by 41% after 3 years of therapy.

This effect becomes credible from the first year of therapy. The relative risk of vertebral fractures accompanied by clinical manifestations (defined as fractures with the development of pain syndrome and/or a decrease in the patient’s height by at least 1 cm) was reduced by 38%.

Strontium ranelate therapy also significantly reduced the number of patients whose height decreased by 1 cm or more compared to placebo.

The efficacy of strontium ranelate in reducing the risk of new vertebral fractures has been confirmed, including in patients with no history of osteoporosis-related fractures.

In the group of patients at high risk of fracture (femoral neck BMI T-criterion value of ≤3 CO) over 74 years of age, administration of strontium ranelate for 3 years reduced the risk of femoral fracture by 36% compared to the group of patients receiving placebo.

In patients over the age of 80, pooled study data showed a 32% reduction in the relative risk of new vertebral fractures over 3 years.

The treatment of osteoporosis in men

. The efficacy of strontium ranelate in treating osteoporosis in men was demonstrated in a two-year clinical study involving 243 patients at high risk for fractures (mean age of patients was 72.7 years and mean T-criterion value of lumbar spine BMD -2.6; 28% with a history of vertebral fractures).

The patients received calcium (1000 mg/day) and vitamin D (800 IU/day) during the study.

A statistically significant increase in BMD was seen after 6 months of therapy (compared to placebo).

After 12 months of therapy with strontium ranelate showed a statistically significant increase in mean lumbar spine BMD (primary efficacy criterion 5.32%; p < 0.001), similar values were noted in studies of the effect of strontium ranelate on fracture prevention in postmenopausal women.

A statistically significant increase in femoral neck BMD and femoral BMD index (p < 0.001) was observed 12 months after initiation of strontium ranelate therapy.

Indications

Osteoporosis in postmenopausal women (to reduce the risk of spine and hip fractures).

Active ingredient

Composition

1 sachet contains:

The active ingredient:

Excipients:

aspartame – 0.02 g,

maltodextrin – 0.4 g,

mannitol – up to 4 g.

How to take, the dosage

Intravenously.

The treatment with STROMETTA should only be prescribed by a physician experienced in the treatment of osteoporosis.

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

Because food, calcium preparations and supplements, milk and dairy products may decrease absorption of strontium ranelate, the drug should be taken between meals, preferably before bedtime, at least 2 hours after meals.

The drug STROMETTA should be taken as a suspension, which can be made by mixing the contents of one sachet in one glass of at least 30 ml of water (about 1/3 of a normal glass).

The suspension is recommended for oral administration immediately after use.

Due to the chronic nature of the disease, STROMETTA is intended to be taken over a long period of time.

Patients with osteoporosis who are taking STROMETTA need to take additional calcium and vitamin D supplements if their dietary intake is insufficient.

Interaction

Special Instructions

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

Cardiac coronary events

In pooled data from randomized placebo-controlled trials, there was a significant increase in the incidence of myocardial infarction in patients with postmenopausal osteoporosis taking strontium ranelate compared to the placebo group.

The treatment of patients with osteoporosis should only be prescribed by a physician experienced in the treatment of osteoporosis.

Physicians are advised to assess the risk of cardiovascular disease before starting treatment and regularly thereafter (every 6-12 months).

Patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes, smoking) strontium ranelate may be prescribed only after careful consideration of the benefit-risk ratio.

The treatment with STROMETTA must be discontinued if the patient develops coronary heart disease, peripheral artery disease, cerebrovascular disease or if arterial hypertension becomes uncontrollable.

Venous thromboembolism

In clinical placebo-controlled studies, there has been an increased incidence of VTE, including pulmonary thromboembolism. The cause of this phenomenon is currently unknown. STROMETTA is contraindicated in patients with a history of VTE (see section “Contraindications”).

Caution should be exercised when treating patients with increased risk of VTE.

When treating patients over 80 years of age with an increased risk of VTE, the physician is advised to reevaluate whether to continue treatment with STROMETTA.

When treating patients at risk of VTE or patients with possible increased risk of VTE, special attention should be given to identifying possible symptoms of this complication, as well as providing adequate prophylaxis.

It should be kept in mind that the risk of venous thrombosis is increased in patients who are on bed rest and/or in preparation for surgery. In conditions that result in immobilization, treatment with STROMETTA should be discontinued immediately.

The decision to resume therapy is possible if the patient has complete restoration of motor activity. If symptoms of VTE occur, treatment with STROMETTA should also be discontinued immediately.

Patients with renal impairment

In patients with chronic renal impairment, monitoring of renal function is recommended. Due to insufficient data, the use of the drug STROMETTA in patients with severe renal impairment (creatinine clearance less than 30 ml/min) is not recommended (see section “Pharmacokinetics”).

Skin reactions

In cases of severe, life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash combined with eosinophilia and systemic symptoms (DRESS syndrome)) have been reported with strontium ranelate.

