Peginterferon alfa-2b (Lyophilisate) Instructions for Use

ATC Code

L03AB10 (Peginterferon alfa-2b)

Active Substance

Peginterferon alfa-2b

Peginterferon alfa-2b (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Interferon. An immunomodulatory drug with antiviral action

Pharmacotherapeutic Group

Cytokine

Pharmacological Action

An immunomodulator and antiviral agent. It is a covalent conjugate of recombinant interferon alfa-2b and monomethoxypolyethylene glycol. The average molecular weight is about 31,300 Daltons.

Recombinant interferon alfa-2b is obtained from an E. coli clone that contains a plasmid hybrid (obtained by genetic engineering) encoding human leukocyte interferon alfa-2b. In vitro and in vivo studies indicate that the biological activity of peginterferon alfa-2b is due to interferon alfa-2b. The cellular effects of interferons are realized through binding to specific receptors on the cell surface. Studies of other interferons have demonstrated their species specificity.

Recombinant interferon alfa-2b also suppresses virus replication in vitro and in vivo. Although the exact mechanism of the antiviral action of recombinant interferon alfa-2b is unknown, it is believed to alter host cell metabolism. This leads to the suppression of virus replication; if replication does occur, the resulting virions are unable to leave the cell.

Pharmacokinetics

After subcutaneous administration, the C_max of the active substance in serum is reached within 15-44 hours and persists for up to 48-72 hours. The C_max and AUC of peginterferon alfa-2b increase proportionally to the dose. The V_d averages 0.99 L/kg. With repeated administration, accumulation of immunoreactive interferons occurs. However, the biological activity increases only slightly.

The T_1/2 of peginterferon alfa-2b averages about 30.7 hours, and the clearance is 22 mL/h/kg. The mechanisms of interferon elimination have not been definitively established. However, it is known that the renal clearance fraction accounts for about 30% of the total clearance of peginterferon alfa-2b.

After a single dose of 1 mcg/kg in patients with impaired renal function, an increase in C_max, AUC, and T_1/2 was observed, proportional to the degree of renal failure. In severe renal impairment (creatinine clearance <50 mL/min), the clearance of peginterferon alfa-2b is reduced.

Indications

As monotherapy for histologically confirmed hepatitis C in adults with serum markers of hepatitis C virus replication (increased aminotransferase activity, presence of HCV RNA or antibodies to HCV in serum in the absence of decompensated liver disease) in case of intolerance to ribavirin or contraindications to its use; as part of combination therapy with ribavirin in patients with chronic hepatitis C.

ICD codes

Dosage Regimen

Lyophilisate

It is administered subcutaneously at a dose of 0.5 mcg/kg or 1 mcg/kg once a week for at least 6 months, or at a dose of 1.5 mcg/kg of body weight when used as part of combination therapy with ribavirin. The dose is established taking into account the expected effectiveness of the drug and the possibility of developing adverse reactions. If HCV RNA is detected in the serum after 6 months, treatment is continued for another 6 months; the total duration of treatment is 1 year.

If adverse reactions occur during treatment, it is recommended to reduce the dose of peginterferon alfa-2b by half. If adverse effects persist or reappear after dose adjustment, treatment should be discontinued.

The dose is adjusted depending on the neutrophil count, platelet count, and renal function. Therapy is discontinued if the neutrophil count decreases to less than 0.50×10⁹/L or the platelet count decreases to less than 25×10⁹/L.

Adverse Reactions

From the digestive system: anorexia, nausea, diarrhea, abdominal pain.

From the musculoskeletal system: pain, myalgia, arthralgia.

From the nervous system: headache, depression, anxiety, dizziness, impaired concentration, insomnia, irritability.

Frequently: itching, dry skin, malaise, sweating, pain in the right hypochondrium, neutropenia, rash, vomiting, dry mouth, emotional lability, nervousness, dyspnea, viral infections, drowsiness, thyroid dysfunction, chest pain, dyspepsia, flushing, paresthesia, cough, agitation, sinusitis, arterial hypertension, hyperesthesia, blurred vision, confusion, abdominal distension, decreased libido, erythema, eye pain, apathy, hypoesthesia, unstable stool, conjunctivitis, nasal congestion, constipation, menorrhagia, menstrual disorders, granulocytopenia, thrombocytopenia.

