INSTRUCTION
medical use of the drug
Actovegin
Pharmacological group. Agents affecting the digestive system and metabolic processes. ATX code A16A X.
Pharmacological properties.
Pharmacological.
The drug Actovegin is a deproteinization of hemoderivat from the blood of calves, containing only physiological substances with a molecular weight of less than 5000 daltons.
Actovegin has three main effects: metabolic, neuroprotective and microcirculatory. Inositol phosphate oligosaccharides (IFO), which are part of the drug Actovegin, are responsible for improving the utilization and absorption of oxygen, as well as for improving energy metabolism and glucose absorption. This action has the potential to be beneficial after injury or damage to tissues and organs, in particular the brain, and reduce lactate production.
Several pathways have been identified by which the neuroprotective mechanism of action of the drug Actovegin is carried out, due to the effect on the structure of beta-amyloid peptides (Aß25-35), which induce apoptosis. Beta-amyloid peptides act as triggers in a number of molecular and cellular processes, including oxidative stress and inflammation, resulting in neuronal death, which in turn leads to impaired memory and cognitive functions.
Nuclear factor kappa B (NF-KB) performs numerous functions in processes in both the central and peripheral nervous systems. It regulates the process of inflammation, which aggravates the course of degenerative and vascular disorders, and is a factor that is involved in the formation of pain syndrome, in the processes of learning, memory and neuroprotection.
Actovegin activates the NF-KB expression reporter gene in a dose-dependent manner, and this transient activation may at least partially explain the neuroprotective properties of Actovegin.
Another important mechanism of action of actovegin is associated with the nuclear enzyme field (ADP-ribose) polymerase (PARP). UARP plays an important role in the detection of single-stranded DNA breaks and in the repair process, however, excessive activation of this enzyme can trigger processes in the cell that lead to the completion of oxidative metabolism. These processes can ultimately lead to cell death due to depletion of energy reserves. It was revealed that Actovegin reduces the activity of PARP, which improves the functioning and optimizes the morphological structure of the central and peripheral nervous system.
The positive effect of the drug Actovegin on microcirculation is due to such effects as an increase in the blood flow rate in the capillaries, a decrease in the pericapillary zone and a decrease in the smooth muscle tone of the precapillary arterioles and capillary sphincters, a decrease in arterio-venular shunting of blood with an increase in blood flow in the capillary bed and an increase in the function of endothelialis. channel.
Clinical efficacy and safety.
Disorders of cerebral circulation, including post-stroke cognitive impairment and dementia. Actovegin has been shown to be beneficial in the symptomatic treatment of dementia and dementia-related conditions in over 450 patients in several small randomized clinical trials. It was shown to be effective compared to placebo on endpoints related to cognitive function, daily activity and overall clinical response, while no statistically significant improvement in the speed of cognitive processes was found.
In a 12-month, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of Actovegin in patients with post-stroke cognitive impairment was compared with placebo. 503 patients (250 patients received Actovegin) were randomized from the 5th to the 7th day after the onset of ischemic stroke. The 6-month treatment period consisted of ≤ 20 infusions (2000 mg daily) followed by a tablet-form (2 tablets 200 mg three times a day), followed by a 6-month follow-up treatment, during which patients were kept in accordance from standard clinical practice. At 6 and 12 months, patients treated with Actovegin showed statistically significant changes in the number of points on the extended cognitive subscales of the Alzheimer's disease scale (ADAS-cog +) and on the Montreal Cognitive Assessment Scale (MoCA) compared with patients who received a placebo.
At the 3rd, 6th and 12th months in the majority of patients in the group receiving the drug Actovegin, there was a response to treatment according to the ADAS-cog + scale. The incidence of serious adverse events and deaths was similar in both treatment groups. The overall incidence of recurrent ischemic stroke during the study was within the limits assumed for this patient population, but a slightly higher incidence was observed in the group receiving Actovegin compared with the placebo group.
Peripheral blood flow disorders and their consequences. Approximately 190 patients with peripheral arterial disease received Actovegin treatment for a period of 10 to 42 days in several small, comparative randomized trials, which showed a short-term advantage of Actovegin infusions over placebo. An improvement in the form of an increase in walking distance of 35-42% was demonstrated in the group receiving the drug Actovegin compared with the placebo group.
In an open, randomized study, 60 patients with large trophic ulcers of the lower extremities with venous insufficiency received a standard therapy regimen with or without the addition of Actovegin. The drug Actovegin was administered in the form of daily intravenous infusions of 250 ml of a 10% solution for 4 weeks. The average healing time for ulcers was 31 days (in the group receiving Actovegin) and 42 days (in the group not receiving Actovegin). An improvement in the number of points on the pain intensity scale compared with the baseline level was observed in both groups, in particular, in the group receiving the drug Actovegin, there was a decrease in the number of points by 4.47 to 1.77, and in the other study group - from 4.13 up to 2.07.
