Composition, structure and packing
Lyophilisates for solution for i / m administration in the form of masses of white or nearly white. 1 vial. interferon beta-1a 30 mcg (6 mln.ME) Excipients: human serum albumin (15 mg), sodium phosphate dibasic, sodium phosphate monobasic, sodium chloride.
Solvent: water w / and - 1 ml.
Clinico-pharmacological group: interferon. The drug, used in multiple sclerosis.
Pharmacological action
Recombinant human interferon beta-1a. Synthesized by different types of cells, including fibroblasts and macrophages.
Interferon beta-1a exists in glikolizirovannom form and incorporates a unique integrated hydrocarbon fragments associated with the atom N (it is known that glikolizirovanie proteins affects their stability, activity, distribution and elimination half-life).
Biological properties of the drug Avonex is determined by its ability to bind to specific receptors on the cell surface and launch a cascade of cellular interactions, leading to interferon-induced expression of multiple gene products and markers (including the main histocompatibility complex class I protein Mx, 2 '/ 5 '-oligoadenilatsintetaza, b2-microglobulin and neopterin). The presence of some of these compounds were detected in serum and cellular fractions of blood of patients treated with Avonex. After i / m administration of 1 dose of the drug content of these compounds in serum remained elevated for 4-7 days.
It is not known whether the mechanism of action related to Avonex in the treatment of multiple sclerosis with the launch of the biological interactions described above, since pathophysiology of multiple sclerosis has been studied enough. The action of the drug in the treatment of multiple sclerosis was assessed in a strictly controlled study conducted in patients with relapsing forms of multiple sclerosis.
It has been shown that the total amount of patients, which showed the progression of disability (defined on a table Kaplan-Meier) to the end of the second year study was 35% for the appointment of a placebo and 22% when using Avonex. To compare the effectiveness of different doses of the drug were conducted double-blind, randomized trial of 802 patients with multiple (disseminated) sclerosis with relapses.
The study revealed no statistically significant differences at doses 30 mcg and 60 mcg for clinical parameters and the overall parameters of the ICTR. It was also found that the use of the drug Avonex for 1 year leads to a reduction in the frequency of relapses during the year to 1 / 3. The effectiveness of the drug in the treatment of multiple sclerosis has been shown in a strictly controlled study in patients with symptoms of demyelinating disease. In the patients receiving placebo, the frequency of relapses during the 2 and 3 years were 39% and 50%, whereas in the group treated with Avonex, the figures were 21% and 35%. The above data show that Avonex slows the progression of disability and reduces the incidence of relapses.
Pharmacokinetics
Pharmacokinetics of interferon beta-1a has been studied by measuring the antiviral activity of interferon.
Absorption
After a single i / m administration peak levels of antiviral activity is achieved in plasma in the period from 5 to 15 h. Bioavailability is 40%.
Putting T1 / 2 was 10 h.
Statement
treatment of relapsing multiple (disseminated) sclerosis, characterized by at least two relapses during the previous 3 years with no signs of disease progression between relapses;
treatment of patients who had been a case of demyelination as a result of active inflammatory process, which required a / v GKS introduction, to the exclusion of other than multiple sclerosis diagnosis.
Dosage regimen
The recommended dose is 30 mcg (6 mln.ME) in / m 1 times per week. Increasing the dose does not lead to increased therapeutic effect. Duration of therapy is determined individually. After 2 years of treatment the patient must undergo clinical examination and the doctor may recommend further course of therapy.
Avonex should be entered in / m immediately after the preparation of the solution. Injections of the drug should, wherever possible, produce in the same time in one and the same day of the week. Injection site should be changed every week. If necessary, your doctor may allow a patient to perform self-injection after proper training.
