INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LAFERON-PHARMBIOTEK® (LAFERON-PHARMBIOTEK®)

Composition:

Active substance: human recombinant interferon alfa-2b;

1 vial contains 1 million, 3 million, 5 million, 6 million, 9 million or 18 million IU of human recombinant interferon alfa-2b;

Excipients: sodium chloride, dextran 70, potassium dihydrogen phosphate, sodium phosphate anhydrous.

Pharmaceutical form. Lyophilisate for solution for injection.

Main physicochemical properties: lyophilized powder or porous mass, white, hygroscopic.

Pharmacotherapeutic group.
Immunostimulants. Interferon alfa-2b. ATC code L03A B05.

Pharmacological properties.

Pharmacodynamics.

Recombinant human interferon alfa-2b is a highly purified, water-soluble protein with a molecular weight of 19,300 daltons.

Laferon-FarmBiotech®, like natural leukocyte interferon, has three main types of biological activity: immunomodulatory, antiviral, and antitumor.

The mechanism of action of Laferon-FarmBiotech® is based on interferon binding to specific cellular receptors in the body, inducing a complex of intracellular mechanisms that lead to the production of enzymes preventing viral replication, enhancing macrophage phagocytic activity, increasing lymphocyte cytotoxicity against target cells, and inhibiting proliferation of metastatic cells.

Pharmacokinetics.

Data are lacking.

Clinical characteristics.

Indications.

Laferon-FarmBioTek® is used in complex therapy for:

• acute and chronic viral hepatitis B (moderate and severe forms);
• chronic hepatitis C;
• acute viral, bacterial, and mixed infections (including acute respiratory viral infections in children, including newborns; acute diarrheal syndrome in newborns; acute intestinal infections in young children with hypocoagulation);
• acute and chronic septic diseases of viral and bacterial origin, including disseminated forms of acute and chronic sepsis;
• herpes infections of various localizations: herpes zoster, multiple cutaneous herpes eruptions; genital herpes infection; herpetic keratoconjunctivitis and keratouveitis; acute herpetic stomatitis in children;
• chronic urogenital chlamydia;
• nervous system disorders with mono- and polyradicular pain syndromes;
• multiple sclerosis;
• laryngeal papillomatosis;
• skin and ocular melanoma; kidney, bladder, ovarian, and breast cancer; Kaposi's sarcoma; myeloma; chronic myeloid leukemia; hairy cell leukemia; non-Hodgkin's malignant lymphomas; basal cell carcinoma; T-cell lymphoma of the skin (mycosis fungoides).

Contraindications.

• Hypersensitivity to interferon alfa-2b or to any of the excipients;
• severe cardiovascular diseases (including decompensated heart failure, recent myocardial infarction, severe arrhythmia);
• severe renal or hepatic dysfunction, including due to metastases;
• epilepsy and/or CNS function disorders (including functional);
• chronic hepatitis with decompensated liver cirrhosis;
• chronic hepatitis in patients undergoing or who have recently completed immunosuppressive therapy, except for a short course of corticosteroid therapy;
• autoimmune hepatitis or history of autoimmune disease; organ transplant recipients on immunosuppressive therapy;
• pre-existing thyroid disorders not controlled by conventional treatment;
• presence of severe visceral involvement in patients with Kaposi's sarcoma;
• psoriasis, sarcoidosis, if the potential benefit does not outweigh the potential risk;
• combination of Laferon-FarmBioTek® with telbivudine;
• pregnancy (the safety of the drug during pregnancy has not been established).

Children and adolescents

Presence or history of severe psychiatric disorders, especially severe depression, suicidal thoughts, or suicide attempts.

Combination therapy with ribavirin

When using Laferon-FarmBioTek® and ribavirin as part of combination therapy for chronic hepatitis C, also refer to contraindications for ribavirin.

Interaction with other medicinal products and other forms of interaction.

Since interferon alfa alters cellular metabolism, there is a potential for modifying the effects of other medicinal products. It may affect oxidative metabolic pathways; therefore, caution is required when co-administering drugs metabolized via these pathways (cimetidine, phenytoin, warfarin, theophylline, aminophylline, diazepam, propranolol). Serum theophylline concentrations should be monitored and dosage adjusted as necessary.

The drug should be used with caution when administered concomitantly with opioid analgesics, analgesics, hypnotics, and sedatives (potentially myelosuppressive effects).

Increased incidence of pulmonary infiltrates, pneumonitis, and pneumonia (in some cases fatal) has been observed during concomitant use of "shosai-koto" (a Chinese herbal medicine) with interferon alfa.

When used in combination with chemotherapeutic agents (cytarabine, doxorubicin, teniposide, cyclophosphamide), the risk of life-threatening toxic effects (in terms of severity and duration) increases.

