Peg interferon

Peg-interferon α-2β is a recombinant interferon-α-2β; the drug is conjugated with a monomethoxypolyethyleneglycol component. The substance is produced from an analogue of E. coli, which contains a plasmid hybrid produced by genetic engineering methods; it codes for interferon-α-2β of human leukocytes. The drug has an immunomodulatory and immunostimulating effect.

In vitro and in vivo testing revealed that the bioactivity of the drug is mediated by interferon-α-2β. Cellular responses of interferons arise from synthesis with specific endings on cell surfaces.

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Indications Peg interferon

It is used for monotherapy in cases of histologically confirmed hepatitis subtype C (in adults) with the presence of markers of viral replication in the serum (increased aminotransferase levels, the presence of RNA-HCV or antibodies to HCV in the serum in the absence of decompensation in liver diseases), when the patient has intolerance to ribavirin or there are contraindications to its use.

In addition, it is prescribed in combination treatment with ribavirin in the chronic stage of the disease.

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Release form

The substance is released in the form of a lyophilisate for injection liquid. The pack contains 1 bottle of medicine.

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Pharmacodynamics

The bioactivity of the isomers of the pegylated nature is similar in quality to the activity of free α-2β-interferon, although slightly weaker. Synthesizing with the cell membrane, interferon forms a sequence of intracellular responses, including the induction of some enzymes (OAS types 2'-5', protein kinase type R, and proteins of the Mx type). Due to this, the transcription of the virus genome is inhibited and the binding of its proteins is slowed down; as a result, viral replication inside the infected cells is suppressed, as well as cell proliferation.

The immunomodulatory effect is provided by potentiating the phagocytic influence of macrophages, as well as the special cytotoxicity of T-lymphocytes together with natural killers relative to target cells.

In addition, α-2β-interferon helps differentiate T-helpers, protects T-cells from the effects of apoptosis, and affects the production of some cytokines (including interferon-γ and IL). All such reactions are capable of mediating the medicinal effect of interferon.

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Pharmacokinetics

With a subcutaneous injection, the serum level of Cmax is noted after 15-44 hours, continuing for up to 48-72 hours. The values of Cmax, as well as AUC of peginterferon-α-2β, increase depending on the dosage.

The Vd values are on average 0.99 l/kg. After repeated injection, immunoreactive interferons begin to accumulate. However, bioactivity increases insignificantly.

The half-life of α-2β-peginterferon is approximately 30.7 hours on average, and the clearance rate is 22 ml/hour/kg. The exact route by which interferons are excreted has not yet been determined. However, it has been determined that the renal clearance portion is approximately 30% of the total clearance of α-2β-peginterferon.

After a single injection of a 1 mcg/kg dose in people with kidney problems, an increase in Cmax with AUC and half-life (proportional to the severity of the disorder) was observed. In severe stages of renal impairment (CC values <50 ml per minute), the clearance rate of α-2β-peginterferon decreases.

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Dosing and administration

The drug should be administered subcutaneously, in a dose of 0.5 or 1 mcg/kg, once a week for at least six months, or in a dosage of 1.5 mcg/kg in the case of complex treatment with ribavirin. The dose is selected taking into account the probable effect of the drug, as well as the possibility of negative signs. If after six months, viral RNA is still isolated from the serum, the therapy is extended for another six months. The total duration of therapy is 12 months.

If adverse symptoms occur during therapy, the dosage of peginterferon-α-2β should be halved. If adverse effects persist after this, therapy should be discontinued.

The dose should be changed taking into account the number of platelets with neutrophils, as well as renal function. Treatment should be discontinued if the number of neutrophils decreases below 0.50x109/l or the platelet level decreases below 25x109/l.

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Use Peg interferon during pregnancy

There is no confirmed data regarding the safety of using Peg-interferon during pregnancy, which is why it is not used during this period.

There is no information regarding whether the medication penetrates into breast milk, so breastfeeding should not be done while using it.

Contraindications

Main contraindications:

• strong sensitivity (also to other interferons);
• autoimmune hepatitis or a history of autoimmune disease;
• thyroid dysfunction that cannot be corrected with medication;
• severe liver or kidney failure or decompensated liver cirrhosis;
• severe mental pathologies (also in the anamnesis), and in addition to this, epilepsy and other disorders of the central nervous system;
• severe stages of cardiovascular pathologies in the anamnesis, including diseases with an uncontrolled or unstable course, over the past six months;
• concomitant use with telbivudine;
• rare hereditary diseases – glucose-galactose malabsorption, fructose malabsorption, sucrase-isomaltase deficiency (due to the presence of sucrose in the drug).

