Alfaferon - instructions for use, dose, side effects, contraindications

Excipients: sodium chloride 8.00 mg, potassium chloride 0.20 mg, potassium dihydrogen phosphate 0.12 mg, sodium hydrogen phosphate dodecahydrate 0.91 mg, water for injection q.s up to 1 ml.

Description:Transparent colorless or light yellow solution.

Pharmacotherapeutic group:Cytokine

ATX: & nbsp

L.03.A.B.01 Interferon alfa

Pharmacodynamics:

Antiviral action. Linking to specific receptors on the surface of yet uninfected cells, interferon alpha increases their resistance to virus penetration, promotes education specific enzymes such as: oligoadenylate synthetase, which in turn activates endoribonuclease, which destroys viral RNA and thereby prevents its replication; protein kinase, phosphorylation protein eIF-2 (eukaryotic translation initiation factor), while eIF-2, forming an inactive complex with the eIF2B factor, disrupts the intracellular synthesis of proteins; the activation of protein kinase induces the induction of another RNase cell enzyme that destroys RNA, which blocks intracellular protein synthesis and leads to the death of the virus and virus-infected host cells.

Interferons induce the formation of proteins known collectively as interferon-stimulated genes that are involved in the destruction of viruses and prevent the proliferation of viruses through the activation of the p53 protein. The P53 protein destroys the virus-infected cells through the mechanism of apoptosis.

Interferons activate the molecules of the main histocompatibility complex of MHCGI and MHCG II and immunoproteasome. An increase in the expression of the genes of HMG1 and MCHC II improves the presentation of viral peptides to cytotoxic T-cells and T-helper cells, respectively; T-helpers produce cytokines that coordinate the interaction of the cells of the immune system.Immunoproteasoma promotes the recognition and destruction of virus-infected cells with T cells.

In this way, interferon alfa has a direct effect not on viruses, but on still uninfected cells, causing a number of changes in them that ensure the ability of the cell to resist the virus.

Antiproliferative action Alfaferon is realized through the activation of the p53 protein.

Immunomodulating The effect of Alfaferon is expressed in direct stimulation of the activity of macrophages and NK cells (natural killer cells) and occurs as follows: macrophages are involved in the process of antigen presentation to immunocompetent cells, and NK cells participate in the immune response of the organism to tumor cells.

Pharmacokinetics:

With intravenous (iv) injection, a high concentration of interferon alfa is rapidly created in the blood and decreases below the minimum detectable value (less than 0.01%) within 24 hours. With intramuscular (IM) and subcutaneous (SC) administration, the concentration of the drug remains in the blood for a longer period.

With the / m introduction, the drug is absorbed from the injection site almost completely.The maximum concentration in the plasma is determined after 1-6 hours, the stable concentration is held for 6-12 hours, followed by a gradual decrease until the drug disappears completely after 18-36 hours. With n / to the introduction of the drug is slowly absorbed through the lymphatic vessels.

Interferon alfa penetrates the blood-brain barrier in a small amount and in liquor it is detected in the minimum concentration (from the administered dose of the drug).

Circulating interferon alfa filtered through the glomerulus of the kidney, then reabsorbed in the proximal tubules of the kidney, undergoing proteolytic degradation by lysosomal enzymes to amino acids. In a small amount, unchanged inferferone alfa and degradation products (peptides) are excreted in the urine. Half-life is about 6 hours.

In patients with normal liver and kidney function, there is no significant cumulation of the drug, even with its long-term use.

Indications:

Neoplastic processes:

- hairy cell leukemia (tricholeukemia)

- multiple myeloma

- non-Hodgkin's lymphoma

- mushroom mycosis

- chronic myelogenous leukemia

- Kalosha sarcoma in patients with acquired immunodeficiency syndrome (AIDS) who have no history of opportunistic infections

- kidney cancer

- malignant melanoma

Viral diseases

- chronic active hepatitis B with the presence of viral replication markers such as HBV DNA, viral DNA polymerase or HBeAg.

- chronic hepatitis C in patients with high activity of "hepatic" enzymes, but without liver failure.

