Roferon-A

Active material: Interferon alfa
When ATH: L03AB04
CCF: Interferon. Antineoplastic, antiviral and immunomodulatory drugs
ICD-10 codes (testimony): A63.0, B18.1, B18.2, B21.0, C43, C64, C82, C83, C84, C90.0, Q91.4, Q92.1
When CSF: 09.01.05.01
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)

Pharmaceutical form, composition and packaging

The solution for the p / to the introduction clear, colorless or light yellow.

Excipients: ammonium acetate, sodium chloride, benzyl alcohol, polysorbate 80, glacial acetic acid or sodium hydroxide, water d / and.

0.5 ml – ampin (1) complete with a sterile needle d / and – packs cardboard.

The solution for the p / to the introduction clear, colorless or light yellow.

Excipients: ammonium acetate, sodium chloride, benzyl alcohol, polysorbate 80, glacial acetic acid or sodium hydroxide, water d / and.

0.6 ml – cartridges (1) – packs cardboard.

Pharmacological action

Antiviral and anticancer agent. Interferon alfa-2a - a highly purified protein, comprising 165 amino acids, with a molecular weight of about 19 000 Dalton. It is produced by recombinant DNA technology using genetically engineered strain of E.coli, DNA which encodes the protein synthesis of human.

Roferon^®-A has antiviral action, inducing a state of resistance in cells to viral infections and modulating an immune response, aimed at neutralizing viruses or destruction of infected cells. Roferon^®-A has antiproliferative effects on a number of human tumors in vitro and inhibit the growth of several human tumor xenografts in athymic nude mice with a mutation.

The human tumor cells, treated with Roferon^®-A (HT29 cells), significantly reduced DNA synthesis, RNA and protein. A limited number of human tumor cell lines, grown in vivo in nude mice with immune deficiency, They were tested for sensitivity to Roferon^®-A. In vivo антипролиферативная активность Роферона^®-A has been studied on such tumors, mucoid like breast carcinoma and adenocarcinoma of the cecum and colon poperechnoobodochnoy, and prostate. The extent of antiproliferative activity varies.

Roferon^®-A leads to clinically significant tumor regression or stabilization of disease in patients with hairy cell leukemia and AIDS patients with Kaposi's sarcoma. Roferon^®-Also effective in the treatment of patients with multiple myeloma. Roferon^®-A has activity in patients with progressive cutaneous T-cell lymphoma, which are insensitive or not suitable for conventional therapy.

Roferon^®-And is effective for the treatment of patients with Ph-positive chronic myeloid leukemia. Roferon^®-A leads to remission in 60% patients in chronic phase CML, regardless of previous treatment. Complete hematological remission has preserved through 18 months after initiation of treatment, 2/3 studied patients. Unlike cytotoxic chemotherapy, interferon alpha-2a can lead to stable cytogenetic remission, continuing more 40 months. Roferon^®-And in combination with intermittent chemotherapy improves overall survival and slows progression of the disease compared with the same chemotherapy.

Roferon^®-And it is effective for the treatment of thrombocytosis in chronic myeloid leukemia and other myeloproliferative diseases. Roferon^®-A few days reduces the number of platelets, reduces the incidence of complications related thrombohemorrhagic and has no potential leykozogennym.

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

In patients with advanced renal cell carcinoma Roferon^®-And in combination with vinblastine more efficient with respect to survival compared to patients with single himioterapiey.U common malignant melanoma treatment Roferon^®-And it resulted in objective tumor regression of cutaneous and visceral localization. Also Roferon^®-A increases the length of time without disease recurrence in patients without lymph node involvement and distant metastases following resection of a melanoma (tumor thickness > 1.5 mm). Roferon^®-A is effective for the treatment of patients with confirmed compensated (without evidence of hepatic decompensation) hepatitis B and C.

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

Pharmacokinetics

Absorption

After s / c injection bioavailability exceeds 80%. After p / to the introduction of Roferon^®-A dose 36 million. ME C_max serum was from 1250 to 2320 pg / ml (average, 1730 pg / ml) and reaches, average, through 7.3 no.

