Bivalis( strontium ranelate) instructions:
"Les Laboratoires Servier Industrie" for "Les Laboratoires Servier", France / France
Bivalos active ingredients:
Granules for suspension 2 g in bags No. 7, No. 14, No. 28, No. 56.
To whom is Bivalos shown?
Treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fracture.
How to use Bivalos?
For oral administration.
The recommended daily dose is 2 grams of strontium ranelate( 1 single dose package) per day, before use dissolve in a glass of water.
Bivalos should be taken at intervals between meals.
Bivalos should be taken before bedtime, preferably not earlier than 2 hours after eating.
The contents of one sachet should be poured into a glass, add water and stir the granules in water until a slurry forms( evenly distributed pellets in water).The suspension should be drunk immediately after preparation.
Shelf life of the finished suspension is 24 hours. If the suspension is not able to drink immediately after preparation, before use, it should be stirred.
Bivalos( strontium ranelate) is intended for long-term use.
Elderly patients, patients with impaired renal function, patients with impaired hepatic function - see "Precautions".
Patients treated with strontium ranelate are advised to take vitamin D and calcium supplements if their intake with food is inadequate.
Food intake, including milk and dairy products, as well as drugs containing calcium, can reduce the absorption and bioavailability of strontium ranelate by about 60-70%.Therefore, between taking the drug Bivalos and the above substances, you must adhere to the interval of at least 2 hours. Given the slow absorption of strontium ranelate, Bivalos should be taken before bedtime, preferably not earlier than 2 hours after eating.
The effectiveness and safety of strontium ranelate have been established in various age categories( up to the age of 100 years at the time of enrollment) of postmenopausal women with osteoporosis. There is no need to adjust the dose depending on age.
Application for renal dysfunction
Patients with mild to moderate renal insufficiency( creatinine clearance 30-70 ml / min.) Do not need a dose adjustment. Strontium ranelate is not recommended for patients with severe renal insufficiency( creatinine clearance less than 30 ml / min) due to lack of data.
In patients with chronic renal failure, periodic assessment of renal function is recommended. The question of the continuation of therapy with the drug Bivalos patients who developed severe renal failure should be addressed on the basis of an individual approach.
Patients with hepatic dysfunction
Strontium ranelate is not metabolized, so patients with impaired liver function do not need a dose adjustment.
Application in children and adolescents
The effectiveness and safety of strontium ranelate for children and adolescents has not been established, therefore its use in these age groups is not recommended.
Venous thromboembolism( VTE)
Clinical studies have shown that strontium ranelate therapy was associated with an increase in the annual incidence of venous thromboembolism( VTE), including pulmonary embolism. The reason for this is not established. Bivalos should be used with caution in patients with an increased risk of VTE, including patients with VTE in the anamnesis. In the treatment of patients at risk or patients who have increased the risk of VTE, special attention should be given to the possible development of signs and symptoms of VTE and to conduct appropriate prevention of venous thromboembolism.
Strontium can affect the parameters of colorimetric methods for determining the concentration of calcium in the blood and urine. Therefore, in order to guarantee an accurate assessment of the concentration of calcium in the blood and urine, it is recommended to use the inductively coupled plasma atomic emission spectrometry method or the atomic absorption spectrometry method in clinical practice.
Bivalos contains a substance( aspartame), which is a source of phenylalanine, which can be harmful to patients with phenylketonuria.
Pregnancy and lactation
The drug Bivalos is intended only for use by women in the postmenopausal period. There are no clinical data on the effect of strontium ranelate during pregnancy. Experimental studies have shown that high doses can cause back effects relative to the bone tissue of the offspring of rats and rabbits that were given the drug during pregnancy. If by negligence Bivalos is used during pregnancy, treatment should be canceled. Strontium is excreted into breast milk. Strontium ranelate is not recommended for prescribing during lactation.
Impact on the ability to drive vehicles and work with precise mechanisms.
Strontium ranelate does not affect the ability to drive vehicles and work with precise mechanisms. If signs of side effects appear, you need to be careful.
Side effects of Bivalos.
Bivalos was studied in clinical trials in which about 8,000 patients participated. The safety of the drug for long-term use was evaluated in women with osteoporosis in the postmenopausal period who were treated for 56 months with strontium ranelate at a dose of 2 g / day( n = 3352) or placebo( n = 3317) during clinical trials. The mean age at the time of enrollment was 75 years, and 23% of the patients enrolled in the study were 80-100 years old.
