This section presents instructions for use of interferons alpha 2b and alpha 2a first generation, which are also called linear, simple or short-lived. The only advantage of these preparations is their relatively low price.
Back in 1943, V. and J. Heile discovered the so-called interference phenomenon. The initial idea of interferon was this: a factor that prevents the reproduction of viruses. In 1957, the English scientist Alik Isaacs and the Swiss researcher Jean Lindenman isolated this factor, clearly described it and called it interferon.
Interferon (IFN) is a protein molecule that is produced in the human body. The human genetic apparatus encodes a “recipe” for its synthesis (interferon gene). Interferon is one of the cytokines, signaling molecules that play an important role in the work immune system.
Over the half century since the discovery of IFN, dozens of properties of this protein have been studied. From a medical point of view, the main ones are antiviral and antitumor functions.
The human body produces about 20 types - a whole family - of interferons. IFN is divided into two types: I and II.
Type I IFNs - alpha, beta, omega, theta - are produced and secreted by most cells of the body in response to the action of viruses and some other agents. Type II IFN includes interferon gamma, which is produced by cells of the immune system in response to the action of foreign agents.
Initially, interferon preparations were obtained only from donor blood cells; They were called that: leukocyte interferons. In 1980, the era of recombinant, or genetically engineered, interferons began. The production of recombinant drugs has become significantly cheaper than obtaining similar drugs from human donor blood or other biological raw materials; not used in their production donor blood which can serve as a source of infection. Recombinant drugs do not contain foreign impurities and therefore have fewer side effects. Their healing potential is higher than that of similar natural drugs.
For treatment viral diseases, in particular hepatitis C, predominantly interferon alpha (IFN-α) is used. There are “simple” (“short-lived”) interferons alpha 2b and alpha 2a and pegylated (peginterferon alfa-2a and peginterferon alfa-2b). “Simple” interferons are practically not used in the EU and the USA, but in our country, due to their comparative cheapness, they are used quite often. In the treatment of hepatitis C, both forms of “short” IFN-α are used: interferon alpha-2a and interferon alpha-2b (differing in one amino acid). Injections with simple interferons are usually done every other day (with peginterferons - once a week). The effectiveness of treatment with short-lived IFNs when administered every other day is lower than with peginterferons. Some experts recommend daily injections of “simple” IFN, since the effectiveness of AVT is slightly higher.
The range of “short” IFNs is quite wide. They are released by different manufacturers under different names: Roferon-A, Intron A, Laferon, Reaferon-EC, Realdiron, Eberon, Interal, Altevir, Alfarona and others.
The most studied (and therefore expensive) are Roferon-A and Intron-A. The effectiveness of treatment with these IFNs in combination with ribavirin, depending on the genotype of the virus and other factors, ranges from 30% to 60%. List of main brands Manufacturers of simple interferons and their descriptions are given in the table.
All interferons should be stored refrigerated (from +2 to +8 degrees Celsius). They should not be heated or frozen. Do not shake or expose the drug to direct sun rays. It is necessary to transport drugs in special containers.
The composition of interferon preparations depends on their release form.
Release form
Interferon preparations have the following release forms:
- lyophilized powder for the preparation of eye and nasal drops, injection solution;
- injection solution;
- eye drops;
- eye films;
- nasal drops and spray;
- ointment;
- dermatological gel;
- liposomes;
- aerosol;
- oral solution;
- rectal suppositories;
- vaginal suppositories;
- implants;
- microenemas;
- tablets (interferon tablets are available under the brand name Entalferon).
pharmachologic effect
IFN drugs belong to the group of drugs with antiviral and immunomodulatory effects.
All IFNs have antiviral and antitumor effects. No less important is their property of stimulating action. macrophages - cells that play an important role in initiation.
IFNs contribute to increasing the body's resistance to penetration viruses , and also block reproduction viruses when they penetrate the cell. The latter is due to the ability of IFN to suppress translation of the messenger RNA of the virus .
