Instructions for Sinarta solution for injection 200 mg/ml 2 ml ampoule with solvent in 1 ml ampoules No. 5
Composition
ampoule A
active ingredient: glucosamine sulfate sodium salt;
1 ml of solution contains glucosamine sulfate sodium salt in terms of 100% substance – 251.25 mg, in terms of glucosamine sulfate – 200 mg, in terms of sodium chloride – 51.25 mg;
excipients: lidocaine hydrochloride, water for injection;
ampoule B (solvent)
diethanolamine, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties:
ampoule A: clear, colorless or light yellow liquid (at the time of release). Clear, colorless or light yellow to yellow liquid (during the shelf life); ampoule B: clear, colorless liquid; ampoule A+B: clear, colorless or light yellow liquid (at the time of release). Clear, colorless or light yellow to yellow liquid (during the shelf life).
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A X05.
Pharmacological properties
Pharmacodynamics
The active ingredient, glucosamine sulfate, is a salt of the aminomonosaccharide glucosamine, which under physiological conditions is present in the human body and is used together with sulfates for the biosynthesis of hyaluronic acid of synovial fluid and glycosaminoglycans of the main substance of articular cartilage.
Thus, the mechanism of action of glucosamine sulfate is to stimulate the synthesis of glycosaminoglycans and, accordingly, articular proteoglycans. In addition, glucosamine has an anti-inflammatory effect and inhibits the process of destruction of articular cartilage mainly due to the possible manifestations of its own metabolic properties, the ability to inhibit the activity of interleukin 1 (IL-1), which on the one hand affects the symptoms of osteoarthritis, and on the other hand potentially delays structural damage to the joints, as evidenced by data from long-term clinical studies.
According to initial in vitro and in vivo studies, exogenous administration of glucosamine sulfate stimulates proteoglycan biosynthesis, which is deficient in osteoarthritis, promotes the fixation of sulfur ions during the synthesis of glycosaminoglycans, and improves trophicity of articular cartilage.
Subsequent studies have shown that glucosamine sulfate inhibits the synthesis of tissue-degrading substances such as superoxide radicals and the activity of lysosomal enzymes in addition to enzymes capable of degrading articular cartilage, such as collagenases and phospholipase A2. This action results in a moderate anti-inflammatory effect that is observed in in vivo animal models, including in some cases in experimental osteoarthritis, even without inhibition of cyclooxygenases, unlike nonsteroidal anti-inflammatory drugs (NSAIDs).
More recent studies have shown that most of the above metabolic and anti-inflammatory effects may be related to the inhibition of intracellular signal transduction of IL-1, one of the cytokines involved in the pathogenesis of osteoarthritis, with subsequent inhibition of cytokine-induced gene transcription. Glucosamine sulfate, at plasma and synovial fluid concentrations reported in patients with osteoarthritis, can actually inhibit IL-1-induced gene expression of a series of pro-inflammatory enzymes in joint tissues, as well as pro-degenerative enzymes in cartilage, such as some metalloproteases, including aggrecanases. The possible potential influence of sulfur ions on the aforementioned pharmacodynamic properties of glucosamine has not been fully elucidated.
All of the above properties have a beneficial effect on the degenerative processes in cartilage that underlie the pathogenesis of osteoarthritis, as well as on the clinical picture of the disease.
Short-term and medium-term studies have shown that the effectiveness of glucosamine sulfate on osteoarthritis symptoms is evident as early as 2-3 weeks after starting its use.
On the other hand, the efficacy of glucosamine sulfate treatment on symptoms, compared to conventional analgesics and nonsteroidal anti-inflammatory drugs, is optimal after a course of continuous use for 6 months or after a course of use for 3 months with an obvious after-effect within 2 months after discontinuation.
Clinical trial results of daily continuous treatment over 3 years show a progressive increase in its effectiveness, with regard to symptoms and slowing of structural joint damage, as confirmed by X-ray.
Glucosamine sulfate has been shown to be well tolerated. No significant effects of glucosamine sulfate on the cardiovascular, respiratory, autonomic, or central nervous systems have been identified.
