Interferon alpha 2a mechanism of action. Medicinal reference book geotar. Use of the substance Interferon alfa

Interferon alpha-2a is a highly purified protein containing 165 amino acids, with molecular weight about 19,000 daltons. It is produced using recombinant DNA technology using a genetically engineered strain E. coli, whose DNA encodes the synthesis of this human protein. The drug is identical to human leukocyte interferon-2 a.

It binds to specific receptors on the cell membrane, triggering a cascade of protein interactions leading to rapid activation of gene transcription. Stimulates genes that regulate many biological processes: suppression of viral replication in an infected cell and cell proliferation, disruption of the synthesis of viral DNA, RNA and viral proteins, immunomodulatory effect. Stimulates the production of effector proteins: neopterin, 2",5"-oligoadenylate synthetase.

The drug increases the phagocytic activity of macrophages and potentiates the cytotoxic effect of lymphocytes. Shows antitumor activity.

The drug has an antiproliferative effect on a number of human tumors in vitro and inhibits the growth of certain human tumor xenografts in nude mice with the mutation nude.

Suction. After subcutaneous administration, bioavailability exceeds 80%. After subcutaneous administration, Cmax in serum was achieved on average after 7.3 hours.

Metabolism and excretion. The main route of excretion of interferon alpha is renal catabolism. Hepatic metabolism and biliary excretion are less significant routes of elimination. In healthy individuals, the period half-life interferon alfa-2a after intravenous infusion of 36 million IU is 3.7-8.5 hours (average 5.1 hours), and total clearance is 2.14-3.62 ml/min/kg (average 2.79 ml/min/kg).

Neoplasms lymphatic system and hematopoietic systems:

Hairy cell leukemia;

Multiple myeloma;

Cutaneous T-cell lymphoma;

Ph-positive chronic myeloid leukemia;

Thrombocytosis in myeloproliferative diseases;

Low-grade non-Hodgkin's lymphoma (in the form of adjuvant therapy to chemotherapy - with or without radiation therapy).

Solid tumors:

Kaposi's sarcoma in patients with AIDS without anamnestic indications of opportunistic infections;

Advanced renal cell carcinoma;

Metastatic melanoma;

Melanoma after surgical resection (tumor thickness more than 1.5 mm) without involvement of lymph nodes and distant metastases.

Viral diseases:

Chronic active hepatitis B in adults who have markers of viral replication, that is, positive for HBV DNA, DNA polymerase or HBeAg and increased activity alanine aminotransferase;

Chronic active hepatitis C in adults with antibodies to the hepatitis C virus or HCV RNA in the serum and increased alanine aminotransferase activity without signs of hepatic decompensation (Child-Pugh class A); in the treatment of chronic hepatitis C, the combination of interferon alpha-2a and ribavirin is optimal; Interferon alfa-2a in combination with ribavirin is indicated both for patients who have not previously received therapy and for those who previously responded to therapy with interferon-alpha and then had a relapse of the disease after discontinuation of therapy;

Condylomas acuminata.

FDA Category C recommendation. No safety data available. Do not use! Use during pregnancy is only possible if the potential benefit to the mother exceeds potential harm for a child. Information about penetration into breast milk No. During treatment with the drug, breastfeeding should be stopped.

The dosage is set individually depending on the diagnosis, stage of the disease and the individual characteristics of the patient.

The drug is administered subcutaneously .

Hairy cell leukemia

Initial dose: 3 million IU subcutaneously, daily, for 16-24 weeks. In case of intolerance daily dose reduce to 1.5 million IU and/or reduce the frequency of administration to 3 times a week.

Maintenance dose: 3 million IU subcutaneously 3 times a week. If intolerance occurs, the dose is reduced to 1.5 million IU 3 times a week.

Duration of treatment: in the presence of positive effect after 6 months, treatment is continued, if it is absent, it is stopped. The maximum duration of treatment is 20 months.

Myeloma

Initial dose: 3 million IU subcutaneously 3 times a week.

Maintenance dose: depending on individual tolerance, the dose can be increased weekly until the maximum tolerated dose is reached (9-18 million IU) 3 times a week.