However, the antiviral effect of IFN is not directed against certain viruses , that is, IFNs are not characterized by virus specificity. This is precisely what explains their versatility and wide range antiviral activity.
Interferon - what is it?
Interferons are a class with similar properties glycoproteins , which are produced by vertebrate cells in response to exposure various kinds inducers of both viral and non-viral nature.
According to Wikipedia, in order to biologically active substance has been qualified as interferon, it must be of a protein nature and have a pronounced antiviral activity in relation to various viruses , at a minimum, in homologous (similar) cells, “mediated by cellular metabolic processes including RNA and protein synthesis.”
The classification of IFNs proposed by the WHO and the Interferon Committee is based on differences in their antigenic, physical, chemical and biological properties. In addition, it takes into account their species and cellular origin.
Based on antigenicity (antigen specificity), IFNs are usually divided into acid-stable and acid-labile. The acid-fast ones include alpha and beta interferons (they are also called type I IFN). Interferon gamma (γ-IFN) is acid labile.
α-IFN is produced peripheral blood leukocytes (B- and T-type leukocytes), therefore it was previously designated as leukocyte interferon . There are currently at least 14 varieties of it.
β-IFN is produced fibroblasts , which is why it is also called fibroblastic .
The former designation of γ-IFN is immune interferon , it is produced by stimulated T-type lymphocytes , NK cells (normal (natural) killers; from English “natural killer”) and (presumably) macrophages .
Basic properties and mechanism of action of IFN
Without exception, all IFNs are characterized by polyfunctional activity against target cells. Their most common property is the ability to induce in them antiviral state .
Interferon is used as a therapeutic and prophylactic agent for various viral infections . A feature of IFN drugs is that their effect weakens with repeated injections.
The mechanism of action of IFN is related to its ability to inhibit viral infections . As a result of treatment with interferon drugs in the patient’s body around source of infection a kind of barrier is formed from resistant to virus uninfected cells, which prevents further spread of infection.
By interacting with still undamaged (intact) cells, it prevents the implementation of the reproductive cycle viruses due to the activation of certain cellular enzymes ( protein kinases ).
Most important functions interferons are considered to have the ability to suppress hematopoiesis ; modulate the body's immune response and inflammation response; regulate the processes of cell proliferation and differentiation; suppress growth and prevent reproduction viral cells ; stimulate the expression of surface antigens ; suppress individual functions B- and T-type leukocytes , stimulate activity NK cells etc..
Use of IFN in biotechnology
Development of methods for synthesis and highly efficient purification leukocyte and recombinant interferons in quantities sufficient for production medicines, made it possible to open up the possibility of using IFN drugs to treat patients diagnosed with viral hepatitis .
A distinctive feature of recombinant IFNs is that they are produced outside the human body.
For example, recombinant interferon beta-1a (IFN β-1a) are obtained from mammalian cells (in particular, from Chinese hamster ovary cells), and similar in properties interferon beta-1b (IFN β-1b) produced by a member of the Enterobacteriaceae family coli (Escherichia coli).
Interferon inducer drugs - what are they?
IFN inducers are drugs that do not themselves contain interferon, but at the same time stimulate its production.
Pharmacodynamics and pharmacokinetics
The main biological effect of α-IFN is inhibition of viral protein synthesis . The antiviral state of the cell develops within several hours after administration of the drug or induction of IFN production in the body.
However, IFN has no effect on the early stages replicative cycle that is, at the stage of adsorption, penetration virus into the cell (penetration) and release of the internal component virus in the process of “undressing” him.
Antivirus action α-IFN appears even when cells are infected infectious RNAs . IFN does not penetrate the cell, but only interacts with specific receptors on cell membranes (gangliosides or similar structures containing oligosugars ).
The mechanism of IFN alpha activity resembles the action of certain glycopeptide hormones . It stimulates activity genes , some of which are involved in coding the formation of products with direct antiviral effect .
β interferons also have antiviral effect , which is associated with several mechanisms of action. Beta interferon activates NO synthetase, which in turn helps to increase the concentration of nitric oxide inside the cell. The latter plays a key role in suppressing reproduction viruses .
