Instruction for use: Roferon-A

Dosage form: Solution for subcutaneous administration

Active substance: Interferonum alpha-2a

ATX

L03AB04 Interferon alfa-2a

Pharmacological groups:

MIBP (medicinal immunobiological drugs) - antiviral and antitumor agents [Antiviral (except HIV) agents]

MIBP (medical immunobiological preparations) is an antiviral and antitumor agent [Interferons]

The nosological classification (ICD-10)

A63.0 Anogenital (venereal) warts: Anogenital warts; Venereal warts; Condylomata genital; Condyloma pointed; Externally pointed genital warts; Externally pointed condyloma; Pointed Condyloma; Flat condyloma

B18.0 Chronic viral hepatitis B with delta-agent: Chronic viral hepatitis B; Chronic active hepatitis B; Chronic viral hepatitis B; Chronic hepatitis B HBeAg-positive

B18.1 Chronic viral hepatitis B without delta-agent: Chronic viral hepatitis B; Chronic active hepatitis B; Chronic viral hepatitis B; Chronic hepatitis B; Chronic hepatitis B HBeAg-negative

B18.2 Chronic viral hepatitis C: Hepatitis C; Recurrence of chronic hepatitis C; Chronic active hepatitis C; Chronic viral hepatitis C; Chronic hepatitis C without cirrhosis; Chronic hepatitis C with compensated cirrhosis; Chronic hepatitis C

C43 Malignant melanoma of skin: Malignant melanoma; Localized malignant melanoma; Localized form of malignant melanoma; Melanoma; Melanoma after surgical resection; Metastatic melanoma; Common metastatic malignant melanoma; Metastasizing form of malignant melanoma; Disseminated malignant melanoma

C46 Kaposi's sarcoma: Kaposi angioreticulosis; Endotheliosarcoma; Kaposi angiosarcomatosis; Kaposi hemangiosarcoma; Kaposi haemorrhagic sarcoma; Kaposi multiple hemorrhagic sarcoma; Kaposi telangiectatic pseudo-sarcoma; Kaposi's Sarcoma in AIDS patients; Varioleiform pustulosis of Kaposi; Kaposi's Sarcoma in AIDS; Kaposi's sarcoma on AIDS; Kaposi's sarcoma on the background of AIDS; AIDS-associated Kaposi's sarcoma

C64 Malignant neoplasm of kidney, other than renal pelvis: Wilms tumor; Kidney Cancer; Metastatic Renal Cell Carcinoma; Renal carcinoma; Inoperable kidney carcinomas; Metastatic kidney carcinoma; Metastatic Renal Cell Carcinoma; Wilms tumor; Wilms swelling; Adenomyosarcoma; Adenomyocystosarcoma; Adenosarcoma of the kidney; Kidney Cancer; Common renal cell carcinoma; Nephroblastoma; Nephroma; Embryonal nephroma; Recurrent carcinoma of the kidney; Birch-Hirschfeld Tumor; Common renal cell carcinoma; Tumors of the kidney

C83 Diffuse non-Hodgkin's lymphoma: Diffuse B-large-cell non-Hodgkin's lymphoma; Malignant lymphoma; Malignant lymphoma, especially of the histiocytic type; Lymphoblastic non-Hodgkin's lymphoma; Lymphoma non-Hodgkin's diffuse; Hepatic Lymphoma; Recurrence of lymphoma; Recurrent non-Hodgkin's lymphoma; Lymphoma of the liver

C84 Peripheral and cutaneous T-cell lymphomas: Malignant lymphoma; Cutaneous lymphoma; Cutaneous T-cell lymphoma; Lymphoma T-cell; T-cell lymphoma

C85 Other and unspecified types of non-Hodgkin's lymphoma: Lymphoma of mixed type; Lymphomas from cells of the mantle zone; Malignant lymphoma; Lymphoma non-Hodgkin's disease; Lymphocytic lymphoma

