Actovegin solution for injection 400 mg ampoule 10 ml No. 5

Instructions Actovegin solution for injection 400 mg ampoule 10 ml No. 5

Composition

active ingredient: 1 ml of the drug contains: deproteinized hemoderivative from calf blood in the form of Actovegin concentrate, 40 mg of dry weight;

Excipients: sodium chloride, water for injections.

Dosage form

Solution for injection.

Main physicochemical properties: yellowish solution.

Pharmacotherapeutic group

Drugs affecting the blood system and hematopoiesis. Other hematological drugs. ATX code B06A B.

Pharmacological properties

Pharmacodynamics

Mechanism of action. Actovegin has three main groups of effects: metabolic, neuroprotective and microcirculatory. Inositol phosphate oligosaccharides (IPO), which are part of Actovegin, are responsible for improving oxygen utilization and absorption, as well as improving energy metabolism and glucose absorption. Such an action can potentially be beneficial after lesions or damage to tissues and organs, in particular the brain, and reduce lactate formation.

Several pathways have been identified by which the neuroprotective mechanism of action of the drug is carried out: Actovegin reduces apoptosis induced by beta-amyloid peptides (Aß25-35). Beta-amyloid peptides act as triggers in a number of molecular and cellular processes, including oxidative stress and inflammation, which ultimately causes neuronal cell death, which, in turn, leads to impaired memory and cognitive functions.

Nuclear factor kappa B (NF-KB) has multiple functions in both the central and peripheral nervous systems. It regulates inflammation, which worsens degenerative and vascular diseases, and is a factor involved in pain, learning, memory, and neuroprotection.

Actovegin dose-dependently activates the NF-KB expression reporter gene, 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 poly (ADP-ribose) polymerase (PARP). PARP plays an important role in the detection of single-strand DNA breaks and their repair, however, excessive activation of this enzyme can cause processes in the cell that lead to the termination of oxidative metabolism. These processes can ultimately lead to cell death due to the depletion of energy reserves. It has been found that Actovegin reduces the activity of PARP, which improves the functioning and optimizes the morphological structure of the central and peripheral nervous systems.

The positive effect of Actovegin on microcirculation is due to its effects such as increasing blood flow velocity in capillaries, reducing the pericapillary zone and reducing the tone of smooth muscles of precapillary arterioles and capillary sphincters, reducing arteriovenous shunting with increasing blood flow in the capillary bed, and enhancing the function of endothelial oxidase synthase in the microcirculatory bed.

Various parameters in animal and clinical studies have shown onset of effect within 30 minutes of administration. The maximum effect is achieved 3 hours after parenteral or oral administration (2–6 hours).

Clinical efficacy and safety.

In a 12-month randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of Actovegin in patients with post-stroke cognitive impairment, the effect of Actovegin was compared with placebo. 503 patients were randomized (250 patients received Actovegin) between the 5th and 7th day after the onset of ischemic stroke. The 6-month treatment period included up to 20 infusions (2000 mg daily) followed by tablet administration (2 tablets of 200 mg three times a day), followed by a 6-month follow-up period during which patients were managed according to standard clinical practice. After 6 and 12 months, patients treated with Actovegin showed statistically significant changes in the number of points on the expanded cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog+) and on the Montreal Cognitive Assessment Scale (MoCA) compared with patients treated with placebo. After 3, 6 and 12 months, a greater proportion of patients in the Actovegin group met the definition of responders on 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 expected range for this patient population, but a slightly higher incidence was observed in the Actovegin group compared with the placebo group.

Peripheral circulatory disorders and their consequences. Approximately 190 patients with peripheral arterial disease were treated with Actovegin for 10 to 42 days in several small, randomized, comparative studies that demonstrated a short-term advantage of Actovegin infusions over placebo. Improvements in walking distance of 35–42% were demonstrated in the Actovegin group compared to the placebo group.

In a 6-month randomized, double-blind, placebo-controlled study, the efficacy and safety of Actovegin in patients with Fontaine stage IIb peripheral arterial circulatory disorders (claudication < 200 m) were compared with placebo. A total of 366 subjects received intravenous infusions of Actovegin (1200 mg/day) (n = 184) or placebo (n = 182) daily for 2 weeks, followed by 2 tablets of Actovegin (1200 mg/day) or placebo 3 times daily for the next 10 weeks. A 12-week observation period without study treatment followed the course of treatment to assess sustained efficacy after treatment, as well as safety. The therapeutic effect of Actovegin was superior to placebo in terms of increasing the initial lameness distance and the absolute lameness distance at 2 and 12 weeks and was maintained for 12 weeks after the end of treatment. The results of this study showed that Actovegin (12-week treatment), administered first intravenously (2 weeks at a dose of 1200 mg/day) and then orally (10 weeks at a dose of 1200 mg/day) in patients with peripheral arterial circulatory disorders (stage IIb according to Fontaine), has an acceptable safety and tolerability profile.

