Betaferon, 9.6 million units, lyophilisate for the preparation of solution for subcutaneous administration, 15 pcs.
Betaferon® contains human albumin, so there is a very low risk of transmitting viral diseases. The theoretical risk of transmission of Creutzfeldt-Jakob disease is also considered extremely unlikely.
Changes in laboratory parameters.
In addition to standard laboratory tests prescribed for the management of patients with multiple sclerosis, before starting therapy with Betaferon®, as well as regularly during treatment, it is recommended to conduct a detailed blood test, including determining the leukocyte formula, platelet count and biochemical blood test, as well as checking liver function ( e.g. AST, ALT and GGTP activity). When managing patients with anemia, thrombocytopenia, leukopenia (single or combined), more careful monitoring of a complete blood count may be required, including determination of the number of red blood cells, white blood cells, platelets and leukocyte formula.
Gastrointestinal disorders.
In rare cases, during the use of Betaferon®, the development of pancreatitis was observed, in most cases associated with the presence of hypertriglyceridemia.
Disorders of the liver and biliary tract.
Clinical studies have shown that Betaferon® therapy can often lead to an asymptomatic increase in liver transaminases, which in most cases is mild and transient.
As with treatment with other beta-interferons, severe liver damage (including liver failure) is rare when using Betaferon®. The most severe cases have been observed in patients exposed to hepatotoxic drugs or substances, as well as in certain concomitant diseases (eg, metastatic malignancies, severe infections and sepsis, alcohol abuse).
When treating with Betaferon®, it is necessary to monitor liver function (including assessment of the clinical picture). Increased levels of transaminases in the blood serum require careful monitoring and examination. If there is a significant increase in serum transaminases or signs of liver damage (for example, jaundice), the drug should be discontinued. In the absence of clinical signs of liver damage or after normalization of liver enzyme levels, it is possible to resume Betaferon® therapy with monitoring of liver function.
Endocrine disorders.
In patients with thyroid dysfunction, it is recommended that thyroid function (thyroid hormones, TSH) be checked regularly, and otherwise as clinically indicated.
Diseases of the cardiovascular system.
Betaferon® should be used
with caution
in patients with heart disease, in particular with heart failure stages III–IV according to the NYHA classification, since such patients were not included in clinical studies.
If cardiomyopathy develops during treatment with Betaferon® and it is suspected that this is associated with the use of the drug, then treatment with Betaferon® should be discontinued.
Diseases of the nervous system.
Patients should be informed that side effects of Betaferon® may include depression and suicidal thoughts, and if they occur, they should immediately consult a doctor.
In two controlled clinical trials involving 1657 patients with secondary progressive multiple sclerosis, there were no significant differences in the incidence of depression and suicidal thoughts when using Betaferon® or placebo. However, caution should be exercised when prescribing Betaferon® to patients with depressive disorders and a history of suicidal thoughts. If such phenomena occur during treatment, the question of the advisability of discontinuing Betaferon® should be considered.
Betaferon® must be used with caution
in patients with a history of epileptic seizures.
General disorders and condition of the injection site.
Serious allergic reactions (rare but acute and severe, such as bronchospasm, anaphylaxis and urticaria) may occur.
If there are signs of damage to the integrity of the skin (for example, leakage of fluid from the injection site), the patient should consult a doctor before continuing with Betaferon® injections.
Cases of necrosis at the injection site have been observed in patients receiving Betaferon® (see "Side Effects"). Necrosis can be extensive and extend into the muscle fascia as well as fatty tissue and, as a result, lead to the formation of scars. In some cases, removal of dead skin or, less commonly, skin grafting is required. The healing process can take up to 6 months.
If multiple foci of necrosis appear, treatment with Betaferon® should be stopped until the damaged areas are completely healed. In the presence of one lesion, if the necrosis is not too extensive, the use of Betaferon® can be continued, since in some patients the healing of the necrotic area at the injection site occurred during the use of Betaferon®.
In order to reduce the risk of reaction and necrosis at the injection site, patients should be advised to:
- administer injections strictly following the rules of asepsis;
- change the injection site each time;
- administer the drug strictly subcutaneously.
You should periodically monitor the correctness of self-injections, especially if local reactions occur.
Neutralizing antibodies.