Duration of treatment: Treatment according to this regimen is continued for a long time in the absence of disease progression and severe intolerance to the drug.

Cutaneous T-cell lymphoma (from 18 years of age)

The drug may have an effect in patients with progressive skin T cell lymphoma, including refractory to traditional therapy or not suitable for its implementation.

Initial dose: 3 million IU per day, subcutaneously, gradually increasing the daily dose to 18 million IU per day for 12 weeks according to the scheme: days 1-3 - 3 million IU per day, days 4-6 - 9 million IU per day, days 7-84 - 18 million IU per day.

Maintenance dose: maximum tolerated dose (but not exceeding 18 million IU) 3 times a week subcutaneously.

Duration of treatment: The duration of treatment before assessing response to therapy should be at least 8 weeks, preferably 12 weeks; If there is a positive effect, the treatment is continued, if it is absent, it is stopped. The maximum duration of treatment is 40 months. In patients who respond positively to treatment, treatment should be continued for at least 12 months to maximize the likelihood of achieving complete remission and increase the likelihood of long-term remission.

Partial remission is usually observed within 3 months of treatment, and complete remission within 6 months, although sometimes to achieve best effect 12 months of therapy are required.

Chronic myeloid leukemia (from 18 years of age and older)

Initial dose: 3 million IU per day with a gradual increase in dose over 8-12 weeks according to the scheme: days 1-3 - 3 million IU per day, days 4-6 - 6 million IU per day, days 7-84 day - 9 million IU per day.

Duration of treatment: at least 8 weeks, preferably 12 weeks; if there is an effect, therapy is continued until complete hematological remission is achieved, but not more than 18 months. If there is no change in hematological parameters, therapy is stopped. With complete hematological remission, treatment is continued at a dose of 9 million IU per day (optimal dose) or 9 million IU 3 times a week (minimum dose), until cytogenetic remission is achieved to the maximum short term. There are observations of cytogenetic remissions lasting 2 years after the start of treatment.

Efficacy, safety and optimal doses of the drug for children with chronic myeloid leukemia not installed.

Unlike cytotoxic chemotherapy, interferon alfa-2a can lead to stable cytogenetic remission lasting more than 40 months.

The drug reduces the number of platelets within a few days, reduces the incidence of concomitant thrombohemorrhagic complications and does not have leukemia potential.

Thrombocytosis associated with myeloproliferative diseases (exceptchronic myeloid leukemia)

Daily: days 1-3 - 3 million IU per day, days 4-30 - 6 million IU per day.

Maintenance dose: 1-3 million IU 2-3 times a week. Each patient should individually select the maximum tolerated dose.

Low-grade non-Hodgkin lymphoma

As maintenance therapy after standard chemotherapy (with radiation therapy or without): 3 million IU subcutaneously 3 times a week for at least 12 months. Treatment should begin as soon as possible when the patient's condition improves, usually 4-6 weeks after chemotherapy and radiation therapy. In combination with traditional chemotherapy regimens (for example, with a combination of cyclophosphamide, prednisolone, vincristine and doxorubicin) - 6 million IU / m 2 from the 22nd to the 26th day of each 28-day cycle. In this case, treatment with the drug can be started simultaneously with chemotherapy.

In patients with low-grade non-Hodgkin's lymphoma, when administered in addition to chemotherapy (with or without radiation therapy), the drug prolongs disease-free survival and progression-free survival.

Kaposi's sarcoma in patients with AIDS

The likelihood that patients with Kaposi's sarcoma and AIDS will respond positively to therapy is higher if they do not have a history of opportunistic infections, group B symptoms (weight loss more than 10%, temperature above 38 ° C in the absence of a known source of infection, night sweating), and the initial number of T4 lymphocytes exceeds 200 cells in 1 μl.

Initial dose (from 18 years of age and older): 3 million IU per day, daily, with a gradual increase in dose over 10-12 weeks to 18 million IU per day, if possible - up to 36 million IU per day according to the scheme: days 1-3 - 3 million IU per day ki, days 4-6 - 9 million IU per day, days 7-9 - 18 million IU per day, days 10-84 - up to 36 million IU per day (if tolerated).

