Avonex

Avoneks - one of the drugs that is used to treat a complex, progressive disease - multiple sclerosis. MS is considered difficult to supervise the 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 way, the therapeutic complex includes drugs that help to arrest periods of exacerbation, drugs that slow the development and progression of pathology. In the group of pathogenetic drugs that change the course of multiple sclerosis (PTIRS), Avonex is an effective immunomodulator capable of enhancing cell interaction, activating the immune system, providing neuroprotective action, and reducing the severity of the symptoms of the disease. In many countries of the world, Avonex is considered one of the most effective means and is included in the so-called gold standard of preventive therapy for MS.

Indications of the avonex

The first clinical manifestations of the breach of the integrity of the myelin sheath at the beginning of the XIXth century were described by Kruevell. Since then, a lot of time has passed, but the etiology of the disease has not been clarified, therefore, unfortunately, there is no truly effective treatment for multiple sclerosis. Nevertheless, MS is being studied, new drugs and techniques are emerging, the main task of which is not only the reduction of symptoms, but also the slowing of the pathological process, the prevention of exacerbations. Avonex (interferon beta-1a) is considered one of the most effective drugs included in the therapeutic complex of PTIRS - drugs that change the course of MS. Indications for the use of Avonex:

• Demyelinating pathology of the central nervous system, recurrent
• Multifocal multiple sclerosis, progressive-recurrent nature - PRRS, with an increase in the intensity of neurological symptoms with exacerbations
• RRRS - relapsing-remitting multiple sclerosis with episodes of exacerbations and periods of remission
• VBRS is a second-progressive multiple sclerosis and a slow increase in neurologic symptoms, exacerbations and relapses
• Primary progressive MS with an increase in symptoms without apparent periods of stabilization and remission

As a rule, indications for the use of Avonex are at least two relapses within the last three years from the onset of the disease. However, many doctors believe that the appointment of the drug from the time of the first clinical signs of MS can significantly slow the progression of pathology. In addition, previously Avonex was not prescribed for progressive forms of the disease, believing that it would not have the desired effect. Researches of the last decade showed the opposite results, the generally accepted international indicator of worsening of the patient's condition - MSFC with Avonex administration decreased by almost 40%, the number of exacerbations and 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 for other diseases, it is effective in controlling any inflammatory processes that destroy myelin structures.

Release form

Avonex is used as a drug for intramuscular injection.

Form release - lyophilizate interferon-beta-1a, which is obtained from cells of the ovaries specially grown hamsters. In the DNA of the animal cells, the human interferon gene is inserted, thereby obtaining a glycosylated polyamino acid polypeptide. All 166 amino acids that enter Avonex are aligned in the sequence that corresponds to the polypeptide chain of human interferon.

Avonex is a lyophysed powder in hermetically sealed bottles, which includes such components as:

• Interferon beta-1a
• Serum albumin - serum albumin
• Sodium Phosphate Monohydrate
• Disodium phosphate - dibasic sodium phosphate
• Sodium chlorine

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

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

[1], [2]

Pharmacodynamics

Because etiopathogenesis, the pathophysiology of multiple sclerosis are not well understood, there is no reliable information about the pharmacodynamics of Avonex. There are only some works in which the possible effect of the drug on demyelination is described, the antiviral effect of interferon beta-1a has been studied in more detail. In the few studies published in specialized medical publications, it has been statistically proven that Avonex as an active cytokine is able to influence the main immune processes and significantly slow the progression of multiple sclerosis.

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

Pharmacodynamics of the Avonex drug is due to a wide spectrum of action of beta-interferon as a mediator of intercellular interaction, an immunomodulator and an antiviral drug. Interferon is a substance that is reproduced by complex structures, eukaryotic cells that can withstand many pathogenic biological factors, including viruses. The peculiarity of interferon beta-1a, like other types of cytokines, is that it is produced at the request of the body, it is not deposited and is not able to stay in the bloodstream for a long time. This substance is directed to the target cells, having a local effect on them, the catabolized interferon is excreted through the kidneys and liver. Avonex as beta-interferon is a recombinant, hybrid variant of the protein structure, which has a pronounced antiviral and antitumor effect.

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 the glycated form. Glycation 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 protein glycolation ensures their stability and active function during the distribution and elimination half-lives.