C91.4 Hairy-cell leucosis

C92 Myeloid leukemia [myeloid leukemia]: Ph-positive chronic myelogenous leukemia; Granulocytic leukemia; Myeloid leukemia; Myeloid leukemia; Myeloma disease; Neuroleukemia; Acute myeloblastic leukemia; Acute non-lymphoblastic leukemia; Acute non-lymphoblastic leukemia in adults; Refractory acute non-lymphoblastic leukemia; Induction of remission in PMLL; Transformation of preleukemias; Subleukemic myelosis; Myeloblastic leukemia; Myeloid leukemia

D75.2 Essential Thrombocytosis: Thrombocytosis; Primary thrombocytosis

Composition and release form

A solution for subcutaneous administration of 1 bar-tube. (0.5 ml)

Interferon alfa-2a 3 million IU; 4.5 million IU; 6 million IU; 9 million IU

Auxiliary substances: sodium chloride; Ammonium acetate; Benzyl alcohol; Polysorbate 80; Acetic acid, ice or sodium hydroxide; water for injections

In a syringe tube (the body is made of glass hydrolytic class I according to the EF, the plunger is made of plastic) to 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 plug of butyl rubber laminated with fluoropolymer; On the other hand, the syringe tube is capped with a tip of butyl rubber laminated with fluoropolymer; Complete with 1 sterile needle in a hermetically sealed container of PE; In a pack of cardboard 1 syringe-tube with a container with a needle for injection and instructions for use.

Solution for subcutaneous administration 1 cartridge

Interferon alfa-2a 18 million IU

Auxiliary substances: ammonium acetate; sodium chloride; Benzyl alcohol; Polysorbate 80; Acetic acid glacial or sodium hydroxide; water for injections

In a glass cartridge (hydrolytic class I glass by EF) of 18 million IU / 0.6 ml, sealed on both sides with plugs of butyl rubber coated with PTFE on the side in contact with the preparation; On the one hand, the plug is rolled up with an aluminum cap; 1 cartridge in a cardboard pallet with instructions for use and a strip of self-adhesive stickers for gluing on a syringe pen (with a place for indicating the date of first use) is placed in a cardboard pack.

Description of dosage form

Solution for subcutaneous administration: a clear, colorless or pale yellow liquid.

Pharmachologic effect

Mode of action - antiviral, antitumor.

Pharmacodynamics

Interferon alfa-2a is a highly purified protein containing 165 amino acids, with a molecular weight of about 19,000 daltons. It is obtained by technology with recombinant DNA using the genetic engineering strain E.coli, whose DNA encodes the synthesis of this human protein.

Roferon®-A has an antiviral effect, inducing in the cells a state of resistance to viral infections and modulating the response of the immune system, aimed at neutralizing the viruses or destroying the cells they infected. Roferon®-A has an antiproliferative effect on a number of human tumors in vitro and suppresses the growth of some human tumor xenografts in athymic mice with a nude mutation.

Clinical efficacy

In human tumor cells treated with Roferon®-A (in HT29 cells), the synthesis of DNA, RNA and protein is significantly reduced. A limited number of human tumor cell lines grown in vivo in nude mice with immune deficiency were tested for sensitivity to the effects of Roferon®-A. In vivo, the antiproliferative activity of Roferon®-A has been studied on tumors such as mucoid carcinoma of the mammary gland and adenocarcinoma of the blind 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 patients with AIDS with Kaposi's sarcoma. Roferon®-A is also effective for treating patients with myeloma. Roferon®-A has activity in patients with progressive cutaneous T-cell lymphoma that are insensitive or unsuitable for conventional therapy.

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

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

In patients with non-Hodgkin's low-grade lymphoma, in addition to chemotherapy (with or without radiotherapy), 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 relation to survival compared to one chemotherapy. In patients with advanced malignant melanoma, treatment with Roferon®-A led to an objective regression of tumors of cutaneous and visceral localization. Also, Roferon®-A increases the duration of time without recurrence 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 hepatitis B (and without signs of hepatic decompensation) with hepatitis B and C.