Studies in humans and animals have shown that after oral administration of 14C-glucosamine, the radiolabeled elements are rapidly and almost completely absorbed systemically. In humans, about 90% of the radiolabeled dose is absorbed. The absolute bioavailability of glucosamine in rats after oral administration of glucosamine sulfate was 26% due to the first-pass effect. The absolute bioavailability in humans is unknown, but allometric calculations suggest that it is similar to that observed in rats, i.e., 20% to 30%.
In healthy volunteers, after multiple oral doses of 1500 mg glucosamine sulfate per day, the maximum steady-state plasma concentration (Cmax,ss) was 1602 ± 425 ng/ml (8.9 µM). This concentration was reached 1.5-4 hours (median: 3 hours) after administration (tmax). At steady state, the AUC of plasma concentrations versus time was 14564 ± 4138 ng/h/ml. These parameters were obtained when the drug was administered in the fasting state, so it is not known whether food intake can significantly affect the absorption of the drug.
Following oral administration, glucosamine is primarily distributed in the extravascular environment (including synovial fluid) following absorption, with a volume of distribution approximately 37 times greater than the total amount of water in the human body. Glucosamine protein binding has not been demonstrated.
The metabolic profile of glucosamine was not studied because this drug, being a natural substance present in the human body, is used for the biosynthesis of some components of articular cartilage.
Only the terminal elimination half-life of glucosamine from human plasma has been determined based on the results of a study of plasma glucosamine levels measured for 48 hours after oral administration of the drug. The calculated value was approximately 15 hours.
Following oral administration of 14C-glucosamine, urinary excretion of radiolabeled elements in humans was 10 ± 9% of the administered dose, while faecal excretion was 11.3 ± 0.1%. Urinary excretion of unchanged glucosamine in humans following oral administration was on average low (approximately 1% of the administered dose). These results indicate that the kidneys do not play a significant role in the excretion of glucosamine and/or its metabolites and/or breakdown products.
Glucosamine pharmacokinetics were linear after multiple dosing of 750-1500 mg once daily, while plasma glucosamine levels were lower than expected with increasing doses at 3000 mg. Steady-state glucosamine pharmacokinetics were independent of time, with no accumulation or reduction in bioavailability compared to the pharmacokinetic profile observed after single administration.
The pharmacokinetics of glucosamine in men and women are similar, and no differences in pharmacokinetics have been found between healthy volunteers and patients with osteoarthritis of the knee. In the latter, the mean plasma concentration 3 hours after the last dose of 1500 mg with repeated administration once daily was 7.2 µM and was similar to that found in healthy volunteers, while the mean concentration in synovial fluid was only 25% lower and therefore also in the range of 10 µM. The pharmacokinetics of glucosamine have not been studied in patients with renal or hepatic insufficiency, since, given the safety profile of the drug and due to the minor involvement of the kidneys in the elimination of glucosamine, a dose reduction in these groups of patients is not envisaged.
The equilibrium concentrations of glucosamine in blood plasma and synovial fluid, after repeated administration of 1500 mg once daily, are in the range of 10 mM and, therefore, correspond to those for which pharmacological activity has been shown in studies in in vitro experimental models, which confirms the mechanism of action and clinical effect of the drug.
Indication
Treatment of osteoarthritis symptoms: pain and functional limitation.
Contraindication
Individual hypersensitivity to the active substance or to any of the excipients, tendency to bleeding.
The drug Cinarta® should not be used in patients with shellfish allergy, because the active substance is obtained from shellfish shells, such patients may be more prone to developing allergic reactions to glucosamine with possible exacerbation of symptoms of their disease.
The injectable form of the drug contains the excipient lidocaine, which has the following contraindications: cardiogenic shock, severe arterial hypotension, severe forms of chronic heart failure, reduced left ventricular function, atrioventricular block of the II-III degree, severe bradycardia, blood clotting disorders, Wolff-Parkinson-White syndrome, Adams-Stokes syndrome; history of seizures caused by the use of lidocaine; sick sinus syndrome, severe liver dysfunction, hypovolemia, myasthenia gravis, infections at the injection site, hypersensitivity to other amide-type anesthetics (since there is an increased risk of developing cross-hypersensitivity reactions).