Synergism of adverse effects (regarding leukocyte count) has been described when interferon alfa and zidovudine are used together. In patients receiving both drugs simultaneously, the incidence of neutropenia was higher than in those treated with zidovudine alone.

Also refer to the ribavirin medical instruction leaflet when Laferon-FarmBioTek® is administered in combination with ribavirin to patients with chronic hepatitis C.

A clinical study of the combination of telbivudine 600 mg daily with pegylated interferon alfa-2a 180 mcg administered once weekly by subcutaneous injection showed an increased risk of peripheral neuropathy. The mechanism of this reaction is unknown. Furthermore, the safety and efficacy of telbivudine in combination with interferons for the treatment of chronic hepatitis B have not been demonstrated. Therefore, the combination of Laferon-FarmBioTek® with telbivudine is contraindicated.

Special precautions for use.

Laferon-FarmBioTek® should be used under medical supervision. Patients should be informed about the benefits of this therapy and possible adverse reactions.

If adverse effects do not diminish or intensify, the dose of the drug should be reduced to 50% or treatment discontinued. Depending on individual sensitivity and the prescribed dose, patients may experience slowed psychomotor performance—drowsiness, weakness, and increased fatigue.

Fever

Since fever may occur as part of the influenza-like syndrome, commonly observed during interferon therapy, other causes of persistent fever should be excluded.

It is recommended to use the drug concomitantly with antihistamine and antipyretic therapy.

Need for adequate hydration

Adequate hydration is essential during treatment, as some patients may develop hypotension associated with dehydration.

Hypersensitivity reactions

In case of immediate-type hypersensitivity reactions (e.g., urticaria, angioedema, bronchospasm, anaphylaxis), the drug should be discontinued immediately and appropriate measures taken. Transient skin rashes do not require discontinuation of therapy.

Psychiatric and central nervous system (CNS) disorders

In some patients, during or even after completion of treatment with interferon alfa-2b (mainly within the following 6 months), severe CNS-related adverse effects have been observed, particularly depression, suicidal ideation, and suicide attempts. In children and adolescents treated with interferon alfa-2b in combination with ribavirin, suicidal thoughts and attempts occurred more frequently than in adults (2.4% vs. 1%), both during and within 6 months after therapy. As in adults, children and adolescents also experienced other psychiatric side effects (e.g., depression, emotional instability, and drowsiness). Other CNS effects, including aggressive behavior (sometimes directed toward others, e.g., homicidal ideation), bipolar disorders, mania, confusion, and mental status changes, have been reported during interferon alfa therapy. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such symptoms occur, the physician should consider the potential seriousness of these adverse effects and decide on the need for appropriate treatment. If psychiatric symptoms persist or worsen, or if suicidal ideation or aggressive behavior toward others occurs, discontinuation of Laferon-FarmBioTek® therapy and provision of appropriate psychiatric care are recommended.

Patients with clinical or historical evidence of severe psychiatric disorders

If interferon alfa-2b treatment is deemed necessary in adults with clinical or historical evidence of severe psychiatric disorders, therapy should only begin after appropriate individual diagnosis and psychiatric treatment.

The use of interferon alfa-2b in children and adolescents with clinical or historical evidence of severe psychiatric disorders is contraindicated.

Patients who use/abuse substances

HCV-infected patients who use substances (alcohol, cannabis, etc.) have an increased risk of developing psychiatric disorders or exacerbation of existing psychiatric conditions during interferon alfa therapy. If interferon alfa therapy is necessary for these patients, concomitant psychiatric conditions and substance use should be carefully evaluated, assessed, and adequately managed before initiating treatment. A multidisciplinary approach involving a psychiatrist or addiction specialist may be required to evaluate, treat, and monitor the patient. Close monitoring is essential during and even after therapy, and timely interventions should be initiated to manage relevant conditions. Alcohol consumption must be avoided during treatment.

HIV/HCV co-infection

In patients co-infected with HIV and undergoing highly active antiretroviral therapy (HAART), the risk of lactic acidosis may increase. Caution is advised when adding Laferon-FarmBioTek® and ribavirin to HAART. In patients receiving Laferon-FarmBioTek® and ribavirin in combination with zidovudine, the risk of anemia may increase.

In co-infected patients with cirrhosis receiving HAART, the risk of hepatic decompensation and death may increase. Additional use of interferon alfa, alone or in combination with ribavirin, increases the aforementioned risks in this patient group.

HCV/HBV co-infection

Cases of hepatitis B reactivation (some with severe outcomes) have been reported in patients co-infected with hepatitis B and C viruses who were treated with interferon agents. The frequency of such reactivation was low. All patients should be tested for hepatitis B before initiating interferon therapy for hepatitis C. Patients co-infected with hepatitis B and C should be monitored and treated according to current clinical guidelines.