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

Pharmacokinetics

Suction. After the sc administration, bioavailability exceeds 80%. After sc administration of a dose of 36 million IU Cmax in the serum (from 1,250 to 2320 pg / ml, an average of 1730 pg / ml), an average of 7.3 hours was achieved.

Distribution. In humans, the pharmacokinetics of Roferon®-A in doses ranging from 3 million to 198 million IU is linear. After intravenous infusion of 36 million IU to healthy volunteers, the volume of distribution in the equilibrium state ranged from 0.22 to 0.75 l / kg (an average of 0.40 l / kg). Both in healthy volunteers and in patients with metastatic cancer, there are large individual fluctuations in the concentration of interferon alpha-2a in the serum.

Metabolism and excretion. The main way to deduce alpha interferon is renal catabolism. Hepatic metabolism and excretion with bile represent less significant ways of elimination. In healthy individuals, the T1 / 2 period of interferon alfa-2a after IV infusion of 36 million IU is 3.7-8.5 hours (an average of 5.1 hours), and the total clearance is 2.14-3.62 ml / Min / kg (average 2.79 ml / min / kg).

Indication of the Roferon-A

Neoplasms of the lymphatic system and hematopoiesis system:

Hairy cell leukemia;

Myeloma;

Cutaneous T-cell lymphoma;

Ph-positive chronic myelogenous leukemia;

Thrombocytosis in myeloproliferative diseases;

Non-Hodgkin's lymphoma of a low degree of malignancy (in the form of adjuvant therapy to chemotherapy-with or without radiotherapy).

Solid tumors:

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

Common 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 viral replication markers, ie, positive for HBV DNA, DNA polymerase or HBeAg, and increased activity of alanine aminotransferase (ALT);

Chronic active hepatitis C in adults with antibodies to hepatitis C virus or HCV RNA in the serum and an increase in ALT activity without signs of hepatic decompensation (Child-Pugh class A); In the treatment of chronic hepatitis C, the optimal combination is Roferon®-A and ribavirin; Roferon®-A in combination with ribavirin is indicated both in patients who were not previously treated, and for those who had previously responded to interferon-alpha therapy and then had a relapse after discontinuing therapy;

Genital warts.

Contraindications

Hypersensitivity to recombinant interferon alpha-2a or any component of the drug;

Available or transferred severe heart disease;

Severe violations of the kidneys, liver, myeloid germ of hematopoiesis;

Convulsive disorders, other disorders of the central nervous system;

Chronic hepatitis with severe decompensation or with cirrhosis of the liver;

Chronic hepatitis in patients receiving or recently received immunosuppressants, except for short-term treatment with steroids;

Chronic myelogenous leukemia, if the patient has an HLA-identical relative and is or is about to have an allogeneic bone marrow transplant in the near future;

Children's age to 3 years (as a preservative contains benzyl alcohol);

Pregnancy - with combined therapy with ribavirin (see also the medical instructions for ribavirin).

Application in pregnancy and breastfeeding

Men and women receiving Roferon®-A should use reliable methods of contraception. In pregnancy, the drug should be prescribed only if the benefit of treatment exceeds the possible risk to the fetus. Although experiments on animals do not indicate a teratogenicity of the drug, it cannot be ruled out that the possibility that its use during pregnancy can harm the fetus. When rhesus macaques in the early and middle stages of pregnancy were administered doses much higher than those recommended for the clinic, they had 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 abolishing the drug should be decided depending on the importance of treatment for the mother.

Benzyl alcohol, contained as a filler in the ready-to-use solution of Roferon®-A, can penetrate the placenta. When administering a solution of Roferon ® A immediately before delivery or by cesarean section, one should remember 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 who receive Roferon®-A in combination with ribavirin should use reliable contraceptive methods (see also the instructions for the use of ribavirin).

