Meldonium-LF solution for intravenous injection 500mg/5ml in ampoules №5×2

Name:
Meldoniy-LF solution for injections 500mg/5ml N10.
Description:
Transparent colorless solution. Composition One ampoule contains: active substance: meldonium dihydrate – 500.0 mg; excipient: water for injection – up to 5 ml. Pharmacotherapeutic group Other drugs for the treatment of heart diseases. ATX code: S01EB22. Pharmacological action Pharmacodynamics Meldonium is a precursor of carnitine, a structural analogue of gamma-butyrobetaine (GBB), in which one carbon atom is replaced by a nitrogen atom. Meldonium, reversibly inhibiting gamma-butyrobetaine hydroxylase, reduces the biosynthesis of carnitine and prevents the transport of long-chain fatty acids through cell membranes, thus preventing the accumulation in cells of a strong detergent, an unoxidized activated form of fatty acids. Thus, damage to cell membranes is prevented. With a decrease in the concentration of carnitine under conditions of ischemia, β-oxidation of fatty acids is delayed and oxygen consumption in cells is optimized, glucose oxidation is stimulated, and ATP transport from biosynthesis sites (in mitochondria) to consumption sites (in the cytosol) is resumed. Essentially, the cells are supplied with nutrients and oxygen, and the use of these substances is optimized. In turn, with an increase in the biosynthesis of the precursor of carnitine, GBB, NO-synthetase is activated, as a result of which the rheological properties of blood improve and peripheral vascular resistance decreases. With a decrease in the concentration of meldonium, the biosynthesis of carnitine is again enhanced and the amount of fatty acids in the cells gradually increases. Coronary heart disease (stable exertional angina) An analysis of clinical data on the course use of meldonium in the treatment of stable exertional angina in combination with other antianginal drugs showed that the drug reduces the frequency and intensity of angina attacks, as well as the amount of nitroglycerin used. The drug exhibits a pronounced antiarrhythmic effect in patients with coronary heart disease (CHD) and cardiac extrasystoles, a lesser effect is observed in patients with supraventricular extrasystoles. The drug has the ability to reduce oxygen consumption at rest, which is considered an effective criterion for antianginal therapy for CAD. Meldonium has a positive effect on atherosclerotic processes in the coronary and peripheral vessels, reducing the total serum cholesterol level and the atherogenic index. Chronic heart failure Relatively numerous clinical studies have analyzed the role of the drug in the treatment of chronic heart failure as a result of CAD and noted its ability to increase exercise tolerance, as well as the volume of work performed in patients with heart failure. Efficacy in cerebrovascular accidents and neurological diseases It has been proved that meldonium is an effective means of complex treatment of acute and chronic cerebrovascular accidents (ischemic stroke, chronic cerebrovascular insufficiency). Meldonium normalizes the tone and resistance of the capillaries and arterioles of the brain. The effect of meldonium on the rehabilitation process in patients with neurological disorders (after past diseases of the blood vessels of the brain, operations on the brain, injuries, past tick-borne encephalitis) was studied. The results of testing the therapeutic activity of the drug indicate its dose-dependent positive effect on physical endurance and restoration of functional activity during the recovery period. It has been established that the drug improves the convalescent quality of life, in addition, the drug helps to eliminate mental disorders in the patient. Meldonium has a positive effect on the regression of disorders of the nervous system in patients with neurological deficits during the recovery period. Pharmacokinetics Pharmacokinetics have been studied in healthy subjects using meldonium intravenously and orally. Absorption After intravenous administration of multiple doses, the maximum concentration of meldonium in blood plasma (Cmax) reached 25.50 ± 3.63 μg / ml. Bioavailability was increased in individuals with an increase in Cmax, area under the time-concentration curve (AUC) and half-life (T1 / 2), in patients with cirrhosis of the liver and in patients with severe renal insufficiency. With intravenous administration, AUC after single and repeated doses of meldonium is different. These results indicate a possible accumulation of meldonium in the blood plasma. Distribution Meldonium is rapidly distributed from the bloodstream into the tissues. Plasma protein binding increases in a time dependent manner after a dose. Meldonium and its metabolites partially