β-IFN activates secondary, effector functions natural killersV , B-type lymphocytes , blood monocytes , tissue macrophages (mononuclear phagocytes) and neutrophilic , which are characterized by antibody-dependent and antibody-independent cytotoxicity.
In addition, β-IFN blocks the release of the internal component virus and disrupts methylation processes RNA virus .
γ-IFN is involved in the regulation of the immune response and regulates the expression inflammatory reactions. Despite the fact that he has independent antivirus And antitumor effect , gamma interferon very weak. At the same time, it significantly enhances the activity of α- and β-IFN.
After parenteral administration, the maximum concentration of IFN is observed after 3-12 hours. The bioavailability indicator is 100% (both after injection under the skin and after injection into the muscle).
The half-life T½ ranges from 2 to 7 hours. Trace concentrations of IFN in blood plasma are not detectable after 16–24 hours.
Indications for use
IFN is intended to treat viral diseases , striking respiratory tract .
In addition, interferon preparations are prescribed to patients with chronic forms of hepatitis, and Delta .
For treatment viral diseases and, in particular, IFN-α is used predominantly (both its forms, IFN-alpha 2b and IFN-alpha 2a). The “gold standard” of treatment hepatitis C pegylated interferons alpha-2b and alpha-2a are considered to be. In comparison, conventional interferons are less effective.
Genetic polymorphisms observed in the IL28B gene, which is responsible for encoding IFN lambda-3, cause significant differences in the effect of treatment.
Patients with genotype 1 hepatitis C with common alleles of the specified gene are more likely to achieve longer and more pronounced treatment results compared to other patients.
IFN is also often prescribed to patients with oncological diseases : malignant , pancreatic endocrine tumors , non-Hodgkin's lymphoma , carcinoid tumors ; Kaposi's sarcoma , conditioned; hairy cell leukemia ,multiple myeloma , kidney cancer etc..
Contraindications
Interferon is not prescribed to patients with hypersensitivity to him, as well as to children and adolescents suffering from heavy mental disorders And disorders nervous system , which are accompanied by thoughts of suicide and suicide attempts, severe and protracted.
In combination with antiviral drug Ribavirin IFN is contraindicated in patients diagnosed with severe impairment kidney (conditions in which CC is less than 50 ml/min).
Interferon preparations are contraindicated in (in cases where appropriate therapy does not produce the expected clinical effect).
Side effects
Interferon belongs to the category of drugs that can cause a large number of adverse reactions from the outside various systems and organs. In most cases, they are a consequence of the administration of interferon intravenously, subcutaneously or intramuscularly, but they can also be provoked by others pharmaceutical forms drug.
The most common adverse reactions to taking IFN are:
- anorexia;
- nausea;
- chills;
- trembling in the body.
Somewhat less common are vomiting, increased blood pressure, a feeling of dry mouth, hair loss (), asthenia ; nonspecific symptoms reminiscent of flu symptoms ; backache, depressive states , musculoskeletal pain , thoughts of suicide and attempted suicide, general malaise, impaired taste and concentration, increased irritability, sleep disorders (often), arterial hypotension , confusion.
Rare side effects include: pain on the right side of the upper abdomen, rashes on the body (erythematous and maculopapular), increased nervousness, pain and severe inflammation at the injection site of the drug into injection form, secondary viral infection (including infection herpes simplex virus ), increased dryness skin, , pain in the eyes , conjunctivitis , blurred vision, dysfunction lacrimal glands , anxiety, mood lability; psychotic disorders , including increased aggression, etc.; hyperthermia , dyspeptic symptoms , respiratory disorders, weight loss, unformed stools, hyper- or hypothyroidism , hearing impairment (up to its complete loss), the formation of infiltrates in the lungs, increased appetite, bleeding gums, in the extremities, dyspnea , renal dysfunction and development renal failure , peripheral ischemia , hyperuricemia , neuropathy etc..
Treatment with IFN drugs may cause violation reproductive function . Studies in primates have shown that interferon violates menstrual cycle among women . In addition, in women undergoing treatment with IFN-α drugs, the level of .
