Roferon-A solution for subcutaneous administration 3 million IU syringes 0.5 ml

Nosological classification (ICD-10)

— A63.0 Anogenital (venereal) warts — B18.0 Chronic viral hepatitis B with delta agent — B18.1 Chronic viral hepatitis B without delta agent — B18.2 Chronic viral hepatitis C — C43 Malignant melanoma of the skin — C46 Kaposi's sarcoma - C64 Malignant neoplasm of the kidney, other than the renal pelvis - C84 Peripheral and cutaneous T-cell lymphomas - C85 Other and unspecified types of non-Hodgkin's lymphoma - C91.4 Hairy cell leukemia - C92 Myeloid leukemia [myeloid leukemia] - D75.2 Essential thrombocytosis

Composition and release form

Solution for subcutaneous administration - 1 spr.-tube.
(0.5 ml) - interferon alpha-2a - 3 million IU - 4.5 million IU - 6 million IU - 9 million IU - excipients: sodium chloride;
ammonium acetate; benzyl alcohol; polysorbate 80; glacial acetic acid or sodium hydroxide; water for injection - in a syringe tube (body - glass, hydrolytic class I according to EP, piston - plastic) 3 million IU/0.5 ml, 4.5 million IU/0.5 ml, 6 million IU/0 .5 ml and 9 million IU/0.5 ml, with a stopper made of butyl rubber laminated with fluoropolymer; on the other side, the syringe tube is sealed with a tip made of butyl rubber laminated with fluoropolymer; complete with 1 sterile needle in a hermetically sealed PE container; in a cardboard pack there is 1 syringe tube with a container with an injection needle and instructions for use. Solution for subcutaneous administration - 1 cartridge
- interferon alpha-2a - 18 million IU - excipients: ammonium acetate; sodium chloride; benzyl alcohol; polysorbate 80; glacial acetic acid or sodium hydroxide; water for injection - in a glass cartridge (hydrolytic glass class I according to EP) 18 million IU/0.6 ml, sealed on both sides with butyl rubber stoppers coated with polytetrafluoroethylene (PTFE) on the side in contact with the drug; on one side the cork is rolled up with an aluminum cap; 1 cartridge in a cardboard tray with instructions for use and a strip of self-adhesive stickers for gluing to a syringe pen (with a place to indicate the date of first use) is placed in a cardboard pack.

Release form and composition

Dosage form - solution for subcutaneous administration: transparent light yellow or colorless liquid (0.5 ml in syringe tubes, 1 syringe tube in a cardboard pack, complete with a sterile injection needle, packed in a sealed polyethylene container).

Active substance: interferon alpha-2a, in 1 syringe tube 3 million IU (international units), 4.5 million IU, 6 million IU or 9 million IU.

Auxiliary components: polysorbate 80, benzyl alcohol, water for injection, sodium hydroxide or glacial acetic acid, sodium chloride, ammonium acetate.

Pharmacokinetics

Absorption
After subcutaneous administration, bioavailability exceeds 80%. After subcutaneous administration of a dose of 36 million IU, Cmax in serum (from 1250 to 2320 pg/ml, average 1730 pg/ml) was achieved in an average of 7.3 hours.

Distribution

In humans, the pharmacokinetics of Roferon®-A in doses from 3 million to 198 million IU is linear. After intravenous infusion of 36 million IU into healthy volunteers, the volume of distribution at steady state ranged from 0.22 to 0.75 L/kg (mean 0.40 L/kg). Large interindividual variations in serum interferon alfa-2a concentrations are observed in both healthy volunteers and patients with metastatic cancer.

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 T1/2 period of interferon alfa-2a after an intravenous infusion of 36 million IU is 3.7-8.5 hours (average 5.1 hours), and the total clearance is 2.14-3.62 ml/ min/kg (average 2.79 ml/min/kg).

Pharmacodynamics

Interferon alpha-2a is a highly purified protein containing 165 amino acids with a molecular weight of about 19,000 daltons.
It is produced using recombinant DNA technology using a genetically engineered E. coli strain, the DNA of which encodes the synthesis of this human protein. Roferon-A has an antiviral effect, inducing a state of resistance to viral infections in cells and modulating the response of the immune system aimed at neutralizing viruses or destroying cells infected by them. Roferon ®-A has an antiproliferative effect on a number of human tumors in vitro and inhibits the growth of some human tumor xenografts in athymic mice with the nude mutation.

Clinical effectiveness

In human tumor cells treated with Roferon®-A (HT29 cells), the synthesis of DNA, RNA and protein significantly decreases. A limited number of human tumor cell lines grown in vivo in immune-deficient nude mice were tested for sensitivity to the effects of Roferon®-A. In vivo, the antiproliferative activity of Roferon®-A was studied on tumors such as mucoid carcinoma of the breast and adenocarcinoma of the cecum and transverse colon), as well as the prostate gland. The degree of antiproliferative activity varies. Roferon-A leads to clinically significant tumor regression or disease stabilization in patients with hairy cell leukemia and in AIDS patients with Kaposi's sarcoma. Roferon®-A is also effective for the treatment of patients with multiple myeloma. Roferon ®-A has activity in patients with advanced cutaneous T-cell lymphoma who are refractory to or unsuitable for conventional therapy.

Roferon®-A is effective for the treatment of patients with Ph-positive chronic myeloid leukemia. Roferon®-A leads to hematological remission in 60% of patients in the chronic stage of CML, regardless of previous therapy. Complete hematological remission still persisted 18 months after the start of treatment in two thirds of the patients studied. Unlike cytotoxic chemotherapy, interferon alfa-2a can lead to stable cytogenetic remission lasting more than 40 months. Roferon®-A in combination with intermittent courses of chemotherapy increases overall survival and inhibits disease progression compared to chemotherapy alone.

Roferon®-A is effective for the treatment of thrombocytosis in chronic myeloid leukemia and other myeloproliferative diseases. Roferon-A reduces the number of platelets within a few days, reduces the incidence of concomitant thrombohemorrhagic complications and does not have leukemia potential.

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

In patients with advanced renal cell carcinoma, Roferon®-A in combination with vinblastine is more effective in terms of survival compared to chemotherapy alone. In patients with advanced malignant melanoma, treatment with Roferon®-A led to objective regression of tumors of the skin and visceral localization. Roferon®-A also 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 >1.5 mm). Roferon-A is effective for the treatment of patients with confirmed compensated (without signs of hepatic decompensation) hepatitis B and C.

Roferon-A is effective for the treatment of patients with genital warts.

Roferon-A

SC (especially recommended for patients with thrombocytopenia (less than 50 thousand/μl) or patients with an increased risk of bleeding) or IM.

Hairy cell leukemia: initial dose - 3 million IU/day for 16-24 weeks. In case of intolerance, the daily dose is reduced to 1.5 million IU and/or the frequency of administration is reduced to 3 times a week. Maintenance dose - 3 million IU 3 times a week. If intolerance occurs, the dose is reduced to 1.5 million IU 3 times a week. The minimum effective dose for hairy cell leukemia has not been determined.

