Авонекс

General characteristics. Structure:

Active agent: Interferon of beta 1а 30 mkg
Excipients: albumine of human serumal 15,0 mg, sodium hydrophosphate of 5,7 mg, sodium dihydrophosphate of 1,2 mg, sodium chloride of 5,8 mg.
Solvent in the syringe:  water for injections of 1,0 ml.

Description: The lyophilized mass of white or almost white color.

Pharmacological properties:

Interferona represent the natural proteins produced by eukaryotic cells in response to infection and on influence of other biological factors. Interferona are the cytokines which are mediators of anti-virus, anti-proliferative and immunomodulatory systems of an organism. Beta interferon is synthesized by different types of cells, including fibroblasts and macrophages. Natural beta interferon and the drug Avoneks® (interferon beta 1а) exist in a glikozilirovanny look and incorporate the only complex hydrocarbon fragment connected with atom N. The glycosylation of proteins influences their stability, activity, biodistribution and an elimination half-life.
Biological properties of the drug Avoneks® are defined by ability of interferon beta 1а to contact specific receptors on a surface of cells of a human body and to start the difficult cascade of intercellular interactions bringing to interferon - the caused expression of numerous gene products and markers, such as main complex of histocompatability of the I class, protein of Mkh, a 2/5-oligoadenilatsintetaza, b2-microglobulin and neopterine. Presence of some of these connections was revealed in serum and cellular fractions of blood of the patients receiving Avoneks®. After intramuscular introduction of one dose of drug, the content of the specified connections in serum remained raised within 4-7 days.
It is unknown whether the mechanism of effect of the drug Avoneks® at treatment of multiple sclerosis (PC) is connected with start of the biological interactions described above as the pathophysiology of multiple sclerosis is studied not enough.
Effect of drug at treatment of PC was estimated in the platsebokontroliruyemy research conducted on patients with the recurrent PC form. It was shown that total quantity of patients at whom the progressing of disability (determined by Kaplana-Maier's table) by the end of the second year of a research was noted made 35% at purpose of placebo and 22% at drug Avoneks® use.
It was also established that use of the drug Avoneks® within one year leads to decrease in frequency of a recurrence within the next year on one third. For the purpose of comparison of efficiency of various doses of drug the double blind research by method of a random sample on 802 patients suffering from recurrent PC was conducted. In a research statistically significant distinctions at use of doses in 30 and 60 mkg in clinical parameters and the general parameters of a magnetic and resonant tomography are not revealed.
Efficiency of drug at treatment of multiple sclerosis was shown in a platsebokontroliruyemy research at treatment of patients with symptoms of a demyelinating disease. In group of the patients receiving placebo, the frequency of repeated demyelinating events during 2nd and 3rd made respectively 39% and 50% whereas in group of the patients receiving Avoneks®, these indicators made 21% and 35%.

Pharmacokinetics. The pharmacokinetics of interferon beta 1а was studied on the basis of measurement of anti-virus activity of interferon. After single intramuscular introduction peak levels of anti-virus activity are reached in plasma during from 5 to 15 h; the elimination half-life made about 10 h. Bioavailability of drug makes about 40%.

Indications to use:

- treatment of the patients having the recurrent multiple sclerosis (RMS) which is characterized by at least two recurrence throughout the previous three-year period in the absence of signs of progressing of a disease between a recurrence.
- treatment of patients at whom the demyelination case in the presence of the active inflammatory process demanding intravenous administration of corticosteroids at an exception of other took place, than PC, the diagnosis and at high risk of development of PC.

Route of administration and doses:

Use of drug should be carried out under control of the doctor having experience of treatment of PC.
Adults: The recommended drug Avoneks® dose at RRS makes 30 mkg (6 million ME) once a week intramusculary.
Purpose of higher dose (60 mkg) once a week does not lead to strengthening of effect.
Children and teenagers: The safety profile at purpose of the drug Авонекс® 30 of mkg intramusculary to teenagers of 12 - 16 years is similar once a week to a safety profile for adults.
Elderly patients: Enough patients did not participate in clinical trials 65 years are more senior to establish possible distinction of reaction to treatment in this age group in comparison with younger patients. However, based on clearance of active agent, the bases for dose adjustment of drug for elderly patients are absent.
Duration of a course of therapy is defined individually. After 2 years of treatment of the patient has to undergo clinical inspection and on an individual basis the attending physician can recommend to continue a therapy course. It is necessary to stop treatment if at the patient the chronic progressing PC develops. Авонекс® it is necessary to enter intramusculary right after solution preparation. Injections of drug should be made, whenever possible, at the same time in the same day of the week. The place of an injection should be changed every week. Before an injection and in addition during 24 h after each injection it is recommended to accept febrifugal drugs to reduce the grippopodobny symptoms connected with introduction of Avoneksa®, which are usually appearing in the first months of treatment.
Before use of any other drug during a course of therapy Avoneksom® consultation of the doctor is necessary. If the doctor recommends antipyretic reception, it is necessary to implement carefully recommendations and not to exceed the recommended dose.
The instruction given below is intended for those who carry out drug Avoneks® injections:
Before dissolution check integrity of a bottle and the Bio-Set device Drug is unsuitable to use if integrity is broken.
1. Dissolution is made just before administration of drug.
- holding for foundation of Bio-Set, turn a cap and remove it. Do not touch a connecting opening.
- remove with tightening a cap from the syringe filled with solvent without touching a tip. Do not press the piston.
- put a bottle with Bio-Set vertically on a smooth surface, combine with a syringe tip. Screw a syringe cannula in Bio-Set clockwise. Following the direction of the movement and holding the syringe for the basis, sharply give it down so that the tip disappeared completely and the click sounded.
- slowly pressing on the syringe piston, enter solvent into a bottle.
- leaving the syringe connected to Bio-Set, carefully rotate a bottle before full dissolution of powder. Drug has to be dissolved completely within 1 minute. Solution, ready to use, has to be transparent, colourless. Weak-yellow color of solution is allowed.
Solution should not have mechanical impurity, and also to be muddy and painted.
Avoid stirring of a bottle since it can cause foaming.
- press on the syringe piston down to an emphasis to remove all air in the syringe.
- turn the syringe and a bottle vertically on 180 °C and slowly pull for the piston so that solution of drug appeared in the syringe.
- open individual packaging of a needle, do not remove a cap from a needle.
- holding the filled syringe for the basis, separate it from the Bio-Set device, turning counterclockwise. Do not concern a syringe cannula!
- get a needle on the filled syringe, turning it clockwise.
Then put the syringe on a plain surface and process the place of an injection the tampon moistened in alcohol.
2. Injection
- tightening remove a protective cap from a needle, without rotating it
- turn the syringe a needle up, for removal of air slightly knock on its basis so that bubbles rose upward. Slightly press the piston for removal of bubbles so that on the end of a needle appeared smaller drop of liquid.
- Stick a needle in a muscle and slowly administer the drug, and then remove the syringe together with a needle.
In case of a drop of blood, it is possible to stick the place of an injection with a plaster.
Preventions: For preparation of solution it is necessary to use the water for injections which is included in the package. Not to use other solvents.
At connection of the syringe to the Bio-Set device do not take further actions, you will not hear click yet. Bystry administration of solvent can cause foaming which will complicate a set of drug in the syringe.
Drug does not contain preservatives. Each bottle with drug is intended only for single use. The remained drug is not subject to use.
The injections which remained later place a bottle and the syringe in an opaque package and together with the paper waste used by tampons throw out in a usual trash bin.

Features of use:

Before an initiation of treatment it is necessary to inform patients on the possible side effects connected using drug. In view of possibility of a misbirth against the background of use of interferon a beta, women with the kept reproductive ability should recommend to use effective methods of contraception. Авонекс®, as well as other interferona, it is necessary to apply with care at treatment of the patients having a depression or depressive frustration. It is known that at use of interferon developing of a depression and suicide thoughts, and in a group of persons, the suffering PC is possible, the frequency of such phenomena increases. Developing of depressions perhaps at any time treatments of Avoneksom®. At emergence of any symptoms of a depression or suicide thoughts, patients need to see the attending physician immediately. For such patients it is necessary to establish careful observation during treatment and if necessary urgently to apply the appropriate medical measures. In some cases there can be a need of phase-out of drug.
Care at purpose of Avoneksa® is necessary for the patients who earlier had convulsive attacks, and also accepting antiepileptic means, in particular if it is not possible to reach adequate control over attacks. If the patients who earlier did not have epilepsy in the course of treatment with drug have epileptopodobny attacks, it is necessary to establish an etiology of attacks and to appoint the corresponding anticonvulsant therapy before to resume use of Avoneks®.
It is necessary to show care at appointment, and also to make careful observation of the patients having the expressed renal and liver failure and also at oppression of a marrowy hemopoiesis. At interferon use a beta emergence of signs of an abnormal liver function, such as increase in level of enzymes of a liver in blood serum, development of hepatitises, including autoimmune, a liver failure is noted. However it is not known whether it is a consequence of reception of interferon beta 1а or it is connected with reception of other drugs which are usually appointed to such patients. It is necessary to control carefully a condition of patients regarding development of signs of an abnormal liver function, especially, if interferon is applied together with other gepatotoksichny drugs.
At use of Avoneks® it is necessary to control carefully a condition of patients with diseases of cardiovascular system: stenocardia, the postponed myocardial infarction, dekompensirovanny heart failure, arrhythmia as manifestations of the grippopodobny syndrome caused by drug use can make on them stressorny impact.
At use of interferon there can be deviations in laboratory indicators therefore except the usual laboratory analyses which are carried out by sick PC during treatment it is recommended to carry out calculation of uniform elements of blood (including thrombocytes), definition of a leukocytic formula, and biochemical analysis of blood (including liver enzymes). The developed blood count research with calculation of number of thrombocytes can be required by that patients who have signs of oppression of a marrowy hemopoiesis.
At use of Avoneks® within one year in blood serum at 8% of patients appear interferon - neutralized antibodies which can reduce activity of interferon beta 1а, and, therefore, and clinical performance of drug.
Influence on ability to drive the car or other mechanisms:
In case of side effects from the central nervous system, perhaps minimum decline in the ability of patients to driving and use of mechanisms.
Use during pregnancy, lactations, and also at women with the kept reproductive ability:
Use of Avoneks® during pregnancy contraindicated. The available data confirm possible increase in risk of spontaneous abortion.
Due to the potential risk of development of side reactions in the baby, Avoneks® it is contraindicated to use in the period of a lactation.
Women with the kept reproductive ability have to use effective methods of contraception. In case of pregnancy or planning of pregnancy during treatment of Avoneksom® the patient should be informed on potential danger and to consider expediency of cancellation of treatment. At patients with high frequency of a recurrence is prior to treatment, it is necessary to compare risk of a heavy recurrence because of cancellation of Avoneksa® in case of pregnancy with possible increase in risk of spontaneous abortion because of its inclusion in pregnancy time.

Side effects:

The most frequent side effect of interferon is the grippopodobny syndrome. It is shown in the form of weakness, feeling of fatigue, muscle pains, fevers, a fever, a headache, nausea, perspiration. These symptoms are usually more expressed in an initiation of treatment, the frequency and intensity decreases in process of treatment continuation.
During any period of treatment emergence of the neurologic symptoms similar to an exacerbation of multiple sclerosis is possible: the passing episodes of a muscle hyper tone and/or muscular weakness limiting a possibility of autokinesias. These episodes limited on duration on time are connected with injections and can repeat at the subsequent introductions. In certain cases these symptoms are followed by grippopodobny manifestations.
In each private category side effects are grouped in system organ class and presented in decreasing order of frequency:
Very often (> 1/10 patsiyento-years *)
Often (from 1/100 to 1/10 patsiyento-years)
Infrequently (from 1/1000 to 1/100 patsiyento-years)
Seldom (from 1/10 000 to 1/1 000 patsiyento-years)
Very seldom (<1/10 000 patsiyento-years)
It is unknown (on the basis of the available data assessment is impossible)
* patsiyento-years represents the sum of individual units of time during which the patient participating in a research received Avoneks® before development in it of adverse reaction.
Laboratory and tool researches:
Often: a lymphocytopenia, a leukopenia, a neutropenia, a reduced hematocrit, increase in content of potassium in blood, increase in maintenance of an urea nitrogen of blood.
Infrequently: decrease in number of thrombocytes in comparison with initial indicators.
It is unknown: a body degrowth, increase in body weight, a deviation of parameters of a functional trial of a liver from norm.
Disturbances from heart:
It is unknown: Cardiomyopathy, congestive heart failure, heart consciousness, arrhythmia, tachycardia.
Disturbances from system of a hemopoiesis and lymphatic system: It is unknown: pancytopenia, thrombocytopenia.
Disturbances from a nervous system:
Very often: headache.
Often: muscular spasms, gipoesteziya
It is unknown: neurologic symptoms, obmorok3, hypertension, dizziness,
paresthesia, spasms, migraine.
Disturbances from a respiratory organs: Often: rhinorrhea. Seldom: asthma.
Gastrointestinal frustration: Often: vomiting, diarrhea, toshnota2.
Disturbances from skin, its appendages and hypodermic fabric:
Often: rash, the increased perspiration, bruises.
Infrequently: alopecia.
It is unknown: Quincke's disease, itch, vesicular rash, small tortoiseshell, exacerbation of psoriasis.
Disturbances from skeletal and muscular and connecting fabric:
Often: muscular spasms, neck pain, mialgiya2, arthralgia, extremity pain, dorsodynia, muscular constraint, skeletal and muscular rigidity.
It is unknown: system lupus erythematosus, muscular weakness, arthritis.