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

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

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Pharmacokinetics

Just like pharmacodynamics, the pharmacokinetics of Avonex have not been fully explored because many etiological, pathogenetic factors of multiple sclerosis remain unexplained. Nevertheless, tests to track the regularities of all kinetic processes - absorption, distribution and excretion (metabolism and excretion), are carried out constantly. The purpose of such studies is to clarify the degree of antiproliferative and antiviral activity of the drug.

The results, which are officially presented by the manufacturer of Avonex:

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

If we consider that the effect of interferon beta-1a was studied only on the group of patients with a relapsing form of MS, it is obvious that the latest information on the positive dynamics of treatment of patients with PPR (primary progressive MS) and VPRS (secondary progressive multiple sclerosis) may become the subject of more detailed studies of the efficacy of Avonex and the specificity of its pharmacokinetic parameters.

As for standard studies, under the supervision of physicians there were two groups - the study and control with the appointment of placebo (placebo). All patients were diagnosed with progression of neurological symptoms and a decrease in the quality of life, the evaluation was carried out using the Kaplan-Mayer method. The decline in the group who took standard treatment and placebo in place of Avonex reached 35%. In patients taking interferon beta-1a, progression slowed, and the figure was not higher than 22%.

Bioavailability of the drug and its ability to adequately synthesize in target cells can reduce the frequency of exacerbations and relapses, provided that Avonex is taken for at least 1 year.

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Dosing and administration

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

• Avonex is administered as an intramuscular injection
• The usual dose of Avonex is 6 million IU (30 μg) or 1 milliliter of dissolved lyophilizate 
• Multiplicity of admission - 1 time per week. A specific day and time of drug administration is determined, which should not be changed
• Place for injection of the injection (muscle) changes weekly to avoid local side effects (hyperemia, burning)
• Injections are made by the medical staff or the patient himself, provided that the necessary skills and permission of the attending physician
• The course of treatment with Avonex can vary, it is determined on an individual basis, based on possible reactions and confirmation or absence of visible positive dynamics

How to prepare an injection for Avonex?

1. The first stage is the preparation of the solution. It should be prepared only before injection, not earlier. One hand should hold the device Bio-Set, unscrew and remove the cap
2. Try not to touch the opening of the bottle, remove the tip from the syringe
3. The bottle with the Bio-Set is placed in an upright position on the table
4. The bottle is combined with a syringe
5. The cannula of the syringe is screwed clockwise into the Bio-Set device
6. The syringe is held by the base and with a sharp movement is fed it downwards so that its tip is completely hidden. At the same time, a characteristic click is heard indicating the correctness of the preparatory actions
7. Pressing the piston, the solvent is introduced into the vial, the syringe is not removed
8. The bottle with powder and solvent should be rotated by slow movements for complete homogeneous combination of substances. Pay attention - the bottle can not be shaken
9. To remove air from the bottle, push the syringe piston to the stop
10. The syringe is rotated through 180 ° without being removed from the vial
11. Slowly pulling the piston up, into the syringe, dial the drug in the right amount
12. Packing from the needle is removed in such a way that the cap itself remains in place
13. The syringe is separated from the Bio-Set by gently turning clockwise
14. A needle is put on the syringe. Put it in a special tray, included in the kit of the drug
15. Carry out the injection in a standard way - pre-treating the injection site
16. Avonex is administered as slowly as possible, thus minimizing uncomfortable sensations

Specific recommendations that relate to the mode of application and doses of Avonex:

• Do not use other substances for the powder solution, in addition to the solvent that is supplied
• Connecting the syringe and the Bio-Set, you must wait for the characteristic sound - click
• Enter the solvent 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). We admit a weak yellowish shade, any other color or particles in solution are considered inadmissible
• The solution is intended for single use, if it remains after the injection, it is disposed of and not reused

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Use of the avonex during pregnancy

During pregnancy, the appointment of any medication is a risk. Multiple sclerosis during pregnancy is diagnosed extremely rarely, rather, it is detected before conception and in principle is not a categorical contraindication to the bearing of a baby. Moreover, according to some European gynecologists, gestation can slow the development of pathology and reduce the severity of symptoms from the nervous system. Women from 12 countries participated in the survey, which lasted more than 2 years - before and after childbirth. The relapse rate decreased in 40% of mothers, especially the last trimester was favorable. Studies of Avonex during pregnancy have not been specifically performed, but it is rarely prescribed, when other drugs do not have the desired effect. Abandonment of Avonex during pregnancy is associated with the pharmacological features of all interferons in principle. Although the information on complications after admission, the toxicity of interferon beta-1a during gestation is absent, it is believed that it can provoke spontaneous miscarriage. The information was obtained after conducting an experiment to study fertility in rhesus monkeys. Interferon administration caused anovulatory action in the animals from the side of the pelvic organs, if the miscarriage did not occur, the course of pregnancy was normal and no teratogenic trait was revealed.

