Intron A - instructions for use, dose, side effects, contraindications

Sodium hydrophosphate anhydrous 1.8 mg, sodium dihydrogen phosphate monohydrate 1.3 mg, disodium edetate 0.1 mg, sodium chloride 7.5 mg, metacresol 1.5 mg, polysorbate-80 0.1 mg, water for injection up to 1, 0 ml.

Description:

A clear, colorless solution.

Pharmacotherapeutic group:Cytokine

ATX: & nbsp

L.03.A.B.05 Interferon alfa-2b

Pharmacodynamics:

Characteristic

The drug Intron® A is a stable sterile solution highly purified interferon alpha-2b, received using recombinant DNA. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of about 19,300 daltons. It is produced using a strain Escherichia withlicontaining a genetically engineered plasmid hybrid encoding an interferon alpha-2 geneb of human leukocytes.

Pharmacodynamics

Activity of the drug Intron^®A expressed in international units (ME), 1 mg of interferon alfa-2b corresponds to 2.6x10⁸ ME. Activity in ME is determined by comparing the activity of recombinant interferon alfa-2b with the standard of human leukocyte interferon of the World Health Organization (WHO).

Interferons are a group of small protein molecules with an approximate molecular weight of 15,000 to 21,000 daltons. They are synthesized and secreted by cells in response to viral infections or various artificial or biological stimuli. There are 3 main classes of interferons: alpha, beta and gamma. These classes are heterogeneous and contain different types of interferons. There are more than 14 genetically distinct human interferons. The active substance of the drug Intron^® A is classified as recombinant interferon alpha-2b.

Cellular effects of interferons are due to binding to specific receptors on the cell surface.Human interferon receptors isolated from the lymphoblastic cell line (Daudi), are highly asymmetric proteins. They showed selectivity for human interferons, but not for mouse, suggesting species-specificity. Studies of other interferons also demonstrated their species specificity. However, certain species of monkeys, such as rhesus monkeys, are sensitive to the pharmacodynamic effects of human type I interferons.

The results of several studies indicate that after binding to the cell membrane interferon causes a complex sequence of intracellular reactions, including. induction of certain enzymes. It is believed that, at least in part, these processes determine the cellular effects of interferon, including suppression of viral replication in infected cells, inhibition of cell proliferation, and immunomodulatory properties of interferon such as increased phagocytic activity of macrophages and the increase in specific cytotoxicity of lymphocytes relative to target cells .Each or all of these effects can mediate the therapeutic activity of interferon.

Recombinant interferon alfa-2b has an antiproliferative effect on both the culture of human and animal cells, and also on human tumor xenografts in animals. A significant immunomodulating activity of recombinant interferon alfa-2b in vitro. Recombinant interferon alfa-2b also suppresses the replication of the virus in vitro and in vivo. Although the exact mechanism of antiviral action of recombinant interferon alfa-2b is unknown, nevertheless it is believed that the drug changes the metabolism of body cells. This leads to suppression of viral replication, and if it does occur, the resulting virions are unable to exit the cell.

Pharmacokinetics:

The pharmacokinetics of the preparation Intron® A were studied in healthy volunteers with a single dose of 5 million IU / m² and 10 million IU / m² subcutaneously, 5 million IU / m²intramuscularly and by intravenous infusion for 30 minutes. The average concentrations of interferon in the serum were comparable after subcutaneous and intramuscular injection.The maximum serum concentration (C_mOh) was achieved 3-12 hours after administration in a dose of 5 million IU / m², after 6-8 hours at a dose of 10 million IU / m² subcutaneously. The half-life was about 2-3 hours and 6-7 hours, respectively. The concentration of interferon in the serum was below the detection limit at 16 and 24 hours after administration, respectively. Bioavailability of the drug with subcutaneous and intramuscular injection was more than 100%.

After intravenous administration, the serum concentration of interferon reached maximal values (135-273 IU / ml) at the end of the infusion, then decreased somewhat faster than after subcutaneous or intramuscular injection, and was not determined 1 hour after the end of the infusion. The half-life was about 2 hours.

The concentration of interferon in the urine was below the detection limit, regardless of the route of administration.

Have patients who received Intron^® And in clinical studies, serum levels of antibodies neutralizing the antiviral activity of interferon were determined. Their detection rate was 2.6% in patients with oncological diseases and 6.2% in patients with chronic hepatitis.In all cases of detection of antibodies, their titer was low, and their presence did not systematically lead to a loss of response or the occurrence of other autoimmune processes. In patients with hepatitis, no loss of response was observed, most likely due to a low antibody titer.

Children

Pharmacokinetic indices of multiple simultaneous application of Intron^® A and ribavirin capsules in children (aged 5 to 16 years) with chronic hepatitis C are shown in Table 1. The pharmacokinetic parameters of the combined use of Intron^® And with ribavirin (normalized for the dose) are the same in adults and children.

Table 1. Mean values (coefficient of variation,%) of the pharmacokinetics values for multiple simultaneous application of Intron^® A and ribavirin capsules in children with chronic hepatitis C.

Index	Ribavirin 15 mg / kg per day, divided into 2 doses (n= 17)	Intron^® A 3 million IU / m² 3 times a week (n=54)
The time to reach the maximum concentration, T_mOh (h)	1,9 (83)	5,9 (36)
FROM_m_Oh (ng / ml)	3275 (25)	51 (48)
The area under the concentration-time curve, AUC*	29774 (26)	622 (48)
Apparent ground clearance, l / h / kg	0.27 (27)	Not conducted

*AUFROM₁₂ (ng^.h / ml) for ribavirin; AUC_0-24(IU^.h / ml) for the preparation Intron® A.

Sperm content

The concentration of ribavirin in the semen is approximately twice as high as in the serum.When evaluating after sexual intercourse, the systemic exposure of ribavirin to partners of patients taking ribavirin, was extremely small in comparison with the therapeutic plasma concentrations of ribavirin.

Indications:

Chronic hepatitis B

Treatment of adults and children (from 1 year old) with chronic hepatitis B with confirmed replication of hepatitis B virus (HBV) (the presence of HBV or HBeAg DNA in the blood serum) in combination with an increase in ALT activity in the blood plasma and histologically confirmed by an active inflammatory process and / or fibrosis of the liver.

Chronic hepatitis C

Monotherapy or in combination with ribavirin:

Adults

Treatment of patients with chronic hepatitis C who have no signs of decompensating liver disease, with increased activity of ALT, seropositive to RNA of hepatitis C virus (HCV).

Therapy with Intron ® A is most effective in this combination in combination with ribavirin.

Only in combination with ribavirin:

Children

Treatment of children aged 3 to 18 years, patients with chronic hepatitis C, seropositive for HCV RNA, who have no signs of decompensation of liver disease, which had not previously been treated.

When prescribing combination therapy, it is also necessary to follow the instructions for the medical use of ribavirin.