Thyroid disorders

Thyroid dysfunction, including hypothyroidism or hyperthyroidism (in 2.8% of patients in clinical trials), has been infrequently observed in adult patients receiving interferon alfa-2b therapy for chronic hepatitis C. Thyroid function abnormalities were managed with conventional therapy. The mechanism by which Laferon-FarmBioTek® may affect thyroid status is unknown. Thyroid function testing is recommended before initiating long-term treatment with doses of 3 million IU or higher. Treatment may be initiated if thyroid-stimulating hormone (TSH) levels are within normal range. If TSH abnormalities are detected, appropriate therapy should be initiated. Laferon-FarmBioTek® therapy may be started if TSH levels can be maintained within the normal range. TSH levels should also be monitored during treatment. If symptoms of thyroid dysfunction develop during therapy, TSH levels should be assessed. Treatment with this drug may continue if TSH levels can be maintained within the normal range. After discontinuation of therapy, thyroid dysfunction caused by the drug may not resolve.

Additional thyroid monitoring specific to children and adolescents

In children and adolescents undergoing long-term interferon therapy, thyroid function should be monitored every 3 months (e.g., TSH levels should be measured).

Laboratory tests

All patients should undergo a complete peripheral blood count before and regularly during treatment, including qualitative and quantitative blood parameter assessments, as well as blood biochemistry tests, including electrolytes, calcium, liver enzymes, bilirubin, and creatinine. Serum albumin levels and prothrombin time should be closely monitored in all patients receiving the drug.

For patients undergoing treatment for chronic hepatitis B or C, the following laboratory monitoring schedule is recommended: weeks 1, 2, 4, 8, 12, 16, and then every two months throughout treatment. If ALT levels increase to twice or more than the pre-treatment values, treatment with Laferon-FarmBioTek® may continue unless signs of hepatic failure appear. In such cases, ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin should be monitored every two weeks.

In patients with malignant melanoma, liver function and leukocyte count (including differential count) should be monitored weekly during induction of remission and monthly during maintenance therapy.

In patients with multiple myeloma, periodic monitoring of renal function is required.

Hypertriglyceridemia

Hypertriglyceridemia and exacerbation of hypertriglyceridemia, sometimes severe, have been observed during interferon alfa therapy; therefore, lipid level monitoring is recommended.

Adverse effects, including prolongation of coagulation markers and liver function abnormalities

Moderate to severe adverse effects may require dose adjustment or, in some cases, discontinuation of Laferon-FarmBioTek® therapy. Interferon alfa increases the risk of hepatic decompensation and death in patients with liver cirrhosis. Discontinuation of treatment is recommended in patients with chronic hepatitis who develop prolonged coagulation parameters, which may indicate hepatic failure. Close monitoring is required for any patient who develops liver function abnormalities during Laferon-FarmBioTek® therapy, and therapy should be discontinued if symptoms progress. Liver enzyme levels and liver function should be carefully monitored in patients with cirrhosis.

Combination therapy with ribavirin

When using combination therapy with ribavirin, the precautions for ribavirin must be observed.

Ribavirin causes serious birth defects when used during pregnancy. Patients receiving Laferon-FarmBioTek® in combination with ribavirin should avoid pregnancy. Women of childbearing potential must use effective contraception during treatment and for 4 months after treatment ends. Male patients and their partners must use effective contraception during treatment and for 7 months after treatment ends.

Concomitant chemotherapy

The use of interferon alfa in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) increases the risk of life-threatening toxicity. The most common life-threatening adverse effects include mucositis, diarrhea, neutropenia, renal failure, and electrolyte imbalances. Due to the risk of increased toxicity, careful dose selection of Laferon-FarmBioTek® is required when used concomitantly with chemotherapeutic agents. When Laferon-FarmBioTek® is used with hydroxyurea, an increased frequency and severity of cutaneous vasculitis may occur.

Autoantibodies and autoimmune disorders

The development of autoantibodies and autoimmune disorders has been observed during interferon alfa therapy. Patients predisposed to autoimmune disorders are at increased risk. Patients with signs of autoimmune disorders require ongoing monitoring, and the benefit-risk ratio of continuing interferon therapy should be re-evaluated. Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C treated with interferon. VKH syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory system, meninges, and skin. If VKH syndrome is suspected, antiviral therapy should be discontinued and corticosteroid therapy considered.

Patients with debilitating conditions

Laferon-FarmBioTek® should be used cautiously in patients with chronic debilitating conditions, such as a history of lung diseases (e.g., chronic obstructive pulmonary disease), and in patients with diabetes prone to ketoacidosis. Close monitoring is also required for patients with coagulation disorders (e.g., thrombophlebitis, pulmonary embolism) or severe myelosuppression.