For this reason, if interferon is prescribed, women of childbearing age should use barrier contraception . Men of reproductive age are also advised to be informed of potential side effects.
In rare cases, treatment with interferon may be accompanied by ophthalmological disorders, which are expressed as hemorrhages in the retina of the eye , retinopathy (including but not limited to macular edema ), focal changes in the retina, decreased visual acuity and/or limited visual fields, disc swelling optic nerves , neuritis of the optic (second cranial) nerve , arterial obstruction or retinal veins .
Sometimes, while taking interferon, they can develop hyperglycemia , symptoms of nephrotic syndrome , . In patients with diabetes mellitus may get worse clinical picture diseases.
The possibility of occurrence cannot be excluded, cerebrovascular hemorrhage , erythema multiforme , tissue necrosis at the injection site, cardiac and cerebrovascular ischemia , hypertriglyceridermia , sarcoidosis (or aggravation of its course), Lyell's syndromes And Stevens-Johnson .
The use of interferon in monotherapy or in combination with Ribavirin in isolated cases it can provoke aplastic anemia (AA) or even PAKKM ( complete red bone marrow aplasia ).
There have also been cases where, during treatment with interferon drugs, a patient developed various autoimmune And immune-mediated disorders (including Werlhof's disease And Moschkowitz disease ).
Interferon, instructions for use (Method and dosage)
The instructions for the use of interferons alpha, beta and gamma indicate that before prescribing the drug to the patient, it is recommended to determine how sensitive the patient is to it , which caused the disease.
The method of administration of human leukocyte interferon is determined depending on the diagnosis given to the patient. In most cases, it is prescribed as a subcutaneous injection, but in some cases the drug can be injected into a muscle or vein.
The treatment dose, maintenance dose and duration of treatment are determined depending on the clinical situation and the patient’s response to the therapy prescribed to him.
By “children’s” interferon we mean a drug in the form of suppositories, drops and ointments.
Instructions for the use of interferon for children recommend using this drug both as a therapeutic and as a prophylactic agent. The dose for infants and older children is selected by the attending physician.
For prophylactic purposes, INF is used in the form of a solution, for the preparation of which distilled or boiled water room temperature. The finished solution is colored red and opalescent. It should be stored refrigerated for no more than 24-48 hours. The drug is instilled into the nose of children and adults.
At viral ophthalmological diseases the drug is prescribed in the form of eye drops.
As soon as the severity of the symptoms of the disease decreases, the volume of instillations should be reduced to one drop. The course of treatment is from 7 to 10 days.
For the treatment of lesions caused by herpes viruses , the ointment is applied in a thin layer to the affected areas of the skin and mucous membranes twice a day, maintaining 12-hour intervals. The course of treatment is from 3 to 5 days (until the integrity of the damaged skin and mucous membranes is completely restored).
For prevention acute respiratory infections and needs to be lubricated with ointment nasal passages . The frequency of procedures during the 1st and 3rd weeks of the course is 2 times a day. It is recommended to take a break during the 2nd week. For preventive purposes, interferon should be used throughout the entire period epidemics of respiratory diseases .
The duration of the rehabilitation course in children who often experience recurrent viral-bacterial infections of the respiratory tract , ENT organs , recurrent infection , caused herpes simplex virus , is two months.
How to dilute and how to use interferon in ampoules?
The instructions for using interferon in ampoules indicate that before use, the ampoule must be opened, water (distilled or boiled) at room temperature must be poured into it up to the mark on the ampoule corresponding to 2 ml.
The contents are gently shaken until completely dissolved. The solution is injected into each nasal passage twice a day, five drops, maintaining intervals of at least six hours between administrations.
For therapeutic purposes, IFN begins to be taken when the first symptoms appear. flu symptoms . The earlier the patient starts taking it, the higher the effectiveness of the drug.
It is considered the most effective inhalation method(through the nose or mouth). For one inhalation, it is recommended to take the contents of three ampoules of the drug, dissolved in 10 ml of water.