Diabetic polyneuropathy (DPN). In a study involving 70 patients with diabetic polyneuropathy, statistically significant changes in walking distance, nerve impulse conduction velocity and pain sensitivity were demonstrated in patients treated with Actovegin compared with a placebo group. The difference in the therapeutic effect of placebo was approximately 6.5 m at walking distance, 0.9 m / s in nerve impulse conduction velocity, and 6.8 points on the pain sensitivity scale (on a 100-point scale).
In a 6-month, double-blind, randomized, placebo-controlled study evaluating the safety and efficacy of 567 patients with type 2 diabetes mellitus and symptomatic diabetic distal polyneuropathy received 20 intravenous infusions of Actovegin (2000 mg / day) (n = 281 ) or placebo (n = 286) once a day for 20-36 days, after which they received 3 tablets of Actovegin (1800 mg / day) or placebo three times a day for 140 days. When using the drug Actovegin, there was a better effect compared to placebo according to the endpoint assessment on the overall symptom score (TSS), including positive neuropathic pain symptoms, burning sensation, paresthesias and numbness of the feet or legs, decreased vibration sensitivity and improved the quality of life of patients. There were no significant differences in the distribution of adverse events between the treatment group and the control group.
Pharmacokinetics.
Using pharmacokinetic methods, it is impossible to study the pharmacokinetic characteristics of Actovegin (absorption, distribution and elimination of active ingredients), since it consists only of physiological components that are usually found in the body.
The results obtained in studies on animals and in the framework of clinical studies have shown that the effect of the drug begins no later than 30 minutes after its administration. The maximum effect is achieved 3:00 after parenteral administration or oral administration of the drug (from 2 to 6:00).
Clinical characteristics.
Indications.
- Treatment of diseases of the brain of vascular origin, including post-stroke cognitive impairment and dementia.
- Treatment of peripheral (arterial, venous) blood circulation disorders and their complications (arterial angiopathy, venous trophic ulcer).
- Treatment of diabetic polyneuropathy (DPN).
Contraindications.
Hypersensitivity to any components of the drug or to drugs of a similar composition.
Interaction with other medicinal products and other types of interactions.
There are no data on the interaction of Actovegin with other drugs.
Features of the application.
Patients who have a rare hereditary fructose intolerance, impaired absorption of glucose-galactose or sucrose-isomaltose should not take the drug, since it contains sucrose.
Application during pregnancy or lactation.
The drug can be used during pregnancy and lactation only when the therapeutic benefit to the mother outweighs the possible risk to the fetus or child. During the use of the drug Actovegin with placental insufficiency, although rarely, deaths were observed, which could be a consequence of the underlying disease. The use of the drug Actovegin during breastfeeding was not accompanied by negative effects for either the mother or the child.
The ability to influence the reaction rate when driving or driving other mechanisms.
Actovegin has no or very little effect on the reaction rate when driving or using other mechanisms. However, one should take into account the possible manifestations of side effects from the nervous system (see Section "Adverse reactions").
Method of administration and dosage.
Actovegin, film-coated tablets, should be taken before meals, swallowed whole with a small amount of liquid.
Dosage: 1-2 tablets 3 times a day.
The duration of the course of treatment, the drug should be used from 4 to 6 weeks. Depending on the severity of the clinical course, treatment can be started with the use of injections or infusions.
With diabetic polyneuropathy.
The initial dose is 50 ml (2000 mg) per day as an intravenous infusion for 3 weeks, followed by switching to tablets - 2-3 tablets 3 times a day (up to 1800 mg) for at least 4-5 months.
Children. There are currently no data on the use of the drug in children; therefore, the drug is not recommended for this category of patients.
Overdose. Cases of overdose with Actovegin are unknown.
Adverse reactions.
The following are the side reactions that may occur in patients as a result of the use of the drug Actovegin. Anaphylactic (allergic) reactions may occur, which may manifest themselves:
on the part of the immune system and skin - possible hypersensitivity reactions, including allergic reactions, anaphylactic and anaphylactoid reactions up to the development of anaphylactic shock, fever, chills, angioedema, skin flushing, skin rashes, itching, urticaria, increased sweating, skin edema and / or mucous membranes, hot flashes;
from the digestive tract - dyspeptic phenomena, including pain in the epigastric region, nausea, vomiting, diarrhea;
on the part of the cardiovascular system - pain in the region of the heart, increased heart rate (tachycardia), shortness of breath, acrocyanosis, pallor of the skin, arterial hypotension or hypertension;
from the respiratory system - an increase in the frequency of breathing, a feeling of compression in the chest, difficulty swallowing and / or breathing, sore throat, an attack of suffocation;
from the nervous system - headache, general weakness, dizziness, loss of consciousness, agitation, tremors (tremors), paresthesia
from the musculoskeletal system - pain in the muscles and / or joints, pain in the lower back.
In such cases, treatment with Actovegin should be discontinued and symptomatic therapy should be applied.
Shelf life. 3 years.
Storage conditions. Store at a temperature not exceeding 25 ° C in its original packaging. Keep out of the reach of children!
Packaging. 50 tablets per bottle; 1 bottle in a cardboard box.