Endocrine disturbances:
It is unknown: hyperthyroidism, hypothyroidism.
Disturbances of metabolism and food: Often: anorexia.
Infectious and parasitic diseases: It is unknown: abscess in the place injektsii1.
Disturbances from vessels: Often: rushes of blood to the person. It is unknown: vazodilatation
System disturbances and states in a drug injection site:
Very often: grippopodobny simptomy2, oznob2, potlivost2.
Often: pain in the place of an injection, an erythema in the place of an injection, a hematoma in the place of an injection, asteniya2, pain, ustalost2, an indisposition, night perspiration.
Infrequently: burning in the place of an injection.
It is unknown: reaction in the place of an injection, an inflammation in the place of an injection, cellulitis in the place of an injection, a necrosis in the place of an injection, bleeding in the place of an injection, a stethalgia.
Disturbances from immune system:
It is unknown: acute anaphylaxis, anaphylactic reaction, hypersensitivity reaction (Quincke's disease, asthma, small tortoiseshell, rash, pruritic rash)
Gepatobiliarny frustration:
It is unknown: liver failure, hepatitis, autoimmune hepatitis.
Disturbances from reproductive system and a mammary gland: Infrequently: metrorrhagia, menorrhagia.
Mental disorders:
Often: depression, sleeplessness.
It is unknown: suicide, psychosis, uneasiness, confusion of consciousness, emotional lability.
1 The Described reactions in the place of an injection include pain, an inflammation and very exceptional cases of abscess or cellulitis which could demand surgical intervention.
2 Frequency of these effects is higher in an initiation of treatment.
3 After an injection of Avoneksa® the syncope, as a rule, such syncope the only episode in an initiation of treatment is possible and does not repeat at the subsequent injections.
Precautionary measures:
Before an initiation of treatment it is necessary to inform patients on the possible side effects connected using drug. In view of possibility of a misbirth against the background of use of interferon a beta, women with the kept reproductive ability should recommend to use effective methods of contraception. Авонекс®, as well as other interferona, it is necessary to apply with care at treatment of the patients having a depression or depressive frustration. It is known that at use of interferon developing of a depression and suicide thoughts, and in a group of persons, the suffering PC is possible, the frequency of such phenomena increases. Developing of depressions perhaps at any time treatments of Avoneksom®. At emergence of any symptoms of a depression or suicide thoughts, patients need to see the attending physician immediately. For such patients it is necessary to establish careful observation during treatment and if necessary urgently to apply the appropriate medical measures. In some cases there can be a need of phase-out of drug.
Care at purpose of Avoneksa® is necessary for the patients who earlier had convulsive attacks, and also accepting antiepileptic means, in particular if it is not possible to reach adequate control over attacks. If the patients who earlier did not have epilepsy in the course of treatment with drug have epileptopodobny attacks, it is necessary to establish an etiology of attacks and to appoint the corresponding anticonvulsant therapy before to resume use of Avoneks®.
It is necessary to show care at appointment, and also to make careful observation of the patients having the expressed renal and liver failure and also at oppression of a marrowy hemopoiesis. At interferon use a beta emergence of signs of an abnormal liver function, such as increase in level of enzymes of a liver in blood serum, development of hepatitises, including autoimmune, a liver failure is noted. However it is not known whether it is a consequence of reception of interferon beta 1а or it is connected with reception of other drugs which are usually appointed to such patients. It is necessary to control carefully a condition of patients regarding development of signs of an abnormal liver function, especially, if interferon is applied together with other gepatotoksichny drugs.
At use of Avoneks® it is necessary to control carefully a condition of patients with diseases of cardiovascular system: stenocardia, the postponed myocardial infarction, dekompensirovanny heart failure, arrhythmia as manifestations of the grippopodobny syndrome caused by drug use can make on them stressorny impact.
At use of interferon there can be deviations in laboratory indicators therefore except the usual laboratory analyses which are carried out by sick PC during treatment it is recommended to carry out calculation of uniform elements of blood (including thrombocytes), definition of a leukocytic formula, and biochemical analysis of blood (including liver enzymes). The developed blood count research with calculation of number of thrombocytes can be required by that patients who have signs of oppression of a marrowy hemopoiesis.
At use of Avoneks® within one year in blood serum at 8% of patients appear interferon - neutralized antibodies which can reduce activity of interferon beta 1а, and, therefore, and clinical performance of drug.
Influence on ability to drive the car or other mechanisms:
In case of side effects from the central nervous system, perhaps minimum decline in the ability of patients to driving and use of mechanisms.
Use during pregnancy, lactations, and also at women with the kept reproductive ability:
Use of Avoneks® during pregnancy contraindicated. The available data confirm possible increase in risk of spontaneous abortion.
Due to the potential risk of development of side reactions in the baby, Avoneks® it is contraindicated to use in the period of a lactation.
Women with the kept reproductive ability have to use effective methods of contraception. In case of pregnancy or planning of pregnancy during treatment of Avoneksom® the patient should be informed on potential danger and to consider expediency of cancellation of treatment. At patients with high frequency of a recurrence is prior to treatment, it is necessary to compare risk of a heavy recurrence because of cancellation of Avoneksa® in case of pregnancy with possible increase in risk of spontaneous abortion because of its inclusion in pregnancy time.
Interaction with other drugs:
Special researches on interaction of Avoneks® with other medicines, including with corticosteroids or AKTG, at people were not conducted. At the same time experience of clinical tests shows that sick PC can accept during an exacerbation of a disease Avoneks® together with corticosteroids or AKTG.
It is known that interferona have ability to reduce activity of the enzymes connected with liver R-450 cytochrome. In this regard it is necessary to show care at purpose of Avoneks® along with drugs which clearance substantially depends on system of R-450 cytochrome, for example, antiepileptic drugs and antidepressants.