The duration of treatment is 6 months; if there is a positive effect, the therapy is continued, if there is no positive effect, it is stopped. The optimal duration of therapy for hairy cell leukemia has not been established (the maximum duration of treatment was 20 consecutive months).

Multiple myeloma: 3 million IU 3 times a week. Depending on individual tolerance, the dose is increased weekly until the maximum tolerated dose is reached (9-18 million IU) 3 times a week. 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 (patients over 18 years of age): initial dose - 3 million IU / day, gradually increasing the daily dose to 18 million IU for 12 weeks according to the scheme: days 1-3 - 3 million IU / day, 4-6 day - 9 million IU/day, days 7-84 - 18 million IU/day. Maintenance dose - the maximum tolerated dose (but not exceeding 18 million IU), 3 times a week.

The duration of treatment is 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 optimal duration of treatment with Roferon-A for cutaneous T-cell lymphoma has not been established (the maximum duration of treatment is 40 consecutive months).

Chronic myeloid leukemia (from 18 years of age and older): initial dose - 3 million IU / day with a gradual increase in dose over 8-12 weeks according to the scheme: 1-3 days - 3 million IU / day, 4-6 days - 6 million IU /day, days 7-84 - 9 million IU/day. The duration of treatment is 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/day (optimal dose) or 9 million IU 3 times a week (minimum dose) until cytogenetic remission is achieved. The optimal duration of treatment for chronic myeloid leukemia with Roferon-A has not been established, although there are observations of cytogenetic remissions lasting 2 years after the start of treatment.

Thrombocytosis due to myeloproliferative diseases: initial dose - 3 million IU/day, followed by dose increase over 12 weeks according to the following scheme: days 1-3 - 3 million IU/day, days 4-6 - 6 million IU/day, 7-84 day - 9 million IU/day. The duration of treatment is at least 8 weeks, preferably at least 12 weeks. If there is an effect, therapy is continued, if there is no change in hematological parameters, it is stopped.

In the case of thrombocytosis in myeloproliferative diseases (except for chronic myeloid leukemia), the following dose increase regimen is recommended: days 1-3 - 3 million IU/day, days 4-30 - 6 million IU/day. Maintenance dose (to maintain the platelet count within normal limits) - 1-3 million IU 2-3 times a week. Each patient should, however, individually select the maximum tolerated dose.

Low-grade non-Hodgkin's lymphoma (as maintenance therapy after standard chemotherapy with or without radiation): 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, prednisone, vincristine and doxorubicin) - 6 million IU/m2 from days 22 to 26 of each 28-day cycle. In this case, treatment with Roferon-A can be started simultaneously with chemotherapy.

Kaposi's sarcoma due to AIDS: initial dose (from 18 years of age and older) - 3 million IU/day with a gradual increase in dose over 10-12 weeks to 18 million IU/day, if possible - up to 36 million IU/day according to the following scheme: Days 1-3 - 3 million IU/day, days 4-6 - 9 million IU/day, days 7-9 - 18 million IU/day, days 10-84 - up to 36 million IU/day (if tolerated). Maintenance dose - at the maximum tolerated dose 3 times a week, but not exceeding 36 million IU/day.

The frequency of remission in patients with Kaposi's sarcoma on the background of AIDS who received Roferon-A at a daily dose of 3 million IU was less than when prescribed the recommended doses.

Tumor dynamics should be documented to determine response to treatment. The duration of treatment is 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 optimal duration of treatment with Roferon-A for Kaposi's sarcoma in the setting of AIDS has not been established (the maximum duration of treatment was up to 20 months in a row). If there is an effect, treatment should be continued at least until the tumor disappears.

Advanced renal cell cancer (Roferon-A monotherapy): initial dose of 3 million IU/day with a gradual increase in dose over 8-12 weeks to 18 million IU/day, and if possible - up to 36 million IU/day according to the following scheme: 1- Day 3 - 3 million IU/day, days 4-6 - 9 million IU/day, days 7-9 - 18 million IU/day, if tolerated, increasing the dose on days 10-84 to 36 million IU/day. A dose of 36 million IU is recommended to be administered intramuscularly. Maintenance dose - at the maximum tolerated dose 3 times a week, but not exceeding 36 million IU/day.

The duration of treatment is 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 optimal duration of treatment for advanced renal cell carcinoma with Roferon-A has not been established (the maximum duration of treatment was 16 consecutive months).

Advanced renal cell carcinoma (Roferon-A + vinblastine): in the first week, Roferon-A 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 week (in case of intolerance, the dose can be reduced to 9 million IU 3 times a week). During this period, vinblastine is administered intravenously at a dose of 0.1 mg/kg once every 3 weeks. The duration of treatment is at least 3 months, maximum up to 12 months or until the disease begins to progress. In case of complete remission, treatment can be stopped 3 months after its onset.

Melanoma: initial dose - 18 million IU 3 times a week for 8-12 weeks. Maintenance dose - 18 million IU (or maximum tolerated dose) 3 times a week. The duration of treatment is 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 optimal duration of treatment for advanced melanoma has not been established (the maximum duration of treatment was 17 months).

Melanoma after surgical resection: 3 million IU 3 times a week. Duration of treatment - 18 months. Treatment should begin no later than 6 weeks after surgery.

Chronic viral hepatitis B: the optimal dosage regimen has not been established. Usually prescribed 4.5 million IU 3 times a week for 6 months.

If the content of viral replication markers or surface antigen of the hepatitis B virus has not decreased after 1 month of treatment, the dose can be increased. 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: the administration of Roferon-A in doses up to 10 million IU/m2 is quite safe, but the effectiveness of this therapy has not been proven.

Chronic viral hepatitis C. Combination therapy with Roferon-A and ribavirin for relapse in adult patients in whom previous monotherapy with interferon alpha gave a temporary effect): Roferon-A - 4.5 million IU 3 times a week for 6 months, ribavirin - 1- 1.2 g/day in 2 divided doses (during breakfast and dinner).

Combination therapy with Roferon-A and ribavirin in previously untreated patients with chronic hepatitis C: Roferon-A - 3-4.5 million IU 3 times a week for at least 6 months, ribavirin - 1-1.2 g / day in 2 doses (during breakfast and dinner). If after 6 months of therapy there is no hepatitis C virus RNA, and the patient is infected with genotype 1 virus and had a high viral load before treatment, then treatment should continue for another 6 months. When deciding whether to continue treatment for up to 12 months, other prognostically unfavorable factors should be taken into account (age over 40 years, male gender, bridging fibrosis). If virological remission (hepatitis C virus RNA below the detection limit) cannot be achieved in the first 6 months of therapy, then stable virological remission (hepatitis C virus RNA below the detection limit 6 months after discontinuation of the drug) is unlikely.

Monotherapy with Roferon-A for chronic viral hepatitis C (if ribavirin is intolerant or if there are contraindications to its use): initial dose - 6 million IU 3 times a week for 3 months. The maintenance dose to secure complete remission in patients with normalized ALT activity in the blood serum is 3 million IU 3 times a week for another 3-9 months. If after 3 months of treatment ALT activity remains elevated, therapy should be discontinued.

