Avonex

Avonex is one of the drugs used in the treatment of a complex, progressive disease - multiple sclerosis. MS is considered a difficult to treat pathology of the nervous system, developing at the age of 15 to 45 years and older. The destruction of the myelin sheath provokes many neurological complications, functional disorders. Currently, this disease is treated in a comprehensive manner, the therapeutic complex includes drugs that help stop periods of exacerbation, drugs that slow the development and progression of the pathology. The group of pathogenetic drugs that modify the course of multiple sclerosis (PTMS) includes Avonex - an effective immunomodulator that can increase the interaction of cells, activate the immune system, have a neuroprotective effect, reduce the severity of disease symptoms. In many countries of the world, Avonex is considered one of the most effective drugs and is included in the complex of the so-called gold standard of preventive therapy for MS.

Indications Avonexa

The first clinical manifestations of myelin sheath integrity disorder were described by Cruveilhier in the early 19th century. Much time has passed since then, but the etiology of the disease has not been clarified, therefore, unfortunately, there is no truly effective treatment for multiple sclerosis. However, MS is being studied, new drugs and methods are emerging, the main goal of which is not only to reduce symptoms, but also to slow down the pathological process, preventing exacerbations. Avonex (interferon beta-1a) is considered one of the most effective drugs included in the therapeutic complex PTIRS - drugs that change the course of MS. Indications for use of Avonex:

• Demyelinating pathology of the central nervous system, recurrent in nature
• Multifocal multiple sclerosis, progressive-relapsing nature - PRMS, with increasing intensity of neurological symptoms with exacerbations
• RRMS – relapsing-remitting multiple sclerosis with episodes of exacerbations and periods of remission
• SPMS – secondary progressive multiple sclerosis with a slow increase in neurological symptoms, exacerbations and relapses
• Primary progressive MS with increasing symptoms without obvious periods of stabilization and remission

As a rule, indications for the use of Avonex are at least two relapses during the last three years from the onset of the disease. However, many doctors believe that prescribing the drug from the moment the first clinical signs of MS appear can significantly slow down the progression of the pathology. In addition, Avonex was not previously prescribed for progressive forms of the disease, believing that it would not have the desired effect. Studies of the last decade have shown the opposite results, the generally accepted international indicator of deterioration in the patient's condition - MSFC when taking Avonex decreased by almost 40%, the number of exacerbations and the activity of the process as a whole also decreased. Thus, interferon beta-1a has not only a preventive effect, but also has a fairly good therapeutic effect in almost all forms of multiple sclerosis.

Avonex can be used as an immunomodulatory, antiproliferative, antiviral drug and for other diseases, it is effective in curing any inflammatory processes that destroy myelin structures.

Release form

Avonex is used as a drug for intramuscular injection.

The release form is a lyophilisate of interferon-beta-1a, which is obtained from the ovarian cells of specially bred hamsters. The human interferon gene is inserted into the DNA of animal cells, thus obtaining a glycosylated polyamino acid polypeptide. All 166 amino acids that are part of Avonex are arranged in the sequence that corresponds to the polypeptide chain of human interferon.

Avonex is a lyophilized powder in sealed vials, which contains the following components:

• Interferon beta-1a
• Serum albumin - serum albumin
• Sodium phosphate monohydrate
• Disodium phosphate – dibasic sodium phosphate
• Sodium chloride

The drug release form assumes its dilution, so the kit should include water for injection in special glass syringes. The powder is in vials with a device that helps to prepare the medicine (Bio-Set), observing sterile conditions. The manufacturer also includes disposable injection syringes in the kit. The package contains 4 complete sets:

• Glass bottles with Bio-Set
• Solvent in syringes
• Needle
• Plastic trays

[ 1 ], [ 2 ]

Pharmacodynamics

Since the etiopathogenesis and pathophysiology of multiple sclerosis have not been sufficiently studied, there is no reliable information on the pharmacodynamics of Avonex. There are only a few studies that describe the possible effect of the drug on demyelination, and the antiviral effect of interferon beta-1a has been studied in more detail. In those few studies that have been published in specialized medical journals, it has been statistically proven that Avonex, as an active cytokine, is able to influence the main immune processes and significantly slow down the progression of multiple sclerosis.