Distribution

In humans, the pharmacokinetics of Roferon^®-A dose of 3 million. to 198 million. ME is linear. After the on / in Infusion 36 million. ME healthy volunteers V_d at steady state ranged from 0.22 to 0.75 l / kg (average, 0.40 l / kg).

As in healthy volunteers, and patients with metastatic cancer there are large individual variations concentration of interferon alpha-2a serum.

Metabolism and excretion

The main route of elimination is renal interferon alfa catabolism. Hepatic metabolism and excretion in the bile are less important way of elimination.

In healthy individuals T_1/2 interferon alfa-2a in the / Infusion 36 million. ME is 3.7-8.5 no (average, 5.1 no), and the total clearance – 2.14-3.62 ml / min / kg (average, 2.79 ml / min / kg).

Testimony

Neoplasms of lymphatic and hematopoietic system:

- Volosatokletochnыy leukemia;

- Myeloma;

- Cutaneous T-cell lymphoma;

- Ph-positive chronic myeloid leukemia;

- Thrombocytosis in the myeloproliferative disorders;

- Non-Hodgkin's lymphoma, low-grade (as adjuvant therapy to chemotherapy, with / without radiotherapy).

Solid tumors:

- Kaposi's sarcoma in AIDS patients without a history of opportunistic infections;

- Advanced renal cell carcinoma;

- Metastaticheskaya zlokachestvennaya melanoma;

- Melanoma following surgical resection (the thickness of the tumor more 1.5 mm) in the absence of lymph node and distant metastasis.

Viral diseases:

- Chronic active hepatitis B in adults, with markers of viral replication (positive for HBV-DNA, DNA polymerase, HBeAg) and increased ALT;

- Chronic active hepatitis C in adults, having antibodies to hepatitis C virus or HCV RNA in the serum ALT activity and improvement without signs of liver decompensation (Class A on Child-Pugh): Roferon^®-And in combination with ribavirin is shown as previously untreated patients, and the, who observed clinical responses to treatment with interferon alpha, But developing relapse after therapy discontinuation;

- Genital warts.

Dosage regimen

Roferon^®-Entering a n / a.

At hairy cell leukemia Roferon^®-A administered in an initial dose 3 mln.ME / d n / a, daily, during 16-24 weeks. When intolerance daily dose is reduced to 1.5 mln.ME and / or to reduce the frequency of administration 3 once a week.

The maintenance dose is 3 Million International Units 3 twice a week n / a. When the dose is reduced to intolerance 1.5 Million International Units 3 times a week.

Use of the drug Roferon^®-And continue 6 Months, then the doctor must decide, whether to continue therapy (with a positive effect) or stop it (in its absence,). The maximum duration of treatment – 20 Months.

At multiple myeloma the drug is prescribed for 3 Million International Units 3 twice a week n / a. Depending on individual tolerance weekly dose can be increased until the maximum tolerated dose (9-18 Million International Units) 3 times a week.

Treatment according to this scheme is continued for a long time in the absence of disease progression or severe intolerance to the preparation.

At cutaneous T-cell lymphoma Roferon^®-And can have an effect in patients with progressive form of the disease, incl. refractory to conventional therapy or appropriate to carry it out.

Patients aged 18 and older the drug is administered during 12 weeks, gradually increasing the daily dose from 3 Million International Units to 18 mln.ME as follows: 1-3 day – 3 mln.ME / day, 4-6 day – 9 mln.ME / day, 7-84 day – 18 mln.ME / day.

Supportive treatment is carried out the maximum tolerated dose of the patient, but not exceeding 18 Million International Units, as p / injection 3 times a week.

The duration of treatment to assess the effectiveness of at least 8 weeks, preferably – 12 weeks; with a positive effect of treatment continues, in its absence, – stop. The maximum duration of treatment – 40 Months. Patients, positive responders, it should be continued for at least 12 Months, to maximize the probability of achieving full remission and increase the likelihood of long-term remission.

Partial remission is usually observed within 3 months of treatment, total – within 6 Months, but sometimes in order to achieve the best effect requires 12 months of therapy.

