Binopheron alfa^® (Solution) Instructions for Use

ATC Code

L03AB05 (Interferon alfa-2b)

Active Substance

Interferon alfa-2b

Interferon alfa-2b (USAN)

Clinical-Pharmacological Group

Interferon. Antitumor, antiviral, and immunomodulatory drug

Pharmacotherapeutic Group

Cytokine

Pharmacological Action

Interferon. It is a highly purified recombinant protein with a molecular weight of 19,300 Daltons. It is obtained from an Escherichia coli clone by hybridizing bacterial plasmids with the human leukocyte gene encoding interferon synthesis. Unlike interferon alfa-2a, it has arginine at position 23.

It has an antiviral effect, which is due to interaction with specific membrane receptors and induction of RNA synthesis and, ultimately, proteins. The latter, in turn, prevent the normal reproduction of the virus or its release.

The immunomodulatory effect of interferon alfa-2b is manifested in an increase in the phagocytic activity of macrophages, enhancement of the specific cytotoxic effect of lymphocytes on target cells, changes in the quantitative and qualitative composition of secreted cytokines; changes in the functional activity of immunocompetent cells; changes in the production and secretion of intracellular proteins.

It has an antiproliferative effect on tumor cells.

Pharmacokinetics

Mean plasma interferon concentrations were comparable after subcutaneous and intramuscular administration. The C_max in blood plasma was reached after 3-12 hours and after 6-8 hours, respectively. Both after intramuscular and subcutaneous administration, the T_1/2 was approximately 2-3 hours. The plasma interferon concentration after 16-24 hours was undetectable.

After intravenous administration, the plasma interferon concentration reached maximum values (135-273 IU/ml) at the end of the infusion, then decreased somewhat faster than after subcutaneous or intramuscular injections, and was undetectable 4 hours after the end of the infusion; T_1/2 was about 2 hours.

The interferon concentration in urine was below the detectable level regardless of the route of administration.

Indications

Acute hepatitis B, chronic hepatitis B, chronic active hepatitis B and D, chronic hepatitis C.

Hairy cell leukemia, chronic myeloid leukemia, renal cell carcinoma, AIDS-related Kaposi’s sarcoma, cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome), malignant melanoma.

Langerhans cell histiocytosis, subleukemic myelosis, essential thrombocythemia.

Multiple sclerosis.

Viral conjunctivitis, keratoconjunctivitis, keratitis, keratoiridocyclitis, keratouveitis.

Prevention and treatment of influenza and other acute respiratory viral infections.

Emergency prevention of tick-borne encephalitis in combination with anti-tick immunoglobulin in adults.

As part of complex therapy in children aged 1 year and older: acute lymphoblastic leukemia during remission after the end of induction chemotherapy (at 4-5 months of remission); juvenile laryngeal respiratory papillomatosis, starting from the day after papilloma removal.

The possibility of use in children depends on the application and the specific drug used.

For rectal and vaginal use: acute and chronic recurrent infection caused by Herpes simplex virus type 1 and 2, including genital and generalized forms. Complex therapy of diseases of the genital area: chlamydia, gardnerellosis, mycoplasmosis, ureaplasmosis.

ICD codes

Dosage Regimen

Administer intramuscularly, subcutaneously, or intravenously for systemic indications. Use topical, intralesional, subconjunctival, intranasal, rectal, or vaginal routes for localized conditions.

For chronic hepatitis C, administer 3 million IU subcutaneously or intramuscularly three times per week for 12-18 months. Combine with ribavirin for enhanced efficacy in specific genotypes.

For chronic hepatitis B, administer 5-10 million IU subcutaneously or intramuscularly three times per week for 16-24 weeks. Adjust dose and duration based on virological and biochemical response.

For hairy cell leukemia, administer 2 million IU/m² subcutaneously or intramuscularly three times per week. Continue therapy for at least 6 months or until response plateaus.

For malignant melanoma, use an induction dose of 20 million IU/m² intravenously five days per week for four weeks. Follow with a maintenance dose of 10 million IU/m² subcutaneously three times per week for 48 weeks.

For influenza and ARVI prevention, administer intranasally twice daily during periods of high epidemiological risk. For treatment, initiate at first symptoms.

For pediatric acute lymphoblastic leukemia maintenance, administer subcutaneously three times per week. For juvenile laryngeal papillomatosis, begin therapy the day after surgical papilloma removal.