As with any other protein-containing drug, there is the possibility of antibody formation when using Betaferon®. In a number of controlled clinical studies, blood serum was analyzed every 3 months to detect the development of antibodies to Betaferon®. In these studies, it was shown that neutralizing antibodies to interferon beta-lb developed in 23–41% of patients, which was confirmed by at least two subsequent positive laboratory test results. Of these patients, 43–55% were consistently found to be negative for interferon beta-1b antibodies on subsequent laboratory testing.
The presence of neutralizing antibodies has not been shown to have any significant effect on clinical outcomes, including MRI findings. The development of neutralizing activity was not associated with the occurrence of any adverse reactions.
The decision to continue or discontinue therapy should be based on clinical disease activity rather than neutralizing activity status.
Immune disorders.
The use of cytokines in patients with monoclonal gammopathy was sometimes accompanied by a systemic increase in capillary permeability with the development of shock and death.
Use in children.
There have been no systematic studies of the effectiveness and safety of Betaferon® in children and adolescents under 18 years of age.
Impact on the ability to drive a car and operate machinery
No special studies have been conducted. Adverse effects from the central nervous system may affect the ability to drive a car and operate machinery. In this regard, caution must be exercised when engaging in potentially hazardous activities that require increased attention.
Betaferon®
Now you are ready to give the injection.
B. Drug packaging containing vials, pre-filled syringes, adapter for the vial with needle and alcohol wipes.
Stages of preparing the solution:
1 — Before starting the procedure, wash your hands thoroughly with soap.
2 - Open the bottle of Betaferon - preferably not with your fingernail, as it can break, but with your thumb - and place it on the table.
3 - Wipe the lid of the bottle with an alcohol wipe. Move the tissue in one direction only and then leave it on the bottle cap.
4 - Open the blister pack that contains the bottle adapter, but leave the adapter inside.
Do not remove the vial adapter from the blister pack.
Also, be careful not to touch the vial adapter. It is important that it remains sterile.
5 - While attaching the adapter, keep the bottle on a flat surface.
6 - Remove the alcohol wipe from the cap of the Betaferon bottle. Place the blister pack containing the solution transfer device with bottle adapter on the bottle cap. Press the blister with your thumb and index finger or palm until it clicks.
7 - Using the edges of the blister pack, remove it from the bottle adapter. You are now ready to attach the prefilled solvent syringe to the solution transfer attachment.
8 - Take the syringe. Twist the orange cap on the tip of the syringe and pull it off the syringe. Discard the cap.
9 - Attach the syringe to the hole on the side of the adapter by inserting the tip of the syringe into it and carefully securing by pressing while turning clockwise (as shown by the arrow) to form a syringe assembly.
10 - Hold the structure with the syringe by the bottom of the bottle. Slowly push the syringe plunger all the way down to displace all the solvent into the vial. Release the piston. In this case, the piston can return to its original position.
11 - Make several careful rotational movements with the bottle so that the dry powder of Betaferon is completely dissolved. In this case, the structure with the syringe remains attached to the bottle.
Do not shake the bottle.
12 - Carefully inspect the solution. It should be transparent and not contain any particles. If the solution has changed color or contains particles, throw it away and start the whole procedure from the beginning with a new package of supplies. If foam appears—which can happen if the bottle is shaken or swirled too much—let the bottle sit until the foam settles.
Preparing the syringe
13 If the piston returns to its original position, push it in again and lock it. To prepare the injection, turn the structure over so that the bottle is on top and the bottle cap is pointing down. This will allow the solution to drain into the syringe.
Hold the syringe horizontally.
Slowly pull back the plunger to draw all the solution from the vial into the syringe.
14 - Turn the syringe structure so that the needle points upward. This will cause air bubbles to rise to the surface of the solution.
15 - Remove any air bubbles by gently tapping the syringe and moving the plunger to the 1 ml mark or the volume prescribed by your doctor.
If too much solution has been forced into the vial along with air bubbles, pull the plunger back slightly to draw the solution from the vial back into the syringe. Do this until all the air has been removed and the syringe contains 1 ml of the prepared solution.
Important Note:
When drawing up the solution again, return the structure with the syringe to a horizontal position, with the bottle on top.
16 - After this, grab the blue bottle adapter along with the bottle attached to it, turn
adapter towards you, and then separate it from the syringe.
When separating the vial adapter from the syringe, grasp only the blue plastic adapter. Keep the syringe horizontal; the bottle should be under the syringe.
17 By disconnecting the bottle and adapter from the syringe, the solution flows out of the needle during injection.
18 - You are now ready to give the injection.