Rarely: suicidal thoughts and attempts, hearing impairment, retinal changes, diabetes mellitus, hepatopathy, and arrhythmias.

Local reactions: inflammation, local hypersensitivity reaction.

Other: asthenia, fatigue, fever, flu-like symptoms, chills, weight loss, alopecia, pharyngitis.

Contraindications

Autoimmune hepatitis or a history of autoimmune disease; severe mental illness or a history of significant mental disorders; thyroid dysfunction resistant to drug therapy; severe impairment of renal or liver function; epilepsy and/or impaired central nervous system function; pregnancy; hypersensitivity to peginterferon alfa-2b and other interferons.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

If use during lactation is necessary, breastfeeding should be discontinued.

It can be used in women of reproductive age provided that they use effective methods of contraception throughout the entire treatment period.

Use in Hepatic Impairment

The safety and efficacy of peginterferon alfa-2b in patients with severe hepatic impairment have not been studied, so it should not be used in this category of patients.

Use in Renal Impairment

During treatment, patients with impaired renal function require constant monitoring.

Pediatric Use

Not recommended for use in children and adolescents under 18 years of age.

Special Precautions

Before starting and during treatment with peginterferon alfa-2b, it is recommended to perform complete blood count, biochemical blood tests, and thyroid function tests. The following baseline blood values are acceptable: platelets – ≥100,000/µL, neutrophils – ≥1,500/µL, TSH – within normal limits.

The safety and efficacy of peginterferon alfa-2b in patients with severe hepatic impairment have not been studied, so it should not be used in this category of patients.

Patients with heart disease are recommended to have an ECG before starting and during treatment. Arrhythmias (mainly supraventricular) are usually amenable to conventional therapy, but discontinuation of peginterferon alfa-2b may be required. Patients with congestive heart failure (including history), myocardial infarction, and/or arrhythmia require constant medical supervision during treatment with peginterferon alfa-2b.

If immediate-type hypersensitivity reactions (including urticaria, angioedema, bronchospasm, anaphylaxis) develop during the administration of peginterferon alfa-2b, treatment should be discontinued and adequate symptomatic therapy should be immediately prescribed. Transient skin rash does not require discontinuation of treatment.

If symptoms appear that may indicate decompensation of liver disease, the use of peginterferon alfa-2b should be discontinued.

Although fever may be a manifestation of the flu-like syndrome, which is often observed during interferon treatment, it is nevertheless necessary to exclude other causes of persistent fever.

During treatment with peginterferon alfa-2b, adequate hydration should be ensured, as some patients have experienced arterial hypotension associated with a decrease in fluid volume in the body. In such cases, fluid administration may be required.

Use with caution in patients with lung diseases (e.g., chronic obstructive pulmonary disease), diabetes mellitus accompanied by ketoacidosis, in patients with coagulation disorders (e.g., thrombophlebitis, pulmonary embolism) or pronounced myelosuppression.

In rare cases, patients receiving interferon alfa developed infiltrates of unclear etiology in the lungs. If fever, cough, shortness of breath, and other respiratory symptoms appear, all patients should undergo chest X-ray. If infiltrates are present on lung X-rays or signs of impaired lung function, patients should be constantly monitored and Peginterferon alfa-2b should be discontinued if necessary.

Patients with diabetes mellitus or arterial hypertension are recommended to have an eye examination before starting treatment with peginterferon alfa-2b.

If mental disorders or changes in the central nervous system occur, including overt depression, it is recommended to constantly monitor patients, given the potential seriousness of such adverse events. If symptoms persist or worsen, Peginterferon alfa-2b should be discontinued.

If any thyroid dysfunction is detected before starting treatment with peginterferon alfa-2b, standard therapy is recommended. Peginterferon alfa-2b should not be used if such therapy does not maintain TSH activity at a normal level.

In patients with psoriasis, Peginterferon alfa-2b should be used only if the expected benefit of therapy outweighs the possible risk.

During treatment, patients with impaired renal function require constant monitoring.

Not recommended for use in children and adolescents under 18 years of age.

Effect on the ability to drive vehicles and operate machinery

If fatigue, drowsiness, or confusion occurs during therapy, it is not recommended to drive a car or operate complex machinery.

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.