Genital warts: 1-3 million IU 3 times a week for 1-2 months.

Indications of the drug Roferon®-A

Neoplasms of the lymphatic system and hematopoietic system:
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 >1.5 mm) in the absence of lymph node involvement and distant metastases.

Viral diseases:

chronic active hepatitis B in adults with markers of viral replication, i.e. positive for HBV DNA, DNA polymerase or HBeAg and increased alanine aminotransferase (ALT) activity; chronic active hepatitis C in adults with antibodies to the hepatitis C virus or HCV RNA in the serum and increased ALT activity without signs of hepatic decompensation (Child-Pugh class A); in the treatment of chronic hepatitis C, the combination of Roferon-A and ribavirin is optimal; Roferon-A in combination with ribavirin is indicated both for patients who have not previously received therapy and for those who previously responded to interferon-alpha therapy and then had a relapse of the disease after discontinuation of therapy; genital warts.

Indications for use

Viral diseases:

• genital warts;
• chronic active hepatitis B in patients who have identified markers of viral replication, i.e. positive for HBV DNA, DNA polymerase or HBeAg and increased ALT (alanine aminotransferase) activity without signs of hepatic decompensation (class A according to the Child-Pugh classification);
• chronic active hepatitis C in adult patients with antibodies to the hepatitis C virus or HCV RNA in the serum and increased ALT (alanine aminotransferase) activity without signs of hepatic decompensation (class A according to the Child-Pugh classification) (usually Roferon-A is prescribed in combination with ribavirin; this combination is indicated both for patients who have not previously received therapy and for patients who responded to interferon alfa therapy but had a relapse of the disease after treatment was discontinued).

Solid tumors:

• metastatic malignant melanoma;
• advanced renal cell carcinoma;
• melanoma after surgical resection in the absence of regional and distant metastases;
• Kaposi's sarcoma in patients with AIDS without a history of opportunistic infections.

Neoplasms of the lymphatic system and hematopoietic system:

• thrombocytosis in myeloproliferative diseases;
• multiple myeloma;
• Ph-positive chronic myeloid leukemia;
• cutaneous T-cell lymphoma;
• hairy cell leukemia;
• low-grade non-Hodgkin's lymphoma (in the form of adjuvant therapy to chemotherapy, including radiation therapy).

Contraindications

- hypersensitivity to recombinant interferon alfa-2a or any component of the drug; - existing or past severe heart disease; - severe dysfunction of the kidneys, liver, myeloid lineage of hematopoiesis; - convulsive disorders, other central nervous system dysfunctions; - chronic hepatitis with severe decompensation or cirrhosis of the liver; - chronic hepatitis in patients receiving or recently receiving immunosuppressants, with the exception of short-term treatment with steroids; — chronic myeloid leukemia, if the patient has an HLA-identical relative and he is undergoing or possible allogeneic bone marrow transplantation in the near future; - children under 3 years of age (contains benzyl alcohol as a preservative); - pregnancy - during combination therapy with ribavirin (see “Contraindications” for the use of ribavirin).

Use during pregnancy and breastfeeding

Men and women receiving Roferon-A should use reliable methods of contraception.
During pregnancy, the drug should be prescribed only if the benefits of treatment outweigh the possible risk to the fetus. Although animal studies do not indicate that the drug is teratogenic, the possibility that its use during pregnancy may cause harm to the fetus cannot be ruled out. When rhesus monkeys were given doses significantly higher than clinically recommended doses during early and mid-pregnancy, they experienced an increase in the number of miscarriages. It is not known whether Roferon-A is excreted in breast milk. The question of stopping breastfeeding or discontinuing the drug should be decided depending on the importance of treatment for the mother.

Benzyl alcohol, contained as an excipient in a ready-to-use solution of Roferon-A, can penetrate the placenta. When prescribing Roferon-A solution immediately before childbirth or cesarean section, one should be aware of the toxic effect on premature infants.

Pregnant women should not use Roferon-A in combination with ribavirin. Women of childbearing age and male partners of women of childbearing age receiving Roferon-A in combination with ribavirin should use reliable methods of contraception (see also instructions for use of ribavirin).

Roferon-A, 3 million IU/0.5 ml, solution for subcutaneous administration, 0.5 ml, 1 pc.

Roferon-A should be administered subcutaneously or intramuscularly. Subcutaneous administration is especially recommended in patients with thrombocytopenia (platelet count less than 50,000/μl) or patients at risk of bleeding. Hairy cell leukemia. Initial dose: 3 million IU daily for 16–24 weeks. In case of intolerance, the daily dose is reduced to 1.5 million IU and/or the frequency of administration is reduced to three times a week. Maintenance dose: 3 million IU 3 times a week. For intolerance - 1.5 million IU 3 times a week. Duration of treatment: for 6 months, after which, if there is a positive effect, it is continued, and if there is no positive effect, it is canceled. Treatment was carried out for up to 20 months in a row. The optimal duration of therapy with Roferon-A for hairy cell leukemia has not been established.

Multiple myeloma. 3 million IU 3 times a week. 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. Treatment with this regimen can be continued indefinitely unless the disease progresses or intolerance to the drug develops.

Cutaneous T-cell lymphoma (CTCL). Roferon-A may have an effect in patients with progressive cutaneous T-cell lymphoma, incl. refractory to traditional therapy or not suitable for it. Initial dose: patients over 18 years of age should be administered Roferon-A subcutaneously or intramuscularly for 12 weeks, gradually increasing the daily dose to 18 million IU. It is recommended to increase the dose according to the following scheme: days 1-3 - 3 million IU/day, days 4-6 - 9 million IU/day, days 7-84 - 18 million IU/day. Maintenance dose: subcutaneously or intramuscularly 3 times a week at the maximum dose tolerated by the patient, but not exceeding 18 million IU. Duration of treatment: patients should receive the drug for at least 8 weeks, preferably 12 weeks, after which, if there is a positive effect, therapy is continued, if there is no positive effect, it is stopped. Treatment was carried out for up to 40 months in a row. The optimal duration of treatment with Roferon-A for CTCL has not been established. For patients who respond well to treatment, treatment should be continued for at least 12 months to maximize the likelihood of achieving complete remission and to increase the likelihood of long-term remission. Attention: in approximately 40% of patients with CTCL it is not possible to achieve an objective antitumor effect. Partial remission is usually observed within 3 months of treatment, complete - 6 months, but sometimes 12 months of therapy are required to achieve the best effect.