Interaction with other medicinal products and other types of interactions
Mixing the contents of ampoules with other injectable drugs should be avoided.
Specific drug interaction studies have not been performed. However, given the physicochemical and pharmacokinetic properties of glucosamine sulfate, the potential for interactions is expected to be low. In addition, glucosamine sulfate has been shown to neither inhibit nor induce the major human CYP450 enzymes.
In fact, the drug does not compete for absorption mechanisms; after absorption, it does not bind to plasma proteins, but is metabolized by incorporation as an endogenous substance into proteoglycans or is broken down without the participation of cytochrome system enzymes, as a result of which it is unlikely to interact with other drugs.
An increased effect of coumarin anticoagulants has been reported in patients receiving concomitant glucosamine therapy. Therefore, it is advisable to monitor coagulation parameters in such patients.
The drug is compatible with nonsteroidal anti-inflammatory drugs and glucocorticosteroids.
Increased gastrointestinal absorption of tetracycline is possible.
The injectable form of the drug contains the excipient lidocaine. Cimetidine, peptidine, bupivacaine, propranolol, quinidine, disopyramide, amitriptyline, nortriptyline, chlorpromazine, imipramine increase the level of lidocaine in the blood serum, reducing its hepatic metabolism. Noradrenaline has a synergistic effect when interacting with lidocaine.
MAO inhibitors should be used with caution, as they increase the risk of developing arterial hypotension and prolong the local anesthetic effect of the latter.
When used simultaneously with class IA antiarrhythmic drugs (including quinidine, procainamide, disopyramide), the QT interval is prolonged, and in very rare cases, AV block or ventricular fibrillation may develop.
The cardiotonic effect of cardiac glycosides is weakened.
When used simultaneously with sedatives, the sedative effects are enhanced.
Phenytoin enhances the cardiodepressive effect of lidocaine.
When used simultaneously with procainamide, delusions and hallucinations are possible.
Lidocaine may enhance the effect of drugs that cause neuromuscular blockade, since the latter reduce the conductivity of nerve impulses. Ethanol enhances the respiratory depressant effect of lidocaine.
Application features
The drug can only be administered by medical professionals.
It should be prescribed with caution to patients with glucose intolerance. At the beginning of treatment, it is advisable to monitor blood sugar levels in patients with diabetes.
Use the drug with caution in the treatment of patients suffering from bronchial asthma, as such patients may be more prone to developing allergic reactions to glucosamine with possible exacerbation of their symptoms.
1 dose of the drug contains 40.3 mg of sodium. This should be taken into account when prescribing to patients who are on a strict salt-free diet.
To avoid accidental intravasal administration of the drug, it is recommended to perform an aspiration test.
The safety of lidocaine anesthetics is questionable in patients prone to malignant hyperthermia, so their use in such cases should be avoided.
Before using lidocaine for heart diseases (hypokalemia reduces the effectiveness of lidocaine), it is necessary to normalize the level of potassium in the blood and monitor the ECG.
Serum creatine phosphokinase activity may increase after intramuscular injection of the drug, which may lead to an error in the diagnosis of acute myocardial infarction.
In case of sinus node dysfunction, prolongation of the P-Q interval, QRS widening, or in case of the occurrence or exacerbation of arrhythmia, the dose should be reduced or the drug should be discontinued.
Special caution should be exercised when using the drug in patients with circulatory failure, arterial hypotension, a history of arrhythmias, moderate hepatic and/or renal dysfunction. Due to the presence of lidocaine in the composition, caution should also be exercised when prescribing to elderly patients, patients with epilepsy, with impaired cardiac conduction, and with respiratory failure.
Use during pregnancy or breastfeeding
There are no data on the use of the drug during pregnancy or breastfeeding, therefore the use of the drug is contraindicated in this category of patients.
The ability to influence the reaction speed when driving or working with other mechanisms
Studies on the effect of the drug on the ability to drive a car and use other mechanisms have not been conducted. Caution should be exercised when driving vehicles and performing work that requires attention. In case of drowsiness, fatigue, dizziness or visual impairment, driving a car and working with other mechanisms is prohibited.