Avonex belongs to the group of cytokines-immunomodulators – substances that regulate the interaction of cells, activate protective properties and suppress pathological processes.

The pharmacodynamics of Avonex is due to the broad spectrum of action of beta-interferon as a mediator of intercellular interaction, immunomodulator and antiviral drug. Interferon is a substance that is reproduced by complex in structure, eukaryotic cells that are capable of resisting many pathogenic biological factors, including viruses. The peculiarity of interferon beta-1a, like other types of cytokines, is that it is produced on demand by the body, is not deposited and is not able to linger in the bloodstream for a long time. This substance is directed at target cells, having a local effect on them, catabolized interferon is excreted through the kidneys and liver. Avonex as beta-interferon is a recombinant, hybrid version of the protein structure, which has a clearly expressed antiviral and antitumor effect.

The pharmacodynamics of Avonex is based on its ability to be synthesized in various cells, including mononuclear phagocytes (macrophages) and fibroblasts.

Interferon beta-1a contains a unique hydrocarbon component, the interferon itself exists in a glycated form. Glycolysis is the ability of substances containing a small amount of glucose to bind to each other without the participation of enzymes. Thus, the property of glycosylation of proteins ensures their stability and active function during the period of distribution and half-life.

Avonex can bind to cell receptors and provoke a whole series of normalizing intercellular actions that lead to the expression of markers, gene structures, and the histocompatibility complex, and this process can last up to 7 days after a single intramuscular injection of the drug.

Prescription and use of Avonex for one year shows a significant reduction in the number of relapses and exacerbations, on average by 30-35%. In addition, the drug is able to slow down and delay the appearance of neurological symptoms leading to disability.

[ 3 ]

Pharmacokinetics

Just like pharmacodynamics, the pharmacokinetics of the drug Avonex has not been fully studied due to the fact that many etiological, pathogenetic factors of multiple sclerosis and remain unclear. Nevertheless, tests to track the patterns of all kinetic processes - absorption, distribution and elimination (metabolism and excretion) are constantly carried out. The purpose of such work is to clarify the degree of antiproliferative and antiviral activity of the drug.

The results officially presented by the manufacturer of Avonex:

• Peak antiviral activity of Avonex is observed 5 hours after the first intramuscular administration of the required dose.
• The antiviral effect of the drug lasts for about 15 hours after administration.
• Half-life (T _1/2 ) – up to 10 hours
• Degree of absorption, bioavailability (F) – about 40%

Considering that the effect of interferon beta-1a was studied only in a group of patients with relapsing MS, it is obvious that the latest information on the positive dynamics of treatment of patients with PPMS (primary progressive MS) and SPMS (secondary progressive multiple sclerosis) can become the subject of more detailed studies of the effectiveness of Avonex and the specifics of its pharmacokinetic parameters.

As for standard studies, two groups were observed by doctors - the study group and the control group with the appointment of placebo. All patients were diagnosed with progression of neurological symptoms and a decrease in quality of life, the assessment was carried out using the Kaplan-Meier method. The decrease in indicators in the group that took standard treatment and placebo instead of Avonex reached 35%. In patients taking interferon beta-1a, progression slowed down, and the indicator was no higher than 22%.

The bioavailability of the drug and its ability to be adequately synthesized in target cells allows for a reduction in the frequency of exacerbations and relapses, provided that Avonex is taken for at least 1 year.

[ 4 ]

Dosing and administration

The method of administration and dosage of Avonex is prescribed by the doctor depending on the form of the disease, the severity of symptoms from the central nervous system and the age of the patient. General standards for the appointment of interferon beta-1a are as follows:

• Avonex is administered as an intramuscular injection.
• The generally accepted dose of Avonex is 6 million IU (30 mcg) or 1 milliliter of dissolved lyophilisate.
• Frequency of administration – once a week. A specific day and time of administration of the drug is determined, which should not be changed
• The injection site (muscle) is changed weekly to avoid local side effects (hyperemia, burning)
• Injections are given by medical personnel or by the patient himself, provided that he has the necessary skills and permission from the attending physician.
• The course of treatment with Avonex may vary and is determined on an individual basis based on possible reactions and confirmation or absence of visible positive dynamics.