When deciding on the need for treatment of children, it is important to consider that combination therapy can cause growth retardation. The decision on the appointment of treatment should be made on a case-by-case basis (see the "Special Assistance" section).

Hairy cell leukemia

Treatment of hairy cell leukemia in adults in the form of monotherapy.

Chronic myelogenous leukemia

Monotherapy: treatment of adult patients with chronic myelogenous leukemia in the presence of the Philadelphia chromosome (Ph +) or translocation bsg / abl.

Clinical data show that hematological remission and cytogenetic response (large / small) are achieved in most patients. In this case, a large cytogenetic response is defined as the number Ph+ -leukinous cells in the bone marrow <34%, and small - from 34% to 90%.

Combination Therapy: application of Intron^® And in combination with cytarabine during the first 12 months of treatment, it is possible to significantly increase the number of large cytogenetic responses and significantly increase the overall survival of patients compared with interferon alpha-2b monotherapy after 3 years of treatment.

Multiple myeloma

As maintenance therapy in adult patients who achieved partial response (reduction of paraprotein in serum by 50%) after initial induction therapy.

Supportive therapy extends the plateau phase, but the effect of Intron^® And the overall survival is not established.

Follicular lymphoma (non-Hodgkin's lymphoma)

Treatment of follicular lymphoma with high tumor mass - in combination with adequate induction chemotherapy (eg, CHOP-regimen) in adult patients. This group includes follicular lymphomas with at least one of the following signs: large tumor size (> 7 cm), involvement of 3 or more lymph nodes (each> 3 cm), general symptoms (weight loss by more than 10%, increase body temperature above 38 ° C for more than 8 days or increased sweating at night), splenomegaly (the border of the spleen extends beyond the navel), compression of important organs or the onset of compression syndrome, involvement of the epidural space or orbital area, leukemia tions, a considerable effusion.

The effectiveness of therapy with Intron^® And in patients with follicular non-Hodgkin's lymphomas with low tumor load was not established.

Metastatic kidney cancer

Treatment of patients with metastatic kidney cancer with a favorable prognosis and minimal symptoms of the disease.

Carcinoid tumors

Treatment of carcinoid tumors in adult patients with lymph node involvement or with metastases in the liver and with "carcinoid syndrome".

Malignant melanoma

Adjuvant therapy of adult patients operated on for a primary tumor, in the presence of a high risk of systemic relapse.

Contraindications:

- Hypersensitivity to interferon alpha-2b and other components of the drug;

- severe diseases of the cardiovascular system (including heart failure in the stage of decompensation, recently suffered myocardial infarction, severe arrhythmias);

- expressed violations of the liver or kidney, incl. caused by metastases;

- epilepsy and other disorders of the central nervous system;

- chronic hepatitis with cirrhosis of the liver in the stage of decompensation;

- chronic hepatitis in patients receiving or receiving immunosuppressants (except for a short-term course of therapyglucocorticosteroids);

- autoimmune hepatitis, an autoimmune disease in the anamnesis, use of immunosuppressants after transplantation;

- Thyroid gland disease if it is not controlled by appropriate therapy;

- simultaneous application with telbivudine;

- mental illness and disorders in children, in particular severe depression, suicidal thoughts, attempted suicide;

- Creatinine clearance below 50 ml / min (when used and combined with ribavirin).

- pregnancy and the period of breastfeeding;

- pregnancy with a female partner of a man who is expected to be treated with Intron^® And in combination with ribavirin;

- children under 1 year of age (chronic hepatitis B); up to 3 years (chronic hepatitis C); up to 18 years (according to other indications).

With the appointment of Intron^® And in combination with ribavirin should also take into account the contraindications specified in the instructions for the use of ribavirin.

Carefully:

- Expressed depression, suicidal thoughts and attempts, incl. according to anamnesis (adults only);

- decompensated lung diseases (including chronic obstructive pulmonary disease);

- Diabetes mellitus, prone to ketoacidosis;

- Hypercoagulation;

- expressed myelosuppression;

- diseases of the cardiovascular system in the anamnesis (myocardial infarction, chronic heart failure, arrhythmias);

- Thyroid disease, if it is controlled by appropriate therapy;

- psoriasis and sarcoidosis;

- reproductive age of men and women (see section "Application during pregnancy and during breastfeeding");

- kidney and liver transplant;

- concomitant chemotherapy.

Pregnancy and lactation:

Women of reproductive age, contraception in men and women

Female patients should use a reliable method of contraception during therapy. In women receiving therapy with human leukocyte interferon, there was a decrease in the concentration of serum estradiol and progesterone.

The drug should be used with caution in men of reproductive age.

Combination therapy with ribavirin

Ribavirin causes serious malformations when applied during pregnancy. Special precautions should be taken to prevent pregnancy in patients receiving combination therapy.Women capable of childbearing should use a reliable method of contraception during therapy and within 4 months after completion of therapy. Male patients or their partners should use a reliable method of contraception during therapy and within 7 months after its completion.

Pregnancy

Clinical data on the use of interferon alfa-2b during pregnancy are absent. In experimental studies on animals, the toxic effect of the drug on reproductive performance was revealed. The value of this data for humans is not established. Use during pregnancy is contraindicated.

Combination therapy with ribavirin

Combination therapy with ribavirin is contraindicated during pregnancy.

Thoracic feeding

It is not known whether the components of Intron^® And with breast milk. Because of the possible risk of unwanted effects of the drug in infants who are breastfed, if necessary, the use of the drug Intron^® And you should stop breastfeeding.

Dosing and Administration:

Treatment is prescribed by a doctor who has experience in the treatment of the corresponding disease.

According to the doctor's decision, the patient can independently administer the drug subcutaneously to continue the selected treatment regimen.

Chronic hepatitis B

Recommended dose for adults is from 30 to 35 million ME per week subcutaneously, or in a dose of 5 million ME daily, or 10 million ME three times a week for 4 months (16 weeks).

Children from 1 year to 18 years Intron^® A is administered subcutaneously at an initial dose of 3 million IU / m² three times a week (every other day) during the first week of treatment, followed by a dose increase of up to 6 million IU / m² (maximum up to 10 million IU / m²) three times a week (every other day). Duration of treatment 4-6 months (16-24 weeks).

LThe treatment is stopped if there is no positive dynamics (according to the study DNK HBV) after 3-4 months of treatment with the drug in the maximum tolerated dose.

Recommendations for dose adjustment

The dose of the drug should be reduced by 50% with the development of violations from the hematopoiesis system (leukocytes less than 1500 / mm³, granulocytes less than 1000 / mm³ in children and less than 750 / mm³ in adults, platelets less than 100,000 / mm³ in children and less than 50,000 / mm³ in adults).