Side effects

The following data on the side effects of the drug are based on the experience of treatment of patients with various malignant diseases, often refractory to previous treatment and were in the late stages, as well as patients with chronic hepatitis B and C.

The following symptoms: often - the flu-like syndrome (lethargy, fever, chills, loss of appetite, muscle and headaches, joint pain and sweating), weight loss. These acute side effects are usually weakened or eliminated with concomitant administration of paracetamol, and their severity during treatment or when the dose of Roferon®-A tends to decrease, although drowsiness, weakness, and lethargy may occur when continuing therapy.

Gastrointestinal: often - about two thirds of cancer patients - anorexia, half - nausea; Quite often - vomiting, changes in taste, dry mouth, diarrhea, and weak or moderate abdominal pain; Rarely - constipation, flatulence, increased peristalsis and heartburn, exacerbation of peptic ulcer, gastrointestinal bleeding, not life-threatening, severe dysfunction of the liver, pancreatitis.

Changes in liver function: sometimes - increased levels of ALT, AP, LDH and bilirubin, which, as a rule, do not require dose adjustment; Rarely - a change in the activity of transaminases in hepatitis B; Very rarely - a serious violation of liver function, liver failure.

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

Organs of vision: sometimes - impaired vision; Rarely - ischemic retinopathy; Very rarely - retinopathy, including hemorrhages in the retina and cotton exudates, edema of the optic nerve, central vein thrombosis 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 - about one fifth of cancer patients - transient arterial hypo- or hypertension, edema, cyanosis, arrhythmias, palpitations and pains in the chest; Rarely - cough and minor shortness of breath, pulmonary edema, pneumonia, congestive heart failure, cardiac arrest and respiratory arrest, myocardial infarction. In patients with hepatitis B, cardiovascular disorders are very rare.

Skin, its appendages and mucous membranes: quite often - in the fifth part of patients - mild or moderate hair loss, reversible after discontinuation of treatment. Heavy hair loss can last for several weeks. Rarely, exacerbation of herpetic eruptions on the lips, rash, itching, dry skin and mucous membranes, discharge from the nose and nosebleeds, exacerbation or manifestation of psoriasis.

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

The system of hematopoiesis: quite often - transient leukopenia (rarely requiring a dose reduction), in patients with myelosuppression - thrombocytopenia, decrease in hemoglobin level; Sometimes - thrombocytopenia in patients without myelosuppression; Rarely - a decrease in the level of hemoglobin and hematocrit. The return of severe hematologic abnormalities to the baseline level was usually observed after -7-10 days after discontinuation 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, interferon alpha therapy, including Roferon®-A, in combination with Copepus, is associated with pancytopenia; Very rarely - with aplastic anemia.

Antibodies to interferon. In some patients, after administration of preparations containing a homologous protein, neutralizing active protein antibodies can be formed. Therefore, it is likely that a certain part of the patients will have antibodies to all interferons, both natural and recombinant. For some diseases (cancer, systemic lupus erythematosus, shingles), antibodies to human leukocyte interferon can spontaneously occur in patients who have never received interferons before. Indications that the presence of such antibodies can adversely affect the response of the patient to Roferon®-A is not available for any of the clinical indications.

When carrying out combination therapy with ribavirin - see also "Side effects" for ribavirin.

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 concurrent administration of drugs that are metabolized by this route. The decrease in the clearance of theophylline after the simultaneous administration of alpha interferons is described.

Interferons can enhance neurotoxic, hematotoxic or cardiotoxic effects of drugs administered earlier or simultaneously with them. Interactions can be observed after the simultaneous administration of drugs of central action.

When combined therapy with ribavirin - see also "Interaction" with ribavirin.

Dosing and Administration

Roferon®-A is administered by SC

Hairy cell leukemia

Initial dose: 3 million IU p / c, daily, for 16-24 weeks. With intolerance, the daily dose is reduced to 1.5 million IU and / or reduce the frequency of administration up to 3 times a week.

Maintenance dose: 3 million IU p / c 3 times a week. With intolerance, the dose is reduced to 1.5 million IU 3 times a week.