- genital warts.

Contraindications:

- Hypersensitivity to interferon alpha or to any other component of the drug

- severe cardiovascular diseases (arrhythmia, cardiovascular failure)

- severe impairment of liver and / or kidney function

- chronic hepatitis complicated by cirrhosis of the liver with the phenomena of liver failure

- chronic hepatitis in patients receiving or recently received immunosuppressant treatment (except for the condition after the recent abolition of short-term glucocorticosteroid therapy)

- autoimmune hepatitis

- epilepsy and / or dysfunction of the central nervous system or severe mental disorders (including in the anamnesis)

- diseases of the thyroid gland uncontrollable by standard therapy.

A study of the safety and efficacy of Alfaferon in children under 18 years of age has not been conducted.

Carefully:Recently suffered myocardial infarction, blood clotting disorder (including thrombocytopenia), suppression of bone marrow hematopoiesis, arterial hypotension and also with the simultaneous use of hypnotics, sedatives and narcotic analgesics.

Pregnancy and lactation:

During pregnancy, Alfaferon is prescribed only if the expected effect for the mother exceeds the potential risk to the fetus.

It is not known whether the drug is excreted in breast milk. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration:

The dosage regimen is established taking into account the form of the disease and changes during the treatment depending on the individual reaction of the patient.

The drug is given in / m or s / c. When thrombocytopenia, with a platelet count of less than 50,000 / μl, it should be administered sc. High doses of the drug (9 million IU / day or more) should be administered intravenously drip slowly (within 30-60 minutes). To do this, the required dose of the drug is diluted in 50 ml of physiological solution.

Hairy cell leukemia (tricholeukemia): the recommended initial dose of 3 million ME per day is given in / m or p / to 3 times a week for 6 months. If the therapy is ineffective, the drug should be discontinued. If there is a positive trend, then the treatment should continue until hematological parameters improve, and after achieving the stability of the indicators, therapy should be continued for another 3 months.

Multiple myeloma: initial dose of 3 million ME Enter in / m or p / to 3 times a week. If the drug is well tolerated, the dose is increased every week to a maximum of 6-12 million ME 3 times a week. This regimen should be maintained for an unlimited time, unless the disease progresses too quickly or the patient becomes intolerant of the drug.

Non-Hodgkin's Lymphoma: recommended dose of 5 million ME injected in / m or n / c 3 times a week for 18 months.

Mushroom mycosis: initial dose of 3 million ME in day enter in / m or p / to. The dose is increased every week with good tolerability of the drug to a maximum dose of 9-12 million IU / day. After the end of 3 months they switch to maintenance therapy with doses of 6-12 million ME 3 times a week.

Chronic myelogenous leukemia: initial dose of 3 million ME in day enter in / m or p / to.This dose is increased every week with a good tolerability of the drug to a maximum dose of 9 million ME daily. After stabilizing the number of white blood cells, the dose can be administered 3 times a week. This regimen should be maintained for an unlimited time, unless the disease progresses too quickly or the patient becomes intolerant of the drug.

Kaposi's sarcoma in patients with AIDS: the initial dose of 3 million IU / day is given in / m or s / c. This dose is gradually increased with good tolerability of the drug to a maximum dose of 9-12 million IU / day. After 2 months go to supportive therapy - 9-12 million ME 3 times a week.

Kidney Cancer: initial dose of 3 million ME in day enter in / m or p / to. The dose is increased every week to a maximum dose of 6-9 million ME in a day. After 3 months, you can start maintenance therapy at a dose of 6-9 million ME 3 times a week for 6 months. Note: Alfaferon in this dosage regimen can be combined with vinblastine at a dose of 0,1 mg / kg iv once every 21 days.

Malignant melanoma: initial dose of 3 million ME per day is given in / m or ri/to. The dose is increased every week to a maximum dose of 6-9 million ME at day. After the end of 3 months, they start maintenance therapy at a dose of 6-9 million ME 3 times a week for 6 months.