Therapy should be discontinued in case of severe leukopenia (leukocytes less than 1200 / mm³), neutropenia (granulocytes less than 750 / mm³ in children and less than 500 / mm³ in adults) or thrombocytopenia (platelets less than 70,000 / mm³ in children and less than 30000 / mm³ in adults).

Treatment can be resumed at the previous dose after normalization or return to the initial value of the number of leukocytes, granulocytes and platelets.

Chronic hepatitis C

Adults

Intron^® A used subcutaneously in a dose of 3 million ME 3 times a week (every other day) as a monotherapy or in combination with ribavirin.

Children from 3 to 18 years old

Intron^® A used subcutaneously in a dose of 3 million IU / m² 3 times a week (every other day) in combination with oral administration of ribavirin at a dose of 15 mg / kg daily, dividing this dose into morning and evening.

Treatment of patients with relapse (adults)

Intron^® And they are used only in combination with ribavirin. Based on the results of clinical trials conducted for 6 months, the recommended duration of combined treatment with ribavirin is 6 months.

Treatment of patients who had not previously received therapy (adults)

Effectiveness of Intron^® A increases with simultaneous use with ribavirin. Monotherapy with the drug is carried out only if there are contraindications to the use or intolerance of ribavirin.

Application of Intron^® And in combination with ribavirin

Based on the results of clinical trials conducted for 12 months, the recommended duration of combination therapy with ribavirin is at least 6 months.

In patients with genotype 1 of the virus and a high content of RNA of the virus (according to the results of a pre-treatment study) who do not detect HCV RNA by the end of the first 6 months of therapy, the treatment continues for another 6 months (i.e.e. a total of 12 months). When deciding whether to perform combination therapy for 12 months, other negative prognostic factors should also be taken into account: age over 40, male gender, Pprogressive fibrosis.

In clinical studies, it has been established that in patients who, after 6 months of therapy, still determine HCV RNA, continued treatment does not lead to elimination PHK HCV.

When using Intron^® And in combination with ribavirin, careful monitoring of patients with impaired liver function and patients older than 50 years should be made in connection with the possible development of anemia.

Monotherapy with Intron^® A

The optimal duration of the course of monotherapy with Intron^® And until the end is not established, the recommended duration is from 12 to 18 months.

Intron^® And it is recommended to use for at least 3-4 months, then a determination of HCV RNA should be made. The treatment is then continued only if no HCV RNA is detected.

Treatment of patients who had not previously received therapy (children from 3 to 18 years)

Efficacy and safety of Intron^® And in combination with ribavirin was studied in children who had not previously received therapy for chronic gepatitis S.

Duration of treatment in children

- Genotype 1: the recommended duration of therapy is 1 year. If the virologic response is not achieved in patients at week 12, the probability of obtaining a stable virologic response is extremely low (a negative predictive value is 96%). Thus, in children receiving combined therapy with Intron^® A and ribavirin, it is recommended that treatment be discontinued if, after 12 weeks, a decrease in HCV RNA is less than 2 log10 (100 times) in comparison with the baseline value or when detecting RNA of the virus after 24 weeks of treatment.

- Genotype 2 or 3: the recommended duration of therapy is 24 months.Doses of ribavirin and recommendations for their selection, see the instructions for the use of ribavirin.

Hairy cell leukemia

The recommended dose of Intron^® And for subcutaneous administration to patients after splenectomy and without it is 2 million IU / m² 3 times a week. In most cases, the normalization of one or more hematological indicators occurs after 1-2 months of treatment. To normalize all three parameters of peripheral blood (number of granulocytes, platelets and hemoglobin concentration), up to 6 months of treatment with Intron^® A. This dosing regimen should be adhered to continuously, unless there is a rapid progression of the disease or the occurrence of severe intolerance to the drug.

Chronic myelogenous leukemia

The recommended dose of Intron^® A is from 4 to 5 million IU / m² daily, subcutaneously.

In some cases, the combination of Intron^® And in a dose of 5 million IU / m², applied daily subcutaneously, with cytarabine (Ara-C) at a dose of 20 mg / m² subcutaneously for 10 days per month (maximum daily dose of 40 mg). After normalization of the number of leukocytes, Intron^® A is administered at the maximum tolerated dose (4 to 5 million IU / m² per day) to maintain hematologic remission.

Intron preparation^® And it should be canceled after 8-12 weeks of treatment, if at this time at least partial hematologic remission or clinically significant decrease in the number of leukocytes is not achieved.

Multiple myeloma

Supportive therapy: patients who, as a result of induction therapy, reached the plateau phase (decrease of paraprotein by more than 50%), Intron^® And can be used as a monotherapy - subcutaneously in a dose of 3-5 million IU / m² 3 times a week.

Follicular lymphoma

Intron^® And used in combination with chemotherapy subcutaneously in a dose of 5 million ME 3 times a week (every other day) for 18 months. It is recommended to use the CHOP mode, however, clinical data are available only for the application of the regimen CHVP (combination of cyclophosphamide, doxorubicin, teniposide and prednisolone).

Metastatic kidney cancer

Monotherapy: Intron^® And it is administered subcutaneously in a dose of 3-6-9 million ME (with escalation of the dose) 3 times a week until the progression or development of intolerable toxicity.

Carcinoid tumors

The standard dose of Intron^® A is 5 million ME (3-9 million ME) subcutaneously 3 times a week (every other day). Patients with a common process may require a dose of up to 5 million ME daily.

In surgical treatment with Intron^® And temporarily suspended for the duration of the operation and the recovery period after it. The drug therapy is continued until a clinical response to the treatment is observed.

Malignant melanoma

For the induction of postoperative remission, Intron^® And administered intravenously in a single dose of 20 million IU / m² per day 5 days a week for 4 weeks. The dose thus calculated is added to 50 ml of a 0.9% solution of sodium chloride and administered as an infusion for 20 minutes. Treatment should be started within 56 days after surgery. For maintenance therapy, the recommended single dose is 10 million IU / m², which is administered subcutaneously 3 times a week (every other day) for 48 weeks.

With the development of severe side effects during therapy with Intron^® A (in particular, with a decrease in the number of granulocytes less than 500 / mm³ or increase in ALT / AST activity to values,exceeding the upper limit of the norm 5 times), the drug is temporarily stopped before the normalization of the indices. The treatment is then resumed using a dose reduced by 50%. If intolerance persists, or if the number of granulocytes decreases to 250 / mm³ or ALT activity and / or ACT increases to values exceeding the upper limit of the norm by 10 times, the drug is canceled.

Although the optimal (minimum) dose to achieve an adequate clinical effect not installed, Intron^® And should be used in recommended doses, taking into account their possible correction due to toxic effects, as described above.

Rules for the preparation, introduction and storage of solutions

Before the introduction, it is necessary to visually verify the absence of visible particles of discoloration of the solution. The solution should be colorless and transparent.

The contents of the vial or syringe-pen are used to treat only one patient.