Patients with cardiovascular disorders

There is no evidence of direct cardiotoxicity of interferon; however, the presence of hyperthermia and chills, commonly associated with therapy, may exacerbate pre-existing cardiac conditions. Interferon alfa-2b therapy in patients with a history of chronic heart failure, myocardial infarction, and/or previous or current arrhythmias should be conducted under strict medical supervision. ECG monitoring is recommended before and during treatment for patients with pre-existing cardiovascular disease and/or advanced cancer. Cardiac rhythm disturbances (mainly supraventricular) usually respond to conventional therapy but may require discontinuation of the drug. Data on the use of combination therapy in children and adolescents with a history of cardiovascular disease are lacking.

Hypotension

Hypotension may occur during or within two days after treatment and may require additional therapy.

Respiratory disorders

Rarely, patients receiving interferon alfa have developed pulmonary infiltrates, pneumonitis, and pneumonia, including fatal cases. The etiology of these events is unclear. These symptoms occurred more frequently when "sho-saiko-to" (a Chinese herbal medicine) was used concomitantly with interferon alfa. In patients developing fever, cough, dyspnea, or other respiratory symptoms, chest X-ray is recommended. Persistent monitoring is required if infiltrates or impaired lung function are detected, and discontinuation of interferon alfa may be necessary. Although these symptoms were more commonly observed in patients with chronic hepatitis C receiving interferon alfa, they have also been reported in cancer patients undergoing interferon alfa therapy. Immediate discontinuation of interferon alfa and corticosteroid treatment usually resolve pulmonary adverse effects.

Stupor, coma, and encephalopathy

In some patients, mainly elderly, receiving higher doses of the drug, cases of stupor, coma, and encephalopathy have been observed. These effects are generally reversible, with full recovery taking up to three weeks in some patients. Seizures are very rare with high-dose therapy.

Ocular side effects

Ocular adverse effects, including retinal hemorrhage, cotton-wool spots, serous retinal detachment, and retinal artery or vein occlusion, have been reported after interferon alfa therapy. All patients should undergo ophthalmologic examination before starting therapy. Any patient reporting decreased visual acuity, visual field defects, or other ophthalmologic symptoms during treatment with Laferon-FarmBioTek® should undergo immediate and complete ophthalmologic evaluation. Periodic ophthalmologic examinations during Laferon-FarmBioTek® therapy are especially recommended for patients with conditions potentially associated with retinopathy, such as diabetes or hypertension. Treatment should be discontinued if new or worsening ophthalmologic disorders occur.

Dental and periodontal disorders

Dental and periodontal disorders, potentially leading to tooth loss, have been reported in patients receiving combination therapy with interferon alfa and ribavirin. Dry mouth during long-term combination therapy with interferon alfa and ribavirin may have a detrimental effect on teeth and oral mucosa. Patients should be advised to brush their teeth thoroughly twice daily and undergo regular dental check-ups. Patients should be advised to rinse their mouth thoroughly after vomiting.

Patients with psoriasis or sarcoidosis

Given that interferon alfa may exacerbate pre-existing psoriasis or sarcoidosis, Laferon-FarmBioTek® should be used in patients with these conditions only if the potential benefit outweighs the potential risk.

Rejection of kidney and liver transplants

Preliminary data suggest that interferon alfa therapy may be associated with an increased incidence of kidney transplant rejection. Cases of liver transplant rejection have also been reported during interferon therapy. In patients after organ or bone marrow transplantation, pharmacological immunosuppression may be less effective because interferons have an immune-stimulating effect.

Effect on fertility

Interferon may reduce fertility. Decreased serum levels of estradiol and progesterone have been reported in women receiving human leukocyte interferon. Therefore, effective contraception is required in women of reproductive age receiving this drug.

Discontinue the drug in the following cases: prolonged coagulation time (in patients with chronic hepatitis), development of pulmonary syndrome with radiological detection of infiltrates, onset or worsening of visual disturbances, thyroid dysfunction (abnormal TSH levels), decreased serum albumin levels, and reduced prothrombin time.

The product contains no preservatives; therefore, to avoid bacterial contamination, the solution for parenteral administration should be used immediately.

Use during pregnancy or breastfeeding.

The use of the drug during pregnancy and breastfeeding is contraindicated (the safety of the drug during pregnancy has not been established).

Ability to affect reaction speed when driving or operating machinery.

Depending on dose, treatment regimen, and individual sensitivity to interferon alfa, treatment may be associated with drowsiness, weakness, fatigue, and reduced psychomotor performance. Patients should be advised to avoid driving or operating complex machinery.