NOTE: The drug should be administered subcutaneously immediately after preparing the solution. If the injection is postponed, the solution should be stored in the refrigerator and used within 3 hours. The solution should not be frozen.
19 - Throw the bottle and remaining unused solution into a waste container.
Brief description of preparation of the drug for injection
1. Remove the contents from the package.
2. Attach the bottle adapter to the bottle.
3. Attach the syringe to the vial adapter.
4. Press down on the plunger to move the solvent into the vial.
5. Turn the syringe assembly over, then pull back the plunger.
6. Separate the vial from the syringe - now you are ready to inject.
NOTE: The drug should be administered subcutaneously immediately after preparing the solution. If the injection is postponed, the solution should be stored in the refrigerator and used within 3 hours. The solution should not be frozen.
Selection and preparation of the injection site and administration of the drug solution
Betaferon (1.0 ml) subcutaneously
— Selecting the injection site
The drug Betaferon (interferon beta-lb) should be administered subcutaneously. Soft areas away from joints and nerves are best for this purpose.
Injection sites can be selected using a drawing. It is best to first determine the injection site and then prepare the syringe.
If you have difficulty reaching any place, ask for help from a person who knows how to give injections.
1- Select the injection site (see the figure “Scheme of alternating injections performed” at the end of the instructions).
IMPORTANT NOTE: Do not inject into areas where there are bumps, swelling, hard knots or pain. In addition, the solution should not be injected into areas where there are changes in skin color, depressions, crusts, or where the integrity of the skin is compromised. If you notice these or other unusual conditions, contact your healthcare provider.
Wipe the skin at the injection site with an alcohol wipe and wait until the skin is exposed to air to dry. Throw away the napkin.
Use a suitable disinfectant to disinfect the skin.
3- Remove the protective cap from the needle. Pull the cap rather than twist it.
4- Gently pinch the skin around
disinfected area (to raise it a little).
5- With a sharp, confident movement, insert the needle directly into the skin at a 90° angle. Hold the syringe like a pencil or dart.
6- Slowly inject the solution using gentle and continuous pressure on the plunger. (Press the plunger all the way until the syringe is empty.)
7- Dispose of the syringe in a waste container.
Alternating injection sites
It is necessary to choose a new injection site each time, as alternating injection sites allows the skin to heal and also helps prevent infection. It is better to choose the injection site in advance and only then prepare the syringe. The diagram shown in the figure will help you correctly alternate injection sites. For example, if you made the first injection in the right half of the abdomen, then make the second in the left half, the third in the right thigh, etc. according to the diagram until you have used all possible injection sites. Write down where and when you had your last injection.
Following the proposed scheme, after 8 injections (after 16 days) you will return to the site of the first injection (for example, the right half of the abdomen). This is called an "alternation cycle." In the diagram we give as an example, each zone is in turn divided into 6 injection sites (for a total of 48 injection sites): left and right, upper, central and lower parts of the corresponding zone. When you return to one of the zones after one cycle of alternation, choose the most distant possible injection site in that zone. If any area becomes painful, discuss other possible injection sites with your doctor.
Alternation scheme:
To help you alternate injection sites correctly, it is recommended to write down when and in which area the injection was given. To do this, you can use the following alternation scheme:
1st cycle
The first 8 injections are made sequentially from the 1st zone to the 8th
alternating
zone, using only the upper left segment of each zone.
2nd cycle
The next 8 injections begin again from the 1st zone, but they must be
alternated
into the lower right segment of each zone.
3rd cycle
The next 8 injections in this cycle start from the 1st zone and
alternation
performed in turn in the central left segments of each
zones.
By following this sequence, each area will have the opportunity to fully recover before the next injection.
Registration of completed injections
Instructions for recording the places and dates of injections performed
Select the injection site. If you are already using Betaferon, then start with the area that was not used during the last rotation cycle, i.e. within the last 16 days.
After injecting, record the area used and the date of injection (see figure “Example of recording injections performed” at the end of the instructions for use).
Betaferon, determination of neutralizing antibodies
Determination of neutralizing antibodies (NAB) to the interferon agent betaferon is the identification of the presence of NAT, their monitoring in NAT-positive individuals in order to prescribe an effective drug, identify the ineffectiveness of the applied IFN therapy and select a replacement for IFN therapy. Typically, this analysis is prescribed to patients who have been receiving interferon drugs for a certain time for various diseases, for example, hepatitis, tumors, multiple sclerosis, etc.