The overall incidence of adverse events in treatment with strontium ranelate did not differ from that with placebo, and adverse events were generally mild and had a reversible character.
The most common side effects were nausea and diarrhea, which were usually reported at the beginning of therapy, after which there were no significant differences between comparable groups. The abolition of therapy was due mainly to nausea( 1.3% and 2.2% in the placebo group and strontium ranelate, respectively).
Adverse reactions that could be associated with the use of strontium ranelate, indicated below, using the following rule: very often( & gt; 1/10);often( & gt; 1/100 and ≤ 1/10);infrequent( & gt; 1/1000 and & lt; 1/100);Rare( & gt; 1 / 10,000 and ≤ 1/1000);very rare( & lt; 1 / 10,000).
From the nervous system
- Often: headache, impaired consciousness, memory.
- infrequently: convulsions.
- Often: nausea, diarrhea, loose stools.
From the skin and subcutaneous tissues
- Often - dermatitis, eczema.
- Infrequent: Venous thromboembolism( VTE).
Clinical studies lasting more than 4 years have shown that the annual incidence of venous thromboembolism( VTE) with strontium ranelate compared with placebo was about 0.7%, with a relative risk of 1.42( confidence interval of 1.02, 1, 98, p = 0.036)( see section "Precautions").
Indicators of laboratory studies
There was a reversible increase in activity( 3 times the upper limit of the norm) of creatine kinase( its musculoskeletal fraction) in the group of people taking strontium ranelate 1.0% compared with placebo 0.4%.In most cases, these rates returned spontaneously to normal levels, without changing the treatment regimen.
Who is Bivalos contraindicated?
Hypersensitivity to the active substance or any of the excipients of the drug.
Interaction of Bivalos.
Taking medications containing calcium can reduce the bioavailability of strontium ranelate by about 60-70%.Therefore, between taking the drug Bivalos and the above drugs should adhere to an interval of at least 2 hours.
Antacid preparations containing aluminum and magnesium hydroxide.
The use of aluminum and magnesium hydroxide at the same time or less than 2 hours before the reception of strontium ranelate leads to a slight decrease in the absorption of strontium ranelate( AUC decrease by 20-25%).The use of antacid agents 2 hours after taking strontium ranelate practically does not affect the absorption of strontium ranelate. This is why antacids, containing aluminum and magnesium hydroxide, are recommended to take at least two hours after taking Bivalos. However, if it is difficult to comply with antacid preparations at least two hours after using Bivalos in connection with the recommended use of Bivalos before bedtime, simultaneous administration of Bivalos and antacid preparations is permitted.
Tetracycline for oral use and antibacterial preparations of the quinolone range for oral use.
Divalent strontium ranelate cations can form in the gastrointestinal tract complexes with tetracycline for the oral base and antibacterial drugs of the quinolone group for oral administration and reduce their absorption. Simultaneous application of strontium ranelate is not recommended with these drugs. During the use of tetracyclines or antibiotics from the quinolone group for oral administration, the Bivalos drug should be discontinued temporarily.
No interaction was observed with oral vitamin D preparations.
Clinical studies did not reveal any interaction or increase in the level of strontium in blood when used with drugs that could probably be administered to a target group of patients concomitantly with Bivalos. Such agents include: non-steroidal anti-inflammatory drugs( including acetylsalicylic acid), anilides( for example, paracetamol), H2 receptor antagonists and proton pump inhibitors, diuretics, digoxin and cardiac glycosides, organic nitrates that are used for heart disease, calcium channel blockers,beta-blockers, ACE inhibitors, angiotensin II antagonists, selective beta2-adrenoreceptor agonists, oral anticoagulants, antiaggregants, statins, fibrates and benzodiazepine derivatives.
Overdose of Bivalos.
In a clinical study on the effect of repeated administration to healthy women in the postmenopausal period of strontium ranelate at a dose of 4 g per day for more than 25 days, a good tolerability of the drug was established. One-time use of strontium ranelate in doses up to 11 g in volunteers( healthy young men) did not cause the development of any clinically significant adverse reactions.
After the episodes of overdose during clinical trials( up to 4 g / day, with a maximum duration of treatment of 147 days), there was no development of any clinically significant adverse reactions.
In order to reduce the absorption of the active substance, it may be beneficial to take milk or antacid agents. In case of a significant overdose, it is recommended to wash the stomach to remove the active substance, which did not have time to absorb.