At chronic myeloid leukemia patients aged 18 and older the drug is administered during 8-12 weeks, gradually increasing the dose according to the following scheme: 1-3 day – 3 mln.ME / day, 4-6 day – 6 mln.ME / day, 7-84 day – 9 mln.ME / day.

Treatment should be continued for at least 8 weeks, preferably – 12 weeks; with a positive effect of the treatment is continued until complete remission, but not more 18 Months. In the absence of the dynamics of hematological therapy is stopped. All patients with complete hematologic remission should continue treatment with a dose of 9 mln.ME / day (the optimal dose) daily, or 9 Million International Units 3 times a week (the minimum dose), to achieve cytogenetic remission to the maximum short term. There are observations of cytogenetic remission duration 2 year after initiation of treatment.

Effectiveness, safety and optimal dose of Roferon^®-And for children with chronic myeloid leukemia have not been established.

Unlike cytotoxic chemotherapy interferon alpha-2a can lead to stable cytogenetic remission, continuing more 40 Months.

Roferon^®-A few days reduces the number of platelets, reduces the incidence of complications related thrombohemorrhagic and has no potential leykozogennym.

At thrombocytosis in the myeloproliferative disorders (except for chronic myeloid leukemia) the drug is prescribed in 1-3 day – 3 mln.ME / day every day; 4-30 day – 6 mln.ME / day every day. The maintenance dose is 1-3 Million International Units 2-3 times a week. Each patient should be individually select the maximum tolerated dose.

At non-Hodgkin's lymphoma, low-grade the drug is prescribed as maintenance therapy after standard chemotherapy (radiotherapy or without) dose 3 mln.ME n / a 3 times / week. for not less than 12 Months. Treatment Roferon^®-And should begin as soon as possible on improving the patient's condition, usually via 4-6 weeks after chemo- and radiation therapy.

Roferon^®-But it is also possible to assign the same time with traditional chemotherapy regimens (eg, a combination of cyclophosphamide, prednisolone, vincristine and doxorubicin) by 6 Million International Units / m² body surface p / c 22 by 26 day of each 28-day cycle. In this case, treatment with Roferon^®-And you can begin simultaneously with chemotherapy.

Roferon^®-A, appointed in addition to chemotherapy (radiotherapy or without), prolongs disease-free survival and progression-free survival.

At Kaposi's sarcoma in AIDS patients probability, that patients with Kaposi's sarcoma and AIDS will respond positively to treatment is higher in the case, if they have a history of opportunistic infections, symptom of group B (weight loss more 10%, the temperature is above 38 ° C in the absence of a known source of infection, night sweat), and the original number of T4 lymphocytes than 200 cells / mm.

Patients in ages 18 and older the drug is prescribed in an initial dose 3 mln.ME / day daily for 10-12 weeks, gradually increasing the daily dose 18 mln.ME / day every day, and possibly – to 36 mln.ME / day daily as follows: 1-3 day – 3 mln.ME / day every day, 4-6 day – 9 mln.ME / day every day, 7-9 day – 18 mln.ME / day every day, while increasing the dose of tolerance 10-84 day before 36 mln.ME / day every day.

Maintenance dose – the maximum tolerated dose, but not more 36 mln.ME / day, 3 times / week.

The duration of treatment to assess response to therapy should be at least 10 weeks, preferably – 12 weeks. If there is a positive effect of continued therapy, in its absence, – stop. To determine the response to treatment should be documented dynamics of tumor. Usually the effect is manifested through 3 months of treatment. The maximum duration of treatment was 20 Months. In the presence of the effect of treatment should be continued, at least, to the disappearance of the tumor. After discontinuation of therapy Roferon^®-A Kaposi's sarcoma often recurs.

At advanced renal cell carcinoma in patients with tumor recurrence or metastasis is the best therapeutic effect observed in the appointment of Roferon^®-A high dose (36 mln.ME / day) as monotherapy or in moderation (18 Million International Units 3 times a week) in combination with vinblastine, compared with monotherapy moderate doses 3 times a week. The duration of response and survival in monotherapy Roferon^®-A combination therapy or Roferon^®-And similar to vinblastine. Patients, receiving Roferon^®-A (2 Million International Units / m²/d) in low doses, treatment was ineffective. The combination of Roferon^®-And with vinblastine results in only a slight increase in the frequency of mild and moderate leukopenia and granulocytopenia compared with monotherapy.