Maintenance dose: at the maximum tolerated dose 3 times a week, but not more than 36 million IU per day.

Duration of treatment: In order to determine the response to treatment, the dynamics of tumor changes should be documented and assessed. The duration of treatment before assessing response to therapy should be at least 10 weeks, preferably 12 weeks. If there is a positive effect, therapy is continued; if it is absent, it is stopped. Usually the effect begins to appear after 3 months of treatment. The maximum duration of treatment is 20 months. If there is an effect, treatment should be continued for at least until the tumor disappears.

Note: After discontinuation of drug therapy, Kaposi's sarcoma often recurs.

Advanced renal cell carcinoma

In patients with tumor recurrence or metastases, the best therapeutic effect was observed when prescribing large doses of interferon alfa-2a (36 million IU per day) as monotherapy or moderate doses of the drug (18 million IU 3 times a week) in combination with vinblastine, compared with monotherapy with moderate doses of interferon alfa-2a 3 times a week week. Duration of response and survival are similar between interferon alfa-2a monotherapy and interferon alfa-2a plus vinblastine combination therapy. In patients receiving small doses of the drug (2 million IU/m2 per day), there was no effect of treatment. The combination of interferon alfa-2a with vinblastine results in only a small increase in the incidence of mild to moderate leukopenia and granulocytopenia compared with monotherapy.

a) Monotherapyinterferon alpha-2a

Initial dose: 3 million IU per day with a gradual increase in dose over 8-12 weeks up to 18 million IU per day, and if possible - up to 36 million IU per day according to the following scheme: days 1-3 - 3 million IU per day, Days 4-6 - 9 million IU per day, days 7-9 - 18 million IU per day, if tolerated, increasing the dose on days 10-84 to 36 million IU per day.

Maintenance dose: at the maximum tolerated dose 3 times a week, but not exceeding 36 million IU per day.

Duration of treatment: at least 8 weeks, preferably at least 12 weeks. If there is an effect, therapy is continued, if there is no effect, it is stopped. The maximum duration of treatment is 16 months.

b) Andinterferon alpha-2a + vinblastine

In the first week, the drug is prescribed at a dose of 3 million IU 3 times a week, in the second week - 9 million IU 3 times a week, then - 18 million IU 3 times a week (in case of intolerance, the dose can be reduced to 9 million IU 3 times a week week). During this period, it is administered intravenously at a dose of 0.1 mg/kg once every 3 weeks.

Duration of treatment: at least 3 months, maximum - up to 12 months or until the onset of disease progression. In case of complete remission, treatment can be stopped 3 months after its onset.

Metastatic melanoma

18 million IU 3 times a week or the maximum tolerated dose for 12 weeks. The duration of treatment before assessing the effectiveness of therapy is preferably at least 12 weeks. If there is an effect, therapy is continued, if there is no effect, it is stopped. The maximum duration of treatment is 24 months. In patients with advanced malignant melanoma, treatment with the drug led to objective regression of tumors of the skin and visceral localization.

Melanoma after surgical resection

Adjuvant therapy with small doses of the drug increases the length of time without relapse of the disease in patients without lymph node involvement and distant metastases after resection of melanoma (tumor thickness more than 1.5 mm). Treatment should begin no later than 6 weeks after surgery. Dose - 3 million IU 3 times a week. The duration of treatment is 18 months.

Chronic viral hepatitis B

Typically, 4.5-9 million IU is prescribed subcutaneously 3 times a week for 4-6 months. Further dose adjustment is carried out depending on the tolerability of the drug. If no improvement is observed after 3-4 months, interruption of therapy should be considered.

Children from 3 years old and older. The drug at a dose of 7.5 million IU/m2 is safe and effective.

Chronic viral hepatitis C

Efficacy is increased when given in combination with ribavirin. Interferon alfa-2a can be prescribed as monotherapy in the presence of intolerance and/or contraindications to ribavirin.

a) Combination therapyInterferon alfa-2a and ribavirin

Combination therapy with interferon alfa-2a and ribavirin in previously untreated patients chronic hepatitis C: 3 million IU subcutaneously 3 times a week for at least 6 months.