How to prepare Avonex injection solution?

1. The first step is to prepare the solution. It should be prepared only before the injection, not earlier. Hold the Bio-Set device with one hand, unscrew and remove the cap
2. Taking care not to touch the opening of the bottle, remove the tip from the syringe.
3. The bottle with the Bio-Set device is placed vertically on the table
4. The bottle is combined with a syringe
5. The syringe cannula is screwed clockwise into the Bio-Set device.
6. The syringe is held by the base and with a sharp movement it is pushed downwards so that its tip is completely hidden. At the same time, a characteristic click is heard, indicating that the preparatory actions are correct.
7. By pressing the plunger, the solvent is introduced into the vial, the syringe is not removed
8. The vial with powder and solvent should be rotated slowly to ensure complete homogeneous mixing of the substances. Please note that the vial should not be shaken.
9. To remove air from the vial, press the syringe plunger all the way down.
10. The syringe is turned 180° without removing it from the vial.
11. Slowly pulling the plunger upwards, draw the required amount of the drug into the syringe.
12. The packaging is removed from the needle in such a way that the cap itself remains in place.
13. The syringe is removed from the Bio-Set by gently turning it clockwise.
14. A needle is put on the syringe. It is placed in a special tray included in the kit
15. Perform the injection in the standard way - after treating the injection site
16. Avonex is administered as slowly as possible to minimize discomfort.

Special recommendations regarding the method of administration and dosage of Avonex:

• Do not use any other substances to dissolve the powder, except for the solvent included in the kit.
• When connecting the syringe and Bio-Set, you must wait for the characteristic sound – a click
• The solvent must be introduced into the bottle slowly to avoid foaming.
• When preparing the solution, pay attention to the integrity of the bottle, the transparency of the product (it should not be cloudy). A slight yellowish tint is acceptable, any other color or particles in the solution are considered unacceptable.
• The solution is intended for single use; if any remains after injection, it is disposed of and not reused.

[ 7 ]

Use Avonexa during pregnancy

During pregnancy, the prescription of any medication is a risk. Multiple sclerosis is diagnosed extremely rarely during pregnancy, rather it is detected before conception and in principle is not a categorical contraindication to bearing a child. Moreover, according to some data from European gynecologists, gestation can slow down the development of pathology and reduce the severity of symptoms from the nervous system. Women from 12 countries took part in the survey, which lasted more than 2 years - before and after childbirth. The frequency of relapses decreased in 40% of mothers, the last trimester was especially favorable. Studies of the drug Avonex during pregnancy were not specifically conducted, but it is prescribed extremely rarely, when other drugs do not have the desired effect. Refusal of Avonex during pregnancy is associated with the pharmacological features of all interferons in principle. Although there is no information on complications after taking, toxicity of interferon beta-1a during gestation, it is believed that it can provoke a spontaneous miscarriage. The information was obtained after conducting an experiment to study fertility in rhesus macaques. Taking interferon caused an anovulatory effect on the pelvic organs in animals, but if a miscarriage did not occur, the pregnancy proceeded normally and no teratogenic signs were detected.

In any case, the poorly understood pharmacokinetics of Avonex during the perinatal period and after childbirth forces doctors to refuse to prescribe the drug to pregnant women with MS. If Avonex is prescribed to women of fertile age, they are also prescribed contraceptives to avoid all possible risks. There is also no precise information on the ability of interferon beta-1a to penetrate into breast milk, but for safety reasons it cannot be administered as injections during the entire period of breastfeeding. An option for treatment with interferon is to transfer the child to artificial feeding, and the mother receives adequate treatment with Avonex.

Contraindications

Like many other interferon preparations, there are contraindications for use of Avonex. Despite its high degree of bioavailability and apparent naturalness, Avonex is not safe, this is due to its activity and multifunctional action.