Intron^® A injectable solution in vials can be used for intravenous or subcutaneous administration as soon as the necessary dose is taken from the vial with a sterile syringe for injection (glass or plastic).

Preparation of a solution for intravenous administration

Infusion should be carried out immediately after the preparation of the solution. A vial of any volume can be used to measure the required dose of the drug; with a final concentration of interferon alpha-2b in a solution of sodium chloride should be not less than 0.3 million IU / ml. Appropriate dose of the drug is taken from the vial, add to 50 ml of a 0.9% solution of sodium chloride in a bag of PBX or in a glass vial for infusion and injected intravenously into the drip for 20 minutes.

The vial containing several doses is stored at a temperature of 2 to 8 ° C for 4 weeks.

Notpermissible simultaneous administration of other drugs with the drug Intron^® A.

The use of other solvents is unacceptable.

Intron^® A injectable solution in syringe pens injected subcutaneously immediately after attaching the needle for injection and recruiting the required dose.

The drug should be taken from the refrigerator 30 minutes before the injection, so that the solution warmed to room temperature (up to 25 ° C). The introduction of each dose should be followed by a new needle. After injection, the needle should be discarded and the handle immediately placed in the refrigerator.

The used vials and syringe-pens are disposed of in accordance with local requirements. After opening the package, the drug is recommended to be used for 4 weeks when stored at a temperature of 2 to 8 ° C.

Side effects:

Side effects of ribavirin when used concomitantly with Intron^® And in patients with chronic hepatitis C are indicated in the instructions for the medical use of ribavirin.

In clinical studies conducted with a wide range of indications and with a large dose range (from 6 million IU / m² a week with hairy cell leukemia up to 100 million IU / m² per week with melanoma), the most common adverse events were fever, fatigue, headache, myalgia. Fever and fatigue often passed 72 hours after discontinuation of the drug.

Adults

In clinical studies in patients with hepatitis C, Intron^® And as a monotherapy or in combination with ribavirin for 1 year. All patients radiated Intron^® And in a dose of 3 million ME 3 times a week.

Table 2 shows the incidence of adverse events (associated with therapy), obtained during clinical trials for 1 year in untreated patients.In general, the observed adverse events were mild or moderate.

The undesirable reactions listed in the table are given on the basis of the clinical trial data and the post-registration period of the drug use. These reactions are listed in the table according to the system-organ class and frequency (very frequent (≥1 / 10), frequent (≥1 / 100 and <1/10), infrequent (≥1 / 1000 and <1/100), rare (≥1 / 10000 and <1/1000) and very rare (<1/10000), is unknown (the frequency can not be estimated based on available data)). In each row, undesirable phenomena are arranged in order of decreasing severity.

Table 2. Unwanted reactions that were reported during clinical trials andor during the post-marketing period when using Intron^® And in the form of monotherapy or in combination with ribavirin

Class system / organ	HifReactive reactions
Infectious and parasitic diseases
Very Frequent:	Pharyngitis , viral infection
Frequent:	Bronchitis, sinusitis, infection caused by persistent herpes simplex virus, rhinitis
Infrequent:	Bacterial infection
Rare:	Pneumonia **, septicemia
Violations of the blood and lymphatic system
Very Frequent:	Leukopenia
Frequent:	Thrombocytopenia, lymphadenopathy, lymphopenia
Very rare:	Aplastic anemia
Unknown:	True erythrocyte aplasia, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura
Immune system disorders **
Very rare:	Sarcoidosis, worsening of sarcoidosis
Unknown:	Systemic lupus erythematosus, vasculitis, rheumatoid arthritis (appearance or deterioration of the course), Vogt-Koyanagi-Harada syndrome, immediate-type hypersensitivity reactions, including hives, angioedema, bronchospasm, anaphylaxis **
Disorders from the endocrine system
Frequent:	Hypothyroidism , hyperthyroidism
Very rare:	Diabetes mellitus, worsening of the course of diabetes mellitus
Disorders from the metabolism and nutrition
Very Frequent:	Anorexia
Frequent:	Hypocalcemia, dehydration, hyperuricemia, thirst
Very rare:	Hyperglycemia, hypertriglyceridemia **, increased appetite
Mental Disorders **
Very Frequent:	Depression, insomnia, anxiety, emotional lability, * excitation, nervousness
Frequent:	Confusion, sleep disturbance, decreased libido
Rare:	Thoughts of suicide
Very rare:	Suicide, suicide attempts, aggressive behavior (sometimes directed at others), psychosis including hallucinations
Unknown:	Thoughts about murder, altered mental status **, mania, bipolar disorders
Nervous system disorders **
Very Frequent:	Dizziness, headache, impaired concentration, dry mouth
Frequent:	Tremor, paresthesia, hypoesthesia, migraine, flushing, somnolence, taste perversion
Infrequent:	Perheumatic neuropathy
Very rare:	Cerebrovascular bleeding, cerebrovascular ischemia, seizures, impaired consciousness, encephalopathy
Unknown:	Mononeuropathy, coma **
Disturbances on the part of the organ of sight
Very Frequent:	Blurred vision
Frequent:	Conjunctivitis, impaired vision, impairment of the lacrimal gland, pain in the eyes
Rare:	bleeding in the retina, retinopathy (including papilledema), occlusion of the vein or artery retina, optic neuritis, papilledema, decreased visual acuity or limitation of zeros, vatopodobnye spots **
Unknown:	Serous retinal detachment
Hearing disorders and labyrinthine disorders
Frequent:	Vertigo, tinnitus
Very rare:	Hearing loss, hearing loss
Heart Disease
Frequent:	Palpitation, tachycardia
Rare:	Cardiomyopathy
Very rare:	Myocardial infarction, ischemia of the heart
Unknown:	Chronic heart failure, pericardial effusion, arrhythmia
Vascular disorders
Frequent:	Increased blood pressure
Very rare:	Peripheral ischemia, lowering of arterial pressure **
Disturbances from the respiratory system, chest and mediastinal organs
Very Frequent:	Dyspnea , cough
Frequent:	Nasal bleeding, respiratory disorders, nasal congestion, rhinorrhea, non-productive cough
Very rare:	Pulmonary infiltrate , pneumonitis , pulmonary fibrosis
Disorders from the gastrointestinal tract
Very Frequent:	Nausea / vomiting, abdominal pain, diarrhea, stomatitis, dyspepsia
HSteady:	Ulcerative stomatitis, pain in the right upper quadrant of the abdomen, glossitis, gingivitis, constipation, loose stools
Very rare:	Pancreatitis, ischemic colitis, ulcerative colitis, bleeding from the gums
Unknown:	Disturbance of the periodontium, a violation of the teeth **
Disturbances from the liver and bile ducts
Frequent:	Hepatomegaly
Very rare:	Hepatotoxicity (including fatal)
Disturbances from the skin and subcutaneous tissues
Very Frequent:	Alopecia, itching , dry skin , rash *, increased sweating
HSteady:	Psoriasis (appearance or deterioration of the flow) **, maculopapular rash, erythematous rash, eczema, erythema, dyskinesia
Very rare:	Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme
Disturbances from musculoskeletal and connective tissue
Very Frequent:	Myalgia, arthralgia, musculoskeletal pain
Frequent:	Arthritis
Very rare:	Rhabdomyolysis, myositis, leg cramps, back pain
Disorders from the kidneys and urinary tract
Frequent:	Frequent urination
Very rare:	Renal failure, nephrotic syndrome
Violations of the genitals and mammary gland
Frequent:	Amenorrhea, pain in the mammary gland, dysmenorrhea, menorrhagia, menstruation, violation of the vagina
General disorders and disorders at the site of administration
Very Frequent:	Inflammation at the injection site, reaction at the injection site , fatigue, chills, fever , flu-like symptoms *, asthenia, irritability, chest pain, malaise
Frequent:	Pain at the injection site
Very rare:	HEdema at the injection site, edema of the face
Laboratory and instrumental data
Very Frequent:	Weight loss