Combination therapy with interferon alfa-2a and ribavirin for relapse in adult patients in whom previous interferon-alpha monotherapy provided a temporary response. Dosage regimen: 4.5 million IU 3 times a week for 6 months. The standard duration of therapy for patients with chronic hepatitis C depends on the initial characteristics of the patient (for example, the genotype of the virus) and is 6-12 months.

b) MonotherapyInterferon alpha-2a

The drug can be prescribed as monotherapy in case of intolerance and/or contraindications to ribavirin. 3-6 million IU 3 times a week for 6-12 months. If after 3 months of treatment the level alanine aminotransferase has not returned to normal, therapy should be discontinued.

If tolerated and with a partial or complete response to interferon alfa-2a therapy, but with a relapse of the disease after its discontinuation, the effect of repeated therapy with the drug at the same or higher dose is possible.

Condylomas acuminata

1-3 million IU 3 times a week subcutaneously for 1-2 months.

From the nervous system: dizziness, depression, nervousness, sleep disturbances, neuropathy, convulsions, cerebrovascular accidents, visual impairment, confusion, anxiety, paresthesia, tremor, severe drowsiness, coma, ischemic retinopathy.

From the gastrointestinal tract: loss of appetite, diarrhea, mild to moderate abdominal pain, increased activityalanine aminotransferase, alkaline phosphatase, constipation, heartburn, nausea, vomiting, weight loss, increased bilirubin concentration in blood serum, flatulence, relapse of peptic ulcer and gastrointestinal bleeding.

From the urinary system: increased levels of urea, creatinine and uric acid in the blood plasma, proteinuria.

From the cardiovascular and circulatory system: swelling, arrhythmias, chest pain, cough, symptoms of chronic heart failure, myocardial infarction, thrombocytopenia, changes blood pressure, cyanosis,palpitations, slight shortness of breath, pulmonary edema, sudden stop heart disease, transient leukopenia, decreased hemoglobin and hematocrit levels.

From the skin: rash, alopecia, itching,dry skin and mucous membranes.

Other: influenza-like syndrome , nose bleed, rhinitis.

Symptoms: repeated administration of large doses of interferon may be accompanied by deep lethargy, lethargy, prostration and coma.

Treatment: such patients should be hospitalized for observation and appropriate supportive measures.

Alpha interferons can disrupt oxidative metabolic processes, reducing the activity of liver microsomal enzymes of the cytochrome P450 system. This should be taken into account when co-administering medicines , which are metabolized by this route. A decrease in the clearance of theophylline has been described after simultaneous administration of alpha interferons.

Interferons can enhance the neurotoxic, hematotoxic or cardiotoxic effects of drugs prescribed previously or simultaneously with them. Interactions may occur after coadministration of drugs central action.

Possible teratogenic effect. The combination with ribavirin is contraindicated in pregnant women and men whose partners are pregnant. Fertile women or men whose partners are capable of bearing children should use effective contraception during treatment and for 6 months after its completion.

The drug should be prescribed under the supervision of a physician experienced in treating the appropriate indications.

Appropriate treatment of the underlying disease and complications is possible only if adequate diagnostic and therapeutic capabilities are available.

With mild and moderate violation functions of the kidneys, liver or bone marrow functional state must be carefully monitored.

Changes in liver function. Changes in transaminase activity in hepatitis B usually indicate improvement clinical condition sick. Caution must be exercised when treating patients with chronic hepatitis with a history of autoimmune diseases with interferon-alpha. Each patient who develops symptoms during treatment with the drug pathological changes liver function tests, you need to carefully monitor and, if necessary, discontinue the drug.

Psychoneurological changes. In patients receiving interferons, including this drug, may manifest severe mental adverse reactions. Depression, suicidal ideation, and suicide may occur in patients with both mental illness with or without a history. Caution should be exercised when treating the drug in patients with a history of depression. Close monitoring of patients receiving the drug to detect depression is recommended. Before starting treatment, patients should be informed about the possibility of developing depression, and patients should immediately report any signs of depression to the doctor; If depression develops, it is necessary to consult a psychiatrist and decide on the advisability of discontinuing therapy.