At monotherapy Roferon^®-A administered in an initial dose 3 mln. / IU / day with gradual increase in the dose for 8-12 weeks before 18 mln.ME / day, and possibly – to 36 mln.ME / day, as follows: 1-3 day – 3 mln.ME / day, 4-6 day – 9 mln.ME / day, 7-9 day – 18 mln.ME / day, while increasing the dose of tolerance 10-84 day before 36 mln.ME / day.

For maintenance therapy Roferon^®-A maximum dose is administered in, patients tolerated, but not more 36 mln.ME / day 3 times / week.

Duration of treatment is at least 8 weeks, preferably – 12 weeks. If there is a positive effect of continued therapy, in its absence, – stop. The maximum duration of treatment – 16 Months.

At combination therapy c винбластином Роферон^®-A administered during the first week at a dose 3 Million International Units 3 times a week, in the second week – 9 Million International Units 3 times a week, then – 18 Million International Units 3 times a week (in case of intolerance to the dose can be reduced to 9 Million International Units 3 times a week). During this period, vinblastine be administered in / in accordance with the instructions for use of the drug in a dose of 100 ug / kg body weight 1 once every 3 of the week. Duration of treatment is at least 3 Months, maximum 12 months or until disease progression. In the case of complete remission after treatment can be discontinued 3 months after its occurrence.

At metastatic melanoma Roferon^®-A prescribe a dose 18 mln.ME n / a 3 once a week or the maximum tolerated dose for 12 weeks. The duration of treatment to assess the effectiveness of therapy is preferred – no less 12 weeks. If there is a positive effect of continued therapy, in its absence, – stop. The maximum duration of treatment – 24 Months. Patients with common malignant melanoma Roferon treatment^®-And it resulted in objective tumor regression of cutaneous and visceral localization.

At melanoma following surgical resection adjuvant therapy with small doses of Roferon^®-A increases the length of time without disease recurrence in patients without lymph node involvement and distant metastases following resection of a melanoma (the thickness of the tumor more 1.5 mm). Treatment should be initiated no later than, than 6 weeks after surgery. The dose is 3 million. ME 3 times / week. Duration of treatment - 18 Months.

At chronic viral hepatitis B Roferon^®-And appoint 4.5-9 ME million 3 once a week for 4-6 Months. Further dose adjustment is carried out based on tolerability. If there is no improvement after 3-4 months should consider discontinuation.

At chronic viral hepatitis B in children 3 and older the use of dose 7.5 Million International Units / m² body surface safely and effectively.

At chronic hepatitis C the effectiveness of Roferon^®-A rising, if it is administered in combination with ribavirin. During the combination therapy in previously untreated patients with Roferon^®-And appoint 3 Million International Units 3 times a week for at least 6 Months. Ribavirin is administered in a dose, specified in the instructions for medical use of ribavirin.

During the combination therapy for relapsed disease in Adult, whose previous interferon alfa monotherapy gave a temporary effect, Roferon^®-And appoint 4.5 Million International Units 3 once a week for 6 Months. Ribavirin is administered in a dose, specified in the instructions for medical use of ribavirin.

The standard duration of therapy in patients with chronic hepatitis C depends on viral genotype and is 6-12 Months.

Monotherapy Roferonom^®-And held with ribavirin intolerance and / or with contraindications to its acceptance. Dose Roferona^®-A is 3-6 Million International Units 3 once a week for 6-12 Months. If after 3 months of treatment, serum ALT levels are not normal, therapy should be discontinued. With portability and partial or complete response to therapy with Roferon^®-A, but recurrence of the disease after its cancellation, possible effect of re-treatment with Roferon^®-And in the same or a higher dose.

At genital warts Roferon^®-A designated n / a for 1-3 Million International Units 3 once a week for 1-2 Months.