^* These adverse events were frequent in patients receiving ionotherapy with Intron ® A.

* * See section "Special instructions".

These adverse events were also observed with monotherapy with Intron ® A.

The adverse events observed in patients with viral hepatitis C are consistent with those observed with the use of Intron ® A on other indications with some dose-related increase in the frequency of development. For example, in the study of adjuvant therapy with high doses of Intron® A in patients with melanoma, the frequency of fatigue, fever, myalgia, neutropenia / anemia, anorexia, nausea, vomiting, diarrhea, chills, flu-like symptoms, depression, alopecia, taste distortion and dizziness was higher than in studies in patients with hepatitis C.The severity also increased with therapy at high doses (WHO grades 3 and 4 were observed in 66% and 14% of patients, respectively) compared with usually mild or moderate severity with low-dose therapy. Adverse events were usually controlled by a dose change.

Undesirable reactions from the cardiovascular system (CCC), in particular, arrhythmia, are most likely associated with a previous CAS disease or previous therapy with drugs that have cardiotoxic action. Cardiomyopathy, which could be reversible after discontinuation of therapy interferon alfa in patients who did not have a history of SSS in the history was rarely observed (see section "Special instructions").

When alpha interferons were used, a wide range of abnormalities were reported, including thyroid disorders, systemic lupus erythematosus, development or deterioration of rheumatoid arthritis, idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura, vasculitis, and neuropathies (including mononeuropathies). section "Special instructions").

Clinically significant changes in laboratory parameters (more often observed with the use of the drug in doses more than 10 million ME per day) included a decrease in the number of granulocytes and leukocytes, a decrease in the hemoglobin concentration and platelet count, an increase in the activity of alkaline phosphatase (LF), lactate dehydrogenase (LDH), serum creatinine and urea nitrogen. There were reported cases of mild pancytopenia, which was usually reversible. There was an increase in ALT activity and ACT in the blood serum when the drug is used in patients without hepatitis, as well as in some patients with chronic hepatitis B in the absence of HBV DNA.

Children from 3 to 18 years old

Chronic hepatitis C - combination therapy with ribavirin

In clinical studies with the participation of 118 children (aged 3 to 16 years) therapy in connection with adverse reactions stopped in 6% of patients. In general, the profile of adverse reactions in children was comparable to that of adults, but for this group of patients there is a specific undesirable reaction - growth retardation, which is expressed in a decrease in the percentile growth (on average by 9 percentile) and weight percentile (on average by 13 percentile) .After five years of follow-up after therapy in children, the mean height was 44 percentile, below the growth median in the general population and less than the mean percentile of growth before therapy (48 percentile). In 20 out of 97 children (21%), the decrease in the percentile of growth was more than 15, in 10 of them the decrease was more than 30 percentile from the beginning of therapy to the end of the observation (up to 5 years). For 14 of these patients, the total growth in adulthood (10-12 years after the end of therapy) is known, which showed that 12 patients had a growth deficit (more than 15 percentile). During combined therapy for up to 48 weeks with Intron^®A and ribavirin observed growth retardation, as a result of which the growth of some patients was lower than expected in adulthood. In particular, a decrease in the average growth percentile from the baseline value at the end of the long-term follow-up period was most pronounced in the treatment of pre-pubertal children.

Among children who received combination therapy with interferon alpha-2b and ribavirin, suicidal ideation or suicide attempts were more frequent than in adult patients (2.4% and 1%, respectively) during therapy and for 6 months after discontinuation of therapy.Just like in adults, children had other mental disorders (eg, depression, emotional stability, drowsiness). Among infants, irregularities at the injection site, fever, anorexia, vomiting, and emotional lability were more common than in adult patients. The dose was changed in 30% of patients, most often due to anemia and neutropenia.

The undesired reactions listed in Table 3 are based on 2 clinical trials in children. These reactions are listed in the table according to the system-organ class and frequency (very frequent (≥1 / 10), frequent (≥1 / 100 and <1/10)). In each row, undesirable phenomena are arranged in order of decreasing severity.

Table 3. Undesirable reactions reported in clinical trials in children with Intron® A in combination with ribavirin