Duration of treatment: in the presence of a positive effect after 6 months, the treatment is continued, in its absence - terminated. The maximum duration of treatment was 20 months.

Myeloma disease

The initial dose: 3 million IU p / to 3 times a week.

Maintenance dose: Depending on the individual tolerability, the dose can be weekly increased to achieve the maximum tolerated dose (9-18 million IU) 3 times a week.

Duration of treatment: treatment under this scheme continues for a long time in the absence of progression of the disease and severe intolerance of the drug.

Cutaneous T-cell lymphoma (CTCL) (from age 18)

Roferon®-A can have an effect in patients with progressive KTKL, incl. Refractory to traditional therapy or not suitable for its conduct.

The initial dose: 3 million IU / day, SC, gradually increasing the daily dose to 18 million IU / day for 12 weeks according to the scheme: 1-3 day - 3 million IU / day, 4-6th day - 9 million IU / day, 7-84 day - 18 million IU / day.

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

Duration of treatment: the duration of treatment to evaluate the 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 not, stop. The maximum duration of treatment was 40 months. In patients who respond positively to treatment, it should be continued for at least 12 months in order to maximize the probability of achieving complete remission and increase the likelihood of prolonged remission.

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

Chronic myelogenous leukemia (CML)

18 and over

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

Duration of treatment: not less than 8 weeks, preferably 12 weeks; If there is an effect, the therapy is continued until a complete hematologic remission is achieved, but no more than 18 months. In the absence of dynamics of hematological parameters, therapy is discontinued. With complete hematologic 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 as soon as possible. There are observations of cytogenetic remissions lasting 2 years after the start of treatment.

The efficacy, safety and optimal doses of Roferon®-A for children with CML are not established.

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

Roferon®-A in a few days reduces the number of platelets, reduces the frequency of concomitant thrombohemorrhagic complications and does not possess a leukogenic potential.

Thrombocytosis associated with myeloproliferative diseases (except CML)

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

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

Non-Hodgkin's lymphoma of low grade

As maintenance therapy after standard chemotherapy (with or without radiotherapy): 3 million IU p / c 3 times a week for at least 12 months. Treatment should be started as early as possible with the improvement of the patient's condition, 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 22 to 26 days of each 28-day cycle. In this case, treatment with Roferon®-A can be started simultaneously with chemotherapy.

In patients with non-Hodgkin's low-grade lymphoma, in addition to chemotherapy (with or without radiotherapy), Roferon®-A prolongs relapse-free survival and progression-free survival.

Kaposi's Sarcoma in AIDS patients

The likelihood that patients with Kaposi's sarcoma and AIDS will respond positively to therapy if they have no history of opportunistic infections, B group symptoms (weight loss greater than 10%, temperature above 38 ° C in the absence of a known foci of infection, nighttime Sweating), and the initial number of T4-lymphocytes exceeds 200 cells in 1 μl.

The initial dose (from 18 years and older): 3 million IU / day, daily, with a gradual increase in dose for 10-12 weeks to 18 million IU / day, if possible - up to 36 million IU / day according to the scheme: 1-3 Day - 3 million IU / day, 4-6 days - 9 million IU / day, 7-9 days - 18 million IU / day, 10-84 day - up to 36 million IU / day (in case of tolerability).

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

Duration of treatment: to determine the response to treatment, document the dynamics of tumor changes. The duration of treatment before evaluating the response to therapy should be at least 10 weeks, preferably 12 weeks. If there is a positive effect, the therapy is continued, in the absence of it - stop. 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.

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

Common renal cell carcinoma

In patients with tumor recurrence or metastases, the best therapeutic effect was observed with the appointment of 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. The duration of response and survival with monotherapy with Roferon®-A and the combination therapy of Roferon®-A with vinblastine are similar. In patients receiving small doses of Roferon®-A (2 million IU / m2 per day), the effect of treatment was absent. The combination of Roferon®-A with vinblastine only leads to a slight increase in the frequency of mild to moderate leukopenia and granulocytopenia compared to monotherapy.