Terms of solution preparation and implementation of i / m injection
The solution is prepared immediately before drug administration. Hold the base unit Bio-Set, rotate the cap and remove it, do not touch the connecting holes. Remove the cap by contracting with a syringe filled with solvent, and avoid touching the tip. Do not push the plunger. Put a bottle of Bio-Set vertically on a smooth surface, align with the tip of the syringe. Screw the syringe into a cannula Bio-Set in a clockwise direction. Following the direction of motion and holding a syringe from the base, snapped it down so that the tip had disappeared completely and a click. Slowly pushing the plunger of the syringe type solvent into the vial. Leaving the syringe connected to the Bio-Set, gently rotate the vial to completely dissolve the powder. The drug should be completely dissolved within 1 min. Avoid shaking the vial, as This can cause the formation of foam. Push the plunger of the syringe down until it locks to remove all air in the syringe. Turn the syringe and vial vertically by 180 ° and slowly pull the plunger so that the solution of the drug was in the syringe. Open the individual packing needle, do not remove the needle cap, holding a syringe filled with the base, separate it from the device Bio-Set, turning counterclockwise. Do not touch the cannula needle! Push on the filled syringe needle, turning it clockwise.
Then place the syringe on a flat surface and treat the injection swab dipped in alcohol. Contractions, remove the needle cap, not turning it, turn the syringe needle upward, to remove the air lightly tap on its base so that the bubbles have risen to the top. Gently press the plunger to remove air bubbles, so that at the end of the needle appeared no more than a small drop of liquid. Vkolite needle into the muscle and slowly enter the drug, and then remove the syringe. If necessary, cover the injection site with a plaster.
To prepare the solution should use the water for injection, which is included in the kit. Do not use other solvents.
When attached to a syringe device Bio Set to take no further action until you hear a click. The rapid introduction of the solvent can cause foaming, which impede recruitment of the drug in the syringe. The product is unfit for use, if you compromise the integrity of the bottle, and if the drug solution will be cloudy, colored (but may be weak yellowish staining), or it will be visible floating particles. The product contains no preservatives. Each vial of the drug is intended for single use only. The remaining after the introduction of solution should be discarded or destroyed.
Side effect
The most frequent side effect is a manifestation of influenza-like syndrome: weakness, fatigue, fever, chills, muscle aches, headache, nausea (occurrence of these symptoms are most likely the beginning of treatment, as they continue to treat the frequency of their occurrence is reduced);
rarely - spastic phenomena and transient muscle weakness until the reversible paralysis of the limbs (these symptoms may be stopped and will appear again and usually of short duration).
In any period of treatment may cause neurological symptoms similar to the exacerbation of multiple sclerosis: episodes of muscle spasms and / or muscle weakness, limiting the possibility of voluntary movements (these episodes by the time associated with injections and may recur during subsequent introductions, and in some cases they may be accompanied by influenza-like symptoms).
Less frequently observed dermatologic reactions: alopecia, pruritus, sweating, rash, exacerbation of psoriasis.
Allergic reactions: urticaria, anaphylactic reaction, anaphylactic shock.
On the part of the digestive system: loss of appetite, nausea, vomiting, diarrhea, abnormal liver function.
Since the cardiovascular system: feeling the heat, tachycardia, arrhythmia, cardiomyopathy, heart failure, vasodilatation.
On the part of the hemopoietic system: rare - thrombocytopenia, lymphocytopenia, neutropenia, leukopenia, pancytopenia, lower hematocrit.
On the part of the reproductive system: menorrhagia, metrorrhagia.
From the side of the central nervous system and peripheral nervous system: headache, decrease in sensitivity, anxiety, dizziness, insomnia, paresthesia; rare - epileptopodobnye seizures, depression, suicidal thoughts, confusion, emotional lability, psychosis, migraine.
On the part of the musculoskeletal system: muscle cramps, myalgia, arthralgia, pain in the limbs, pain in the neck and back pain, muscular rigidity, transient decrease or increase muscle tone in the beginning kupca treatment.
The respiratory system: rhinorrhea, dyspnea, shortness of breath.
From the Endocrine: hypothyroidism, hyperthyroidism.
On the part of the organism as a whole: flu-like symptoms, sweating at night, change of body weight, pain in the chest.
Local reactions: flushing, pain, burning pain, inflammation, abscess at the injection site.
Other: transient increase of urea level in blood serum, hyperkalemia, systemic lupus erythematosus.
Contraindications
marked depression,
the emergence of suicidal thoughts;
epilepsy resistant to therapy;
childhood and adolescence to 16 years;
Pregnancy
lactation (breastfeeding);
indicate a history of increased susceptibility to natural or recombinant interferon beta, human serum albumin or other components of the drug.