Class system / organ	Undesirable reactions
Infectious and parasitic diseases
Very Frequent:	Viral infection, pharyngitis
Frequent:	Fungal infection, bacterial infection, pulmonary infection, otitis media, tooth abscess, infection caused by the herpes simplex virus, urinary tract infection, vaginitis, gastroenteritis
Dmalignant, malignant and unspecified neoplasms (includingcysts and polyps)
Frequent:	Neoplasms (unspecified)
Violations of the blood and lymphatic system
Very Frequent:	Anemia, neutropenia
Frequent:	Thrombocytopenia, lymphadenopathy
Disorders from the endocrine system
Very Frequent:	Hypothyroidism *
Frequent:	Hyperthyroidism, virilism
Disorders from the metabolism and nutrition
Very Frequent:	Anorexia
Frequent:	Hypertriglyceridemia *, hyperuricemia, increased appetite
Mental disorders *
Very Frequent:	Depression, emotional lability, insomnia
Frequent:	Thoughts of suicide, aggression, confusion, impaired behavior, agitation, somnambulism, anxiety, nervousness, sleep disturbance, unusual dreams, apathy
Disturbances from the nervous system *
Very Frequent:	Headache, dizziness
Frequent:	Hyperkinesia, tremor, dysphonia, paresthesia, hypesthesia, hyperesthesia, impaired concentration, drowsiness
Frequent:
Infringements from organs of vision
Frequent:	Conjunctivitis, pain in the eyes, impaired vision, impaired tear gland
Vascular disorders
Frequent:	"Tides", pallor
Disturbances from the respiratory system, chest and mediastinal organs
HSteady:	Shortness of breath, tachypnea, epistaxis, cough, nasal congestion, irritation in the nasal cavity, rhinorrhea, sneezing
Disorders from the gastrointestinal tract
Very Frequent:	Diarrhea, vomiting, nausea, abdominal pain
Frequent:	Ulcers in the oral cavity, ulcerative stomatitis, stomatitis, pain in the right upper quadrant of the abdomen, dyspepsia, glossitis, gastroesophageal reflux disease, rectal disorders, gastrointestinal disturbances, constipation, loose stools, toothache, disturbances from the side teeth
*Disturbances from the liver and bile ducts*
Frequent:	Impaired liver function
Disturbances from the skin and subcutaneous tissues
Very Frequent:	Alopecia, rash
Frequent:	Photosensitivity reactions, maculopapular rash, eczema, acne, skin disorders, nail abnormalities, skin discoloration, itching, dry skin, erythema, bruising, sweating increase
Disturbances from musculoskeletal and connective tissue
Very Frequent:	Arthralgia, myalgia, musculoskeletal pain
Disorders from the kidneys and urinary tract
Frequent:	Enuresis, urination disorder, urinary incontinence
Violations of the genitals and mammary gland
Frequent:	Women: amenorrhea, menorrhagia, violation of menstruation, violation of the vagina Men: pain in the testicles
General disorders and disorders at the site of administration
Very Frequent:	Inflammation at the injection site, reaction at the injection site, fatigue, chills, fever , flu-like symptoms , malaise, irritability
Frequent:	Pain in the chest, asthenia, swelling, pain at the injection site
Laboratory and instrumental data
Very Frequent:	Growth retardation (decrease in height and / or body weight within the age limit) *
Trauma, intoxication and complications of manipulation
Frequent:	Damage to the skin

* See section "Special instructions".

Overdose:

To date, no cases of overdose, accompanied by any acute clinical symptoms. However, as with an overdose of any medication, symptomatic therapy should be performed with monitoring the functions of vital organs and with regular monitoring of the patient's condition.

Interaction:

Use with caution the preparation of Intron ® A concomitantly with opioid analgesics, hypnotics and sedatives.

The interaction between the drug Intron ® A and other drugs is not fully understood.

It should be used with caution in the preparation of Intron ® A with drugs that potentially have a myelosuppressive effect.

Interferons can affect oxidative metabolic processes. This should be taken into account when used simultaneously with drugs metabolized by oxidation, for example, with xanthine derivatives (aminophylline and theophylline). When using the drug Intron ® A with xanthine derivatives, it is necessary to control the serum concentration of theophylline and, if necessary, change the dosage regimen.

In patients receiving interferon alfa therapy (including Intron ® A), in rare cases, pulmonary infiltrates, pneumonitis and pneumonia (in some cases with a fatal outcome) of unclear etiology were observed. Similar symptoms were more often observed against a background of simultaneous application with "shosayikoto" - the means of Chinese traditional medicine of plant origin (see section "Special instructions").

The use of Intron ® A in combination with chemotherapeutic drugs (cytarabine, teniposide, cyclophosphamide, doxorubicin) increases the risk of developing toxic effects (contributes to increasing their severity and increasing the duration) (see section "Special instructions").

When using Intron ® A in combination with ribavirin, the instructions for the use of ribavirin should also be followed.

A clinical study comparing the combined use of telbivudine (600 mg daily) with pegylated interferon alpha-2a (180 μg subcutaneously, once a week) showed that the use of this combination is associated with an increased risk of peripheral neuropathy. The mechanism of this phenomenon is unknown. In addition, the safety and efficacy of telbivudine in combination with interferons for the treatment of chronic hepatitis B have not been confirmed. The combined use of Intron ® A and telbivudine is contraindicated.

Special instructions:

Violations of the psyche and violations of the central nervous system (CNS)

Serious violations by the Central CommitteeC, in particular depression, suicidal thoughts and suicide attempts,Some patients were treated with Intron ® A, and after discontinuing therapy (mainly for 6 months).

Among children who received combined therapy with Intron ® A and ribavirin, suicidal ideation or suicide attempts were more frequent than in adult patients (2.4% and 1%, respectively) during therapy and within 6 months after discontinuation of treatment. Just like in adults, children had other mental disorders (depression, emotional instability, drowsiness).

Other CNS disorders, including aggressive behavior (in some cases directed at other people, for example, thoughts of murder), bipolar disorders, mania, confusion and changes in mental status have been observed in patients receiving interferon alfa therapy.

Care should be taken to monitor patients for any signs or symptoms of mental disorders. If such symptoms appear, you should evaluate the potential hazard and consider the need for drug therapy for these conditions. With the persistence or worsening of symptoms of mental disorders or the appearance of suicidal thoughts or mAfter the murder it is recommended to stop therapy with Intron ® A and continue monitoring the patient, if necessary, to consult a psychiatrist.

Patients with serious mental disorders, at t.in the anamnesis

If therapy using interferons alpha-2b it is recognized necessary in adult patients with serious mental disorders (including history), it should be started only if appropriate individual screening and therapy for mental disorders are carried out.

Use of interferon alfa-2b in children c serious violations of the psyche (including in the anamnesis) is contraindicated.

Patients who use narcotic substances

In patients with HCV who use narcotic substances (alcohol, marijuana, etc.), the risk of developing mental disorders (or worsening of the current) increases with interferon alpha therapy. If such patients with interferon alfa therapy are necessary, then before the initiation of therapy, the presence of concomitant mental illness and the risk of using drugs should be carefully evaluated and adequate therapy should be conducted.If necessary, a specialist in the field of mental illness or drug addiction should conduct screening, therapy and monitoring of such patients. Careful monitoring of such patients during and after completion of interferon therapy is necessary. Early intervention is recommended to prevent the recurrence or development of mental disorders and drug use.

Children from 3 to 18 years: influence on growth and development (chronic hepatitis C)

In the course of a course of monotherapy with interferons (pegylated or not) or combined therapy with ribavirin for up to 48 weeks in children, frequent undesirable effects were weight loss and stunting. Long-term follow-up data for children who received combination therapy with interferon and ribavirin also indicated significant growth retardation (a decrease in the percentile of growth by more than 15 percentile compared with baseline) in 21% of childrenn= 20), despite the fact that the treatment was terminated more than 5 years ago. For 14 of these patients, the total growth in adulthood (10-12 years after the end of therapy) is known, which showed that 12 patients had a growth deficit (more than 15 percentile).

Assessment of the benefit / risk ratio in children in each case

The expected benefit of treatment should be carefully weighed against all risks of use in children identified in clinical trials.

- It is important to consider that combination therapy causes growth retardation, which in some patients has led to a reduction in the total growth in adulthood.