Administration and Dosage

The solution of Laferon-FarmBiotech® is administered intramuscularly, subcutaneously, intravenously, endolymphatically, intraperitoneally, intravesically, rectally, parabulbarly, intranasally.

Acute viral hepatitis B:

• Administer intramuscularly 1 million IU (in severe cases – 2 million IU) twice daily for 10 days. This course may be extended up to 2–3 weeks depending on the patient's clinical status, or continued at 1 million IU twice weekly for several weeks.

Chronic viral hepatitis B:

• Administer intramuscularly 3–4 million IU three times weekly for 2 months.

Chronic viral hepatitis C:

• Administer intramuscularly 3 million IU three times weekly for 6 months as monotherapy or in combination with nucleoside analogs. The drug should be used for 3–4 months, after which HCV RNA should be tested; treatment should continue only if HCV RNA is undetectable. Monotherapy course lasts 12–18 months; in combination with ribavirin – 6 months. For genotype 1 and high baseline viral RNA load, if HCV RNA is undetectable by the end of 6 months of treatment, combination therapy may be extended for another 6 months; however, negative predictive factors such as age over 40 years, male gender, and progressive fibrosis should be considered.

Acute respiratory viral infection in children, including newborns:

• Administer intranasally 2–3 drops into each nostril 3–6 times daily for 3–5 days. Dosage for newborns: 20,000–50,000 IU/mL; for other children: 100,000 IU/mL. It is permissible to insert cotton swabs moistened with Laferon-FarmBiotech® into the nasal passages (alternately) for 10–15 minutes.

Acute respiratory viral infection (including influenza) in adults:

• Administer intramuscularly 1–3 million IU starting on days 1–2 of illness for 3 days;
• Intranasally, 4–6 drops of Laferon-FarmBiotech® solution (100,000 IU/mL) into each nostril 6–8 times daily (before use, warm the dose in a syringe [use needle-free syringe] to body temperature; store the remaining solution in the refrigerator, avoiding bacterial contamination).

Acute and recurrent pneumonia of viral or viral-bacterial etiology:

• Administer Laferon-FarmBiotech® intramuscularly 1 million IU for 5–7 days as part of comprehensive therapy (antibacterial, detoxification, anti-inflammatory, etc.).

Acute diarrheal syndrome in newborns:

• Administer rectally as daily micro-enemas containing 100,000 IU of Laferon-FarmBiotech® for 3–7 days.

Acute intestinal infections in young children with signs of hypocoagulation:

• Administer rectally at a dose of 10,000 IU/kg body weight three times with 48-hour intervals.

Pyoseptic conditions, peritonitis, multiple abdominal abscesses:

• Intravenously 2–4 million IU once daily; total course dose 12–16 million IU. Simultaneous endolymphatic administration of the same dose (2–4 million IU once daily) may also be indicated.

Herpes infections:

• Herpes zoster: daily 1 million IU intramuscularly + 2 million IU in 5 mL of 0.9% sodium chloride solution administered subcutaneously at multiple points around the affected area. Treatment duration: 5–7 days;
• Skin herpes eruptions: daily intramuscular or subcutaneous (around the lesion) administration of 2 million IU; treatment may be combined with local application (dressings) to herpes papules; treatment duration determined by physician;
• Genital herpes infection: daily intramuscular administration of 2 million IU combined with local application of the drug as dressings to the affected area; treatment duration determined by physician;
• Herpetic keratoconjunctivitis: administer Laferon-FarmBiotech® solution – 1 million IU in 5 mL of 0.9% sodium chloride solution – subconjunctivally, 2–3 drops every 2 hours for 7–10 days; after symptom resolution, administer every 4 hours; treatment duration determined by physician;
• Acute herpetic stomatitis in children: 250,000 IU per dose, 4 times daily as local dressings, combined with intranasal administration. Dilute 1 million IU of Laferon-FarmBiotech® in 4 mL of injection water; use 1 mL of solution per dressing and intranasal administration: administer 2 drops intranasally, apply the remainder locally as dressings after hygienic cleaning of the oral mucosa. Treatment course: 7–10 days.

Chronic urogenital chlamydia:

Treatment of urogenital chlamydia consists of two stages:

• Stage 1 – preparatory: use enterosorbents and polyvitamins at therapeutic doses for 2 weeks. From day 10, administer the immunotropic agent thymalin 10 mg intramuscularly every other day in the evening; total course: 5 injections;
• Stage 2 – main: perform basic antibacterial therapy as follows: first antibiotic for 5 days; after a 7-day break, administer a second antibiotic for 10 days. During the break and after completion of antibacterial therapy, administer Laferon-FarmBiotech® 1 million IU intramuscularly once daily in the evening; total course: 10 injections.