Pregnancy and lactation
In connection with the potential risk of adverse reactions using the product Avonex during pregnancy is contraindicated. In view of the possibility of spontaneous abortion because of side effects associated with the use of interferon beta, patients of childbearing age in the period of treatment should take appropriate contraceptive measures. In connection with the potential risk of adverse reactions in infant Avonex is contraindicated during lactation.
Application for violations of liver function
With caution and under close medical supervision should be used Avonex in patients with severe hepatic insufficiency. Should closely monitor the state of patients for signs of liver problems, especially when interferon is used in conjunction with other hepatotoxic drugs.
Application for violations of renal function
With caution and under close medical supervision should be used Avonex in patients with severe renal insufficiency.
Cautions
Before treatment should inform patients about possible side effects associated with the use of the drug. Avonex should be used with caution in treating patients with depression or depressive disorders. It is known that the application of interferons may cause depression and suicidal thoughts, with a group of persons suffering from multiple sclerosis, the frequency of such events increases. The emergence of depressive states may at any time of treatment with Avonex. Patients should be warned that if there are any signs of depression or suicidal thoughts should immediately contact your doctor. For such patients should be closely monitored during treatment and the urgency to take appropriate therapeutic measures. In some cases it may be necessary to discontinue using the product.
In the case of progressive forms of multiple sclerosis drug Avonex use should be discontinued.
Caution is required in the appointment of the drug Avonex patients who have previously been observed seizures. If the patient has not previously been observed manifestations of epilepsy, and in the process of treatment Avonex appeared epileptopodobnye seizures, should establish the etiology of seizures and assign the appropriate anticonvulsant therapy before you resume using the product.
With caution and under close medical supervision should be used Avonex in patients with severe renal and hepatic failure, as well as in cases of marked inhibition of bone marrow hematopoiesis. Should closely monitor the state of patients for signs of liver problems, especially when interferon is used in conjunction with other hepatotoxic drugs. Patients with heart disease (angina, myocardial infarction, congestive heart failure, arrhythmia) requires careful medical supervision during treatment Avonex. Symptoms of influenza-like syndrome caused by the use of the drug may have a stressor effects on patients with cardiac disease.
To reduce flu-like symptoms, you can assign an analgesic, antipyretic, which should be taken before introducing Avonex, and additionally after 24 hours after each injection. Before taking any medication in conjunction with treatment with Avonex necessary to consult a doctor. Patients should be cautioned against exceeding the recommended dose of analgesic-antipyretic. Besides the usual laboratory tests which are conducted in patients with multiple sclerosis during treatment with Avonex is recommended to control the pattern of peripheral blood count of formed elements (including platelets) to determine leukocyte counts, to conduct biochemical analysis of blood (including liver enzymes). If symptoms mielodepressii may require more thorough investigation of blood. When using Avonex in the serum may appear interferon-neutralizing antibodies, which reduce the activity of interferon beta-la, and, consequently, clinical efficacy of the drug. Available data indicate that after 12 months of therapy in approximately 8% of patients in the serum antibodies appear to interferon beta-1a. Effects on ability to drive vehicles and management mechanisms Avonex may impair the ability of patients to the driving and other activities that require a high concentration of attention and speed of psychomotor reactions.
Overdose
Thanks to the drug dosage form and route of administration overdose is unlikely.
Treatment: In case of overdose the patient should be hospitalized for medical supervision and implementation of appropriate symptomatic therapy. Drug Interactions: Specific interaction studies Avonex with other drugs (including the SCS, or ACTH) a person is not conducted. However, experience in clinical trials shows that patients with multiple sclerosis in exacerbation can be assigned in conjunction with Avonex SCS or ACTH. It is known that interferons possess the ability to reduce the enzyme activity of cytochrome P450. In this regard, caution should be exercised in the appointment of the drug Avonex in conjunction with drugs, clearance of which largely depends on the cytochrome P450, for example, antiepileptic drugs and antidepressants.
Terms and Conditions of storage
The drug should be kept in the dark, away from children at or above 25 ° C; not freeze. Shelf life - 2 years.