Neutralizing antibodies are produced in response to interferon drug therapy. They prevent interferons from binding to target cell receptors and reduce the effectiveness of treatment with such drugs.
Interferons are one of the most important components of the innate defense (immune system) of the human body. These proteins are capable of providing resistance to various types of infections (including viral ones); Interferons enhance the body's immune response. Another important function of interferons is to control the processes of development and death of tumor and normal cells. The activity of interferon genes directly affects resistance to viral infections and a number of other diseases.
Interferon drugs (IFN) are used to treat various chronic diseases, including severe ones, such as multiple sclerosis. The effectiveness of such drugs is due to their immunomodulatory effect on chronic inflammation. The protective barrier against viruses and other microorganisms, which is “erected” by interferon immunomodulators, begins to act before the onset of immunity, causing cellular resistance.
Betaferon is used to treat multiple sclerosis, having antiviral and immunoregulatory activity. Beta interferons are often prescribed for diseases and disorders that result in a decrease in the synthesis of these substances in the body. In addition to multiple sclerosis, these include chronic viral hepatitis, tumor diseases, herpes and other infections.
When and why is a blood test prescribed for the semi-quantitative determination of NAT to interferon beta (betaferon)
This study is prescribed:
— in order to identify antibodies that reduce the activity of betaferon, and to monitor the effectiveness of treatment
- to prevent the emergence of resistance to betaferon during long-term use (in this case, the analysis should be prescribed every 3-6 months)
- when the effectiveness of treatment of the disease decreases while taking betaferon
Instructions for use BETAFERON
Patients should be informed that side effects of the drug may include depression and suicidal thoughts, which should immediately consult a doctor if they occur. In rare cases, these conditions can lead to suicide attempts. If depression or suicidal thoughts are present, therapy should be discontinued immediately.
In patients with a history of depressive reactions or seizures, as well as in patients receiving antiepileptic drugs, the drug should be used with caution.
The drug should be used with caution in patients with heart disease, in particular in patients with heart failure of functional class III-IV according to the NYHA classification, in patients with cardiomyopathies.
Before prescribing Betaferon and during its use, a detailed blood test should be regularly performed, including determination of the leukocyte formula, as well as determining the activity of AST, ALT and GGT. In case of increased serum transaminase activity, the patient should be carefully monitored and examined. The drug should be discontinued if there is a significant increase in the activity of liver enzymes or the appearance of symptoms of hepatitis. In the absence of clinical signs of liver damage, after normalization of liver enzyme levels, an attempt can be made to resume therapy under close monitoring of liver function.
There is no information on the use of the drug in patients with impaired renal or liver function.
In clinical studies, 41% of patients with relapsing-remitting multiple sclerosis had serum antibodies neutralizing interferon beta-1b (two consecutive titers >20). In a study of patients with secondary progressive multiple sclerosis, the appearance of neutralizing antibodies was detected in 28% of cases. The effect of antibody formation on the clinical efficacy of the drug is currently being studied. The available results are contradictory and do not allow us to draw a clear conclusion. There were no signs of a negative effect of neutralizing antibodies on the course of the disease in secondary progressive multiple sclerosis.
In vitro, neutralizing antibodies against recombinant interferon beta-1b have been shown to also interact with naturally occurring interferon beta, although to a lesser extent. This effect has not been studied in vivo and its clinical significance is unknown.
Information about patients who completed drug therapy despite the appearance of neutralizing antibodies is scarce and inconclusive.
Cases of necrosis at the injection site of the drug in a number of patients have been described. If multiple foci of necrosis appear, treatment with the drug should be stopped until they are completely healed, which can last up to 6 months. In the presence of one lesion and the absence of extensive necrosis, treatment with the drug can be continued.
To reduce the risk of necrosis at the injection site, patients should be advised to observe aseptic rules when performing injections; constantly change injection sites. The doctor should periodically monitor the correctness of self-injections, especially if local reactions occur.
Caution must be exercised when treating patients with impaired bone marrow hematopoiesis (including anemia or thrombocytopenia).
The use of cytokines in patients with monoclonal gammopathy was sometimes accompanied by a systemic increase in capillary permeability with the development of shock and death.
Impact on the ability to drive vehicles and operate machinery
This effect has not been studied. Side effects observed from the central nervous system during the use of the drug in predisposed patients may affect the ability to drive a car or operate machinery.