Caution is required in the following conditions:

• CHF, arrhythmia or myocardial infarction;
• women of childbearing age and their male partners;
• moderate or severe renal failure (with monotherapy);
• people with HIV;
• persons who use drugs whose metabolism occurs with the help of hemoprotein P450 isoenzymes CYP2D6, as well as CYP2 C8/9, especially drugs with a narrow drug “window”;
• when using methadone;
• mental disorders;
• diabetes mellitus, which causes a tendency to develop ketoacidosis;
• obstructive pulmonary pathology in the chronic stage;
• bleeding disorders (including pulmonary embolism and thrombophlebitis);
• pronounced suppression of hematopoietic processes within the bone marrow;
• psoriasis;
• people who consume alcoholic beverages, marijuana or other substances;
• individuals predisposed to autoimmune disorders;
• eye diseases;
• compensated forms of thyroid pathologies;
• people who have received organ transplants;
• sarcoidosis;
• people who operate machinery or vehicles.

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Side effects Peg interferon

Side effects include:

• damage to the nervous system function: paresthesia, dizziness, depression, drowsiness or nervousness, the appearance of hyperesthesia, as well as emotional instability. Rarely, agitation, suicidal thoughts or suicide attempts, as well as confusion occur;
• digestive disorders: bloating, diarrhea or constipation, vomiting, dry mouth and dyspeptic symptoms. Rarely, hepatopathy or pain in the right hypochondrium is observed;
• problems associated with the activity of the cardiovascular system: arrhythmia and increase or decrease in blood pressure;
• respiratory disorders: sinusitis or nasal congestion. Rarely – dyspnea, cough or pulmonary infiltrates of unknown origin;
• damage to the sense organs: development of conjunctivitis. Occasionally, there is a weakening of visual acuity or a strong limitation of its fields, pain in the eye area, obstruction affecting the retinal veins or arteries, development of hemorrhages in the retinal area or focal changes affecting it, as well as hearing impairment;
• disorders affecting the endocrine system: problems with the thyroid gland, diabetes mellitus and menstrual cycle disorders (including menorrhagia);
• allergy symptoms: rashes (erythematous or urticaria), epidermal itching and dryness, bronchial spasm, anaphylaxis and Quincke's edema;
• changes in test results: thrombocytopenia, neutro- or granulocytopenia, as well as the appearance of autoantibodies;
• others: malaise, pain in the sternum area, hyperhidrosis, infections of viral origin, as well as flu-like syndrome, fever, decreased libido and blood "flushes" to the face.

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Overdose

After accidental administration of a dosage more than twice the normal dose, no obvious signs of intoxication were observed.

Negative symptoms disappear on their own; discontinuing the medication is not necessary.

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Interactions with other drugs

Does not have medicinal compatibility with other medications.

With a single use of the drug, no effect on the activity of hemoproteins CYP1A2 and CYP2C8 with CYP2C9, as well as CYP2D6 and CYP3A4 together with N-acetyltransferase is observed. But it should be taken into account that other types of interferon-α lead to a 50% decrease in the clearance values of theophylline (this is a substrate of the CYP1A2 element), and also a twofold increase in its plasma indicators.

Metabolic processes of peginterferon-α-2β are accompanied by an increase in the activity of hemoprotein isoenzymes P450CYP2D6, as well as CYP2C8/9, in the case of combination with drugs that are metabolized using these isoenzymes - therefore such a combination is used very carefully. In particular, this concerns phenytoin with warfarin (CYP2C9), as well as flecainide CYP2D6.

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Storage conditions

Peg-interferon should be stored in a place inaccessible to small children. Temperature marks - in the range of numbers 2-8°C. The prepared solution should be used immediately, but if this is not possible, it can be stored at 2-8°C - a maximum of 24 hours.

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Shelf life

Peg-interferon is allowed to be used within a 24-month period from the date of sale of the drug.

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Application for children

For monotherapy and 3rd treatment, it is not prescribed to persons under 18 years of age; 2nd therapy is not used for children under 3 years of age (due to the lack of confirmed information regarding the effectiveness and safety of using the drug).

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Analogues

Analogues of the drug are substances Alfaron, Laferobion, Rekoferon with B-immunoferon-1β, Avonex and Blastoferon with B-immunoferon-1α, and in addition to this Virogel and Ingaron with Alpha-inzone and Pegferon with Alfarekin. In addition to this, the list includes Betabioferon, Realdiron, Genferon light ib, Nazoferon with Shanferon, Dong-a and Pegintron with Lipoferon and Rebif.

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