The water is preheated to a temperature of no more than +37 °C. Inhalation procedures are carried out twice a day, maintaining an interval of at least one to two hours between them.
When sprayed or instilled, the contents of the ampoule are dissolved in two milliliters of water and 0.25 ml (or five drops) is administered into each nasal passage three to six times a day. The duration of treatment is 2-3 days.
Nasal drops for children for preventive purposes are instilled (5 drops) twice a day, for initial stage development of the disease, the frequency of instillations increases: the drug should be administered at least five to six times a day every hour or two.
Many people are interested in whether interferon solution can be dripped into the eyes. The answer to this question is yes.
Overdose
Cases of interferon overdose have not been described.
Interaction
β-IFN is compatible with corticosteroid drugs and ACTH. It should not be taken during treatment myelosuppressive medicines , incl. cytostatics (this may provoke additive effect ).
Beta-IFN should be administered with caution with agents whose clearance is largely dependent on cytochrome P450 system (antiepileptic drugs , some antidepressants and etc.).
You should not take α-IFN and Telbivudin . The simultaneous use of α-IFN provokes a mutual enhancement of action in relation to. At joint use With phosphazide can mutually increase myelotoxicity both drugs (it is recommended to carefully monitor changes in the amount granulocytes And;
IFN is also used in therapy, the purpose of which is the rehabilitation of frequently ill people. respiratory infections children.
The most optimal option for children is nasal drops: when used in this way, interferon does not penetrate the gastrointestinal tract (before diluting the drug for the nose, the water should be heated to a temperature of 37°C).
For infants, interferon is prescribed in the form of suppositories (150 thousand IU). Suppositories for children should be administered one at a time 2 times a day, maintaining 12-hour intervals between administrations. The course of treatment is 5 days. To completely cure a child ARVI As a rule, one course is enough.
For treatment, you should take 0.5 g of ointment twice a day. Treatment lasts on average 2 weeks. Over the next 2-4 weeks, the ointment is used 3 times a week.
Numerous positive reviews about the drug indicate that in this dosage form he has also established himself as effective remedy for treatment stomatitis And inflamed tonsils . Interferon inhalations for children are no less effective.
The effect of using the drug increases significantly if a nebulizer is used to administer it (it is necessary to use a device that sprays particles with a diameter of more than 5 microns). Inhalations through a nebulizer have their own specifics.
First, interferon must be inhaled through the nose. Secondly, before using the device, you must turn off the heating function (IFN is a protein; at temperatures above 37°C it is destroyed).
For inhalation in a nebulizer, the contents of one ampoule are diluted in 2-3 ml of distilled or mineral water(you can also use saline solution for these purposes). The resulting volume is enough for one procedure. The frequency of procedures during the day is from 2 to 4.
It's important to remember that long-term treatment Interferon is not recommended for children, since addiction develops to it and, therefore, the expected effect does not develop.
Interferon during pregnancy
An exception may be cases when the expected benefit of therapy for the expectant mother exceeds the risk of adverse reactions and harmful effects on fetal development.
It is possible that the components of recombinant IFN can be isolated from breast milk. Due to the possibility of exposure to the fetus through milk, IFN is not prescribed to nursing women.
As a last resort, when the administration of IFN cannot be avoided, the woman is advised not to breastfeed during therapy. To soften side effect drug (occurrence of symptoms similar to those of influenza), simultaneous administration with IFN is recommended .
With parenteral administration of the drug, chills, fever, fatigue, headache, malaise, and flu-like syndrome are possible. These side effects are partially relieved by paracetamol or indomethacin.When the drug is applied topically to the mucous membrane of the eye, conjunctival infection, hyperemia of the mucous membrane of the eye, single follicles, and swelling of the conjunctiva of the lower fornix are possible.
When using the drug, deviations from the normal laboratory parameters are possible, manifested by leukopenia, lymphopenia, thrombocytopenia, increased levels of alanine aminotransferase, alkaline phosphatase. For timely detection of these deviations during therapy, general clinical tests blood tests must be repeated every 2 weeks, and biochemical tests every 4 weeks. In general, these changes are usually minor, asymptomatic and reversible.
