Use of Actovegin in elderly patients with organic syndrome. Multicenter study of 1549 patients

Many will be interested to know that Actovegin is prohibited for import into the United States. What does Actovegin’s treatment of spinal hernia have to do with it? Everything should be told in order.

There are two fundamentally different approaches to drug trade. It is normal when a medicine is bought because it helps with a particular disease and has proven effectiveness. But, unfortunately, in the CIS countries (and in Russia in particular), a significant number of products are sold, not at all because they help, but because they are recommended, or because patients are accustomed to buying them. Their effectiveness has not been proven in any way; the product is sold as is. Why spend money on lengthy studies that could end catastrophically for the reputation of the “drug”? As a result, homeopathic pills, chondroprotectors, and various immunomodulators are on the shelves of pharmacies. Actovegin is one of these drugs.

Moreover, back in 2008, one of the leaders of the Russian branch of Nycomed, which produces Actovegin, said that an evidence base is not at all necessary, since Actovegin is already selling very well. And after a considerable time the situation has not changed at all. If you visit the Nycomed company website, which has now been renamed Takeda, you will find that information about Actovegin is only on the Russian-language page. The international version of this site, the page in English, does not say anything about Actovegin. Moreover, in those same developed countries, nothing is known at all about Actovegin as a medicinal drug. One gets the strange impression that this drug only helps citizens of Russia and residents of the CIS. The original source is here. https://www.kommersant.ru/doc/894934

Composition, release form and packaging

Actovegin for intravenous injection is produced in the form of a solution in ampoules of 2, 5, 10 and 20 ml.
One ampoule contains 80, 200 or 400 mg of the main active ingredient. The ampoules are placed in a plastic container, the secondary packaging is made of thick cardboard. It allows you to maintain the integrity of the bottles. The packaging contains information about the manufacturer, release date of the drug, expiration date and series. Detailed instructions for using the drug are contained inside the package. Actovegin solution in ampoules has a yellowish color with various shades. The difference in shades depends on the batch of the drug and does not affect the effectiveness of the drug.

Actovegin solution is administered intravenously, which is contained in 250 ml bottles. The bottles are placed in cardboard packaging. If necessary, the medical staff of the Yusupov Hospital dissolves the contents of the ampoules in 250 ml of 5% glucose or physiological sodium chloride solution and administers it intravenously.

The main component is hemoderivat deproteinized with a dosage of 40 mg of Actovegin per 1 ml of solution for injection. It is obtained from the blood of healthy calves that feed exclusively on milk. The drug is produced in tablets, ointments and gels, ampoules for injections and solutions for droppers. In addition to the main component, the solution contains sodium chloride and water for injection.

The outer packaging for ampoules is made of cardboard, the inner one is a plastic container. The production series and expiration date are indicated on the cardboard container. The package contains instructions (guidelines) for use. The transparent solution has a yellowish color with different shades depending on the production series. The color of the drug does not in any way affect the effectiveness of the drug.

You can also buy Actovegin in 250 ml dropper bottles at the pharmacy:

• based on dextrose with 10% active ingredient;
• in saline solution with 10 and 20 percent hemoderivative content.

Features of intravenous use of the drug

Actovegin is available in ampoules of 2 ml, 5 ml and 10 ml. 1 ml contains 40 mg of active substance. Intravenously, it is injected into a vein by drip or jet (in cases where pain is urgently needed). When administered by drip, the medication is mixed with saline or glucose. It is allowed to administer no more than 10 ml of Actovegin per day, in severe cases - up to 50 ml. The number of injections and dose are determined by the attending physician based on the patient’s disease and the body’s reaction. The course is at least a week and reaches 45 days.

For diabetes, treatment is prescribed only by 2 ml drips. Therapy lasts about 4 months.

Intravenous injections are performed only by qualified nurses who know the rules for preparing the drug for the procedure.

Intravenous injections are performed only by qualified nurses who know the rules for preparing the drug for the procedure.

The order of injections:

1. Prepare a syringe, cotton wool, disinfectant, tourniquet, medicine.
2. Tighten the tourniquet above the elbow - the patient clenches his fist. Palpate the vein.
3. Clean the needle insertion site with alcohol and insert it.
4. Remove the tourniquet and administer the injection or adjust the operation of the dropper.
5. After the procedure, remove the needle and apply sterile cotton wool.
6. The patient keeps the elbow flexed for about 4 minutes.

The injection is simple, but it must be performed by a specialist to avoid unpleasant consequences and infection in the bloodstream.

For drip administration, mixing Actovegin with other medications, except saline solution and glucose 5%, is prohibited.

The product should be used during pregnancy, breastfeeding and children only according to indications at the discretion of the attending physician.