In an open randomized study, 60 patients with large trophic ulcers of the lower extremities on the background of venous insufficiency received a standard therapy regimen with or without the addition of Actovegin. Actovegin was administered as daily intravenous infusions of 250 ml of a 10% solution for 4 weeks. The average time to ulcer healing was 31 days (in the group receiving Actovegin) and 42 days (in the group not receiving Actovegin). Improvement in the number of points on the pain intensity scale compared to the baseline was observed in both groups, in particular, in the group receiving Actovegin, a decrease in the number of points was noted from 4.47 to 1.77, and in the other study group - from 4.13 to 2.07.

Diabetic polyneuropathy (DPN). A study involving 70 patients with diabetic polyneuropathy demonstrated statistically significant changes in walking distance, nerve impulse conduction velocity, and pain sensitivity in patients treated with Actovegin compared to the placebo group. The difference in therapeutic effect compared to placebo was approximately 6.5 m in 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 profile, 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 daily for a maximum of 36 days, followed by 3 tablets of Actovegin (1800 mg/day) or placebo three times daily for 140 days. Actovegin was superior to placebo in the primary endpoint of the Total Symptom Score (TSS), including positive neuropathic pain symptoms, burning, paresthesia, and numbness of the feet or legs. No significant differences in the incidence of adverse events were found between the treatment and control groups.

Using pharmacokinetic methods, it is impossible to study the pharmacokinetic characteristics of the drug Actovegin (absorption, distribution and elimination of active ingredients), since it consists only of physiological components that are normally present in the body.

Indication

- Treatment of vascular brain diseases, including post-stroke cognitive impairment and dementia.

- Treatment of peripheral (arterial, venous) circulatory disorders and their complications (arterial angiopathy, venous trophic ulcer).

- Treatment of diabetic polyneuropathy (DPN).

Contraindication

Hypersensitivity to the active substance, any component of the drug or to drugs of similar composition. Decompensated heart failure, pulmonary edema, oliguria, anuria are general contraindications to infusion therapy, therefore, the administration of the drug in the form of infusions in these conditions is contraindicated due to possible hyperhydration.

Interaction with other medicinal products and other types of interactions

There is no data on the interaction of Actovegin with other drugs.

Application features

In a study involving patients with post-stroke cognitive impairment, a higher incidence of recurrent ischemic stroke was observed in the group using Actovegin. The overall incidence of recurrent ischemic stroke during the study was within the expected range for this patient population, but a slightly higher incidence was observed in the group receiving Actovegin compared to the placebo group (see section "Pharmacodynamics"). The benefit-risk ratio should be considered when continuing to use Actovegin in patients who have recently had a stroke.

It is advisable to administer no more than 5 ml intramuscularly per day, since the solution is hypertonic.

The solution for injection is compatible with 0.9% sodium chloride solution and 5% glucose solution.

Actovegin, solution for injection, should be used under sterile conditions. Since the product does not contain preservatives, the contents of the ampoule are intended for single use. Opened ampoules and the prepared solution should be used immediately. Unused product and waste materials should be disposed of in accordance with local requirements.

Due to the potential risk of anaphylactic reactions, it is recommended to perform a test injection (hypersensitivity test). After a test injection of Actovegin, solution for injection, it is necessary to monitor the condition of patients for the development of signs and symptoms of hypersensitivity. Patients should be under the supervision of a doctor for at least 30 minutes after the injection of the drug with full medical and instrumental equipment for the administration of anti-shock measures, if necessary.

In case of development of water and electrolyte disturbances (e.g. hyperchloremia, hypernatremia), appropriate correction should be made.

The solution for injection has a slightly yellowish tint. The intensity of the color may vary from batch to batch depending on the characteristics of the starting materials used, but this does not adversely affect the activity of the drug or sensitivity to it.

Do not use cloudy solutions or solutions with visible particles.

The active ingredient of Actovegin contains phenylalanine, which may be harmful to patients with phenylketonuria.

The drug Actovegin contains up to 13.7 mg of sodium in 1 ml of the drug, which should be taken into account by patients who follow a diet low in salt (sodium).

The active substance of Actovegin contains potassium. 1 ml of Actovegin, solution for injection, contains up to 2.5 mg of potassium, which should be taken into account in patients with reduced kidney function and patients on a controlled potassium diet.

Use during pregnancy or breastfeeding

The drug can be used during pregnancy or breastfeeding only when the therapeutic benefit to the mother outweighs the possible risk to the fetus or child. During the use of Actovegin for placental insufficiency, although rare, fatal cases were observed, which could be a consequence of the underlying disease. It is not recommended to use Actovegin for placental insufficiency. The use of Actovegin during breastfeeding was not accompanied by any negative effects for either the mother or the child.

Ability to influence reaction speed when driving vehicles or other mechanisms

Actovegin has no or very little effect on the speed of reaction when driving or using other mechanisms. However, possible manifestations of side effects from the nervous system should be taken into account (see the section "Adverse reactions").

Method of administration and doses

Actovegin, a solution for injection, is contained in ampoules with a break point.

How to open ampoules with a break point:

Actovegin, solution for injection, is administered intravenously, intraarterially, or intramuscularly and can be added to infusion solutions.