Handling the drug

Multidose cartridges (18 Million International Units in 0.6 ml) intended for single patient use only. They apply only to the syringe handle Roferon^®-And. Together with syringe pen and cartridges should be used needle Penfayn. Each injection should take a new sterile needle. Cartridges Roferon^®-A should be used within 30 days after the first injection. After each injection, the pen Roferon^®-Pen with the inserted cartridge should be stored in the refrigerator, in a dark place, However, if necessary it can be stored at room temperature (25 ° C) during 28 days.

The date of first use of the cartridge should be noted on the sticker, supplied with the cartridge, and stick the sticker on the box of syringe-pen. Detailed instructions on the use of Roferon^®-Pen is embedded in the package with the syringe-pen.

Side effect

The following data on the side effects of the drug based on the experience of treatment of patients with a variety of malignant diseases, often refractory to previous therapy and are at the later stages, as well as patients with chronic hepatitis B and chronic hepatitis C.

From the body as a whole: often – flu-like symptoms (slackness, temperature rise, chills, loss of appetite, muscle aches, headache, joint pain and increased sweating), weight loss. These acute side effects get better or cropped paracetamol, and their expression in the course of treatment or change the dose of Roferon^®-A tends to decrease, although continuing therapy can cause drowsiness, weakness and lethargy.

From the digestive system: often – anorexia (about 2/3 cancer patients), nausea (1/2 cancer patients); often – vomiting, change in taste, dry mouth, diarrhea, mild or moderate abdominal pain; rarely – constipation, flatulence, heartburn, increased peristalsis, exacerbation of peptic ulcer disease, gastrointestinal bleeding (not life-threatening), pancreatitis, increased ALT, Alkaline phosphatase, LDH, increase in bilirubin (dose adjustment is required); rarely – changes in the activity of transaminases in hepatitis B; rarely – severe liver dysfunction, hepatic failure.

From the central and peripheral nervous system: sometimes – systemic and non-systemic dizziness, blurred vision, deterioration in mental status, forgetfulness, depression, drowsiness, confusion, behavioral disturbances (nervousness, alarm), sleep disorders, paresthesia, numbness, Neuropathy, itching and tremor; rarely – severe drowsiness, convulsions, coma, cerebrovascular accidents, temporary impotence, suicide attempts and suicidal behavior (in the latter case, the drug should be discontinued).

On the part of the organ of vision: sometimes – blurred vision; rarely – ishemicheskaya retinopathy; rarely – retinopathy, including retinal hemorrhages, and “Quilted” exudates, papilledema, thrombosis of the central retinal vein and artery, zadnyaya ishemicheskaya neuropathy.

Cardio-vascular system: often – tranzïtornaya arterïalnaya hypo- and hypertension (approximately 1/5 cancer patients), swelling, cyanosis, Arrhythmia, palpitations, chest pain; rarely – a little shortness of breath, pulmonary edema, congestive heart failure, cardiac arrest, myocardial infarction. In patients with hepatitis B, cardiovascular disorders observed very rarely.

The respiratory system: rarely – cough, pneumonia, respiratory arrest, nasal discharge, nosebleeds.

From the urinary system: rarely – worsening of renal function, acute renal failure (mainly, in cancer patients with kidney disease or treatment, while nephrotoxic drugs), proteinuria, increase of cell elements in the urine sediment, increased BUN, creatinine and uric acid in blood serum.

Metabolism: rarely – electrolyte abnormalities, especially with anorexia or dehydration, giperglikemiâ, diabetes; very rarely - asymptomatic hypocalcemia, hypertriglyceridemia / hyperlipidemia.

From the hematopoietic system: often – transient leukopenia (rarely require dose reduction), in patients in a state of myelosuppression – thrombocytopenia, decrease in hemoglobin; possible thrombocytopenia in patients without myelosuppression; rarely – reduction in the level of hemoglobin and hematocrit; rarely – idiopaticheskaya trombotsitopenicheskaya purpura. The return of severe haematological disorders to baseline is usually marked by 7-10 days after cessation of treatment with Roferon^®-A. In rare cases, therapy with alpha interferon, including Roferon^®-A, plus ribavirin is associated with pancytopenia; very rare - with aplastic anemia.