Interaction with other medicines:

Special researches on interaction of Avoneks® with other medicines, including with corticosteroids or AKTG, at people were not conducted. At the same time experience of clinical tests shows that sick PC can accept during an exacerbation of a disease Avoneks® together with corticosteroids or AKTG.
It is known that interferona have ability to reduce activity of the enzymes connected with liver R-450 cytochrome. In this regard it is necessary to show care at purpose of Avoneks® along with drugs which clearance substantially depends on system of R-450 cytochrome, for example, antiepileptic drugs and antidepressants.

Contraindications:

- the known hypersensitivity to natural or recombinant interferon a beta, to a seralbumin of the person or any other component of drug
- period of pregnancy and lactation
- the expressed depression
- emergence of suicide thoughts
- age less than 12 years (due to the lack of clinical data on use in this age group)
- the progressing PC form.

Overdose:

Thanks to a way of introduction and a dosage form, the overdose is improbable. In case of overdose of the patient it is necessary to hospitalize for medical observation and performing symptomatic therapy.

Storage conditions:

Period of validity 2 years. Not to use after expiry date. At a temperature not above 25 °C. Not to freeze. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for intramuscular introduction
30 mkg/ml (6 million ME/ml).
Lyophilisate on 30 mkg (6 million ME) in the glass bottles corked with brombutilovy traffic jams and the Bio-Set device.
Solvent (water for injections) on 1,0 ml in the glass syringe closed by a brombutilovy cap and a stopper plunger from polypropylene.
1 bottle with lyophilisate, 1 syringe with solvent and a needle is placed in the soldered plastic tray. 4 soldered plastic trays together with the application instruction in a cardboard pack.