Chronic myeloid leukemia (CML). Roferon-A is indicated for the treatment of patients in the chronic stage of chronic myeloid leukemia who are positive for the Philadelphia chromosome. Whether it cures this disease is still unclear. Roferon-A leads to hematological remission in 60% of patients in the chronic stage of CML, regardless of previous therapy. In 2/3 of these patients, complete hematological remission is still maintained 18 months after the start of treatment. Unlike cytotoxic chemotherapy, interferon alfa-2a can lead to stable cytogenetic remission lasting more than 40 months. Dosing recommendations: For patients aged 18 years or older, Roferon-A should be administered subcutaneously or intramuscularly for 8–12 weeks. The following scheme of gradual dose increase is recommended: days 1-3 - 3 million IU/day, days 4-6 - 6 million IU/day, days 7-84 - 9 million IU/day. Duration of treatment: patients should receive the drug for at least 8 weeks, preferably 12 weeks, after which, if there is a positive effect, therapy is continued (until complete hematological remission is achieved, but not longer than 18 months). All patients with complete hematological remission should continue treatment with 9 million IU daily (optimal dose) or 9 million IU 3 times a week (minimum dose) to quickly achieve cytogenetic remission. The optimal duration of treatment for chronic myeloid leukemia has not been established, but there are observations of cytogenetic remissions lasting 2 years after the start of treatment. The effectiveness, safety and optimal doses of Roferon-A for children with CML have not been established.

Thrombocytosis associated with myeloproliferative diseases. Thrombocytosis often accompanies chronic myeloid leukemia and is the main symptom of essential thrombocytopenia. Clinically, severe thrombocytosis is manifested by a high frequency of severe thrombotic diathesis. Roferon-A reduces the number of platelets within a few days, reduces the incidence of concomitant thrombohemorrhagic complications and does not have leukemic potential. Therefore, when treating patients with excessive thrombocytosis in chronic myeloid leukemia and other myeloproliferative diseases, it is recommended to use non-leukosogenic therapy with Roferon-A. In the case of thrombocytosis in chronic myeloid leukemia, the following dose escalation scheme is recommended: days 1-3 - 3 million IU/day, days 4-6 - 6 million IU/day, days 7-84 - 9 million IU/day. The duration of treatment is 8 weeks, preferably at least 12 weeks, after which, if there is a positive effect, the therapy is continued, if there is no change in hematological parameters, it is stopped. In the case of thrombocytosis, for myeloproliferative diseases (except for chronic myeloid leukemia), the following dose increase scheme is recommended: days 1–3 - 3 million IU/day, days 4–30 - 6 million IU/day. Duration of treatment: A well-tolerated dose of 1–3 million IU 2–3 times per week is usually sufficient to maintain platelet counts within normal limits. The maximum tolerated dose is selected individually for each patient.

Low-grade non-Hodgkin's lymphoma. When prescribed in addition to chemotherapy (with or without radiation therapy), Roferon-A prolongs disease-free survival and progression-free survival. Dosing recommendations: as maintenance therapy after standard chemotherapy (with or without radiation therapy) subcutaneously at a dose of 3 million IU 3 times a week for 12 months. Treatment with Roferon-A should be started as early as possible when the patient’s condition improves (usually 4-6 weeks after chemotherapy and radiation therapy). Roferon-A can also be prescribed simultaneously with traditional chemotherapy regimens (for example, with a combination of cyclophosphamide, prednisolone, vincristine and doxorubicin), subcutaneous or intramuscular, 6 million IU/m2 from days 22 to 26 of each 28-day cycle. In this case, treatment with Roferon-A begins simultaneously with chemotherapy.

Kaposi's sarcoma due to AIDS. The optimal dosage regimen for Roferon-A has not been established. The likelihood that patients with Kaposi's sarcoma on the background of 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 focus of infection, night sweating), and the initial number of T4 lymphocytes exceeds 200 cells/μl. Initial dose: patients aged 18 years and older should be administered subcutaneously or intramuscularly for 10–12 weeks, gradually increasing the daily dose to at least 18 million IU, and, if possible, to 36 million IU. It is recommended to increase the dose according to the following scheme: days 1-3 - 3 million IU/day, days 4-6 - 9 million IU/day, days 7-9 - 18 million IU/day, if tolerated, increase the dose on days 10-84 to 36 million IU/day. Maintenance dose: subcutaneously or intramuscularly at the maximum dose tolerated by the patient, but not more than 36 million IU 3 times a week. The frequency of remission in patients with Kaposi's sarcoma on the background of AIDS who received Roferon-A at a daily dose of 3 million IU was less than when prescribed the recommended doses. Duration of treatment: Tumor dynamics should be documented to determine response to treatment. Patients should receive the drug for at least 10 weeks, preferably 12 weeks, after which, if there is a positive effect, therapy is continued, if there is no positive effect, it is stopped. Usually the effect begins to appear after 3 months of treatment. Treatment was carried out for up to 20 months in a row. The optimal duration of treatment with Roferon-A for Kaposi's sarcoma in the setting of AIDS has not been established. If there is a clinical effect, treatment should be continued until the tumor disappears. Note: after cessation of therapy with Roferon-A, 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 Roferon-A (36 million IU/day) as monotherapy or moderate doses of Roferon-A (18 million IU 3 times a week) in combination with vinblastine, compared with monotherapy with moderate doses of Roferon-A 3 times a week. In patients receiving small doses of Roferon-A (2 million IU/m2/day), no treatment effect was observed. The combination of Roferon-A with vinblastine leads to a slight increase in the incidence of mild or moderate leukopenia and granulocytopenia compared to monotherapy. Monotherapy with Roferon-A. Initial dose: subcutaneously or intramuscularly for 8–2 weeks, gradually increasing the daily dose to 18 million IU, and, if possible, to 36 million IU. A dose of 36 million IU is recommended to be administered intramuscularly. It is recommended to gradually increase the dose according to the following scheme: (s.c. or i.m.) days 1–3 — 3 million IU/day, days 4–6 — 9 million IU/day, days 7–9 — 18 million IU/day, if tolerated, increase the dose on days 10–84 to 36 million IU/day. Maintenance dose: at the maximum dose, but not more than 36 million IU 3 times a week. Duration of treatment: patients should receive the drug for at least 8 weeks, preferably 12 weeks, after which, if there is a positive effect, therapy is continued, if there is no positive effect, it is stopped. Treatment was carried out for up to 16 consecutive months. The optimal duration of treatment for advanced renal cell carcinoma has not been established. Combination therapy with Roferon-A and vinblastine. Combination therapy produces an overall remission rate of approximately 20%, slows disease progression, and prolongs overall survival in patients with advanced kidney cancer. Dosage: Roferon-A (s.c. or i.m.) - in 1 week - 3 million IU 3 times a week, in 2 weeks - 9 million IU 3 times a week, then - 18 million IU 3 times a week weeks During this period, vinblastine should be administered intravenously, according to the manufacturer's instructions, at a dose of 0.1 mg/kg body weight once every 3 weeks. If the patient does not tolerate a dose of 18 million IU, it can be reduced to 9 million IU 3 times a week. Duration of treatment is 3–12 months or until the onset of disease progression. In case of complete remission, treatment can be stopped 3 months after its onset.