Chronic active hepatitis B: the recommended dose is 2.5-5 million IU / m² the body surface is injected / m or n / c 3 times a week for 4-6 months. If the number of viral replication markers or HBeAg Do not decrease after 1 month of treatment, should increase the dose of the drug. Dose adjustment is individual depending on the patient's tolerability. If after 3-4 months of therapy there is no positive dynamics, then the drug should be discontinued. The treatment regimen described above is also suitable for the treatment of chronic viral hepatitis D.

Chronic hepatitis C: recommended dose of 3 million ME Enter in / m or p / to 3 times a week no more than 6 months. If during 16 weeks of therapy there is no decrease in the activity of "hepatic" transaminases, the drug should be discontinued.

With combined treatment with ribavirin, the recommended dose of Alfaferon is 3 million ME п / к 3 times a week. Ribavirin used in capsules of 200 mg in a daily dose of 1000 to 1200 mg, divided into two doses, in the morning and evening during meals. Combination therapy should be continued for at least 6 months.

In previously untreated patients or those infected with virus 1 of the genotype or with high initial viremia or with persistent serum clearance of HCV-RNA for 6 months, the combined treatment should be continued up to 12 months.

Genital warts: Alfaferon can be injected in / m, n / k or locally into the lesion. In the presence of a large lesion, the drug is injected with a thin needle into the base of the injured area. Depending on the area of the lesion, the dose varies from 0.1 to 1 million ME. To calculate the total single dose administered, the amount of damage should be counted. The once-administered dose should not exceed 3 million ME. Each therapy cycle involves the administration of 3 doses per week for at least 3 weeks. Improvement is usually noted in 4-6 weeks from the start of the first cycle of therapy. In some cases, repeat the treatment cycle using similar doses.

Side effects:

Flu-like symptoms: chills, fever, headache, arthralgia, myalgia, asthenia, malaise.

From the gastrointestinal tract and liver: decreased appetite, nausea, vomiting, diarrhea, impaired liver function, abdominal pain.

On the part of the blood and organs of hemopoiesis: anemia, transient leukopenia, thrombocytopenia, granulocytopenia, eosinophilia.

From the cardiovascular system: decrease or increase in blood pressure (BP), arrhythmia (especially in patients with heart disease).

From the central nervous system (CNS): dizziness, drowsiness, ataxia, confusion, depression, acute psychosis, irritability, changes in EEG.

From the side of the organ of vision: edema of the nipple of the optic nerve, visual impairment.

From the side of the system of skin and subcutaneous fat: erythema and skin rash, exfoliative dermatitis, itching, dry skin, in rare cases, alopecia.

Other: impaired thyroid function (increase or decrease), skin reactions at the injection site, pituitary hypofunction, weight loss.

In clinical trials, asthenia, cough, sore throat, headache, fever, chills, dyspnea, fatigue, myalgia, arthralgia, increased nervous excitability, insomnia, depression, hallucinations, erythema, cutaneous itching, dry skin, abdominal pain, nausea, dyspepsia,hyperuricemia, polyuria, anemia, hemolytic anemia, thyroid dysfunction (increase or decrease), fungal skin damage.

Overdose:At present, no cases of an interferon alpha overdose have been reported.

Interaction:

The use of the drug reduces the clearance and half-life of theophylline.

When combined, the metabolism of cimetidine, phenytoin, warfarin, diazepam, and propranolol is disrupted.

It should avoid joint use with drugs that depress the function of the central nervous system, immunosuppressants, ethanol.

5% dextrose solution can not be used for the dilution of Alfaferon It is inadmissible to add any other medications to the dropper containing Alfaferon.

Special instructions:

Symptoms from the CNS are usually quickly reversible, but in some cases they completely disappear only within 3 weeks, the entire period of the patient should be monitored, if necessary, treatment should be interrupted. Side effects from the CNS may be more pronounced in elderly patients receiving high doses of Alfaferon.

If serious side effects occur, you should change the dosage regimen or stop using the drug.