Adjust dosage for hematological toxicity. Reduce dose by 50% for ANC 0.5-0.75 x 10⁹/L or platelets 25-50 x 10⁹/L. Withhold therapy for ANC <0.5 x 10⁹/L or platelets <25 x 10⁹/L.

Premedicate with acetaminophen to mitigate flu-like symptoms. Administer injections in the evening to minimize impact on daily activities. Rotate subcutaneous injection sites.

Reconstitute lyophilized powder with provided diluent. Use immediately after reconstitution. Do not shake vial vigorously. Inspect solution for particulate matter before administration.

Adverse Reactions

Flu-like symptoms often – fever, chills, bone pain, joint pain, eye pain, myalgia, headache, increased sweating, dizziness.

From the digestive system possible decreased appetite, nausea, vomiting, diarrhea, constipation, taste disturbance, dry mouth, weight loss, mild abdominal pain, slight changes in liver function parameters (usually normalize after treatment).

From the nervous system rarely – dizziness, impaired mental activity, sleep disturbance, memory impairment, anxiety, nervousness, aggressiveness, euphoria, depression (after long-term treatment), paresthesia, neuropathy, tremor; in some cases – suicidal tendency, drowsiness.

From the cardiovascular system possible – tachycardia (with fever), arterial hypotension or hypertension, arrhythmia; in some cases – disorders of the cardiovascular system, coronary artery disease, myocardial infarction.

From the respiratory system rarely – chest pain, cough, slight shortness of breath; in some cases – pneumonia, pulmonary edema.

From the hematopoietic system possible slight leukopenia, thrombocytopenia, granulocytopenia.

Dermatological reactions possible itching, reversible alopecia.

Other rarely – muscle stiffness; in isolated cases – antibodies to natural or recombinant interferons.

Contraindications

Severe cardiovascular diseases (including decompensated heart failure, recent myocardial infarction, severe arrhythmias); severe liver dysfunction (including those caused by metastases); chronic hepatitis with decompensated liver cirrhosis; chronic hepatitis in patients receiving or having received immunosuppressants (except for a short course of corticosteroid therapy); autoimmune hepatitis; epilepsy and other disorders of the central nervous system function, mental illnesses and disorders in children and adolescents; history of autoimmune diseases; use of immunosuppressants after transplantation; thyroid disease if it is not controlled by appropriate therapy; creatinine clearance <50 ml/min (when prescribed in combination with ribavirin); simultaneous use with telbivudine; hypersensitivity to Interferon alfa-2b.

Some drugs containing Interferon alfa-2b are contraindicated during pregnancy, during breastfeeding; for prescription to men whose partners are pregnant; children under 18 years of age.

When used in children and adolescents under 18 years of age, only those dosage forms intended for this age category should be used.

With caution

Severe depression, suicidal thoughts and attempts, including according to medical history (for adults only), decompensated lung diseases (including COPD), diabetes mellitus (with a tendency to ketoacidosis), hypercoagulation, severe myelosuppression, history of cardiovascular disease (myocardial infarction, chronic heart failure, arrhythmias), thyroid disease if it is controlled by appropriate therapy; psoriasis and sarcoidosis; reproductive age in men and women; kidney and liver transplantation; concomitant chemotherapy.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is not recommended.

Some drugs containing Interferon alfa-2b are contraindicated during pregnancy, during breastfeeding; for prescription to men whose partners are pregnant.

Use in Hepatic Impairment

Contraindicated in decompensated liver cirrhosis. Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Special Precautions

With parenteral use of drugs containing Interferon alfa-2b, patients require strict clinical monitoring, especially in patients with impaired renal, hepatic, or bone marrow function, in those with suicidal tendencies, with arrhythmia, in patients prone to autoimmune diseases, due to an increased risk of autoimmune reactions.

Effect on ability to drive vehicles and machinery

The patient should be warned about the possibility of developing weakness, drowsiness, and impaired consciousness during therapy and should be advised to avoid driving vehicles and operating machinery.

Drug Interactions

Interferon alfa-2b inhibits the metabolism of theophylline and reduces its clearance.

Interferon alfa-2b is capable of reducing the activity of cytochrome P450 isoenzymes and, consequently, affecting the metabolism of cimetidine, phenytoin, dipyridamole, theophylline, diazepam, propranolol, warfarin, and some cytostatics.

May enhance the neurotoxic, myelotoxic, or cardiotoxic effects of drugs previously administered or administered simultaneously with it.

Concomitant administration with drugs that have a depressant effect on the central nervous system and immunosuppressive drugs (including oral and parenteral forms) should be avoided.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.