During antibacterial therapy, antifungal agents (nystatin, fluconazole, clotrimazole, nizoral) and hepatoprotectors (carsil) should be used at therapeutic doses.

Neurological disorders with mono- and polyradicular pain syndromes:

• Administer intramuscularly 1 million IU for 5–10 days as part of comprehensive therapy.

Laryngeal papillomatosis:

• Subcutaneously 3 million IU/m² three times weekly (every other day) for 6 months or longer; adjust dose based on tolerability. Begin treatment after surgical (laser) removal of tumor tissue.

Multiple sclerosis:

• Administer intramuscularly 1 million IU 2–3 times daily for 10–15 days, followed by 1 million IU once weekly for 6 months.

Cutaneous melanoma:

• As adjunct to surgical treatment and for induction of remission: intravenously 20 million IU/m² (infusion over 20 minutes) 5 times weekly for 4 weeks; maintenance therapy: subcutaneously 10 million IU/m² three times weekly (every other day) for 48 weeks.

In case of severe adverse effects, specifically granulocyte count reduction (less than 500/mm³) or elevated ALT/AST (exceeding upper normal limit by 5 times), discontinue the drug until parameters normalize. Resume treatment at half dose. If intolerance persists and granulocyte count drops to 250/mm³ or ALT/AST activity increases (exceeding upper normal limit by 10 times), discontinue the drug.

Uveal melanoma:

• Parabulbarly, 1 million IU daily for 10 days; repeat 10-day courses after 20 days, twice; total course: 48 weeks. Repeat courses after 45 days may be necessary; treatment with Laferon-FarmBiotech® is combined with photodestruction of the tumor and beta-applications.

Renal cell carcinoma:

• As induction therapy: 10 million IU/m² (up to 18 million IU/m² daily) administered intramuscularly or subcutaneously; increase dose every 3 days by 3 million IU/m² (first 3 days: 3 million IU/m², next 3 days: 6 million IU/m², next 3 days: 9 million IU/m², etc., up to 18 million IU/m²); adjust doses based on tolerability; with good tolerability, maximum dose may be 36 million IU/m²; induction therapy duration: 3 months, after which decision on discontinuation or continuation of treatment should be made based on presence of remission or disease stabilization. For maintenance therapy, administer the same doses 3 times weekly for at least 6 months.

Bladder cancer:

• Intravesically 30–50 million IU weekly for 8–12 weeks; for carcinoma in situ, 60–100 million IU per instillation weekly for 12 weeks. Patients should refrain from fluid intake for 8 hours before administration. The bladder should be emptied before drug administration. Administer the drug sterilely via catheter into the bladder cavity, where it should remain for 2 hours; patient should change body position every 15 minutes (to enhance drug interaction with bladder mucosa). After 2 hours, the bladder should be emptied.

Ovarian cancer:

• Intraperitoneally during surgery and for the next 5 days into the drainage: 5 million IU; subsequent administration of Laferon-FarmBiotech® – intramuscularly 3 million IU for 10 days between chemotherapy cycles; total drug dose: 90 million IU. Subsequent courses may be administered every 2–3 months for 1–1.5 years: 3 million IU daily for 10 days.

Breast cancer:

• Intramuscularly daily for 10 days at 3 million IU per injection. Repeat courses every 1.5–2 months for the first year, then every 2–3 months (depending on clinical status); alternating courses of Laferon-FarmBiotech® therapy with chemotherapy (or radiotherapy) is advisable.

Kaposi's sarcoma: possible treatment regimens:

• Intramuscularly daily for 10 days at 3 million IU per injection; combine treatment with monotherapy using prosidin; repeat courses once monthly for 6 months;
• Intravenous infusion over 30 minutes at 50 million IU (30 million IU/m²) daily for 5 days or every other day, followed by a minimum 9-day break before starting a new 5-day course; treatment duration determined by physician.

Multiple myeloma:

• Intramuscularly daily for 10 days at 3 million IU per injection; repeat courses every 1.5–3 months (4–6 times per year).

Chronic myeloid leukemia:

• Subcutaneously 3 million IU/m² daily or every other day, gradually increasing dose under medical supervision to 5 million IU/m² daily or every other day until complete hematological remission is achieved (leukocyte count in peripheral blood ≤10×10⁹/L) or for up to 18 months.

Hairy cell leukemia:

• Intramuscularly 3 million IU three times weekly (every other day) for 4–6 weeks. After remission is achieved, maintenance therapy: 3 million IU every other day up to 12 months.

Non-Hodgkin's malignant lymphomas:

• Intramuscularly 3 million IU three times weekly for 12–18 months as maintenance therapy after achieving remission through chemotherapy. During partial remission, other chemotherapy protocols should be used, followed by therapy with Laferon-FarmBiotech® 3 million IU intramuscularly three times weekly for 18 months.

