Peg-interferon

Peg-interferon α-2β is a recombinant interferon-α-2β; the drug is conjugated to the monomethoxy polyethylene glycol component. The substance is produced from an analogue of Escherichia coli, which contains a plasmid hybrid produced by genetic engineering methods; it encodes human interferon α-2β. The drug has an immunomodulatory and immunostimulating effect.

When testing in vitro, as well as in vivo, it was found that the bioactivity of the drug develops under the influence of interferon-α-2β. Interferon cell reactions occur due to synthesis with specific endings on cell surfaces.

[1], [2], [3]

Indications Interferon peg

It is used for monotherapy in case of hepatitis subtype C  (adult) confirmed by histological methods with the presence of viral replication markers inside the serum (increased aminotransferase values, the presence of PHK-HCV inside the serum or antibodies against HCV in the absence of decompensation in liver diseases) when the patient is intolerable Ribavirin or there are contraindications for its use.

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

[4], [5], [6], [7],

Release form

The release of the substance produced in the form of a lyophilisate for injection fluid. Inside the pack contains 1 bottle of medicine.

[8], [9], [10]

Pharmacodynamics

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

The immunomodulating effect is provided by potentiation of the phagocytic effect 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-helper cells, protects T-cells from the effects of apoptosis and affects the production of some cytokines (among them interferon-γ and IL). All such reactions are able to mediate the drug effect of interferon.

[11], [12], [13], [14], [15], [16]

Pharmacokinetics

With s / c injection, the serum level of Cmax is noted after 15-44 hours, then persisting until 48-72 hours. The values of Cmax and AUC of peginterferon-α-2β increase depending on the dosage.

Vd values are on average 0.99 l / kg. After re-injection, immunoreactive interferons begin to accumulate. But bioactivity increases insignificantly.

The term half-life of α-2β-peginterferon is on average about 30.7 hours, and the clearance level is 22 ml / hour / kg. How interferons are excreted is not precisely identified. But it was determined that part of the renal clearance is approximately 30% of the total clearance of α-2β-peginterferon.

After a single injection of a portion of 1 µg / kg in people with kidney problems, there was an increase in Cmax values with AUC, as well as the term half-life (in proportion to the severity of the disorder). In the case of severe stages of renal disorders (CC values - <50 ml per minute), the indicator of α-2β-peginterferon clearance decreases.

[17], [18], [19], [20], [21]

Dosing and administration

It is necessary to use the drug p / c method, in portions of 0.5 or 1 mg / kg, 1 times per week within at least six months, or at a dosage of 1.5 mg / kg in the case of complex treatment with ribavirin. The portion is selected taking into account the likely effect of the drug, as well as the possibility of negative signs. If, after half a year, the viral RNA is still released from the serum, the therapy is extended for another six months. The total duration of therapy is 12 months.

If side effects occur during therapy, it is necessary to halve the dose of peginterferon-α-2β. If negative manifestations persist after that, the therapy is canceled.

It is necessary to change a portion, considering the number of platelets with neutrophils, as well as renal work. Cancel treatment is required when reducing the number of neutrophils below 0.50 x109 / l or platelet levels below 25x109 / l.

[27], [28], [29]

Use Interferon peg during pregnancy

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

There is no information about whether the drug penetrates into the mother's milk, so during its use can not breastfeed.

Contraindications

The main contraindications:

• strong sensitivity (also for other interferons);
• a history of autoimmune hepatitis or the presence of an autoimmune disease;
• a thyroid disorder that cannot be adjusted with medications;
• insufficiency of the liver or kidneys in the severe stage or decompensated form of hepatic cirrhosis;
• mental pathologies of a severe nature (also in history), and in addition epilepsy and other disorders of the central nervous system;
• severe stages of cardiovascular disease in history, among which are diseases with uncontrolled or unstable course, in the past six months;
• sharing 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 for such conditions:

• CHF, arrhythmias, or myocardial infarction;
• women of child-bearing age and their male partners;
• lack of activity of the kidneys of moderate or severe nature (with monotherapy);
• people with HIV;
• persons who use drugs whose metabolism proceeds with the help of P450 CYP2D6 hemoprotein isoenzymes, as well as CYP2 C8 / 9, especially drugs with a narrow medication window;
• when using methadone;
• mental disorders;
• diabetes mellitus, in which there is a tendency to the appearance of ketoacidosis;
• pulmonary pathology of obstructive nature in the chronic stage;
• blood coagulation disorders (including pulmonary embolism and thrombophlebitis);
• marked suppression of blood-forming processes within the bone marrow;
• psoriasis;
• people who take alcohol, marijuana or other substances;
• individuals who are susceptible to autoimmune disorders;
• eye disease;
• compensated forms of thyroid abnormalities;
• people who have undergone organ transplants;
• sarcoidosis;
• people who drive appliances or car.