The product should be used during pregnancy, breastfeeding and children only according to indications at the discretion of the attending physician.

Description

The drug has earned the trust of doctors and patients as a reliable remedy. It is well tolerated by both adults and children. And even the relatively high price of the medicine is not an obstacle to this. For example, the average price for a package of 50 tablets is approximately 1,500 rubles. Such a high price is due to both the complexity of the technology for obtaining the drug and the fact that it is manufactured by a foreign manufacturer - an Austrian pharmaceutical company. And at the same time, the drug is in demand, which means that Actovegin is an effective remedy.

What does the drug help with? The main purpose of the drug is the treatment of diseases associated with blood circulation. Ointments are widely used to treat bruises, abrasions and bedsores. The drug is also used to treat diseases associated with circulatory disorders.

The main component of the drug is hemoderivat (hemodialysate). It contains a complex of nucleotides, amino acids, glycoproteins and other low-molecular substances. This extract is obtained by hemodialysis of the blood of dairy calves. Hemoderivat is devoid of actual proteins, which significantly reduces its ability to cause allergic reactions.

At the biological level, the effect of the drug is explained by stimulation of cellular oxygen metabolism, improvement of glucose transport, increase in the concentration of nucleotides and amino acids involved in energy metabolism in cells, and stabilization of cell membranes. The effect of the drug begins half an hour after administration and reaches its maximum after 2-6 hours.

Since the drug is made from natural biological components, it has not yet been possible to trace their pharmacokinetics. We can only note that the pharmacological effect of the drug does not decrease due to impaired renal and liver function even in old age - that is, in cases where such an effect would be expected.

Actovegin, instructions for use and dosage

The optimal way to take Actovegin tablets according to the instructions is 1-2 tablets 2 times a day. It is recommended to take the drug before meals. The course of treatment usually lasts 2-4 weeks.

In the treatment of diabetic polyneuropathy, intravenous administration is used. The dose is 2 g/day, and the course of treatment is 3 weeks. After this, therapy is carried out using tablets - 2-3 pcs. in a day. Reception is carried out within 4-5 months.

The ointment is used for wounds, ulcers, burns. The bandage with ointment must be changed 4 times a day, for bedsores and radiation burns - 2-3 times a day.

The gel has a less greasy base than ointment. Actovegin gel, as the instructions say, is used to treat wounds, ulcers, bedsores, burns, including radiation burns. For burns, Actovegin gel is applied in a thin layer, for ulcers - in a thick layer, and covered with a bandage. The bandage should be changed once a day, for bedsores - 3-4 times a day.

The cream is used to treat wounds, weeping ulcers, and prevent bedsores (after using the gel).

Injections

Injections can be carried out in two ways: intravenously and intramuscularly. Since injections increase the risk of allergic reactions, it is recommended to pre-test for hypersensitivity.

For ischemic stroke and angiopathy, 20-50 ml of Actovegin, previously diluted in 200-300 ml of solution, is administered. The course of treatment is 2-3 weeks. Injections are given every day or several times a week.

For metabolic and vascular disorders of the brain, 5-25 ml should be administered daily for two weeks. After this, the course of treatment must be continued with tablets.

For ulcers and burns, 10 ml intravenously or 5 ml intramuscularly is prescribed. Injections must be given one or more times a day. In this case, additional therapy is carried out using ointment, gel or cream.

Doses for children are calculated based on their weight and age:

• 0-3 years – 0.4-0.5 ml/kg 1 time per day
• 3-6 years – 0.25-0.4 ml/kg 1 time per day
• 6-12 years – 5-10 ml per day
• over 12 years – 10-15 ml per day

The instructions for using Actovegin intravenously inform that the drug can be administered by drip and jet route. Actovegin is administered intravenously if it is necessary to quickly achieve an effect. Before administering actovegin intravenously, the solution contained in the ampoule is dissolved in physiological sodium chloride solution or 5% glucose. When administered intravenously, the daily dose of the drug should not exceed 20 mg. Actovegin is administered intravenously slowly.

In order to prevent allergic reactions, the drug is titrated. At the beginning of therapy, 2 ml of Actovegin is administered intravenously, having previously dissolved it in saline, then 5 ml. Severe cases of diseases for which intravenous administration of Actovegin is indicated are discussed at a meeting of the Expert Council, in which professors and doctors of the highest category take part. Leading specialists collectively decide on intravenous administration of 20-50 ml of the drug.

In case of exacerbation of chronic diseases and moderate severity of the patient, doctors prescribe 5 ml of Actovegin intravenously for two weeks. For mild cases of the disease, intravenous administration of two milliliters of the drug is possible. The duration of treatment can vary from several days to a month.