overcome the placental barrier. Studies on the release of meldonium into human breast milk have not been conducted. Metabolism Meldonium is metabolized primarily in the liver. Withdrawal Renal excretion plays a significant role in the excretion of meldonium and its metabolites. After a single intravenous application of meldonium at doses of 250 mg, 500 mg and 1000 mg, the early elimination half-life of meldonium is 5.56-6.55 hours, the final elimination half-life is 15.34 hours. Special groups of patients Elderly patients The dose of meldonium should be reduced in elderly patients with impaired liver or kidney function, who have increased bioavailability. Patients with impaired renal function Patients with impaired renal function, who have reduced metabolism and excretion, should reduce the dose of meldonium. There is an interaction between the renal reabsorption of meldonium or its metabolites (eg, 3-hydroxymeldonium) and carnitine, resulting in increased renal clearance of carnitine. There is no direct effect of meldonium, GBB and meldonium/GBB combinations on the renin-angiotensin-aldosterone system. Patients with impaired liver function Patients with impaired liver function, who have reduced metabolism and excretion, should reduce the dose of meldonium. No changes in liver function have been observed in humans following doses of 400-800 mg. A possible infiltration of fats into the liver cells cannot be ruled out. Indications for use Meldonium-LF is used in complex therapy in the following cases: – diseases of the heart and circulatory system: stable exertional angina, chronic heart failure (NYHAI-III functional class), cardiomyopathy, functional disorders of the cardiovascular system; – acute and chronic disorders of cerebral circulation; – reduced performance, physical and psycho-emotional overload; – the recovery period after cerebrovascular accidents, head injuries and encephalitis. Method of application and dosageIntravenously. Due to the possible stimulating effect, it is recommended to apply in the morning. The use of the drug does not provide for special preparation before administration. As part of complex therapy, 0.5-1.0 g of meldonium (5-10 ml of solution for intravenous administration) is administered intravenously per day, using the entire dose at once or dividing it into 2 injections for 10-14 days, followed by a transition to intake. The general course of treatment is 4-6 weeks. The course of treatment can be repeated 2-3 times a year. Elderly patients Elderly patients with impaired liver and / or kidney function should reduce the dose of meldonium. Patients with impaired renal function Since the drug is excreted from the body through the kidneys, patients with mild to moderate renal impairment should use a lower dose of meldonium. Patients with hepatic impairment Patients with mild to moderate hepatic impairment should use a lower dose of meldonium. Children There are no data on the safety and efficacy of meldonium in children and adolescents under the age of 18, so the use of this drug in children and adolescents is contraindicated. Side effects In the following, the listed side effects are classified according to the groups of the organ system and the frequency of occurrence of MedDRA: often (> 1/100 to < 1/10), rarely (> 1/10,000 to < 1/1000). On the part of the immune system Often: allergic reactions. Rarely: hypersensitivity, allergic dermatitis, urticaria, angioedema, anaphylactic reaction. On the part of the psyche Rarely: agitation, fear, obsessive thoughts, sleep disturbances. From the side of the nervous system Often: headaches *. Rare: paresthesia, tremor, hypoesthesia, tinnitus, vertigo, dizziness, gait disturbances, presyncope, loss of consciousness. From the side of the heart Rarely: arrhythmia, palpitations, tachycardia / sinus tachycardia, atrial fibrillation, chest discomfort / chest pain. On the part of the vessels Rarely: increase / decrease in blood pressure, hypertensive crisis, hyperemia, pallor of the skin. On the part of the respiratory system, chest and mediastinum Rarely: inflammation in the throat, cough, dyspnea, apnea. From the gastrointestinal tract Often: dyspepsia *. Rare: dysgeusia (metallic taste in the mouth), loss of appetite, gagging, nausea, vomiting, gas accumulation, diarrhea, abdominal pain. On the part of the skin and subcutaneous tissues Rarely: rashes, general / macular / papular rashes, itching. From the musculoskeletal system and related system Rarely: back pain, muscle weakness, muscle spasms. From the side of the kidneys and urinary system Rarely: pollakiuria. General disorders and reactions at the injection site Rarely: general weakness, trembling, asthenia, edema, swelling of the face, swelling of the legs, sensation