Melanoma. In 10–25% of patients with advanced malignant melanoma, treatment with Roferon-A led to objective regression of cutaneous and visceral tumors. When using doses less than 18 million IU 3 times a week, the therapeutic effect was observed less frequently. Patients who responded to treatment had longer survival than those who did not respond. Initial dose: 18 million IU subcutaneously or intramuscularly 3 times a week for 8–12 weeks. Maintenance dose: 18 million IU (or the maximum tolerated dose) subcutaneously or intramuscularly 3 times a week. Duration of treatment: patients should receive the drug for at least 8 weeks, preferably at least 12 weeks, after which, if there is a positive effect, therapy is continued, if there is no positive effect, it is stopped. Treatment was carried out for up to 17 consecutive months. The optimal duration of treatment for advanced melanoma has not been established.

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

Chronic viral hepatitis B. The optimal dosage regimen has not yet been established. Usually prescribed (s.c. or i.m.) 4.5 million IU 3 times a week for 6 months. If the content of viral replication markers or HBe antigen has not decreased after a month of treatment, the dose can be increased. Further dose adjustment is carried out depending on the tolerability of the drug. If no improvement is observed after 3–4 months, therapy should be interrupted. Children. In children with chronic hepatitis B, administration of Roferon-A at a dose of up to 10 million IU/m2 is safe, but the effectiveness of this therapy has not been proven. Warning. The effectiveness of Roferon-A in patients with chronic hepatitis B who are simultaneously infected with the human immunodeficiency virus (HIV) has not been proven.

Chronic viral hepatitis C. Combination therapy with Roferon-A and ribavirin The effectiveness of interferon alfa-2a increases if it is prescribed in combination with ribavirin.

Combination therapy with Roferon-A and ribavirin for relapse in adult patients in whom previous monotherapy with interferon-alpha gave a temporary effect. Dosage regimen of Roferon-A: (s.c. or i.m.) 4.5 million IU 3 times a week for 6 months. Ribavirin dosage regimen: 1000–1200 mg/day in 2 divided doses (during breakfast and dinner) - see instructions for use of ribavirin. Combination therapy with Roferon-A and ribavirin in previously untreated patients with chronic hepatitis C Dosage regimen of Roferon-A: (s.c. or i.m.) 3–4.5 million IU 3 times a week for 6 months (at least). Ribavirin dosage regimen: see above. If after 6 months of therapy there is no HCV RNA, and the patient was infected with genotype I virus and had a high viral load before treatment, then treatment should continue for another 6 months. When deciding whether to continue treatment for up to 12 months, other negative prognostic factors should be taken into account (age over 40 years, male gender, bridging fibrosis). If, after the first 6 months of therapy, virological remission (HCV RNA below the detection limit) cannot be achieved, then further persistent virological remission (HCV RNA below the detection limit 6 months after discontinuation of the drugs) is unlikely. Monotherapy with Roferon-A Used in cases of intolerance to ribavirin or if there are contraindications to it. Initial dose: (s.c. or i.m.) 6 million IU 3 times a week for 3 months. Maintenance dose: to secure complete remission in patients with normalized serum ALT levels - 3 million IU 3 times a week for another 3-9 months. If after 3 months of treatment the serum ALT level has not returned to normal, treatment should be discontinued. Note. Most cases of disease relapse after adequate therapy occur no later than 4 months after the end of treatment.

Genital warts SC or IM 1–3 million IU 3 times a week for 1–2 months.

Side effects of the drug Roferon®-A

The following data on the side effects of the drug are based on the experience of treating patients with various malignant diseases, often refractory to previous treatment and in late stages, as well as patients with chronic hepatitis B and C.
General symptoms: often - flu-like syndrome (lethargy, fever, chills , loss of appetite, muscle pain, headaches, joint pain and sweating), weight loss. These acute side effects are usually weakened or eliminated with the simultaneous administration of paracetamol, and their severity during treatment or when changing the dose of Roferon-A tends to decrease, although drowsiness, weakness and lethargy may occur with continued therapy.

Gastrointestinal tract: often - approximately two thirds of cancer patients have anorexia, half have nausea; quite often - vomiting, changes in taste, dry mouth, diarrhea, as well as mild or moderate abdominal pain; rarely - constipation, flatulence, increased peristalsis and heartburn, exacerbation of peptic ulcer, gastrointestinal bleeding that is not life-threatening, severe liver dysfunction, pancreatitis.

Changes in liver function: sometimes - increased levels of ALT, alkaline phosphatase, LDH and bilirubin, which, as a rule, do not require dose adjustment; rarely - changes in transaminase activity in hepatitis B; very rarely - severe liver dysfunction, liver failure.

CNS: sometimes - systemic and non-systemic dizziness, visual impairment, deterioration of mental state, forgetfulness, depression, drowsiness, confusion, behavioral disorders (anxiety, nervousness) and sleep disorders; rarely - severe drowsiness, convulsions, coma, cerebrovascular accidents, temporary impotence and ischemic retinopathy, as well as suicidal behavior (at the first signs of suicidal behavior, the drug should be discontinued).

Visual organs: sometimes - visual impairment; rarely - ischemic retinopathy; very rarely - retinopathy, including retinal hemorrhages and cotton wool exudates, papilledema, thrombosis of the central vein and retinal artery, posterior ischemic neuropathy.

Peripheral nervous system: sometimes - paresthesia, numbness of the extremities, neuropathy, itching and tremor.

Cardiovascular and respiratory systems: quite often - in about one fifth of cancer patients - transient arterial hypo- or hypertension, edema, cyanosis, arrhythmias, palpitations and chest pain; rarely - cough and slight shortness of breath, pulmonary edema, pneumonia, congestive heart failure, cardiac arrest and respiratory arrest, myocardial infarction. In patients with hepatitis B, cardiovascular disorders are observed very rarely.

Skin, its appendages and mucous membranes: quite often - in a fifth of patients - mild or moderate hair loss, reversible after cessation of treatment. Increased hair loss may continue for several weeks. Rarely - exacerbation of herpetic eruptions on the lips, rash, itching, dry skin and mucous membranes, nasal discharge and nosebleeds, exacerbation or manifestation of psoriasis.

Kidneys and urinary tract: rarely - deterioration of renal function, acute renal failure (mainly in cancer patients with risk factors such as kidney disease or concomitant treatment with nephrotoxic drugs), electrolyte disturbances, especially with anorexia or dehydration, proteinuria, increased cellular elements in urine sediment, increased levels of urea, as well as creatinine and uric acid in blood serum.

Hematopoietic system: quite often - transient leukopenia (rarely requiring dose reduction), in patients in a state of myelosuppression - thrombocytopenia, decreased hemoglobin levels; sometimes - thrombocytopenia in patients without myelosuppression; rarely - a decrease in hemoglobin and hematocrit levels. The return of severe hematological disorders to the initial level was usually observed 7-10 days after cessation of treatment with Roferon-A. Very rarely - idiopathic thrombocytopenic purpura.