In any case, the poorly understood pharmacokinetics of Avonex during the perinatal period and after childbirth makes the doctors refuse to prescribe the drug to pregnant women with MS. If Avonex is assigned to women of childbearing age, in parallel they are shown taking contraceptives to avoid all sorts of risks. Also, there is no precise information on the ability of interferon beta-1a to enter breast milk, but for safety reasons it can not be injected during the entire breastfeeding period. The variant of treatment with interferon - the child is transferred to artificial nutrition, and the mother receives adequate treatment with Avonex.

Contraindications

As with many other interferon preparations, there are contraindications to the use of Avonex. Despite the high degree of bioavailability and apparent naturalness, Avonex is not safe, it is due to its activity and polyfunctional action.

Contraindications to the use of Avonex:

• Severe cardiovascular pathology
• Angina pectoris
• Persistent arrhythmia
• Exacerbations of liver diseases
• Kidney pathology
• Myocardial infarction and stroke
• Non-curable epilepsy
• Pathology of the hematopoiesis system
• Decompensated hepatic cirrhosis
• Hepatomegaly
• Chronic hepatitis during treatment with immunosuppressants
• Pregnancy and lactation
• Caution in thyroid disorders
• Individual intolerance to recombinant interferons, albumins
• Depressive states with suicidal tendencies
• Children under 16 years old

In addition, many doctors consider it a contraindication to the progressive form of multiple sclerosis, although nowadays many specialists successfully apply Avonex both in the treatment of VPSS (secondary-progressive form) and PPR (primary progressive form).
 

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Side effects of the avonex

As side effects, which causes Avonex, it is necessary to name typical influenza-like manifestations. This is considered almost inevitable an adequate complication in the introduction of all interferons and is explained by the primary response of the immune system to the introduction of any protein substances. Primary symptoms can be:

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

Such conditions are characteristic for the beginning of treatment by Avonex, as soon as the body adapts to the drug, the symptomatology subsides, it takes from one week to 14 days. In addition, Avonex's side effects may appear as transient neurological complications throughout the course of treatment-periodic muscle spasms, loss of sensitivity, or temporary paralyzes of a functional type are considered acceptable if not associated with typical symptoms of exacerbation of the disease. Check and distinguish the side effect of the present exacerbation simply, the first occurs soon after the administration of the drug and subsides within 24 hours.

Side effects of Avonex can appear in almost all systems and organs, since it affects the body systematically. These complications are considered secondary, following the typical neurological and influenza-like effects. Secondary side effects may be:

Organs, systems	Complications, side effects
Skin covers	Itching, hair loss, rash, sweating, exacerbation of dermatitis or psoriasis
GIT	Nausea, vomiting, loss of appetite, diarrhea, pain in the liver, vomiting is possible
The immune system	Allergic reactions, anaphylaxis
The cardiovascular system	Arrhythmia, exacerbation of cardiac pathologies
System of blood circulation, hematopoiesis	Reduction of the level of lymphocytes, platelets, neutrophils, leukocytes. Reduction in hematocrit
Respiratory system	Shortness of breath, sensation of lack of air, rhinorrhea
Musculoskeletal system	Myalgia, arthralgia. Muscle spasms. Perhaps a decrease in muscle tone, atony
Sexual system	Bleeding, dysmenorrhea, metrorrhagia
Endocrine system	Thyroid dysfunction - hypo or hyperthyroidism
CNS	Paresis, paresthesia, temporary paralysis. Dizziness, epipodic convulsions. Depressive state, migraine-like attacks of headache. Mood swings, psychoemotional lability
Local side effects	Redness at the injection site, itching, burning, rarely - abscess

In addition to the aforementioned side effects, weight loss or gain may be possible, a change in blood composition - hyperkalaemia, an increase in the level of urea.