- Risk should be assessed taking into account the features of the course of the disease in the child, such as signs of progression of the disease (especially fibrosis), the presence of co-morbidities that may affect the progression of the disease (eg, co-infection with HIV), and factors affecting the prognosis of response to therapy (HCV genotype, viral load). If possible, the child should be treated after a puberty growth jump to reduce the risk of growth retardation. There is no evidence of a long-term effect on puberty.

Hypersensitivity reactions

In the case of the development of immediate-type hypersensitivity reactions (urticaria, angioedema, bronchospasm, anaphylaxis), when Intron® A is used, the drug should be immediately discontinued and appropriate treatment initiated.

Transient skin rash does not require discontinuation of treatment.

Deterioration of blood clotting and impaired hepatic function

With the development of severe and moderate side effects, it may be necessary to adjust the dosage regimen or, in some cases, discontinue therapy. In patients with chronic hepatitis, the use of Intron® A should be discontinued if the blood coagulability (increase in duration) worsens, which may indicate liver damage.

When using the drug Intron ® A in patients with cirrhosis of the liver, the risk of decompensation of liver function and death is increased.

If there are signs of a liver function disorder against the background of the use of the Intron® A preparation, careful monitoring of the patient should be established and, in case of a progression of the symptoms, cancel the drug.

It is necessary to monitor liver function by determining serum bilirubin, ALT, ACT, APF and LDH at 2, 8 and 12 weeks after initiation of therapy and then every 6 months during therapy with Intron A. It is necessary to completely stop therapy with Intron ® A in case of severe liver damage (grade 3) or liver decompensation on the Child-Pugh scale> 6 (class B and C)).

Arterial hypotension

Against the background of the use of the drug Intron ® A or within 2 days after the withdrawal of treatment, it is possible to develop arterial hypotension, which may require application with appropriate therapy.

The need for adequate hydration

When therapy with Intron ® A is necessary to ensure adequate hydration of the body, tk. in some cases, arterial hypotension may develop as a result of a decrease in the volume of circulating blood (BCC). Additional fluid may be required.

Fever

Fever may be a manifestation of influenza-like syndrome, often encountered with the use of interferon, but other causes of its occurrence should be excluded.

Patients with severe illnesses

The drug Intron ® A should be used with caution in patients with severe chronic diseases, such as a history of lung disease (eg, chronic obstructive pulmonary disease), diabetes mellitus with a tendency to ketoacidosis. Special caution is required when using the drug in patients with bleeding disorders (including thrombophlebitis, pulmonary embolism), as well as with pronounced myelosuppression.

Pulmonary diseases

In patients receiving interferon alfa therapy (including Intron ® A), in rare cases, pulmonary infiltrates, pneumonitis and pneumonia (in some cases with fatal outcome) of unclear etiology are observed. Similar symptoms are more common against the background of simultaneous application with "shosayikoto" - the means of Chinese traditional medicine of plant origin. Each patient with a cough, fever, dyspnea, or other symptoms on the part of the respiratory system should perform an x-ray examination of the chest. If infiltrates or other pulmonary function disorders are identified, the patient should be carefully monitored and, if necessary, abolished by interferon alfa therapy. These adverse events are more common in patients with chronic hepatitis C who are receiving interferon alfa therapy, but are also reported in patients with oncological diseases receiving interferon alfa therapy. Timely withdrawal of interferon alfa and the use of GCS contribute to the management of pulmonary syndromes.

Unwanted phenomena from the side of the organ of vision

Impaired vision (including bleeding, cotton spots, serous retinal detachment, occlusion of veins and arteries) is reported rarely after interferon alpha therapy. All patients need to have an ophthalmological examination before starting therapy. Each patient receiving Intron ® A should undergo an ophthalmological examination in case of complaints of a change in acuity or field of vision, or other ophthalmic symptoms.

Patients with diseases in which retinal changes can occur, such as diabetes mellitus or hypertension, are recommended to undergo an ophthalmic examination regularly during therapy with Intron®. When there is or worsening of vision disorders, consideration should be given to discontinuing therapy with Intron ® A.

Impaired consciousness, coma, encephalopathy

In some patients, especially the elderly, who received the drug in high doses, there was a violation of consciousness, coma, including cases of encephalopathy. Although these effects are usually reversible, some patients require up to 3 weeks to terminate them.Very rarely, the use of Intron ® A in high doses in patients developed convulsions. In case of ineffectiveness of dose reduction and / or drug correction of these disorders, it is necessary to resolve the issue of discontinuing therapy with Intron ® A.

Disorders from the cardiovascular system

Patients with a history of cardiovascular disease (myocardial infarction, chronic heart failure, arrhythmias) require careful medical supervision with the use of the drug Intron ® A. Patients with heart disease and / or late stages of oncological diseases are recommended to carry out ECG before and during therapy with the drug Intron® A.

Emerging arrhythmias (mostly supraventricular), as a rule, are amenable to standard therapy, but may require the withdrawal of the drug Intron ® A. There is no data on the use of the drug in children with a history of cardiovascular disease.

Hypertriglyceridemia

Due to the fact that cases of the development of hypertriglyceridemia or worsening of hypertriglyceridemia are reported (in some cases, severe), lipid content control is recommended.

Psoriasis and sarcoidosis

The drug Intron® A is not recommended for patients with psoriasis and sarcoidosis due to the possibility of exacerbation of these diseases, except when the intended benefit of the treatment justifies the potential risk.

Kidney and liver transplantation

Preliminary data suggest that interferon alpha therapy may increase the risk of kidney transplant rejection. Liver transplant rejection has also been reported.

Autoantibodies and autoimmune diseases

Etcand the treatment of alpha interferons, the appearance of autoantibodies and the occurrence of autoimmune diseases have been observed. The risk of developing these phenomena is higher in patients with an existing predisposition to autoimmune diseases. When symptoms similar to manifestations of autoimmune diseases occur, a thorough examination of the patient should be made and the possibility of continuing therapy with interferon should be assessed.

In patients with chronic hepatitis C who are receiving interferon therapy, cases of Vogt-Koyanagi-Harada syndrome (FKH) have been reported. This syndrome is a granulomatous inflammatory disease affecting the organ of vision, hearing, soft membranes and skin.In case of suspicion of syndrome PKH should stop antiviral therapy and consider the need for glucocorticosteroids.

Simultaneous chemotherapy

The use of Intron ® A in combination with chemotherapeutic drugs (cytarabine, teniposide, cyclophosphamide, doxorubicin) increases the risk of toxic effects (contributes to their increased severity and duration), which can endanger life or lead to death (due to increased toxicity in the joint use of drugs).

The most frequent toxic effects that can endanger life or lead to death are mucositis, diarrhea, neutropenia, impaired renal function and electrolyte balance. Given the risk and severity of toxic effects, it is necessary to carefully select doses of Intron ® A and chemotherapeutic drugs. Simultaneous use with hydroxyurea can increase the frequency and severity of skin vasculitis.