Basal cell carcinoma:

• Inject 10 million IU (dissolved in 1 mL of injection water) into the base and center of the tumor (using a 1 mL syringe); if the affected area is less than 2 cm², administer 0.15 mL of drug solution (1.5 million IU) three times weekly (every other day) for 3 weeks; total dose should not exceed 13.5 million IU; if the affected area is 2–10 cm², drug dose should be 0.5 million IU/cm² (but not less than 15 million IU in the first injection); administer three times weekly for 3 weeks; treat only one lesion area at a time; if no positive dynamics (appearance, size of lesion, degree of redness, biopsy findings) after 2–3 months of treatment, surgical treatment should be considered.

T-cell lymphoma (mycosis fungoides) in ulcerative stage:

• Intradermally (into the superficial dermal layer beneath the patch or ulcer) 1–2 million IU (dissolved in 0.5 mL of injection water) three times weekly for 4 weeks; before injection, clean the affected area with a cotton swab moistened with alcohol; administer the drug solution with a fine needle (30 gauge) using a 1 mL syringe; during injection, the needle should be almost parallel to the body surface; avoid deeper subcutaneous administration.

Preparation of the drug solution.

The drug solution should be prepared immediately before use. Use water for injections as solvent for subcutaneous, intradermal, or intramuscular administration. Dissolve the contents of the vial in 1 mL of water for injections.

If the solution is prepared for intraperitoneal or intravesical administration, use 0.9% sodium chloride solution as solvent (calculated so that the concentration of Laferon-FarmBiotech® is not less than 0.3 million IU/mL).

Preparation and administration of intravenous infusion.

Begin infusion of 0.9% sodium chloride solution (at 200 mL/hour) 30 minutes before starting Laferon-FarmBiotech® infusion and continue until immediately before drug administration. To prepare the infusion solution, first dissolve Laferon-FarmBiotech® in water for injections (1 mL of water per administered dose), then withdraw the required amount and add to 50 mL of 0.9% sodium chloride solution. Administer the prepared solution intravenously by drip infusion over 30 minutes. After completing Laferon-FarmBiotech® administration, continue infusion of 0.9% sodium chloride solution at 200 mL/hour for 10 minutes.

The injectable solution should be used immediately. For intranasal use, the solution may be stored for up to 1 day at 2–8°C.

Children.

Used in pediatric practice for acute respiratory viral infection in children, including newborns, acute diarrheal syndrome in newborns, acute intestinal infections in young children with hypocoagulation signs, and acute herpetic stomatitis in children (see section "Administration and Dosage").

Overdose.

No cases of overdose with Laferon-FarmBiotech® have been reported to date. However, as with any drug overdose, symptomatic therapy is recommended, with monitoring of vital organ functions and careful observation of the patient's condition.

Side effects

Parenteral administration of the medicinal product Laferon-FarmBiotech**®**, as with all other alpha interferon preparations, is in most cases accompanied by a flu-like syndrome characterized by fever, chills, headache, myalgia, arthralgia, fatigue, and malaise. These adverse effects are dose-dependent and usually occur only during the first days of treatment, then gradually diminish and disappear. These symptoms can be controlled or significantly reduced by administering paracetamol at a dose of 0.5–1 g 30–40 minutes prior to injection. Nausea, dizziness, and flushing may rarely occur.

Cardiac disorders, including palpitations, tachycardia, arrhythmia§, chest pain, cardiomyopathy.

Vascular disorders, including arterial hypertension, hypotension§.

Skin and subcutaneous tissue disorders, including alopecia, pruritus*, dry skin*, rash*, hyperhidrosis, psoriasis (newly diagnosed or exacerbation)§, maculopapular rash, erythematous rash, eczema, erythema, skin disorders.

Musculoskeletal and connective tissue disorders, including myalgia, arthralgia, musculoskeletal pain.

Endocrine disorders, including hypothyroidism§, hyperthyroidism§, worsening of diabetes.

Eye disorders, including decreased visual acuity, conjunctivitis, visual disturbances, lacrimal gland disorders, eye pain, retinal hemorrhage§, retinopathy (including macular edema), obstruction of retinal vein or artery§, optic neuritis, optic disc edema, loss of visual acuity or visual fields, "cotton wool" spots on retina§.

Metabolism and nutrition disorders, including anorexia, hypocalcemia, dehydration, hyperuricemia, thirst, hyperglycemia, hypertriglyceridemia§, increased appetite, electrolyte imbalance.

Hepatobiliary disorders, including hepatotoxicity (including fatal outcomes).

Renal and urinary disorders, including frequent urination, renal failure.