Other: rarely - hyperglycemia, diabetes mellitus, reactions at the injection site; very rarely - necrosis, autoimmune pathology (vasculitis, arthritis, hemolytic anemia, thyroid dysfunction, lupus-like syndrome), very rarely - asymptomatic hypocalcemia, sarcoidosis, hypertriglyceridemia/hyperlipidemia. In rare cases, therapy with alpha-interferon drugs, including Roferon-A, in combination with Copegus is associated with pancytopenia; very rarely - with aplastic anemia.

Antibodies to interferon. In some patients, after administration of drugs containing a homologous protein, antibodies that neutralize the active protein may be formed. Therefore, it is likely that a certain proportion of patients will have antibodies to all interferons, both natural and recombinant. In some diseases (cancer, systemic lupus erythematosus, herpes zoster), antibodies to human leukocyte interferon can spontaneously arise in patients who have never previously received interferons. There are no indications that, for any clinical indication, the presence of such antibodies may negatively affect the patient’s response to Roferon®-A.

When carrying out combination therapy with ribavirin, see also “Side effects” for ribavirin.

Side effects

• general symptoms: often - weight loss, flu-like syndrome (sweating, chills, lethargy, joint pain, loss of appetite, fever, muscle pain and headaches) (these side effects can be weakened or eliminated by the simultaneous use of paracetamol);
• central nervous system: sometimes - sleep disturbances, drowsiness, anxiety, nervousness, depression, deterioration of mental state, confusion, dizziness, forgetfulness; rarely - cerebrovascular accidents, severe drowsiness, temporary impotence, suicidal thoughts and attempts, convulsions, coma;
• cardiovascular and respiratory systems: relatively often - chest pain, palpitations, transient arterial hypo- and hypertension, arrhythmias, cyanosis, edema; rarely - slight shortness of breath, cough, pulmonary edema, pneumonia, respiratory arrest, myocardial infarction, congestive heart failure, cardiac arrest (in patients with hepatitis B, cardiovascular disorders are observed in very rare cases);
• gastrointestinal tract: often – nausea, anorexia; relatively often - dry mouth, mild or moderate abdominal pain, diarrhea, changes in taste, vomiting; rarely - flatulence, constipation, heartburn, exacerbation of peptic ulcer, increased peristalsis, pancreatitis, non-life-threatening gastrointestinal bleeding;
• kidneys and urinary tract: rarely - an increase in the content of cellular elements in urine sediment, proteinuria, electrolyte disturbances (especially in the case of dehydration and anorexia), deterioration of kidney function, increased levels of urea, uric acid and serum creatinine, acute renal failure (mainly in cancer patients with risk factors such as kidney disease and/or concomitant use of nephrotoxic drugs);
• liver: sometimes - increased levels of LDH, ALT, bilirubin, alkaline phosphatase; rarely - a change in transaminase activity (with hepatitis B, this reaction usually indicates an improvement in the patient’s clinical condition);
• peripheral nervous system: sometimes – neuropathy, itching, paresthesia, tremor, numbness of the extremities;
• hematopoietic system: relatively often – transient leukopenia; in patients in a state of myelosuppression - a decrease in hemoglobin levels and platelet counts; sometimes – thrombocytopenia in patients without myelosuppression; rarely – a decrease in hematocrit and hemoglobin levels; very rarely - idiopathic thrombocytopenic purpura;
• skin, its appendages and mucous membranes: relatively often - mild or moderate hair loss (reversible after cessation of treatment); rarely - itching, rash, nasal discharge and nosebleeds, dry mucous membranes and skin, exacerbation of herpes;
• organ of vision: sometimes – visual impairment; rarely – ischemic retinopathy; very rarely - posterior ischemic neuropathy, papilledema, retinopathy, including cotton wool exudates and retinal hemorrhages;
• other: rarely - diabetes mellitus, hyperglycemia, reactions at the injection site, including necrosis (very rare); in some cases - autoimmune pathology (dysfunction of the thyroid gland, arthritis, lupus-like syndrome, hemolytic anemia, vasculitis), hypertriglyceridemia or hyperlipidemia, sarcoidosis, asymptomatic hypocalcemia, transplant rejection.

When Roferon-A is combined with ribavirin, pancytopenia occurs in rare cases, and aplastic anemia occurs very rarely.

Interaction

Alpha interferons can disrupt oxidative metabolic processes, reducing the activity of hepatic microsomal enzymes of the cytochrome P450 system.
This should be taken into account when simultaneously prescribing drugs that 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 following concomitant administration of centrally acting drugs.

When carrying out combination therapy with ribavirin, see also “Interaction” with ribavirin.

Drug interactions

Interferons can enhance the cardiotoxic, hematotoxic and neurotoxic effects of drugs used simultaneously or previously.

Interferon alfa-2a can disrupt oxidative metabolic processes and reduce the activity of hepatic microsomal enzymes of the cytochrome P450 system, which should be taken into account if it is necessary to simultaneously use drugs that are metabolized by this pathway.

Interactions may occur when centrally acting drugs are coadministered.

When conducting combination therapy with ribavirin, its possible drug interactions must also be taken into account.

Directions for use and doses

Roferon-A is administered subcutaneously
Hairy cell leukemia

Initial dose: 3 million IU subcutaneously, daily, for 16-24 weeks. In case of intolerance, the daily dose is reduced to 1.5 million IU and/or the frequency of administration is reduced 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. The duration of treatment is 6 months; if there is a positive effect, therapy is continued; if there is no positive effect, it is stopped. The maximum duration of treatment was 20 months.

Myeloma

3 million IU subcutaneously 3 times a week. 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. 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 (CTCL) (from 18 years of age)

Roferon-A may have an effect in patients with progressive CTCL, incl. refractory to traditional therapy or not suitable for it. Initial dose: 3 million IU/day, subcutaneously, gradually increasing the daily dose to 18 million IU/day for 12 weeks according to the scheme: 1-3 days - 3 million IU/day, 4-6 days - 9 million IU/day, 7-84 days - 18 million IU/day. Maintenance dose: maximum tolerated dose (but not exceeding 18 million IU) 3 times a week s.c. The duration of treatment is 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 was 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 to increase the likelihood of long-term remission.

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

Chronic myeloid leukemia (CML)

From 18 years of age and older: initial dose - 3 million IU / day with a gradual increase in dose over 8-12 weeks according to the scheme: 1-3 days - 3 million IU / day, 4-6 days - 6 million IU / day, 7 —84 day — 9 million IU/day. The duration of treatment is 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/day (optimal dose) or 9 million IU 3 times a week (minimum dose), until cytogenetic remission is achieved in the shortest possible time. There are observations of cytogenetic remissions lasting 2 years after the start of treatment.

The effectiveness, safety and optimal doses of Roferon-A for children with CML have not been established.