A) Monotherapy with Roferon®-A

The initial dose: 3 million units / day with a gradual increase in dose for 8-12 weeks to 18 million IU / day, and if possible - up to 36 million IU / day as follows: 1-3 days - 3 million IU / day, 4-6 days - 9 million IU / day, 7-9 days - 18 million IU / day, with tolerability increasing the dose for 10-84 days to 36 million IU / day.

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

Duration of treatment: not less than 8 weeks, preferably not less than 12 weeks. If there is an effect, therapy is continued, in the absence of the 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 three times a week, in the second week - 9 million IU three times a week, then 18 million IU three 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 iv in 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 at the maximum tolerated dose for 12 weeks. The duration of treatment to evaluate the effectiveness of therapy - preferably - at least 12 weeks. If there is an effect, therapy is continued, in the absence of the effect, it is stopped. The maximum duration of treatment is 24 months. In patients with advanced malignant melanoma, treatment with Roferon®-A led to an objective regression of tumors of cutaneous and visceral localization.

Melanoma after surgical resection

Adjuvant therapy with small doses of Roferon®-A increases the duration of time without recurrence of the disease in patients without lymph node involvement and distant metastases after resection of melanoma (tumor thickness> 1.5 mm). Treatment should be started no later than 6 weeks after the operation. The dose is 3 million IU 3 times a week. Duration of treatment - 18 months.

Chronic viral hepatitis B

Usually, 4.5-9 million IU is given SC 3 times a week for 4-6 months. Further correction of the dose is carried out depending on the tolerability of the drug. If after 3-4 months no improvement is observed, consideration should be given to discontinuing therapy.

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

The effectiveness of interferon alfa-2a increases if it is prescribed in combination with ribavirin. Roferon-A can be prescribed as a monotherapy in the presence of intolerance and / or contraindications to ribavirin.

A) Combination therapy with Roferon®-A and ribavirin

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

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

B) Monotherapy with Roferon®-A

Roferon®-A can be prescribed as monotherapy for 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 of ALT is not normalized, therapy should be discontinued.

With tolerability and with partial or complete response to therapy with Roferon®-A, but with a relapse of the disease after its withdrawal, the effect of repeated therapy with Roferon®-A at the same or a higher dose is possible.

Genital warts

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

Overdose

No overdose reports.

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 activities.

Special instructions

Roferon®-A should be administered under the supervision of a physician with experience of treatment according to appropriate indications.

Proper therapy of the underlying disease and complications is possible only if there are adequate diagnostic and therapeutic options.

With mild and moderate impairment of kidney, liver or bone marrow function, their functional state must be carefully monitored.

Changes in liver function. The change in transaminase activity in hepatitis B usually indicates an improvement in the clinical state of the patient. Care should be taken when treating interferon-alpha in patients with chronic hepatitis with autoimmune diseases in the anamnesis. Every patient who has pathological changes in functional liver samples during the treatment with Roferon®-A should be carefully monitored and, if necessary, abolished the drug.

Psychoneurological changes. In patients receiving interferons, incl. And Roferon®-A, can manifest severe psychic side effects. Depression, suicidal ideation and suicide may occur in patients with or without a history of mental illness. Caution should be exercised in the therapy of Roferon®-A in patients with a history of depression. It is recommended to closely monitor patients receiving Roferon®-A in order to detect depression. Before starting treatment, patients should be informed of the possibility of developing depression, and patients should immediately inform the doctor of any sign of depression; In the case of development of depression, a consultation of a psychiatrist is necessary and a decision on whether to cancel therapy is necessary.

Myelosuppression. With extreme caution, use of Roferon®-A in patients with severe myelosuppression should be used. The drug depresses the bone marrow, causing a drop in the number of leukocytes (especially granulocytes), the number of platelets and, more rarely - the level of hemoglobin. This can lead to an increased risk of infection or bleeding. It is necessary to monitor these changes closely and conduct detailed blood tests before the treatment with Roferon®-A and, regularly, in its process.

