Pegylated interferons: types, composition, properties, indications and contraindications

Pegylated interferons are synthesized from the usual ones by their modification. The resulting product has improved characteristics that are used in the treatment of viral diseases (mainly hepatitis). There are 2 main varieties of such drugs. Most often they are used together with Ribavirin and an NS3 / 4A protease inhibitor.

Appointment

Pegylated interferons are antiviral drugs that affect the human immune system. Their other names are peginterferons, peg-INF. The prefix “peg” came from the shortened version of “polyethylene glycol”. Its molecules are introduced into conventional interferon in order to increase the duration of exposure to the active substance in the body.

Pegylated interferon preparations have the following advantages compared to their standard modifications:

• greater efficiency (clinically proven);
• the possibility of reducing the number of injections (due to the increased half-life);
• higher stability of the active substance;
• fewer side effects (allergic reactions and unwanted immunogenicity processes).

The first pegylation technology was described in 1977. Prior to this, it was believed that proteins can only be integrated into the structure of low molecular weight compounds. At the same time, the high molecular weight of the modified interferons causes the main drawback of these drugs - a difficult conclusion from the body. Excretion occurs mainly through the kidneys and with feces.

Polydispersity (a combination of molecules that differ in the number and localization of polyethylene glycol addition) and a large volume of distribution in the body impair the filtration of the substance through the kidneys. In this regard, a promising direction in the technology of these drugs is to improve the pegylation process. The history of the use of modified interferons in medicine has about 10 years.

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In therapeutic practice, the following drugs of this group are used:

• 2 types of alpha modification (pegylated interferon alpha-2a and 2b). Means made on their basis are characterized by a different chemical structure. There are no fundamental differences between them. Pegylated interferon alpha has a higher molecular weight (of the order of 40 kDa) than the second species. Therefore, it is characterized by a more prolonged action.
• Beta Peg-INF. The manufactured drugs with pegylated interferon beta are a new generation of drugs. They are used to treat multiple sclerosis. This substance is obtained using biotechnology of recombinant proteins grown on a culture of cells that are isolated from hamster ovaries. The exact mechanism of influence of the active substance is unknown. It involves the stimulation of anti-inflammatory and the suppression of pro-inflammatory polypeptide information molecules.

According to recent medical studies, the best antiviral efficacy is shown by the combined administration of both alpha interferons, as well as the simultaneous administration of the drug Ribavirin.

Release forms and storage conditions

Pegylated interferons alfa-2b and 2a in the Russian pharmaceutical market are sold in 4 preparations:

• Pegasis (manufactured by Roche, Switzerland). Subcutaneous solution, clear or light yellow. Available in finished form in syringe tubes of 180 (135) mcg. The package contains 1 or 4 syringes.
• Pegintron (Schering-Plow Pharmaceutical Corporation, USA). Available in the form of a two-chamber syringe pen, in one compartment there is a dry lyophilisate, in the second - a solvent.
• PegAltevir (BioProcess, Russia). The package contains 2 bottles - one with the active substance in the form of a white powder, the second with a solvent.
• "Algeron" (production of the international innovative company "Biocad"). Colorless or yellowish solution. The package contains 1 or 4 syringes.

All preparations should be stored and transported in a dark place at an ambient temperature of +2 ... + 8 ° C. The shelf life of the first three drugs from the above list is 3 years, the last 2 years.

The properties

The main properties of pegylated interferons are as follows:

• the suppression of the activity and reproduction of viruses occurs due to the influence on the transcription mechanism of their genes;
• the active substance is found in human blood after 3-6 hours, and its maximum level is reached on the 3-4th day;
• a smoother increase in blood concentration as a result of the slow release of the drug;
• the active substance accumulates mainly in the blood and in functionally active liver cells;
• the half-life is 80 and 160 hours, respectively, with intravenous and subcutaneous injection (for standard interferon - 4 hours);
• Peginterferon-alpha 2b molecules are smaller, so they penetrate more actively into peripheral blood, lymph nodes, kidneys and other organs;
• excretion occurs mainly through the kidneys.

Due to the increased half-life of these substances in the human body, the number of necessary injections per week is reduced - from 3 (for standard interferon) to 1 (for pegylated modification). At the same time, a large number of bound molecules reduces the biological activity of the product. So, for peg-INF alpha 2b it is at the level of 37% of the standard non-pegylated interferon, and for alpha 2a modification it is 7%.

Structure

The composition of preparations based on peg interferons is indicated in the table below.

PEGylated interferons: indications

Peginterferons alfa are recommended in the treatment of hepatitis:

• type B - with positive and negative anti-HBe antigen of hepatitis B, with an increased level of the enzyme alanine aminotransferase in the blood, with inflammation, fibrosis and other liver lesions;
• type C - for patients with or without cirrhosis, HIV-infected.

The drugs can be used both in monotherapy and in combination with each other and other antiviral agents.

Application features

Treatment with pegylated interferons is characterized by the features listed below:

• "Pegasis" - an injection is injected into the thigh or abdomen once every 7 days. The duration of therapy is 48 weeks.
• "Algeron", "PegAltevir" - subcutaneous injection into the thigh or abdominal wall. The injection site must be changed. An injection is done once a week, it is recommended to inject before bedtime. The duration of treatment is the same as for the previous remedy. In the absence of an early virological effect (PBO) after 12 weeks or the detection of virus RNA after 24 weeks, therapy is stopped. Each virus genotype has its own standard treatment regimen.
• "Pegintron" is administered subcutaneously, the duration of therapy is 24-52 weeks and 6 months for hepatitis B and C, respectively. To reduce pain, the injection site is changed. If the virus is still detected after a course of RNA treatment, then the therapy is extended for another six months. When a pathogen is re-detected, it is stopped.

The dosage of drugs is observed according to the instructions. Its calculation is based on the patient’s mass and treatment regimen - double (with Ribavirin), triple (with Ribavirin and NS3 / 4A protease inhibitor) or monotherapy. Ribavirin is taken daily with food. Medicines are used only as prescribed by a doctor and under his supervision.

Contraindications

Therapy with pegylated interferons is not carried out in the following conditions:

• pregnancy and lactation (since there are no studies on the excretion of active substances in milk and their effect on the fetus);
• hypersensitivity to the components of the drug;
• decompensated cirrhosis of the liver;
• autoimmune hepatitis;
• decompensated diabetes mellitus;
• age up to 18 years (with triple and monotherapy) and up to 3 years (with double therapy);
• pathology of the thyroid gland (lack and excess of its hormones).

With caution, these medications are prescribed for those patients who have mental disorders, kidney diseases, cardiovascular system, autoimmune pathologies and when taking medications with myelotoxic effect (suppressing hematopoietic function of the bone marrow).

Side effects

The most common side effects (in 20-30% of patients) when using these drugs are:

• general weakness;
• increase in body temperature;
• headache;
• sleep disturbances;
• irritability;
• depression.

In 10-14% of patients, drugs are not used because of their intolerance.

Other possible side effects include the following:

• neutropenia (a life-threatening condition in which the number of neutrophils in the blood decreases);
• nausea, vomiting;
• diarrhea;
• joint and muscle pain;
• itchy skin;
• hair loss;
• increase in blood pressure;
• tachycardia;
• growth and development retardation in children and adolescents;
• severe mental disorders (suicidal thoughts, mania, bipolar disorders and others).