Dermatological reactions: often (1/5 cancer patients) - Mild to moderate hair loss (reversible after cessation of treatment), increased hair loss may continue for several weeks; rarely – exacerbation of herpes sores on the lips, rash, itch, dryness of skin and mucous membranes, exacerbation of psoriasis or demonstration.

Other: rarely – reactions at the injection site (including very rare – necrosis), autoimmune pathology (vasculitis, arthritis, gemoliticheskaya anemia, thyroid dysfunction, lupus-like syndrome); very rarely - sarcoidosis.

In some patients, after administration of drugs, containing a homologous protein, possible formation of neutralizing antibodies active protein. It is therefore likely, that a certain proportion of patients may be detected by antibodies to all interferons (both natural, and recombinant). In some diseases (cancer, systemic lupus erythematosus, shingles) antibodies to human leukocyte interferon can spontaneously occur in patients, I have never been treated with interferons.

Indications, that in any of the clinical indications of such antibodies can affect the patient's response to Roferon^®-A, not available.

In combination therapy with ribavirin should be considered a side effect of ribavirin.

Contraindications

- Severe heart disease (incl. history);

- Severe renal dysfunction;

- Severe liver;

- Severe violations of myeloid hematopoiesis;

- Seizure disorders and / or dysfunction of the central nervous system;

- Chronic hepatitis with severe or decompensated cirrhosis of the liver;

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

- Chronic myelogenous leukemia, if the patient has an HLA-identical relative and he will be available, or allogeneic bone marrow transplantation in the near future;

- Children up to age 3 years (tk. preparation as a preservative contains benzyl alcohol);

- Pregnancy (during combination therapy with ribavirin,);

- Hypersensitivity to recombinant interferon alfa-2a or any component of the drug.

Pregnancy and lactation

Men and women, receiving Roferon^®-A, We should use reliable methods of contraception. During pregnancy, the drug should be prescribed only, if the benefits of treatment exceeds potential risk for the fetus. Although animal studies do not indicate teratogenic, one can not exclude the possibility, that its use during pregnancy can harm the fetus. When rhesus monkeys in the early and middle stages of pregnancy dosed, greatly exceeding recommended for clinic, they noted an increase in the number of abortions.

Unknown, whether it is allocated Roferon^®-A breast milk. The question of the cessation of breastfeeding or the cancellation of the drug should be decided according to the importance of treatment for the mother.

Benzyl alcohol, contained as a filler, It can cross the placental barrier. In appointing the solution Roferon^®-And just before birth or caesarean section should be aware of toxic effects on premature babies.

Pregnant women should not use Roferon^®-A plus ribavirin. Women of childbearing age and the male partners of women of childbearing age, receiving Roferon^®-A plus ribavirin, We should use reliable methods of contraception (cm. and instructions for use of ribavirin).

Cautions

Roferon^®-A should be used under medical supervision, with experience in the treatment of the relevant indications.

Proper treatment of the underlying disease and complications is possible only when adequate diagnostic and therapeutic options.

In mild and moderate renal impairment, liver or bone marrow their function must be carefully controlled.

Changes in the activity of transaminases in hepatitis B usually indicates an improvement in the clinical condition of the patient. Care should be taken in the treatment of interferon-alpha in patients with chronic hepatitis with autoimmune diseases in history. Each patient, in which the treatment with Roferon^®-But there are pathological changes of functional liver samples, It needs to be carefully monitored and, if necessary, stop the drug.

Patients, receiving interferons, incl. Roferon^®-A, may manifest severe psychiatric adverse reactions. Depression, suicidal thoughts and suicide may occur in patients with both mental illness history, or without. Caution should be exercised in the appointment of Roferon^®-A patient with a history of depression. It is recommended that careful monitoring of patients, receiving Roferon^®-A, to detect symptoms of depression. Before treatment, patients should be informed about the possibility of depression, and patients should immediately tell your doctor about any symptoms of depression; in the case of depression should consult a psychiatrist and deciding whether discontinuation.