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

Ophthalmic changes. As during therapy with other interferons, the cases of retinopathy (retinal haemorrhage, cotton swelling, optic nerve disc swelling, central artery thrombosis and retinal veins) and posterior ischemic neuropathy, which can lead to loss of vision, have been reported in therapy with Roferon®-A. If you have a complaint about a worsening of visual acuity or loss of vision for these patients, an ophthalmological examination should be carried out. Patients with diabetes, arterial hypertension before the appointment of therapy should conduct an ophthalmological examination to identify pathology of the fundus. Therapy with Roferon®-A or Roferon®-A / ribavirin should be discontinued if worsening or occurrence of ophthalmic diseases occurs.

Hypersensitivity reactions. During therapy with interferons, incl. And interferon alpha-2a, there are serious reactions of immediate type hypersensitivity (hives, angioedema, bronchospasm and anaphylaxis). If such reactions develop with the treatment with Roferon®-A or Roferon®-A / ribavirin, therapy is withdrawn and appropriate medication is immediately prescribed. Transient rashes do not require the abolition of therapy.

Changes in endocrine organs. Rarely on the background of therapy with Roferon®-A hyperglycemia is observed. In the presence of clinical symptoms of hyperglycemia, blood glucose monitoring and appropriate monitoring are necessary. Patients with diabetes may need to adjust the dose of hypoglycemic drugs.

Autoimmune disorders. During the treatment with alpha interferons, cases of the formation of various autoantibodies were recorded. Clinical manifestations of autoimmune diseases in interferon therapy are more common in patients predisposed to the development of such diseases.

Therapy with alpha interferons is rarely associated with the onset or exacerbation of psoriasis. In patients after transplantation (eg, a kidney or bone marrow), drug-induced immunosuppression may be less effective because Interferons have a stimulating effect on the immune system.

There are no direct cardiotoxic effects of the drug, but it is likely that acute, self-extinguishing toxic effects (eg, fever, chills) often accompanying treatment with Roferon®-A can exacerbate existing heart diseases.

It is not recommended to administer Roferon®-A to newborns, especially premature infants, and children under 3 years of age, because it contains benzyl alcohol as a preservative, which, according to reports, can lead to persistent disturbances in the neuropsychic area and multiple organ failure.

When carrying out combined therapy with ribavirin - see also "Precautions" for ribavirin.

Preclinical study. In rhesus monkeys, who were prescribed doses much higher than those recommended for the clinic, transient disorders of the menstrual cycle were observed, including. Lengthening the period of menstruation.

Instructions for handling the drug

Multi-dose cartridges of 18 million IU in 0.6 ml are for use by only one patient. They are used only in the syringe-pen of Roferon®-Pen. With the syringe pen and the cartridge, only Penfine needles should be used. For each injection, a new sterile needle should be used. Cartridges with Roferon®-A should be used within 30 days after the first injection. After each injection, the syringe pen with the cartridge inserted should be stored in a refrigerator in a dark place, but if necessary, the syringe handle with the cartridge can be stored at room temperature (up to 25 ° C) for up to 28 days.

The date of the first use of the cartridge should be noted on the sticker, supplied with the cartridge, and paste it on the box with a syringe-pen. Detailed Instructions for Use Roferon®-Pen is enclosed in the packaging.

Influence on ability to drive vehicles and work with machines and mechanisms. Depending on the dosage regimen and individual sensitivity of the patient, Roferon®-A can exert an effect on reaction speed, affecting the performance of certain operations, for example driving vehicles, working with machines and mechanisms.

Storage conditions of the drug Roferon-A

In the dark place at a temperature of 2-8 ° C (don’t freezing).

Keep out of the reach of children.

Shelf life of the drug Roferon-A

2 years.

Do not use after the expiry date printed on the package.