Before the start of treatment, and then regularly in the process of treatment, patients should perform a standard clinical blood test with counting the number of platelets, as well as monitor the biochemical parameters of the blood, the content of electrolytes in the blood, the indicators of the functional activity of the liver and kidneys.

Patients with heart disease, especially those who have recently undergone a myocardial infarction and / or with an arrhythmia (including anamnesis) should be closely monitored, including an electrocardiographic examination prior to therapy and regularly during treatment.

In patients with impaired blood clotting and with oppression of bone marrow hematopoiesis, the drug should be used with caution. When thrombocytopenia is below 50 000 / μl, it is preferable to use s / s Alfaferon.

In patients with hairy cell leukemia before and during treatment with Alfaferon, the content of hemoglobin, platelets, granulocytes and hair cells should be checked (the latter should be determined in the bone marrow).

Although severe hypersensitivity reactions are not observed with Alfaferon, however, when they occur, treatment should be discontinued immediately and appropriate therapy prescribed. Sometimes there may be a skin rash, which does not require the abolition of therapy.

It is known about cases of increased activity of "liver" transaminases followed by seroconversion in patients with chronic active hepatitis B 3 months after the end of treatment with Alfaferon. The effectiveness of the drug in patients with chronic hepatitis B, both infected with HIV (human immunodeficiency virus), has not been demonstrated.

In patients with genital warts, a clinical response to Alfaferon therapy may occur within a month after its termination.

Patients should be warned that it is impossible to change interferon preparations without consulting a doctor, since the recommended doses are different for them.

Flu-like symptoms are most pronounced in the first week of treatment and gradually weaken as a result of tachyphylaxis, at 2-4 weeks. In rare cases, it is possible to increase the intensity of the pain syndrome, which can cause the drug to be discontinued.For relief of such influenza-like symptoms as chills, fever, headache, arthralgia, myalgia, can be effective paracetamol. In clinical practice, it has been observed that the severity of these symptoms is reduced if Alfaferon is used before bedtime.

Some patients may have prolonged asthenia, which sometimes requires withdrawal of the drug.

In patients with hepatitis C who are receiving Alfaferon, sometimes (less than 1%) patients may have thyroid dysfunction, expressed in hypo- or hyperthyroidism. In cases of hypo- or hyperthyroidism, standard therapy should be performed. The mechanism of these violations is not clear. Therefore, before the start of the course of treatment with Alfaferon should determine the concentration of thyroid-stimulating hormone (TSH) in the blood serum. The use of Alfaferon can be started only under the condition of normal TSH content in the blood. If symptoms of thyroid dysfunction occur during the treatment with Alfaferon, then it can be continued if normal TSH concentration is maintained. Symptoms of thyroid dysfunction that occurred during the treatment with Alfaferon do not disappear after the withdrawal of Alfaferon.

Patients should ensure sufficient hydration, especially at the initial stage of treatment.

Women of childbearing age during treatment with Alfaferon should use reliable methods of contraception.

The site of the I / m injection should be changed.

Effect on the ability to drive transp. cf. and fur:Patients receiving high doses of Alfaferon or those who developed side effects from the CNS should refrain from driving motor vehicles and practicing potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Solution for injection, 1mln IU / ml, 3 million IU / ml or 6 million IU / ml.

Packaging:1 million IU / ml, 3 million IU / ml or 6 million IU / ml solution into ampoules of transparent neutral glass type I (Hept. F) with a capacity of 1 ml with a dot or a black line. 1 ampoule per plastic pallet along with instructions for medical use in a cardboard bundle.

Storage conditions:

Store at temperatures between + 2 ° C and + 8 ° C. Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N015743 / 01

Date of registration:20.05.2009

Expiration Date:Unlimited

The owner of the registration certificate:Alfa Wassermann SpAAlfa Wassermann SpA Italy

Manufacturer: & nbsp

ALFA WASSERMANN, S.p.A. Italy

Representation: & nbspALPHA VASSERMANN LLC ALPHA VASSERMANN LLC Italy

Information update date: & nbsp18.07.2017

Illustrated instructions

Instructions

Alfaferon (Alfaferone)