Unlike cytotoxic chemotherapy, interferon alfa-2a can lead to stable cytogenetic remission lasting more than 40 months. Roferon-A 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 (except CML)

1-3 days - 3 million IU/day, 4-30 days - 6 million IU/day. Maintenance dose (to maintain the platelet count within normal limits) - 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 or without radiation therapy): 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/m2 from days 22 to 26 of each 28-day cycle. In this case, treatment with Roferon-A can be started simultaneously with chemotherapy. In patients with low-grade non-Hodgkin's lymphoma, when prescribed in addition to chemotherapy (with or without radiation therapy), Roferon-A 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 focus of infection, night sweats), 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/day with a gradual increase in dose over 10-12 weeks to 18 million IU/day, if possible - up to 36 million IU/day according to the scheme: 1-3 days - 3 million IU/day, 4-6 days - 9 million IU/day, 7-9 days - 18 million IU/day, 10-84 days - up to 36 million IU/day (if tolerated). Maintenance dose - at the maximum tolerated dose 3 times a week, but not more than 36 million IU/day.

Tumor dynamics should be documented to determine response to treatment. The duration of treatment is 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 was 20 months. If there is an effect, treatment should be continued at least until the tumor disappears.

Advanced renal cell carcinoma

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

a) Monotherapy with Roferon-A Initial dose - 3 million IU/day with a gradual increase in dose over 8-12 weeks to 18 million IU/day, and if possible - up to 36 million IU/day according to the following scheme: 1-3 days - 3 million IU/day, days 4-6 - 9 million IU/day, days 7-9 - 18 million IU/day, if tolerated, increasing the dose on days 10-84 to 36 million IU/day. Maintenance dose - at the maximum tolerated dose 3 times a week, but not exceeding 36 million IU/day. The duration of treatment is 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 was 16 months.

b) Roferon-A + vinblastine In the first week, Roferon-A 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). During this period, vinblastine is administered intravenously at a dose of 0.1 mg/kg once every 3 weeks. The duration of treatment is at least 3 months, maximum up to 12 months or until the disease begins to progress. In case of complete remission, treatment can be stopped 3 months after its onset.

Metastatic melanoma

18 million IU 3 times a week or at 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 Roferon-A led to objective regression of tumors of the skin and visceral localization.

Melanoma after surgical resection

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

Chronic viral hepatitis B

Usually 4.5-9 million IU are 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. Roferon-A at a dose of 7.5 million IU/m2 is safe and effective.

Chronic viral hepatitis C

Combination therapy with Roferon-A and ribavirin. The effectiveness of interferon alfa-2a is increased when it is given in combination with ribavirin. Roferon-A can be prescribed as monotherapy in cases of intolerance and/or contraindications to ribavirin.

Combination therapy with Roferon-A and ribavirin in previously untreated patients with chronic hepatitis C. 3 million IU subcutaneously 3 times a week for at least 6 months: see above and the instructions for medical use of ribavirin.

Combination therapy with Roferon-A and ribavirin for relapse in adult patients in whom previous monotherapy with interferon-alpha gave a temporary effect. 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. Ribavirin dosage regimen: see instructions for medical use of ribavirin.

Monotherapy with Roferon-A

Roferon-A can be prescribed as monotherapy in cases 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 ALT level has not returned to normal, therapy should be discontinued. If tolerated and with a partial or complete response to therapy with Roferon-A, but with a relapse of the disease after its discontinuation, the effect of repeated therapy with Roferon-A at the same or higher dose is possible.

Condylomas acuminata

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

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 the Roferon-Pen syringe pen. Only Penfine needles should be used with the syringe pen and cartridge. A new, sterile needle should be used for each injection. Cartridges with Roferon-A should be used within 30 days after the first injection. After each injection, the pen syringe with the inserted cartridge should be stored in the refrigerator, away from light, however, if necessary, the pen syringe with the cartridge can be stored at room temperature (up to 25 ° C) for 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. Detailed instructions for using Roferon-Pen are included in the package.

Impact on the ability to drive vehicles and work with machines and mechanisms

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

Roferon-A solution for subcutaneous administration 3 million IU syringes 0.5 ml

Roferon®-A is administered subcutaneously (s.c.).

Hairy cell leukemia Initial dose: 3 million IU daily for 16-24 weeks. In case of intolerance, the daily dose is reduced to 1.5 million IU and/or the frequency of administration is reduced to three times a week. Maintenance dose: 3 million IU 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 absence of a positive effect after 6 months. therapy is stopped, and if there is an effect, therapy is continued. The maximum duration of treatment was 20 months.

Myeloma Initial dose: 3 million IU 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 (CTCL) (from 18 years of age) Initial dose: 3 million IU/day, gradually increasing the dose to 18 million IU/day for 12 weeks according to the scheme: days 1-3 - 3 million IU/day daily; 4-6 days - 9 million IU/day daily; Days 7-84 - 18 million IU/day daily.

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

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 was 40 months. In patients who respond positively to treatment, it 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. treatment, and complete - within 6 months, although sometimes 12 months are required to achieve the best effect. therapy.

Chronic myeloid leukemia

Thrombocytosis associated with chronic myeloid leukemia (from 18 years of age and older) Initial dose: 3 million IU / day with a gradual increase in dose to 9 million IU / day over 8-12 weeks according to the scheme: days 1-3 - 3 million IU / day daily; 4-6 days - 6 million IU/day daily; Days 7-84 - 9 million IU/day daily.

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/day (optimal dose) daily or 9 million IU 3 times a week (minimum dose), until cytogenetic remission is achieved in the shortest possible time. There are observations of cytogenetic remissions lasting 2 years after the start of treatment.

The effectiveness, safety and optimal doses of Roferon®-A for children with CML have not been established.

Thrombocytosis associated with myeloproliferative diseases (except chronic myeloid leukemia) days 1-3 - 3 million IU/day daily; 4-30 days - 6 million IU/day daily.

To maintain platelet counts within normal limits, a dose of 1-3 million IU/day 2-3 times a week is usually sufficient and well tolerated. Each patient should individually select the maximum tolerated dose.

Low-grade non-Hodgkin's lymphoma As maintenance therapy after standard chemotherapy (with or without radiation): 3 million IU 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/m2 from days 22 to 26 of each 28-day cycle. In this case, treatment with Roferon®-A can be started simultaneously with chemotherapy.

Kaposi's sarcoma in patients with AIDS Roferon®-A is indicated for the treatment of Kaposi's sarcoma in patients with AIDS without anamnestic indications of opportunistic infections. Initial dose (from 18 years of age and older): 3 million IU/day daily, with a gradual increase in dose over 10-12 weeks to 18 million IU/day daily if possible - up to 36 million IU/day daily according to the scheme: 1-3 day - 3 million IU/day daily, days 4-6 - 9 million IU/day daily, days 7-9 - 18 million IU/day daily, if tolerated: days 10-84 - up to 36 million IU/day daily.

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

Duration of treatment: Tumor changes should be documented and assessed to determine response to treatment. 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. treatment. The maximum duration of treatment was 20 months. If there is an effect, treatment should be continued at least until the tumor disappears.

Note: after cessation of therapy with Roferon®-A, Kaposi's sarcoma often recurs.