of heat, sensation of cold, cold sweat. Investigations Rare: Electrocardiogram (ECG) abnormalities, accelerated heart rate, eosinophilia*. * Side effects observed in previous uncontrolled clinical trials. Epigastric pain and migraine have also been reported in connection with the use of meldonium. Reporting suspected adverse reactions It is important to report suspected adverse reactions after registration of a medicinal product in order to ensure continuous monitoring of the benefit-risk balance of the medicinal product. Medical professionals are encouraged to report any suspected adverse drug reactions through the national system for reporting adverse reactions (RCE Center for Expertise and Testing in Healthcare, http://www.rceth.by). Contraindications - Hypersensitivity to meldonium dihydrate. - Increased intracranial pressure (in violation of venous outflow, intracranial tumors). - Severe renal and / or hepatic insufficiency (there is not enough data on the safety of use). - Pregnancy and lactation. - Children under 18 years of age (safety of use has not been established) Overdose There are no reports of cases of overdose of meldonium. The drug has low toxicity and does not cause threatening side effects. Symptoms: in case of low blood pressure, headaches, dizziness, tachycardia, general weakness are possible. Treatment: symptomatic. In case of severe overdose, it is necessary to monitor the functions of the liver and kidneys. Hemodialysis is not significant due to the pronounced binding of meldonium to proteins. Precautions: Patients with chronic liver and / or kidney disease should be careful when using the drug (monitoring of liver and / or kidney function is necessary). Many years of experience in the treatment of acute myocardial infarction and unstable angina in cardiology departments shows that meldonium is not a first-line drug in acute coronary syndrome. Interaction with other drugs Meldonium-LF can be used in conjunction with long-acting nitrates and other agents for the treatment of stable exertional angina, together with cardiac glycosides and diuretics for the treatment of heart failure. Meldonium-LF can be combined with anticoagulants, antiaggregants, antiarrhythmic drugs and drugs that improve microcirculation. Meldonium-LF may enhance the effect of drugs containing glyceryl trinitrate, nifedipine, beta-blockers, other antihypertensive drugs and peripheral vasodilators. In patients with chronic heart failure, taking both meldonium and lisinopril to reduce symptoms, a positive effect of combination therapy was revealed (vasodilation of the main arteries, improvement of peripheral circulation and quality of life, reduction of psychological and physical stress). When using meldonium in combination with orotic acid to eliminate damage caused by ischemia / reperfusion, an additional pharmacological effect was observed. As a result of the simultaneous use of Sorbifer and meldonium in patients with anemia caused by iron deficiency, the composition of fatty acids in red blood cells improved. Meldonium helps eliminate pathological changes in the heart caused by azidothymidine (AZT), and indirectly affects the oxidative stress reactions caused by AZT, leading to mitochondrial dysfunction. The use of meldonium in combination with AZT or other drugs for the treatment of acquired immunodeficiency syndrome (AIDS) has a positive effect on AIDS therapy. An overdose of meldonium may increase the cardiotoxicity caused by cyclophosphamide. It is not recommended to use together with other drugs containing meldonium, as the risk of side effects may increase. Use during pregnancy and lactation Animal studies are insufficient to assess the effect of meldonium on pregnancy, embryonic and fetal development, childbirth and postpartum development. The potential risk to humans is unknown. The drug during pregnancy is contraindicated. It is not known whether the drug is excreted in human breast milk. A risk to newborns/infants cannot be ruled out, so this drug should not be used while breastfeeding. Influence on the ability to drive vehicles and control mechanisms There are no data on the effect on the ability to drive vehicles and maintain mechanisms. Storage conditionsStore at a temperature not exceeding 25 °C. Keep out of the reach of children. Shelf life 3 years. Do not use after the expiry date stated on the package. Packing: 5 ml solution for intravenous administration in colorless glass ampoules with a break ring. 5 ampoules in a cell package. 1 or 2 cell packs together with instructions for medical use in a cardboard pack. Conditions of release By prescription. Buy Meldonium-LF solution for intravenous injection 500mg / 5ml in ampoules No. 5x2 in injections 500mg/5ml in ampoules No. 5x2