Contraindications for the use of Avonex:

• Severe pathology of the cardiovascular system
• Angina pectoris
• Persistent arrhythmia
• Exacerbation of liver diseases
• Renal pathologies
• Myocardial infarction and stroke
• Untreated epilepsy
• Pathologies of the hematopoietic system
• Decompensated liver cirrhosis
• Hepatomegaly
• Chronic hepatitis during treatment with immunosuppressants
• Pregnancy and lactation period
• HS with caution in thyroid diseases
• Individual intolerance to recombinant interferons, albumins
• Depressive states with suicidal tendencies
• Children under 16 years of age

In addition, many doctors consider the progressive form of multiple sclerosis to be a contraindication, although currently many specialists successfully use Avonex in the treatment of both SPMS (secondary progressive form) and PPMS (primary progressive form).

[ 5 ]

Side effects Avonexa

The side effects caused by Avonex include typical flu-like symptoms. This is considered to be an almost inevitable adequate complication when administering all interferons and is explained by the primary response of the immune system to the introduction of any protein substances. Primary signs may be as follows:

• Myalgia (muscle pain)
• Chills
• Headache
• Transient spasms
• Nausea
• Hyperthermia up to 38-39 degrees
• General weakness, feeling of fatigue
• Temporary paresis, paralysis (rare)

Such conditions are typical for the beginning of treatment with Avonex, as soon as the body adapts to the drug, the symptoms subside, this takes from one week to 14 days. In addition, side effects of Avonex can manifest themselves in the form of transient neurological complications throughout the course of treatment - periodic muscle spasms, loss of sensitivity or temporary paralysis of the functional type are considered acceptable if not associated with typical symptoms of exacerbation of the disease. It is easy to check and distinguish a side effect from a real exacerbation, the first occurs shortly after the administration of the drug and subsides within 24 hours.

Side effects of Avonex can occur in almost all systems and organs, as it affects the body systemically. These complications are considered secondary, following typical neurological and flu-like effects. Secondary side effects may include:

Organs, systems	Complications, side effects
Skin	Itching, hair loss, rash, sweating, exacerbation of dermatitis or psoriasis
Gastrointestinal tract	Nausea, vomiting, loss of appetite, diarrhea, pain in the liver area, vomiting is possible
Immune system	Allergic reactions, anaphylaxis
Cardiovascular system	Arrhythmia, exacerbation of cardiac pathologies
Circulatory system, hematopoiesis	Decreased levels of lymphocytes, platelets, neutrophils, leukocytes. Decreased hematocrit.
Respiratory system	Shortness of breath, feeling of lack of air, rhinorrhea
Musculoskeletal system	Myalgia, arthralgia. Muscle spasms. Possible decrease in muscle tone, atony
Reproductive system	Bleeding, dysmenorrhea, metrorrhagia
Endocrine system	Thyroid dysfunction - hypo or hyperthyroidism
CNS	Paresis, paresthesia, temporary paralysis. Dizziness, epileptic seizures. Depressive state, migraine-like headache attacks. Mood swings, psychoemotional lability.
Local side effects	Redness at the injection site, itching, burning, rarely - abscess

In addition to the above side effects, weight loss or gain, changes in blood composition – hyperkalemia, and increased urea levels are possible.

[ 6 ]

Overdose

Overdose of Avonex is extremely rare, it happens when the patient wants to independently adjust the course of treatment. The introduction of two vials at once, of course, will cause complications, since even with the prescribed dosage, side effects are still possible, which are considered acceptable. At the first alarming symptoms and confirmed overdose, the patient is hospitalized to conduct adequate detoxification therapy. When the symptoms subside, maintenance treatment is carried out, then Avonex can be prescribed again. If Avonex is administered by the patient independently, and the patient has neurological complications - depression, apathy, other psychoemotional disorders, relatives and close people should monitor compliance with the regimen and dosage of the drug.

As a rule, after prescribing interferon beta-1a, the doctor conducts explanatory work with the patient with multiple sclerosis or with his relatives, who will monitor the correct and timely treatment. The patient and his family should be aware of all possible side effects, the first signs of possible complications, including flu-like symptoms.

In general, an overdose is unlikely, since the manufacturer has taken care of the most convenient form of the drug and the complete set with all the necessary items.