Lyophilisates for solution for i / m administration in the form of masses of white or nearly white. 1 vial. interferon beta-1a 30 mcg (6 mln.ME) Excipients: human serum albumin (15 mg), sodium phosphate dibasic, sodium phosphate monobasic, sodium chloride.
Solvent: water w / and - 1 ml.
Clinico-pharmacological group: interferon. The drug, used in multiple sclerosis.
Pharmacological action
Recombinant human interferon beta-1a. Synthesized by different types of cells, including fibroblasts and macrophages.
Interferon beta-1a exists in glikolizirovannom form and incorporates a unique integrated hydrocarbon fragments associated with the atom N (it is known that glikolizirovanie proteins affects their stability, activity, distribution and elimination half-life).
Biological properties of the drug Avonex is determined by its ability to bind to specific receptors on the cell surface and launch a cascade of cellular interactions, leading to interferon-induced expression of multiple gene products and markers (including the main histocompatibility complex class I protein Mx, 2 '/ 5 '-oligoadenilatsintetaza, b2-microglobulin and neopterin). The presence of some of these compounds were detected in serum and cellular fractions of blood of patients treated with Avonex. After i / m administration of 1 dose of the drug content of these compounds in serum remained elevated for 4-7 days.
It is not known whether the mechanism of action related to Avonex in the treatment of multiple sclerosis with the launch of the biological interactions described above, since pathophysiology of multiple sclerosis has been studied enough. The action of the drug in the treatment of multiple sclerosis was assessed in a strictly controlled study conducted in patients with relapsing forms of multiple sclerosis.
It has been shown that the total amount of patients, which showed the progression of disability (defined on a table Kaplan-Meier) to the end of the second year study was 35% for the appointment of a placebo and 22% when using Avonex. To compare the effectiveness of different doses of the drug were conducted double-blind, randomized trial of 802 patients with multiple (disseminated) sclerosis with relapses.
The study revealed no statistically significant differences at doses 30 mcg and 60 mcg for clinical parameters and the overall parameters of the ICTR. It was also found that the use of the drug Avonex for 1 year leads to a reduction in the frequency of relapses during the year to 1 / 3. The effectiveness of the drug in the treatment of multiple sclerosis has been shown in a strictly controlled study in patients with symptoms of demyelinating disease. In the patients receiving placebo, the frequency of relapses during the 2 and 3 years were 39% and 50%, whereas in the group treated with Avonex, the figures were 21% and 35%. The above data show that Avonex slows the progression of disability and reduces the incidence of relapses.
Pharmacokinetics
Pharmacokinetics of interferon beta-1a has been studied by measuring the antiviral activity of interferon.
Absorption
After a single i / m administration peak levels of antiviral activity is achieved in plasma in the period from 5 to 15 h. Bioavailability is 40%.
Putting T1 / 2 was 10 h.
Statement
treatment of relapsing multiple (disseminated) sclerosis, characterized by at least two relapses during the previous 3 years with no signs of disease progression between relapses;
treatment of patients who had been a case of demyelination as a result of active inflammatory process, which required a / v GKS introduction, to the exclusion of other than multiple sclerosis diagnosis.
Dosage regimen
The recommended dose is 30 mcg (6 mln.ME) in / m 1 times per week. Increasing the dose does not lead to increased therapeutic effect. Duration of therapy is determined individually. After 2 years of treatment the patient must undergo clinical examination and the doctor may recommend further course of therapy.
Avonex should be entered in / m immediately after the preparation of the solution. Injections of the drug should, wherever possible, produce in the same time in one and the same day of the week. Injection site should be changed every week. If necessary, your doctor may allow a patient to perform self-injection after proper training.