Method of administration and doses
For intramuscular use! The drug is not intended for intravenous administration.
Adult and elderly patients.
The prepared solution of the drug should be administered intramuscularly in 3 ml or 6 ml (solution A+B) 3 times a week for 4-6 weeks.
The presence of a yellowish color of the solution in ampoule A does not affect the efficacy and tolerability of the medicinal product.
Injections of the drug can be combined with oral administration of the drug in the form of a powder for preparing a solution.
Glucosamine is not indicated for the treatment of acute pain.
Relief of symptoms (especially pain relief) may occur only after several weeks of treatment, and in some cases even after a longer time. No dose adjustment recommendations are given for patients with impaired renal and/or hepatic function, as no relevant studies have been conducted.
Children
Do not use in children and adolescents, as the safety and efficacy of the drug in such patients have not been established.
Overdose
No cases of overdose have been reported. In cases of overdose, symptomatic treatment should be carried out, aimed at restoring water and electrolyte balance.
The injectable form of the drug contains the excipient lidocaine. The first symptoms of an overdose of lidocaine hydrochloride from the central nervous system may be numbness of the tongue and lips, excitement, euphoria, anxiety, tinnitus, dizziness, blurred vision, nystagmus, tremor, depression, drowsiness, loss of consciousness, up to coma, tonic-clonic convulsions. As indicated in the literature, symptoms of an overdose associated with lidocaine hydrochloride from the cardiovascular system and respiratory function may be a decrease in blood pressure, collapse, AV block and respiratory depression. It is necessary to monitor the patient's cardiovascular and respiratory function.
Changes in these parameters may indicate an overdose of the drug, so the patient should be provided with oxygen immediately. All complications require symptomatic treatment.
Side effects
On the part of the digestive system: abdominal pain, flatulence, dyspepsia, diarrhea, constipation, nausea, vomiting; hyperglycemia in patients with impaired glucose tolerance;
from the nervous system: headache, drowsiness, increased fatigue, dizziness;
from the immune system: hypersensitivity reactions, including allergic reactions, exacerbation of bronchial asthma;
On the part of the organs of vision: visual disturbances;
Skin and subcutaneous tissue disorders: erythema, pruritus, rash; angioedema, urticaria, hair loss, abscess;
local reactions: reactions at the injection site.
The injectable form of the drug contains lidocaine. In exceptional cases, side effects characteristic of this component are possible:
from the digestive system: nausea, vomiting;
from the nervous system: numbness of the tongue and lips, photophobia, diplopia, headache, confusion, muscle twitching, when used in high doses - tinnitus, excited state, anxiety, paresthesia, convulsions, loss of consciousness, coma, hyperacusis;
From the side of the organs of vision: visual impairment, conjunctivitis; when used in high doses - nystagmus;
mental disorders: sleep disorders;
Cardiovascular system: arterial hypotension, transverse heart block; increased blood pressure; when used in high doses - arrhythmia, bradycardia, slowing of cardiac conduction, cardiac arrest, peripheral vasodilation, collapse, tachycardia, pain in the heart area;
Immune system disorders: immune system suppression, allergic reactions including edema, skin reactions, itching; urticaria, hypersensitivity reactions including anaphylactoid reactions (including anaphylactic shock), generalized exfoliative dermatitis;
from the respiratory system: respiratory depression or respiratory arrest, shortness of breath;
others: feeling of heat, cold or numbness of the extremities, malignant hyperthermia; when used in high doses - rhinitis;
local reactions: tingling of the skin at the injection site, abscess, slight burning sensation (disappears with the development of the anesthetic effect within 1 minute), thrombophlebitis.
Expiration date
2 years.
Do not use the drug after the expiration date indicated on the package.
The prepared solution should be used immediately.
Storage conditions
Store in a place protected from light at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
Ampoule A: 2 ml of solution in a brown transparent glass ampoule.
Ampoule B: 1 ml of solvent in a colorless, transparent glass ampoule.
5 ampoules A and 5 ampoules B in blisters, respectively.
1 blister with ampoules A and 1 blister with ampoules B in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