Reproductive system and breast disorders, including menstrual disorders, vaginal disorders, breast pain.

Ear and labyrinth disorders, including dizziness, tinnitus, hearing loss, hearing disturbances.

Blood and lymphatic system disorders, including leukopenia, thrombocytopenia, which resolve with dose reduction; lymphadenopathy, lymphopenia, aplastic anemia.

Psychiatric disorders§, including depression, insomnia, anxiety, emotional lability*, agitation, nervousness, confusion, sleep disturbances, decreased libido, suicidal ideation, suicide attempts, aggressive behavior (sometimes directed toward others), psychosis (including hallucinatory), homicidal ideation, mental status changes§, mania, bipolar disorder.

Nervous system disorders§, including dizziness, headache, difficulty concentrating, dry mouth, tremor, ataxia, paresthesia, hypoesthesia, migraine, flushing, somnolence, taste disturbances, altered consciousness, peripheral neuropathy, seizures, encephalopathy.

Respiratory, thoracic and mediastinal disorders, including dyspnea*, cough*, pulmonary infiltrates§, pneumonia§, respiratory disturbances, pulmonary fibrosis, pulmonary arterial hypertension#.

Gastrointestinal disorders, including nausea/vomiting, abdominal pain, stomatitis, dyspepsia, right upper quadrant abdominal pain, glossitis, gingivitis, constipation, diarrhea.

Infections and infestations, including pharyngitis*, viral infection*, reactivation of hepatitis B in patients co-infected with HCV/HBV.

Immune system disorders§, including acute hypersensitivity reactions (including urticaria, angioedema, bronchospasm, anaphylactic reaction§, anaphylactic shock), sarcoidosis, exacerbation of sarcoidosis, Vogt-Koyanagi-Harada syndrome, systemic lupus erythematosus, hemorrhagic and thrombotic thrombocytopenic purpura, vasculitis, rheumatoid arthritis (newly diagnosed or exacerbation)§.

General disorders and administration site conditions, including allergic reaction at injection site*, fatigue, chills, pyrexia§, flu-like symptoms§, asthenia, irritability, chest pain, malaise.

Laboratory test abnormalities, including weight loss.

* These adverse effects are common only during monotherapy with alpha interferon-2b

§ See section "Special precautions for use"

Interferon product class warning, see below: Pulmonary arterial hypertension

The severity of adverse effects also increases with high-dose therapy (WHO grade 3 and 4 in 66% and 14% of patients, respectively), compared to mild and moderate severity when lower doses are administered. Adverse effects are usually managed by dose adjustment.

Cardiovascular adverse effects, particularly arrhythmias, are mainly associated with pre-existing cardiovascular disease and occur after therapy with cardiotoxic agents. Cardiomyopathy, which is reversible upon discontinuation of alpha interferon therapy, has been rarely observed in patients without prior symptoms of heart disease.

Cases of pulmonary arterial hypertension (PAH) have been reported in association with alpha interferon products, particularly in patients with risk factors for PAH (e.g., portal hypertension, HIV infection, liver cirrhosis). Events have been reported at various times, usually several months after initiation of alpha interferon therapy.

A wide range of autoimmune and immune-mediated disorders may occur during treatment with alpha interferons, including thyroid dysfunction, systemic lupus erythematosus, rheumatoid arthritis (newly diagnosed or exacerbation), hemorrhagic and thrombotic thrombocytopenic purpura, and vasculitis.

Clinically significant laboratory abnormalities, more frequently observed at doses exceeding 10 million IU per day, include decreased granulocyte and leukocyte counts; reduced hemoglobin levels and thrombocyte counts; increased serum alkaline phosphatase, LDH, serum creatinine, and blood urea nitrogen. Moderate, usually reversible pancytopenia has also been observed. Elevated ALT/AST levels as deviations from normal have been observed in some patients without hepatitis C, as well as in some patients with chronic hepatitis B, coinciding with clearance of viral DNA polymerase.

Shelf life. 3 years.

Storage conditions.

Store at 2°C to 8°C in a place inaccessible to children.

Packaging.

10 vials of lyophilisate with dosage of 1 million IU, 3 million IU, or 5 million IU in a cardboard box.

5 vials of lyophilisate with dosage of 1 million IU, 3 million IU, or 5 million IU, supplied with solvent (water for injections) 2 ml in 5 ampoules, in a cardboard box.

1 vial of lyophilisate with dosage of 3 million IU, 5 million IU, 6 million IU, 9 million IU, or 18 million IU, supplied with solvent (water for injections) 2 ml in 1 ampoule, in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

LLC "Scientific and Production Company "Interpharmbiotech".

Manufacturer's address and place of business.

150 Zabolotnoho Street, Kyiv, 03143, Ukraine.