Myelosuppression. The drug should be used with extreme caution in patients with severe myelosuppression, since the drug depresses the bone marrow, causing a drop in the number of leukocytes (especially granulocytes), platelet count and, less commonly, hemoglobin levels. This may lead to increased risk infection or bleeding. It is necessary to closely monitor these changes and conduct detailed blood tests for patients before starting treatment with the drug and regularly during its course.

Infections. Fever may be associated with a flu-like syndrome, which is often observed with interferon therapy. For persistent fever, especially in patients with neutropenia, infection (bacterial, viral, fungal) should be excluded. If severe infectious complications Interferon should be discontinued and appropriate therapy should be prescribed.

Ophthalmological changes. As with other interferons, cases of retinopathy (retinal hemorrhages, cotton wool exudates, disc edema) have been reported during interferon alfa-2a therapy. optic nerve, thrombosis of the central retinal artery and vein) and posterior ischemic neuropathy, which can lead to vision loss. If there are complaints of deterioration in visual acuity or loss of vision, these patients should undergo ophthalmological examination. Patients with diabetes mellitus, arterial hypertension Before prescribing therapy, it is necessary to conduct an ophthalmological examination to identify fundus pathology. Therapy with interferon alfa-2a or interferon alfa-2a/ribavirin should be discontinued if ophthalmic disease worsens or occurs.

Hypersensitivity reactions. Serious hypersensitivity reactions have occurred during therapy with interferons, including interferon alfa-2a. immediate type(urticaria, angioedema, bronchospasm and anaphylaxis). If such reactions occur during therapy with interferon alfa-2a or interferon alfa-2a/ribavirin, therapy is discontinued and appropriate therapy is immediately prescribed. drug therapy. A transient rash does not require discontinuation of therapy.

Changes in endocrine organs. Rarely, hyperglycemia has been observed during interferon alfa-2a therapy. In the presence of clinical symptoms hyperglycemia requires monitoring of blood glucose levels and appropriate monitoring. Patients with diabetes may require dose adjustment of glucose-lowering medications.

Autoimmune disorders. During therapy with alpha interferons, cases of formation of various autoantibodies have been reported. Clinical manifestations autoimmune diseases during interferon therapy, they occur more often in patients predisposed to the development of such diseases.

Alpha interferon therapy is rarely associated with the occurrence or exacerbation of psoriasis. In patients undergoing transplantation (eg, kidney or bone marrow), drug immunosuppression may be less effective because interferons have a stimulating effect on immune system.

There are no indications of a direct cardiotoxic effect of the drug, but there is a possibility that acute, self-limiting toxic effects(for example, fever, chills), which often accompany treatment with the drug, can cause exacerbation of existing heart diseases.

It is not recommended to prescribe the drug to newborns, especially premature infants, and children under 3 years of age, since it contains benzyl alcohol as a preservative, which, according to reports, can lead to persistent neuropsychiatric disorders and multiple organ failure.

Preclinical study. In rhesus macaques that were prescribed doses of the drug significantly higher than those recommended for the clinic, transient disorders menstrual cycle, including prolongation of the menstrual period.

Instructions for handling the drug

Multi-dose cartridges of 18 million IU in 0.6 ml are intended for use by only one patient. They are used only in a syringe pen. A new, sterile needle should be used for each injection. Cartridges with the drug must be used within 30 days after the first injection. After each injection, the syringe pen with the inserted cartridge should be stored in the refrigerator, away from light, however, if necessary, the syringe pen with the cartridge can be stored at room temperature(up to 25 °C) up to 28 days.

The date of first use of the cartridge should be noted on the sticker supplied with the cartridge and affixed to the box with the syringe pen.

Impact on the ability to drive vehicles and other technical devices

Depending on the dosage regimen and the individual sensitivity of the patient, the drug may have an effect on the reaction rate, affecting the performance of certain operations, such as driving vehicles, working with machines and mechanisms.