Side effects of Interferon beta.
Leukopenia. Thrombocytopenia. Anemia. Autoimmune hemolysis. Anorexia. Diarrhea. Increased transaminase levels. Hypotension. Tachycardia. Dyspnea. Dizziness. Sleep disorders. Pain in bones and joints. Fever. Weakness. Myalgia. Headache. Nausea. Vomit; with long-term use - hair loss. IM, SC, IV, intravesical, intraperitoneal, into the lesion and under the lesion. Patients with a platelet count less than 50 thousand/μl are administered subcutaneously.Treatment should be started by a doctor. Then, with the doctor’s permission, the patient can administer the maintenance dose to himself (if the drug is prescribed subcutaneously).
Chronic hepatitis B: adults - 5 million IU daily or 10 million IU 3 times a week, every other day, for 4-6 months (16-24 weeks).
Children - subcutaneous injection at an initial dose of 3 million IU/sq.m 3 times a week (every other day) for 1 week of treatment, followed by increasing the dose to 6 million IU/sq.m (maximum up to 10 million IU/sq.m ) 3 times a week (every other day).
Duration of treatment is 4-6 months (16-24 weeks).
If there is no improvement in serum hepatitis B virus DNA levels after treatment for 3-4 months at the maximum tolerated dose, the drug should be discontinued.
Recommendations for dose adjustment in case of a decrease in the number of leukocytes, granulocytes or platelets: if the number of leukocytes, granulocytes or platelets decreases to less than 1.5 thousand/µl, platelets to less than 100 thousand/µl, granulocytes to less than 1 thousand/µl - the dose is reduced by 50%, in case of a decrease the number of leukocytes is less than 1200/μl, platelets are less than 70 thousand/μl, granulocytes are less than 750/μl - treatment is stopped and re-prescribed at the same dose after normalization of these indicators.
Chronic hepatitis C - 3 million IU every other day (as monotherapy or in combination with ribavirin). In patients with recurrent disease, it is used in combination with ribavirin. The recommended duration of treatment is currently limited to 6 months.
In patients who have not previously received treatment with interferon alfa2b, the effectiveness of treatment increases when using combination therapy with ribavirin. The duration of combination therapy is at least 6 months. Therapy should be carried out for 12 months in patients with genotype I of the virus and a high viral load, in whom by the end of the first 6 months of treatment hepatitis C virus RNA in the blood serum is not detected. When deciding to extend combination therapy to 12 months, other negative prognostic factors (age over 40 years, male gender, presence of fibrosis) should also be taken into account.
As monotherapy, Intron A is used mainly in cases of intolerance to ribavirin or in the presence of contraindications to its use. The optimal duration of Intron A monotherapy has not yet been established; Currently, treatment is recommended for 12 to 18 months. During the first 3-4 months of treatment, the presence of hepatitis C virus RNA is usually determined, after which treatment is continued only for those patients in whom hepatitis C virus RNA has not been detected.
Chronic hepatitis D: subcutaneously at an initial dose of 5 million IU/m2 3 times a week for at least 3-4 months, although longer therapy may be indicated. The dose is selected taking into account the tolerability of the drug.
Laryngeal papillomatosis: 3 million IU/sq.m subcutaneously 3 times a week (every other day). Treatment begins after surgical (laser) removal of the tumor tissue. The dose is selected taking into account the tolerability of the drug. Achieving a positive response may require treatment for more than 6 months.
Hairy cell leukemia: 2 million IU/m2 subcutaneously 3 times a week (every other day). The dose is selected taking into account the tolerability of the drug.