Terms of solution preparation and implementation of i / m injection
The solution is prepared immediately before drug administration. Hold the base unit Bio-Set, rotate the cap and remove it, do not touch the connecting holes. Remove the cap by contracting with a syringe filled with solvent, and avoid touching the tip. Do not push the plunger. Put a bottle of Bio-Set vertically on a smooth surface, align with the tip of the syringe. Screw the syringe into a cannula Bio-Set in a clockwise direction. Following the direction of motion and holding a syringe from the base, snapped it down so that the tip had disappeared completely and a click. Slowly pushing the plunger of the syringe type solvent into the vial. Leaving the syringe connected to the Bio-Set, gently rotate the vial to completely dissolve the powder. The drug should be completely dissolved within 1 min. Avoid shaking the vial, as This can cause the formation of foam. Push the plunger of the syringe down until it locks to remove all air in the syringe. Turn the syringe and vial vertically by 180 ° and slowly pull the plunger so that the solution of the drug was in the syringe. Open the individual packing needle, do not remove the needle cap, holding a syringe filled with the base, separate it from the device Bio-Set, turning counterclockwise. Do not touch the cannula needle! Push on the filled syringe needle, turning it clockwise.
Then place the syringe on a flat surface and treat the injection swab dipped in alcohol. Contractions, remove the needle cap, not turning it, turn the syringe needle upward, to remove the air lightly tap on its base so that the bubbles have risen to the top. Gently press the plunger to remove air bubbles, so that at the end of the needle appeared no more than a small drop of liquid. Vkolite needle into the muscle and slowly enter the drug, and then remove the syringe. If necessary, cover the injection site with a plaster.
To prepare the solution should use the water for injection, which is included in the kit. Do not use other solvents.
When attached to a syringe device Bio Set to take no further action until you hear a click. The rapid introduction of the solvent can cause foaming, which impede recruitment of the drug in the syringe. The product is unfit for use, if you compromise the integrity of the bottle, and if the drug solution will be cloudy, colored (but may be weak yellowish staining), or it will be visible floating particles. The product contains no preservatives. Each vial of the drug is intended for single use only. The remaining after the introduction of solution should be discarded or destroyed.
Side effect
The most frequent side effect is a manifestation of influenza-like syndrome: weakness, fatigue, fever, chills, muscle aches, headache, nausea (occurrence of these symptoms are most likely the beginning of treatment, as they continue to treat the frequency of their occurrence is reduced);
rarely - spastic phenomena and transient muscle weakness until the reversible paralysis of the limbs (these symptoms may be stopped and will appear again and usually of short duration).
In any period of treatment may cause neurological symptoms similar to the exacerbation of multiple sclerosis: episodes of muscle spasms and / or muscle weakness, limiting the possibility of voluntary movements (these episodes by the time associated with injections and may recur during subsequent introductions, and in some cases they may be accompanied by influenza-like symptoms).
Less frequently observed dermatologic reactions: alopecia, pruritus, sweating, rash, exacerbation of psoriasis.
Allergic reactions: urticaria, anaphylactic reaction, anaphylactic shock.
On the part of the digestive system: loss of appetite, nausea, vomiting, diarrhea, abnormal liver function.
Since the cardiovascular system: feeling the heat, tachycardia, arrhythmia, cardiomyopathy, heart failure, vasodilatation.
On the part of the hemopoietic system: rare - thrombocytopenia, lymphocytopenia, neutropenia, leukopenia, pancytopenia, lower hematocrit.
On the part of the reproductive system: menorrhagia, metrorrhagia.
From the side of the central nervous system and peripheral nervous system: headache, decrease in sensitivity, anxiety, dizziness, insomnia, paresthesia; rare - epileptopodobnye seizures, depression, suicidal thoughts, confusion, emotional lability, psychosis, migraine.
On the part of the musculoskeletal system: muscle cramps, myalgia, arthralgia, pain in the limbs, pain in the neck and back pain, muscular rigidity, transient decrease or increase muscle tone in the beginning kupca treatment.
The respiratory system: rhinorrhea, dyspnea, shortness of breath.
From the Endocrine: hypothyroidism, hyperthyroidism.
On the part of the organism as a whole: flu-like symptoms, sweating at night, change of body weight, pain in the chest.
Local reactions: flushing, pain, burning pain, inflammation, abscess at the injection site.
Other: transient increase of urea level in blood serum, hyperkalemia, systemic lupus erythematosus.
Contraindications
marked depression,
the emergence of suicidal thoughts;
epilepsy resistant to therapy;
childhood and adolescence to 16 years;
Pregnancy
lactation (breastfeeding);
indicate a history of increased susceptibility to natural or recombinant interferon beta, human serum albumin or other components of the drug.