Advanced renal cell carcinoma

a) Monotherapy with Roferon®-A

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

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

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 was 16 months.

b) Roferon®-A + vinblastine

In the first week, Roferon®-A 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). During this period, vinblastine is administered intravenously according to the instructions for use of the drug 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 before the onset of disease progression. In case of complete remission, treatment can be stopped after 3 months. after its onset.

c) Roferon®-A + Avastin (bevacizumab)

9 million IU 3 times a week up to 12 months. or before the onset of disease progression. Treatment can be started with a dose of 3 or 6 million IU and gradually increased to 9 million IU (recommended dose) during the first 2 weeks (in case of intolerance, the dose can be reduced to 3 million IU 3 times a week).

Roferon®-A is administered after the infusion of Avastin (on the same day or on days 2-3) (see also instructions for use of Avastin).

Metastatic melanoma 18 million IU 3 times a week or at the maximum tolerated dose for at least 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 was 24 months.

Melanoma after surgical resection Adjuvant therapy with small doses of Roferon®-A increases the duration of time without disease relapse in patients without lymph node involvement and distant metastases after melanoma resection (tumor thickness >1.5 mm). Treatment should begin no later than 6 weeks after surgery. Dose: 3 million IU 3 times a week. Duration of treatment - 18 months.

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

Children aged 3 years and older: Roferon®-A at a dose of 7.5 million IU/m2 is safe and effective.

Chronic viral hepatitis C The effectiveness of interferon alfa-2a is increased if it is prescribed in combination with ribavirin. Roferon®-A can be prescribed as monotherapy in cases of intolerance and/or contraindications to ribavirin.

a) Combination therapy with Roferon®-A and ribavirin

Combination therapy with Roferon®-A and ribavirin in previously untreated patients with chronic hepatitis C: 3 million IU 3 times a week for 6 months. Ribavirin dosage regimen: see above and in the instructions for medical use of ribavirin.

Combination therapy with Roferon®-A and ribavirin for relapse of chronic hepatitis C: 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.

Ribavirin dosage regimen: see the appropriate ribavirin prescribing information.

b) Monotherapy with Roferon®-A

3-6 million IU 3 times a week for 6-12 months.

If after 3 months. treatment, the ALT level has not returned to normal, therapy should be discontinued.

If tolerated and with a partial or complete response to therapy with Roferon®-A, but if the disease relapses after its discontinuation, the effect of repeated therapy with Roferon®-A at the same or higher dose is possible.

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

Precautionary measures

Roferon-A should be prescribed under the supervision of a physician experienced in treating the relevant indications.
With mild to moderate impairment of the kidneys, liver or bone marrow, their functional state must be carefully monitored.

Changes in transaminase activity in hepatitis B usually indicate an improvement in the patient's clinical condition. Caution must be exercised when treating patients with chronic hepatitis with a history of autoimmune diseases with interferon-alpha. Any patient who develops pathological changes in liver function tests during treatment with Roferon-A should be carefully monitored and, if necessary, the drug should be discontinued. In patients receiving interferons, incl. and Roferon-A, may manifest severe mental adverse reactions. Depression, suicidal ideation, and suicide may occur in patients with or without a history of mental illness. Caution should be exercised when treating Roferon-A in patients with a history of depression. Close monitoring of patients receiving Roferon-A is recommended to identify depression. 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.

Roferon-A should be used with extreme caution in patients with severe myelosuppression, because the drug depresses the bone marrow, causing a drop in the number of white blood cells (especially granulocytes), the number of platelets and, less commonly, the level of hemoglobin. This may lead to an increased risk of infection or bleeding. It is necessary to closely monitor these changes and conduct detailed blood tests for patients before starting treatment with Roferon-A and, regularly, during the treatment process.

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 occur, interferon should be discontinued and appropriate therapy should be prescribed.

As during therapy with other interferons, during therapy with Roferon-A, cases of retinopathy (retinal hemorrhages, cotton wool exudates, papilledema, thrombosis of the central retinal artery and vein) and posterior ischemic neuropathy, which can lead to vision loss, have been reported. If there are complaints of deterioration in visual acuity or loss of vision, these patients should undergo an ophthalmological examination. Patients with diabetes mellitus and arterial hypertension must undergo an ophthalmological examination to identify fundus pathology before prescribing therapy. Therapy with Roferon-A or Roferon-A/ribavirin should be discontinued if ophthalmic diseases worsen or occur. During interferon therapy, incl. and interferon alfa-2a, serious immediate hypersensitivity reactions (urticaria, angioedema, bronchospasm and anaphylaxis) have been observed. If such reactions develop during therapy with Roferon-A or Roferon-A/ribavirin, therapy is canceled and appropriate drug therapy is immediately prescribed. A transient rash does not require discontinuation of therapy.

Hyperglycemia is rarely observed during therapy with Roferon-A. If clinical symptoms of hyperglycemia are present, monitoring of blood glucose levels and appropriate monitoring is necessary. Patients with diabetes may require dose adjustment of glucose-lowering medications.

During therapy with alpha interferons, cases of formation of various autoantibodies have been reported. Clinical manifestations of autoimmune diseases during interferon therapy more often occur in patients predisposed to the development of such diseases. In patients undergoing transplantation (eg, kidney or bone marrow), drug immunosuppression may be less effective because interferons have a stimulating effect on the immune system. Alpha interferon therapy is rarely associated with the occurrence or exacerbation of psoriasis.

There are no indications of a direct cardiotoxic effect of the drug, however, there is a possibility that acute, self-limiting toxic effects (for example, fever, chills), which often accompany treatment with Roferon-A, may cause an exacerbation of existing heart diseases. It is not recommended to prescribe Roferon-A 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.

When conducting combination therapy with ribavirin, see also “Precautions” for ribavirin.

Preclinical study: In rhesus macaques, which were prescribed doses of the drug significantly higher than those recommended for the clinic, transient menstrual irregularities were observed, incl. prolongation of the menstrual period.

special instructions

Therapy with the drug should be carried out under the supervision of a physician who has experience in treating the relevant indications.

In cases of mild or moderate functional impairment of the bone marrow, liver or kidneys, their functions must be carefully monitored.

Caution must be observed when treating patients with chronic hepatitis who have a history of autoimmune diseases.

Roferon-A can cause severe psychiatric side effects even in patients without a history of mental illness. During treatment, it is recommended to monitor the condition of patients in order to identify possible signs of depression in time.

The drug should be used with extreme caution in cases of severe myelosuppression, since interferon alfa-2a inhibits the bone marrow, resulting in a decrease in the number of leukocytes and platelets, and less often in hemoglobin levels, which can lead to the development of infections or bleeding. You should closely monitor these indicators, as well as conduct detailed blood tests before prescribing Roferon-A and regularly during its use.

In case of complaints of deterioration or loss of vision, an ophthalmological examination is indicated. Before starting therapy, patients with arterial hypertension and diabetes mellitus must undergo an examination to identify fundus pathologies.

Sometimes Roferon-A contributes to the development of hyperglycemia. In this case, it is necessary to monitor blood glucose levels. Patients with diabetes mellitus may require dose adjustment of hypoglycemic drugs.

When carrying out combination therapy, it is necessary to take into account the precautions specified in the instructions for the relevant drugs.