[ 8 ], [ 9 ]

Interactions with other drugs

As a recombinant interferon, Avonex is quite compatible with many drugs used in the treatment of multiple sclerosis. However, the interaction of Avonex with other drugs should be taken into account in accordance with the complex course of the pathology and the possible risk of unexpected side effects.

What does Avonex combine with:

• All types and forms of glucocorticosteroids - Hydrocortisone, Prednisolone, Dexamethasone, Methylprednisolone
• ACTH – adrenocorticotropic hormones – Synacthen, Depomedrol, Soludrol

Avonex as an active immunomodulator is not combined with immunosuppressants - Imuran, Cyclophosphamide, Mitoxantrone, with MCAT - monoclonal antibodies - it is prescribed after a course of these drugs or as a monodrug.

Caution should be exercised when prescribing anticonvulsants and beta-IFN (interferon beta-1a) simultaneously; also, concurrent use of Avonex and antidepressants may cause an exacerbation of depressive symptoms, including suicide attempts. Therefore, beta-IFN is prescribed with caution to patients with unstable psyche, given the risk of complications and potential therapeutic efficacy.

During long-term treatment with Avonex, the ability of beta interferons to reduce the productivity of cytochrome P450-dependent monooxygenase should be taken into account. All antiepileptic drugs, TCAs (tricyclic antidepressants), SSRIs (selective serotonin reuptake inhibitors), MAOIs (monoamine oxidase inhibitors), SSRIs (selective serotonin uptake inhibitors) have clearance dependent on cytochrome monooxygenase enzymes. Such a combination will not give a noticeable therapeutic result and treatment may be useless.

In practice, complications have been noted with the simultaneous administration of interferon and the use of antipyretics, which reduce flu-like symptoms characteristic of the beginning of treatment. If signs of intoxication appear, the headache intensifies, antipyretics are recommended to be taken 12 hours before the injection of Avonex, then a day later. Also, one should be extremely careful in the treatment of patients with MS with hepatosis in any form. Avonex can activate the hepatotoxicity of GCS (glucocorticosteroids).

In general, a detailed study of the interaction of Avonex with other drugs has not been conducted; it is believed that its once-weekly administration regimen is not a direct contraindication to the administration of other drugs included in the treatment of multiple sclerosis.

[ 10 ]

Storage conditions

The storage conditions for interferon beta-1a are identical to the storage rules for all peptides on List B, known to all workers in the pharmaceutical industry.

Storage conditions of Avonex:

• The lyophilisate should be stored in a dry, dark place.
• The storage temperature of the drug is not higher than 4°C, provided that Avonex is stored for no more than 2 months.
• The storage temperature of interferon beta-1a during long-term storage (up to several years) should be lower (-18-20°C)
• Lighting, access to light negatively affects the interferon powder, as well as access to air, the peptide can be destroyed. Therefore, it is necessary to follow the rules for maximum preservation of the hermeticity of the drug and open it immediately before injection
• Do not freeze the prepared solution. One bottle of Avonex is intended for single use.
• The solution is stored together with the powder, in the original packaging, that is, at a temperature not exceeding 4°C.
• Avonex is stored out of the reach of children.

The storage conditions for Avonex are indicated on the packaging and should be followed without violating the rules so as not to disrupt the stability of the amino acid sequence in the drug.

Shelf life

The expiration date of Avonex must be indicated both on the factory packaging and on each bottle, and the production date is indicated in the same way. The drug is stored for no more than two years, the use of beta IFN with an expired shelf life or in case of violation of storage rules is not recommended. The solution prepared for injection is stored for no more than six hours, it is better to use it immediately. The storage temperature of the prepared solution, which is not used as an injection for any reason, should not exceed 8 ° C. Frozen prepared solution will not be effective even with a normal expiration date. Unused drug remaining in the bottle should be disposed of, it is not suitable for the next injection.

Avonex is considered one of the most effective drugs that helps prevent the progression of multiple sclerosis and reduces the potential likelihood of exacerbations by 30%. This significantly improves the quality of life of the patient, since without adequate treatment, MS quickly leads to complete disability and immobility.