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

. If signs or symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g., spreading skin rash, often with blistering or mucosal lesions) or DRESS syndrome (skin rash, fever, eosinophilia and systemic symptoms such as adenopathy, hepatitis, interstitial nephropathy, interstitial lung disease) are noted, use of STROMETTA should be stopped immediately.

The best results in the treatment of the described skin reactions are achieved with early diagnosis and immediate discontinuation of any suspected drug.

In most cases, DRESS syndrome resolved after withdrawal of the drug and initiation of glucocorticosteroid therapy. The process of resolution of this side effect could be lengthy. There have been cases of relapse of DRESS syndrome when glucocorticosteroids are withdrawn.

Patients who have discontinued strontium ranelate due to the development of hypersensitivity reactions should not resume therapy with strontium ranelate.

Severe cases of hypersensitivity reactions, including skin rash, Stevens-Johnson syndrome, or toxic epidermal necrolysis, have been reported with greater frequency in Asian patients, although generally rare.

Laboratory tests

Strontium affects the results of colorimetric methods of estimating calcium concentrations in blood and urine. Methods such as inductively coupled plasma atomic emission spectrometry or atomic absorption spectrometry should be used to more accurately estimate blood calcium concentrations.

Auxiliary substances

The excipients of the drug STROMETTA include aspartame, which may cause an undesirable reaction in patients with phenylketonuria (a rare metabolic disorder).

The effect on the ability to drive:

Strontium ranelate does not affect the ability to drive vehicles or perform work requiring increased attention and rapid psychomotor reactions.

Even so, the possibility of side effects of the drug (headache, impaired consciousness, seizures, dizziness, vertigo) must be taken into account and caution must be exercised while driving vehicles and operating machinery.

Contraindications

In patients at increased risk of venous thromboembolism (VTE); in patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes, smoking).

Side effects

The incidence of adverse reactions is presented as follows: very common (≥1/10 cases), common (≥1/100 and <1/10 cases), infrequent (≥1/1000 and <1/100 cases), rare (≥1/10000 and <1000 cases) very rare (<1/10000 cases including individual reports).

Unwanted reactions that have been noted in the post-marketing period of use of strontium ranelate and whose incidence cannot be calculated from available data are designated “incidence unknown”.

Nervous system disorders: often – headache, impaired consciousness, memory loss, paresthesia, dizziness; infrequently – seizures.

Vascular disorders: frequently – venous thromboembolism.

Cardiac disorders: often – myocardial infarction.

Gastro-intestinal tract: frequently – nausea, diarrhea, loose stools, vomiting, abdominal pain, flatulence, constipation, dyspepsia, gastroesophageal reflux; rarely – lesions of the oral mucosa, including stomatitis and/or ulceration of the oral mucosa, dry mouth.

Skin and subcutaneous tissue: very common – skin hypersensitivity reactions, including rash, pruritus, urticaria, angioedema (see section “Special Indications”); often – eczema; infrequent – dermatitis, alopecia; rarely – DRESS syndrome (see section “Particular Indications”). (see section “Particular indications”); very rarely – severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (see section “Particular indications”).

Laboratory and instrumental data: often – transient acute increase in the activity of muscle fraction of creatine phosphokinase (CPK), more than 3 times the upper limit of normal (in most cases it returned to normal by itself when strontium ranelate treatment was continued without changing therapy).

Muscular and connective tissue disorders: very often – muscle spasm, myalgia, bone pain, arthralgia and pain in the extremities.

Mental disorders: often – insomnia; infrequently – confusion.

Hepatic and biliary tract disorders: frequent – hepatitis; infrequent – increased “hepatic” transaminase activity (due to skin hypersensitivity reactions).

Respiratory system, thoracic and mediastinal organs: often – bronchial hyperresponsiveness.

The blood and lymphatic system: infrequent lymphadenopathy (due to skin hypersensitivity reactions); rarely – bone marrow failure, eosinophilia (due to skin hypersensitivity reactions).

Hearing and labyrinth disorders: often – vertigo.

Metabolic and nutrition disorders: often – hypercholesterolemia.

General disorders: frequently – peripheral edema; infrequently – hyperthermia (due to skin hypersensitivity reactions), malaise.

Overdose

When using strontium ranelate up to 4 g per day for a maximum duration of 147 days, no clinically significant adverse events were observed.

In healthy volunteers, a single dose of up to 11 g did not result in any particular symptoms.

In cases of overdose, administration of milk or antacids is recommended to reduce absorption of the active substance in the gastrointestinal tract. If the recommended dose is significantly exceeded, vomiting should be induced to remove the unabsorbed active ingredient.

Pregnancy use

Pregnancy

Strontium ranelate is intended only for the treatment of women in the postmenopausal period.

There are no clinical data on the use of strontium ranelate during pregnancy. The drug is contraindicated in pregnancy.

If pregnancy occurs while taking the drug, the treatment should be stopped immediately.

Breast-feeding period

Strontium penetrates into the breast milk. The drug is contraindicated during breastfeeding.