With extreme caution should be used Roferon^®-And in patients with severe myelosuppression, tk. the drug inhibits the bone marrow, causing a reduction in the number of leukocytes (particularly granulocytes), platelet, less often, hemoglobin levels. This can lead to increased risk of infection or bleeding. It is necessary to closely monitor these developments and to carry out detailed analyzes of the patients blood before treatment Roferon^®-A and, regularly, in its process.

Fever may be associated with the flu-like syndrome, which is often observed with interferon therapy. If persistent fever, particularly in patients with neutropenia, should be ruled out infection (bacterial, vyrusnuyu, hrybkovuyu). In the event of severe infectious complications should be discontinued interferon and assign appropriate therapy.

As in treatment with other interferons, during therapy Roferon^®-A reported cases of retinopathy (retinal hemorrhages, “Quilted” exudates, papilledema, thrombosis of the central retinal artery and vein) and posterior ischemic neuropathy, which can lead to vision loss. When complaints about the deterioration of visual acuity or vision loss in these patients should be performed ophthalmologic examination. Patients with diabetes mellitus, hypertension before prescribing treatment is necessary to conduct eye examination to detect the pathology of the fundus. Therapy with Roferon^®-A or Roferon^®-A / ribavirin should be discontinued in the event of deterioration or ophthalmic diseases.

During interferon therapy, incl. and interferon alpha-2a, have severe immediate hypersensitivity reaction (hives, angioedema, bronchoconstriction and anaphylaxis). In the case of such reactions during therapy with Roferon^®-A or Roferon^®-A / ribavirin therapy immediately cancel and prescribe the appropriate drug therapy. Transient rashes do not require discontinuation of therapy.

Rarely during therapy with Roferon^®-And there hyperglycemia. In the presence of clinical symptoms of hyperglycemia requires monitoring of blood glucose and appropriate monitoring. Patients with diabetes mellitus may require adjustment of the dose of hypoglycemic drugs.

During therapy, interferon alfa-reported cases of the formation of various autoantibodies. Clinical manifestations of autoimmune disease during interferon therapy occur more frequently in patients, predisposed to such diseases.

Alpha interferon therapy is rarely associated with the onset or exacerbation of psoriasis. Patients after transplantation (eg, kidney or bone marrow) drug immunosuppression may be less effective, tk. Interferons have a stimulating effect on the immune system.

Indications of direct cardiotoxic effects of the drug are no, However, there is a possibility, that acute, independently endangered toxic effects (eg, temperature rise, chills), often accompany treatment Roferon^®-A, can exacerbate existing heart disease.

During the combination therapy with ribavirin should be considered precautions for ribavirin.

In preclinical studies in rhesus monkeys, which was administered dose, significantly higher than the recommended for the clinic, observed transient menstrual irregularities, incl. lengthening of the period of menstruation.

Use in Pediatrics

Appoint Roferon^®-A newborn, especially premature, and children up to 3 years should not, because it contains benzyl alcohol as a preservative, which, reportedly, can lead to persistent violations in the field of neuro-psychological and multiple organ failure.

Effects on ability to drive vehicles and management mechanisms

Depending on the dosage and individual susceptibility of the patient Roferon^®-A can have an effect on the rate of reaction, the ability to potentially dangerous activities, including driving vehicles, work with machines and mechanisms.

Overdose

Cases overdose unknown.

Symptoms: repeated administration of high doses of interferon may be accompanied by profound lethargy, slackness, prostration and coma.

Treatment: It shows surveillance and maintenance therapy in hospital.

Drug Interactions

Interferons alpha may violate oxidative metabolic processes, reducing the activity of hepatic microsomal enzymes of the cytochrome P450. The possibility of such an impact must be considered in a joint application Roferon^®-A and drugs, which are metabolized by the data. Described decrease in clearance of theophylline when co-administration of interferon alpha.

Interferons may increase neurotoxic, haematological or cardiotoxic effects of drugs, Assigns before or simultaneously with them. The interaction may also occur simultaneously with the prescribed drugs of the central action.

During the combination therapy with ribavirin should be considered drug interactions ribavirin.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C; Do not freeze. Shelf life - 2 year.