With intravenous jet or drip administration of Actovegin, side effects of the drug may develop:

• Allergic reactions;
• Dyspeptic phenomena;
• Complications from the nervous system.

The skin at the intravenous injection site may become red. In this case, use a warm compress. Sometimes after a drip, a patient’s vein becomes inflamed. Then the nurse, as prescribed by the doctor, applies a bandage with heparin or troxevasin. One of the complications of intravenous injections is air embolism, but the medical staff of the Yusupov Hospital masterfully performs the procedures and does not allow this terrible complication.

Psychotherapist, doctor of the highest category

And outside of Russia and the CIS?

It was said above that Actovegin cannot be imported into the USA. Moreover, if a doctor in the USA uses it for any reason, the doctor will be held accountable by law, regardless of the outcome of the treatment, based solely on the fact of use, since it is prohibited. The same applies to Canadian medicine, and this is the situation in some other countries that cannot be called backward in the field of healthcare.

Naturally, no one will ban the import of a drug just because it has no proven effect. So, does Actovegin have a special feature? Yes, the “dog has rummaged” that Actovegin is a biological agent, the main component of Actovegin is specially processed calf’s blood. This is the so-called “hemoderative”, that is, blood plasma that has undergone deproteinization.

In other words, large blood proteins such as albumins and globulins were eliminated, leaving light and short-chain amino acid residues. How the destruction or extraction of proteins is carried out is unknown; Nycomed, and now Takeda, does not provide such information. It is also unknown whether dairy calves are donors or whether they are mercilessly destroyed.

But the main reason for the ban on the use and import of this drug is the indication for intravenous administration of Actovegin. Ampoules cannot be imported, but ointment and gel can be imported. In other words, a biological product obtained from animal blood is allowed in the instructions to be directly introduced into the human circulatory system. That is why the drug is prohibited in a number of countries, and not at all for religious reasons. And it will soon become clear why.

Where then is Actovegin sold? 70% is the Russian market, the rest is the Korean, Chinese market and CIS countries. It is completely unclear what kind of livestock farms these are, where they are located, how the process of collecting blood from calves is carried out, how it is tested, transported, preserved or stored - nothing can be found out. But the point is not at all about the “sanitary and epidemiological regime”. The fact is that essentially unknown substances are injected into a person’s blood, even if the entire production is sterile and impeccable.

These extreme precautions are immediately understandable when you remember that the UK recently experienced an outbreak of the rare and incurable disease Creutzfeldt-Jakob disease, or mad cow disease. Its victim was a huge livestock, about 180 thousand heads. But there have also been deaths among humans: about 200 people have fallen victim to this rare, incurable and mysterious disease, which is caused by prion proteins.

However, Russia, Korea and China, together with the CIS countries, are not afraid of such prospects. But let's leave China alone. This is a special country, with its own quirks and cruel gastronomic habits. What do Russian doctors know? It's no secret that they are so overwhelmed with paperwork that they often prescribe to patients what they ask for, rather than what they need. If a grandmother comes to the doctor with complaints and asks to prescribe her a “drip” in the day hospital with Actovegin, saying that last time everything helped a lot, she began to see and hear, then the doctor with a light heart prescribes these infusions for her, just to it didn't interfere with work.

But when prescribing Actovegin, you should still assume at least approximately the mechanism of its action. What is a “deproteinized hemoderivative” and what effect can it have?

Side effects and contraindications

The medicine is made from natural ingredients, so the likelihood that any side effects will occur is extremely low. However, in some cases there are:

• rash
• pain at the injection site
• skin hyperemia
• hyperthermia
• hives
• swelling
• fever
• anaphylactic shock
• headache
• dizziness
• weakness
• nausea
• vomit
• diarrhea
• pain in the stomach area
• tachycardia
• hypertension or hypotension
• increased sweating
• heartache

When using ointments and creams to treat wounds, there may often be soreness in the area where the drug touches the skin. Such pain usually goes away within 15-30 minutes and does not indicate intolerance to the drug.

It is not recommended to use the medicine simultaneously with alcohol, as the latter can neutralize the therapeutic effect.

At the moment there is no data on the interaction of Actovegin with other drugs. It is not recommended to add foreign substances to the infusion solution.

Actovegin has few contraindications. These include:

• Oliguria or anuria
• Pulmonary edema
• Decompensated heart failure
• Component intolerance

Dosage forms and their composition

The drug is available in various dosage forms - tablets, ointment, cream, gel, solutions for infusions and injections. The price of dosage forms varies. The most expensive are tablets; creams and ointments are much cheaper.