For use as infusions, it is necessary to add 10–50 ml of Actovegin, solution for injection, to 200–300 ml of the main solution (isotonic saline or 5% glucose solution).

When using the drug as an infusion, infusion systems with 15 μm filters should be used. The recommended infusion rate is approximately 2 ml/min.

The solution is administered intramuscularly slowly, no more than 5 ml per day, since it is hypertonic.

For specific indications, dosage selection is based on clinical trial data. General dosage recommendations are also provided.

In the treatment of brain diseases of vascular origin.

General dosage regimen:

Initially 10 ml (400 mg) intravenously daily for 2 weeks, then 5-10 ml (200-400 mg) intravenously several times a week for at least 4 weeks.

Dosage for post-stroke cognitive impairment and dementia:

Initially 50 ml (2000 mg) per day as an intravenous infusion up to a maximum of 20 infusions with subsequent transition to treatment with the tablet form of Actovegin.

In the treatment of peripheral (arterial, venous) circulatory disorders and their complications (arterial angiopathy, venous trophic ulcer).

General dosage regimen:

Depending on the severity of the patient's condition and clinical picture, initially 10-20 ml (400-800 mg) is administered intravenously or intraarterially daily; for further treatment, 5 ml (200 mg) is administered intravenously or slowly intramuscularly daily or several times a week.

Dosage regimen for peripheral arterial circulatory disorders of Fontaine stage IIb:

Initially, 30 ml (1200 mg) per day as an intravenous infusion for 2 weeks, followed by a transition to treatment with the tablet form of Actovegin.

Dosage regimen for arterial angiopathy:

Initially 20-50 ml (800-2000 mg) intravenously or intraarterially daily or several times a week; total duration up to 4 weeks.

Dosage regimen for venous trophic ulcers:

Initially 10 ml (400 mg) intravenously or 5 ml (200 mg) intramuscularly daily or several times a week depending on the healing process. In case of a large ulcer – 25 ml (1000 mg) as an intravenous infusion daily for 4 weeks.

In the treatment of diabetic polyneuropathy (DPN).

General dosage regimen:

Depending on the severity of the clinical picture, initially 10-20 ml (400-800 mg) intravenously or intraarterially daily; for further treatment 5 ml (200 mg) intravenously or slowly intramuscularly daily or several times a week.

Dosage for symptomatic diabetic distal polyneuropathy in patients with type 2 diabetes mellitus:

Initially 50 ml (2000 mg) per day as an intravenous infusion up to a maximum of 20 infusions for a maximum of 36 days, followed by a switch to treatment with the tablet form of Actovegin.

Children

There are currently no data on the use of the drug in children, so the drug is not recommended for use in this category of patients.

Overdose

Cases of overdose with Actovegin are unknown. Given the pharmacological properties of the drug, no additional undesirable effects are expected.

Adverse reactions

The following criteria are used to classify the frequency of adverse reactions, based on the guidelines of the Council of International Organizations of Medical Sciences (CIOMS): very common (≥ 1/10); common (≥ 1/100 but < 1/10); uncommon (≥ 1/1,000 but < 1/100); rare (≥ 1/10,000 but < 1/1,000); very rare (< 1/10,000).

On the part of the immune system:

Rare: hypersensitivity reactions, including allergic reactions. Anaphylactoid (allergic) reactions may occur, which may manifest as:

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, increased body temperature, chills, angioedema.

Rare: skin hyperemia, skin rashes, itching, urticaria, increased sweating, swelling of the skin and/or mucous membranes, hot flashes, changes at the injection site;

from the digestive tract - dyspeptic phenomena, including pain in the epigastric region, nausea, vomiting, diarrhea;

from the cardiovascular system - pain in the heart area, increased heart rate (tachycardia), shortness of breath, acrocyanosis, pale skin, arterial hypotension or hypertension;

on the part of the respiratory system – increased respiratory rate, feeling of tightness in the chest, difficulty swallowing and/or breathing, sore throat, shortness of breath;

from the nervous system - headache, general weakness, dizziness, loss of consciousness, agitation, tremor, paresthesia;

Musculoskeletal system: pain in muscles and/or joints, back pain.

In such cases, treatment with Actovegin, solution for injection, should be discontinued and symptomatic therapy should be applied.

Expiration date

3 years.

Storage conditions

Store at a temperature not exceeding 25 °C in the original packaging. Keep out of the reach of children!

The drug should not be mixed in the same container with other solutions, except those specified in the "Method of administration and dosage" section.

Packaging

2 ml in an ampoule; 25 ampoules in a cardboard box.

5 ml in an ampoule; 5 ampoules in a cardboard box.

10 ml in an ampoule; 5 ampoules in a cardboard box.

Vacation category

According to the recipe.

Producer

LLC "KUSUM PHARM", Ukraine/LLC "KUSUM PHARM", Ukraine.

(packaging of in-bulk manufacturer Takeda Austria GmbH, Austria).

Location of the manufacturer and its business address

Skryabina St., 54, Sumy, Sumy region, 40020, Ukraine/54, Skryabina str., Sumy, Sumy region, 40020, Ukraine.

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