Pregnancy and lactation
In connection with the potential risk of adverse reactions using the product Avonex during pregnancy is contraindicated. In view of the possibility of spontaneous abortion because of side effects associated with the use of interferon beta, patients of childbearing age in the period of treatment should take appropriate contraceptive measures. In connection with the potential risk of adverse reactions in infant Avonex is contraindicated during lactation.
Application for violations of liver function
With caution and under close medical supervision should be used Avonex in patients with severe hepatic insufficiency. Should closely monitor the state of patients for signs of liver problems, especially when interferon is used in conjunction with other hepatotoxic drugs.
Application for violations of renal function
With caution and under close medical supervision should be used Avonex in patients with severe renal insufficiency.
Cautions
Before treatment should inform patients about possible side effects associated with the use of the drug. Avonex should be used with caution in treating patients with depression or depressive disorders. It is known that the application of interferons may cause depression and suicidal thoughts, with a group of persons suffering from multiple sclerosis, the frequency of such events increases. The emergence of depressive states may at any time of treatment with Avonex. Patients should be warned that if there are any signs of depression or suicidal thoughts should immediately contact your doctor. For such patients should be closely monitored during treatment and the urgency to take appropriate therapeutic measures. In some cases it may be necessary to discontinue using the product.
In the case of progressive forms of multiple sclerosis drug Avonex use should be discontinued.
Caution is required in the appointment of the drug Avonex patients who have previously been observed seizures. If the patient has not previously been observed manifestations of epilepsy, and in the process of treatment Avonex appeared epileptopodobnye seizures, should establish the etiology of seizures and assign the appropriate anticonvulsant therapy before you resume using the product.
With caution and under close medical supervision should be used Avonex in patients with severe renal and hepatic failure, as well as in cases of marked inhibition of bone marrow hematopoiesis. Should closely monitor the state of patients for signs of liver problems, especially when interferon is used in conjunction with other hepatotoxic drugs. Patients with heart disease (angina, myocardial infarction, congestive heart failure, arrhythmia) requires careful medical supervision during treatment Avonex. Symptoms of influenza-like syndrome caused by the use of the drug may have a stressor effects on patients with cardiac disease.
To reduce flu-like symptoms, you can assign an analgesic, antipyretic, which should be taken before introducing Avonex, and additionally after 24 hours after each injection. Before taking any medication in conjunction with treatment with Avonex necessary to consult a doctor. Patients should be cautioned against exceeding the recommended dose of analgesic-antipyretic. Besides the usual laboratory tests which are conducted in patients with multiple sclerosis during treatment with Avonex is recommended to control the pattern of peripheral blood count of formed elements (including platelets) to determine leukocyte counts, to conduct biochemical analysis of blood (including liver enzymes). If symptoms mielodepressii may require more thorough investigation of blood. When using Avonex in the serum may appear interferon-neutralizing antibodies, which reduce the activity of interferon beta-la, and, consequently, clinical efficacy of the drug. Available data indicate that after 12 months of therapy in approximately 8% of patients in the serum antibodies appear to interferon beta-1a. Effects on ability to drive vehicles and management mechanisms Avonex may impair the ability of patients to the driving and other activities that require a high concentration of attention and speed of psychomotor reactions.
Overdose
Thanks to the drug dosage form and route of administration overdose is unlikely.
Treatment: In case of overdose the patient should be hospitalized for medical supervision and implementation of appropriate symptomatic therapy. Drug Interactions: Specific interaction studies Avonex with other drugs (including the SCS, or ACTH) a person is not conducted. However, experience in clinical trials shows that patients with multiple sclerosis in exacerbation can be assigned in conjunction with Avonex SCS or ACTH. It is known that interferons possess the ability to reduce the enzyme activity of cytochrome P450. In this regard, caution should be exercised in the appointment of the drug Avonex in conjunction with drugs, clearance of which largely depends on the cytochrome P450, for example, antiepileptic drugs and antidepressants.
Terms and Conditions of storage
The drug should be kept in the dark, away from children at or above 25 ° C; not freeze. Shelf life - 2 years.
No comments:
Post a Comment