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Overdose

Overdose Avoneks extremely rare, it happens if you want to independently adjust the course of treatment from the patient. The introduction of two vials at once will, of course, cause complications, since even with the prescribed dosage, side effects, considered acceptable, are still possible. At the first alarming symptoms and a confirmed overdose, the patient is hospitalized to conduct adequate detoxification therapy. When the symptomatology subsides, supportive treatment is carried out, then Avonex can be reassigned. If Avonex is administered by the patient independently, and the patient has neurological complications such as depression, apathy, other psychoemotional disorders, relatives and close people should monitor compliance with the regimen and dosage of the drug.

As a rule, after the appointment of 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 acceptable complications, including symptoms of influenza-like conditions.

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

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Interactions with other drugs

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

What does Avonex do:

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

Avonex as an active immunomodulator is not combined with immunosuppressors - Imuran, Cyclophosphamide, Mitoxantrone, with MKAT - monoclonal antibodies - it is prescribed after the course of these drugs or as a mono drug.

Caution should be exercised when concomitantly prescribing anticonvulsant drugs and beta-IFN (interferon beta-1a), also the parallel administration of Avonex and antidepressants may cause an aggravation of depressive symptoms, up to attempts at suicide. Therefore, the beta-IFN is cautiously assigned to patients with a labile psyche, taking into account the risk of complications and the potential therapeutic effectiveness.

With prolonged treatment with Avonex, the ability of beta-interferons to decrease the productivity of cytochrome P450-dependent monooxygenase should be considered. All antiepileptic drugs, TCAs (tricyclic antidepressants), SSRIs (selective serotonin reuptake inhibitors), MAOI (monoamine oxidase inhibitors), IIPS (selective serotonin uptake inhibitors) have a clearance dependent on cytochrome monooxygenase enzymes. Such a combination will not give a tangible therapeutic result and treatment may be useless.

In practice, there were complications with the simultaneous administration of interferon and the intake of antipyretics, which reduce the flu-like symptoms characteristic for the initiation of treatment. If signs of intoxication appear, the headache intensifies, antipyretic drugs are recommended to be taken 12 hours before the Avonex injection, then a day later. You should also be as cautious as possible in the treatment of MS patients with hepatoses in any form. Avonex can activate hepatotoxicity of GCS (glucocorticosteroids).

In general, detailed study of the interaction of Avonex with other drugs has not been conducted, it is considered that the mode of its administration - once a week is not a direct contraindication to the appointment of other drugs included in the complex of treatment for multiple sclerosis.

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Storage conditions

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

Avonex storage conditions:

• The lyophilizate must be stored in a dry, dark place
• The temperature of storage of the preparation is not more than 4 ° C, provided that Avonex is stored for no more than 2 months
• The storage temperature of interferon beta-1a for long-term storage (up to several years) should be lower (-18-20 ° C)
• Lighting, light access negatively affects the interferon powder, as well as air access, the peptide is able to break down. Therefore, you should follow the rules of maximum preservation of the drug and open it immediately before the injection
• You can not freeze a ready-made solution. One vial of Avonex is for single use only
• The solution is stored together with the powder in the original packaging, that is, at a temperature not exceeding 4 ° C
• Avonex is stored in a place inaccessible to children

The storage conditions for Avonex are indicated on the packaging, they must be observed without violating the rules, so as not to disrupt the stability of the amino acid sequence in the preparation.

Shelf life

The validity period of Avonex must be indicated both on the factory packaging and on each vial, and the date of release is similarly designated. The drug is stored for no more than two years, the use of beta IFN with expired shelf life or in case of violation of storage rules is not recommended. The solution prepared for injection is stored no more than six hours, it is better to use it immediately. The storage temperature of the finished solution, which is not applied as an injection for any reason, should not exceed 8 ° C. Frozen ready-made solution will not be effective even at normal shelf life. The unused product remaining in the vial should be disposed of, it is not suitable for the next injection.

Avonex is considered one of the most effective drugs, helping to prevent the progression of multiple sclerosis and reduces the potential for exacerbations by 30%. This greatly improves the quality of life of a sick person, since without adequate treatment, MS quickly leads to complete disability and immobility.