Patients with chronic hepatitis C

Combination therapy with ribavirin

When using Intron ® A in combination with ribavirin, the instructions for the use of ribavirin should also be followed.

In clinical studies, all patients underwent liver biopsy before starting therapy with Intron®. However, in certain cases (in patients with genotypes 2 and 3 of the hepatitis virus) treatment can be initiated without histological confirmation of the diagnosis. When deciding whether pre-biopsies should be carried out, existing standards of treatment for such patients should be followed.

Montotherapy

When monotherapy in adult patients with the drug Intron ® A, there was rarely a violation of the thyroid gland - hypothyroidism or hyperthyroidism. In clinical trials, 2.8% of patients receiving Intron ® A developed thyroid disorders. These disorders were controlled by appropriate therapy. The mechanism of the development of thyroid dysfunction in the use of the drug Intron ® A is unknown.

Before starting therapy with Intron ® A, the concentration of thyroid-stimulating hormone (TSH) should be determined. If any violation is detected, appropriate treatment should be carried out.If the drug therapy allows to maintain the concentration of TSH within the limits of the norm, the use of the drug Intron ® A is possible. If during treatment there was a suspicion of thyroid dysfunction, the concentration of TSH should be determined. With disrupted thyroid function, treatment with Intron® A can be continued if the concentration of TSH can be maintained within normal limits with the help of drug therapy. The withdrawal of Intron ® A did not lead to the restoration of thyroid function.

Additional monitoring of the thyroid gland in children

Approximately 12% of children who received interferon alfa-2 therapyb in combination with ribavirin, the concentration of TSH increased. In the other 4% the concentration of TSH temporarily decreased to the lower limit of the norm. Before the start of therapy with Intron ® A, the concentration of TSH should be determined. If any violation is detected, appropriate treatment should be carried out. If the drug therapy allows to maintain the concentration of TSH within the limits of the norm, the use of the drug Intron ® A is possible.

It was reported on the development of thyroid dysfunction during combined therapy with interferon alpha-2b and ribavirin.If such violations are detected, the nature of the thyroid gland lesion should be established and appropriate therapy should be carried out. Children should check the concentration of TSH every 3 months.

Co-infection of HCV and HIV

In patients infected with both HCV and HIV and receiving highly active antiretroviral therapy (HAART), the risk of developing lactic acidosis may be increased. In this regard, when using the drug Intron ® A and ribavirin in addition to HAART should be more careful. In patients receiving combination therapy with Intron ® A, ribavirin and zidovudine, the risk of developing anemia is increased.

In the presence of formed cirrhosis, the risk of decompensating liver function and death in patients infected with both HCV m and HIV receiving HAART is increased. The use of interferons alpha (without ribavirin or in combination with ribavirin) in addition to ongoing therapy in this group of patients may increase this risk.

Dental and periodontal disorders

Dental and periodontal disorders that can lead to tooth loss have been reported in patients receiving combination therapy with Intron ® A and ribavirin.Dry mouth can lead to damage to the teeth and mucous membranes of the mouth during long-term combined therapy with Intron ® A and ribavirin. Patients should brush their teeth 2 times a day and undergo regular dental check-ups. Some patients may experience vomiting. If it occurs, patients should be thoroughly rinsed.

Laboratory test data

Before starting treatment with Intron ® A and periodically during therapy, all patients should undergo a general clinical blood test (with the definition of the leukocyte formula and platelet count), a biochemical blood test, including the determination of the concentration of electrolytes, hepatic enzymes, serum bilirubin, whey protein and serum creatinine .

During the therapy of patients with hepatitis B or C, the following scheme for monitoring laboratory indicators is recommended: 1, 2, 4, 8, 12, 16 weeks and then one month during therapy. If the activity of ALT is increased 2 or more times from the initial value, treatment with Intron® A can be continued under the condition that there are no signs of hepatic insufficiency.In this case, the determination of prothrombin time, activity of ALT, ALP, albumin and bilirubin concentration should be carried out every 2 weeks.

In patients with malignant melanoma, liver function and the number of leukocytes should be monitored every week during the first phase of treatment (remission induction) and monthly during maintenance therapy.

When using Intron ® A in combination with ribavirin in patients with impaired renal function and over the age of 50, careful monitoring should be made after them in connection with a possible risk of anemia.

Further information on excipients

The drug contains less than 1 mmol sodium (23 mg) per 0.5 ml solution, that is, practically "not contains sodium. "

Effect on the ability to drive transp. cf. and fur:

Patients should be warned about the possibility of developing weakness, drowsiness, impaired consciousness on the background of therapy with Intron^®A and recommend avoiding the management of vehicles and mechanisms.

Form release / dosage:

Solution for intravenous and subcutaneous administration, 18 million IU, 25 million IU, 30 million IU and 60 million IU.

Packaging:

The drug in vials:

For 18 million IU / 3 ml (6 doses of 3 million ME) or 25 million IU / 2.5 mL (5 doses of 5 million ME) in bottles of colorless glass.

For 1 bottle in a plastic pallet along with instructions for use in a cardboard bundle.

The drug in syringe-pens:

For 18 million IU / 1.2 ml (6 doses of 3 million ME), 30 million IU / 1.2 mL (6 doses of 5 million ME) or 60 million IU / 1.2 mL (6 doses of 10 million ME) in syringe pens.

1 syringe pen complete with 6 needles and 6 napkins (for disinfecting the skin at the injection site) in a plastic pallet along with the instruction for use and a leaflet (recommendations for preparing and performing subcutaneous injection with a syringe pen) in a cardboard bundle .

Storage conditions:

At a temperature of 2 to 8 ° C. Do not freeze.

Keep out of the reach of children.

Transportation conditions

At a temperature of 2 to 8 ° C.

Transportation at a temperature of up to 25 ° C is allowed for not more than 7 days. During this period, the drug can be returned to further storage in the refrigerator (storage temperature from 2 to 8 ° C), the shelf life of the drug is preserved. If the drug has not been used and has not been returned to storage in the refrigerator for 7 days, it can not be used further.

After opening the vial or packing of the syringe pen, the chemical and physical stability of the preparation,the microbiological purity of the solution and the suitability of the preparation for use are maintained for 28 days when stored at a temperature of 2 to 8 ° C.

Shelf life:

The drug in vials: 2 of the year.

The drug in the syringe-pens: 1 year 3 months.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014632 / 01

Date of registration:15.01.2009 / 04.02.2015

Expiration Date:Unlimited

The owner of the registration certificate:Schering-Plau N. Labo.Schering-Plau N. Labo. Belgium

Manufacturer: & nbsp

SCHERING-PLOUGH (Brinny) Co. Ireland

SCHERING-PLOUGH LABO, N.V. Belgium