[22]

Side effects Interferon peg

Among the side effects are:

• HC function damage: paresthesia, dizziness, depression, drowsiness or nervousness, the appearance of hyperesthesia, as well as emotional instability. Occasionally, anxiety, suicidal thoughts or attempted suicide, as well as confusion;
• Digestive disorders: bloating, diarrhea or obstipation, vomiting, dry oral mucous membranes and dyspeptic symptoms. Occasionally, there is hepatopathy or pain in the area of the right hypochondrium;
• problems associated with the activity of the cardiovascular system: arrhythmia and increase or decrease in blood pressure
• impaired respiratory function: sinusitis or nasal obstruction of the nose. Occasionally, dyspnea, cough, or pulmonary infiltrates of unknown nature;
• lesions of the senses: the development of conjunctivitis. Occasionally, there is a weakening of visual acuity or a strong limitation of its fields, pain in the eye area, an obstruction affecting the retinal veins or arteries, the development of hemorrhages in the retinal zone or affecting its focal changes, as well as auditory frustration;
• disorders affecting the endocrine system: problems with the work of the thyroid gland, diabetes and menstrual disorders (among them menorrhagia);
• allergy symptoms: rash (erythematous nature or urticaria), epidermal itching and dryness, bronchial spasm, anaphylaxis and angioedema;
• change in test results: platelet, neutro or granulocytopenia, as well as the occurrence of autoantibodies;
• others: malaise, pain in the sternum area, hyperhidrosis, infections with viral genesis, and in addition flu-like syndrome, fever, weakening of the libido and blood "flushes" to the face.

[23], [24], [25], [26]

Overdose

After an accidental administration of a dosage that more than doubled the normal level, no pronounced signs of intoxication were observed.

Negative symptoms disappear on their own; cancellation of the medication is not needed.

[30], [31], [32],

Interactions with other drugs

Does not possess drug compatibility with other medicines.

With 1-time use of drugs, exposure to the activity of hemoproteins CYP1A2 and CYP2C8 with CYP2C9, as well as CYP2D6 and CYP3A4 together with the N-acetyltransferase is not observed. But it should be borne in mind that other types of interferon-α lead to a 50% reduction in the theophylline clearance values (this is a substrate of the CYP1A2 element), and also doubling its plasma parameters.

Peginterferon-α-2β metabolic processes are accompanied by an increase in the activity of the hemoprotein P450CYP2D6 isoenzymes, as well as CYP2C8 / 9, in the case of combination with medications that are metabolized using these isoenisms, therefore this combination is used very carefully. This is especially true for phenytoin with warfarin (CYP2C9), as well as flekainida CYP2D6.

[33], [34]

Storage conditions

Peg-interferon must be kept in a place inaccessible to small children. Temperature marks - in the range of numbers 2-8 ° C. The finished solution should be used immediately, but in the absence of such a possibility it can be stored at 2-8 ° C - a maximum of 24 hours.

[35], [36]

Shelf life

Peg-interferon is allowed to apply within a 24-month term from the date of sale of the drug.

[37], [38], [39], [40], [41]

Application for children

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

[42], [43], [44], [45], [46]

Analogs

Analogs of drugs are the substances Alfaron, Laferobion, Rekoferon with B-Imunoferon-1β, Avonex and Blastopheron with B-Imunoferon-1α, and in addition Virogel and Ingaron with Alfa-Inzon and Pegferon with Alfarekin. In addition, Betabiferon, Realdiron, Genferon Light ib, Nazoferon with Shanferon, Dong-a and Pegintron with Lipoferon and Rebif are on the list.

[47], [48], [49], [50], [51], [52], [53], [54], [55], [56],