Actovegin ointment

Used to treat the healing of wounds, abrasions, ulcers, burns, various inflammatory processes on the skin and mucous membranes. The basis of the ointment is fatty substances. The ointment softens the skin; active ingredients are better absorbed into the skin from ointment than from other dosage forms.

Actovegin gel

Used for the same purposes as ointment. The gel is water based. It does not clog skin pores, spreads faster over the surface of the skin and begins to act compared to ointment.

Actovegin tablets

Tablets are prescribed for circulatory disorders, treatment of trophic ulcers, encephalopathies, and consequences of traumatic brain injuries. Taking tablets is more convenient and has a lower risk of side effects than parenteral administration of the drug.

How Actovegin can act

The most important document for any drug is the official instructions. In the case of Actovegin, it says that it is a solution for parenteral administration (intravenous and intramuscular), a local product for application to the skin, and they all contain the same deproteinized hemoderivative prepared from the blood of calves. Translating into Russian, we can say that deproteinized means “devoid of proteins.” The result is depleted whey, from which all proteins heavier than 5 kilodaltons (kDa) have been removed.

Manufacturers claim that this restriction on molecular weight eliminates Actovegin from allergic and immune reactions, since they are mediated by heavier proteins. As a result, the risk of an anaphylactic process, high fever, itching, urticaria and other complications is minimized to almost zero, even in the case of intravenous use.

However, if you carefully study the instructions, it says that before the first use, a test intramuscular injection is advisable in order to check how the body tolerates Actovegin and whether there will be any adverse reactions. Why then is this test necessary? It is known that the lightest protein molecules that exhibit immunogenic properties and can cause side effects weigh about 6 kilodaltons, and they should not be in Actovegin. Therefore, a sample is not needed?

It turns out that manufacturers have no confidence in the composition of the finished product. What does the Actovegin ampoule contain? What's in it? From a biochemical point of view, the average size of the amino acids that make up any protein is 150 daltons per molecule. This value is average, because 20 amino acids take part in the construction of proteins in one or another sequence and in one or another quantity and composition. If we have an amino acid residue of about 30 molecules, then it will weigh slightly less than 5000 daltons and will end up in the drug. The chemical structure of the prion protein is shown below.

Yes, indeed, the prions that cause mad cow disease do not pass through the Actovegin production filter, since they are seven times heavier, having a mass of about 35 kilodaltons. But no one knows, if mad cow disease is caused by a light protein of 208 amino acids, then can a protein of 30 to 35 amino acids cause any similar disease? Nothing is known about this at the moment. It is precisely because Actovegin can be a potential source of unknown and severe slow infections, it, as a biological product, is prohibited for use and import into the USA and many other countries. But the manufacturer is not afraid, because demand is stable in our country, and he still recommends using it intravenously.

And as a result, a perfect panopticon of many, many compounds that are lighter than proteins is poured into the vein of an unsuspecting patient. These are vitamins and inorganic ions, short-chain fatty acids, many molecules of hormones characteristic of animals, as well as other substances. Biochemists know that if we take one liter of human blood plasma and completely remove all proteins from it, then in the dry residue we will get as much as 20 grams, which will consist of hundreds and even thousands of different compounds, many of which have not even been discovered or described yet .

It turns out that Actovegin is characterized not by the presence of the active substance, but by its absence, vagueness, and incomprehensibility of the composition. However, Takeda states that:

• Actovegin stimulates tissue regeneration;
• improves their trophism;
• and also (a very strange phrase) activates metabolism. I wonder why?

Each official instruction for this medicine usually indicates pharmacodynamics and pharmacokinetics indicators. These are branches of pharmacology that talk about how:

• a substance is transformed in the body;
• what active metabolites does it form;
• how its concentration changes after a certain period of time and what its half-life is;
• what routes does the medicine take to leave the body?
• does it accumulate (cumulation);
• what drugs this remedy cannot be combined with, and so on.

If we take any “honored drug”, for example, Carbamazepine or acetylsalicylic acid, then we can learn many facts. But what happens to Actovegin in the body, and whether anything happens at all, is fundamentally impossible to understand. It’s easier to say that a little bit of cow’s blood plasma, which is depleted in proteins, was simply splashed into human blood plasma. Accordingly, no assurances from the manufacturers of Actovegin regarding its value as a medicine have any value. All talk about “improving metabolism”, “stimulating repair”, “changing metabolic processes” is nothing more than empty words, until there are scientific studies and corresponding conclusions.

The author may be reproached for the fact that there are examples of some substance “working,” but it is not really clear how it works. An example is propolis or mumiyo. But in this case, on the contrary, we are talking about the local use of natural compounds, and no one considers them medicines. There is no patented “propolis maker”. And finally, no one uses these complex natural compounds intravenously. I wonder what is in the blood of calves that humans do not have?