Patients with and without splenectomy responded similarly to treatment and reported similar reductions in transfusion requirements. Normalization of one or more blood parameters usually begins within 1-2 months after the start of treatment. It may take 6 months or more for all 3 blood parameters (granulocyte count, platelet count, and Hb level) to improve. Before starting treatment, it is necessary to determine the Hb level and the number of platelets, granulocytes and hairy cells in the peripheral blood and the number of hairy cells in the bone marrow. These parameters should be monitored periodically during treatment to assess response. If the patient responds to therapy, it should be continued until there is no further improvement and laboratory values are stable for approximately 3 months. If the patient does not respond to therapy within 6 months, treatment should be discontinued. Therapy should not be continued in cases of rapid disease progression and severe adverse events.
In case of a break in treatment with Intron A, its repeated use was effective in more than 90% of patients.
Chronic myeloid leukemia. The recommended dose as monotherapy is 4-5 million IU/m2 per day daily, subcutaneously. To maintain the number of leukocytes, it may be necessary to use a dose of 0.5-10 million IU/sq.m. If treatment allows to achieve control of the number of leukocytes, then to maintain hematological remission the drug should be used at the maximum tolerated dose (4-10 million IU/sq.m daily). The drug should be discontinued after 8-12 weeks if therapy has not resulted in at least partial hematological remission or a clinically significant decrease in the number of leukocytes.
Combination therapy with cytarabine: Intron A - 5 million IU/sq.m daily subcutaneously, and after 2 weeks cytarabine is added at a dose of 20 mg/sq.m daily subcutaneously for 10 consecutive days monthly (maximum dose - up to 40 mg/day). Intron A should be discontinued after 8 to 12 weeks if therapy has not resulted in at least partial hematologic remission or a clinically significant decrease in white blood cell count.
Studies have demonstrated a greater likelihood of achieving a response to Intron A therapy in patients with the chronic phase of the disease. Treatment should be started as soon as possible after diagnosis and continued until complete hematological remission or for at least 18 months. In patients who respond to treatment, improvement in hematological parameters is usually observed within 2-3 months. In such patients, treatment should be continued until complete hematological remission, the criterion of which is the number of leukocytes in the blood of 3-4 thousand / μl. In all patients with complete hematological effect, treatment should be continued in order to achieve a cytogenetic effect, which in some cases develops only 2 years after the start of therapy.
In patients with a white blood cell count of more than 50 thousand/μl at the time of diagnosis, the doctor may begin treatment with hydroxyurea at a standard dose, and then, when the white blood cell count drops below 50 thousand/μl, replace it with Intron A. In patients with newly diagnosed chronic phase of Ph-positive chronic myeloid leukemia was also carried out combination therapy Intron A and hydroxyurea. Treatment with Intron A began with doses of 6-10 million IU/day subcutaneously, then hydroxyurea was added at a dose of 1-1.5 g 2 times a day if the initial leukocyte count exceeded 10 thousand/μl, and its use was continued until until the leukocyte count dropped below 10 thousand/µl. Then hydroxyurea was discontinued, and the dose of Intron A was adjusted so that the number of neutrophils (band and segmented leukocytes) was 1-5 thousand/μl, and the number of platelets was more than 75 thousand/μl.
Thrombocytosis associated with chronic myeloid leukemia: 4-5 million IU/sq.m per day, daily, s.c. To maintain the platelet count, it may be necessary to use the drug in doses of 0.5-10 million IU/sq.m.
Non-Hodgkin's lymphoma: subcutaneous - 5 million IU 3 times a week (every other day) in combination with chemotherapy.
Kaposi's sarcoma in the setting of AIDS: the optimal dose has not been established. There is data on the effectiveness of Intron A at a dose of 30 million IU/sq.m 3-5 times a week. The drug was also used in smaller doses (10-12 million IU/sq.m/day) without a clear decrease in effectiveness.
If the disease stabilizes or responds to treatment, therapy is continued until tumor regression occurs or drug discontinuation is required (development of severe opportunistic infection or unwanted side effect). IN clinical studies patients with AIDS and Kaposi's sarcoma received Intron A in combination with zidovudine according to the following regimen: Intron A - at a dose of 5-10 million IU/m2, zidovudine - 100 mg every 4 hours. The main toxic effect that limited the dose was neutropenia. Treatment with Intron A can be started
