BETABIOFERON-1a

General characteristics. Structure:

Active ingredient: 1 ampoule contains 3 000 000 ME or 6 000 000 ME, or 12 000 000 ME of recombinant interferon beta 1а the person;

excipients: Mannitolum, albumine of human 20%.

Physics – chemical properties: transparent yellowish slightly opalescent liquid.

Pharmacological properties:

Pharmacodynamics. Interferona are group of endogenous glycoproteins to which inherent immunomodulatory, antiviral and anti-proliferative properties. The Betabioferon-1a - recombinant interferon beta 1а, the beta represents the native amino-acid sequence identical to natural human interferon. Receive with use of cells of mammals (ovaries of the Chinese hamster). The mechanism of action Betabioferona-1a at multiple sclerosis is studied not completely. Safety and efficiency of Betabioferona-1a was estimated concerning patients with recurrent multiple sclerosis at introduction in a dose of 12 000 000 ME - 3 times a week. The Betabioferon-1a in a dose of 12 000 000 ME reduced frequency (approximately by 30% within 2 years) and weight of a recurrence of a disease.

For 4 years decrease in average frequency of aggravations made 29% at the patients receiving Betabioferon-1a 6 000 000 MO in comparison with the patients receiving within 2 years of placebo, and then for the next two 2 years – Betabioferon-1a 6 000 000 MO or Betabioferon-1a 12 000 000 MO.

Pharmacokinetics. The mechanism of action Betabioferona-1a at multiple sclerosis is up to the end not studied. It is known that drug promotes restriction of damages of TsNS which are the cornerstone of a disease. The pharmacodynamics does not depend on a way of introduction of Betabioferona-1a. Concentration of interferon a beta after hypodermic and intramuscular introduction are equivalent. After single introduction in a dose of 60 mkg the maximum concentration when determining by an immunological method makes about 6-10 ME/ml and is reached on average in 3 h after introduction.

After 4-fold hypodermic introduction to that й to a dose with an interval of 48 h moderate cumulation was observed (AUC increased approximately by 2,5 times). After a single injection within 24 h intracellular and serumal activity 2-5A sintetaza and levels beta-2 microglobulin and neopterine in blood serum which gradually decrease within 2 days raise. Intramuscular and hypodermic introduction causes identical reactions. After 4-fold hypodermic introduction with an interval of 48 h the specified biological effects remain, signs of tolerance do not develop. Interferon beta 1а is metabolized in an organism and removed with bile and urine.

Indications to use:

Multiple sclerosis with a recurrent remittiruyushchim current type which is characterized by not less than 2 aggravations within 3 previous years. Lack of signs of its continuous progressing current between a recurrence.

Route of administration and doses:

12 000 000 ME – subcutaneously 3 times a week. To patients who badly transfer drug in this dose appoint  Betabioferon-1a 6 000 000 (or 2 ampoules on 3 000 000) ME subcutaneously 3 times a week. Treatment is begun under control of the doctor which has experience of treatment of multiple sclerosis. Drug at the same time and days of the week. In an initiation of treatment of Betabioferonom-1a for decrease in adverse side effects it is recommended to appoint 24 000 000 during the first 2 weeks of treatment, during the 3-4th week on 6 000 000 ME, and since 5th week and further on 12 000 000 ME.  It is not established how long it is necessary to use drug. Not less once in 2 years on an extent of 4 years from an initiation of treatment is recommended to estimate the patient's condition. The doctor in each case has to make the decision on continuation of treatment.

Features of use:

With care appoint the patient with a depression. Patients with displays of a depression have to be under observation, they should carry out the corresponding therapy. If necessary therapy by interferon beta 1а is stopped. It is necessary to show care at treatment by interferon beta 1а patients at whom convulsive attacks were observed earlier. If epileptic seizures for the first time developed during therapy by interferon beta 1а, it is necessary to find out their etiology and to appoint anticonvulsant therapy before resuming therapy by interferon beta 1а.

Patients with coronary heart disease, congestive heart failure or arrhythmia have to be under observation of the doctor in order to avoid deterioration in a clinical state at the beginning of therapy интерферонм beta 1а. At the patients applying Betabioferon-1a the necrosis in the place of injections is sometimes noted. For decrease in risk of its development it is necessary to change every time the place of an injection.

The procedure of self-administration of drug patients needs to be checked periodically, especially, if local reactions develop. If multiple skin damages are noted, use of Betabioferona-1a should be stopped before healing of damages. The patients having single damages can continue treatment provided that the necrosis size insignificant. Patients should be warned about ability of interferon to cause abortions. During treatment careful contraception is necessary.

During therapy of Betabioferonom-1a it is recommended to define quantity of leukocytes and thrombocytes in peripheral blood, a leukocytic formula, biochemical indicators, in particular functional hepatic tests. In an initiation of treatment of Betabioferonom-1a in a dose 12 000 0000th these researches need to be conducted more often. At administration of interferon beta 1а the patient with a heavy liver or renal failure, and also with a heavy miyelosupressiya it is necessary to observe extra care and to carry out careful monitoring. To interferon beta 1а antibodies can be developed. Results of clinical trials demonstrate that in 24-48 months use of Betabioferona-1a 12 000 0000 ME approximately at 13-14% of patients serumal antibodies to interferon beta 1а are defined. Existence of antibodies reduces pharmakodinamichesky effects of interferon beta 1а (levels beta-2 microglobulin and neopterine).

Development of neutralized antibodies can be followed by decrease in clinical effect of treatment. Therefore if the patient poorly reacts to therapy of Betabioferonom-1a and at the same time it defines neutralized antibodies, it is necessary to consider expediency of continuation of use of Betabioferona-1a. Some adverse effects caused by use by Betabioferona-1a from TsNS can influence ability of patients to control of vehicles and work with potentially dangerous mechanisms. There is no experience of use of Betabioferona-1a for children aged up to 16 years therefore it should not be applied to treatment of patients of this age category.

Side effects:

The grippopodobny syndrome, mialgiya, arthralgia, fever, fever, the general weakness, headache and nausea is most often noted. Also reactions in the place of an injection are noted: reddening, a swelling, blanching of skin, morbidity, is extremely rare – a necrosis in the place of injections. Other side effects are diarrhea, vomiting, appetite loss, anorexia, insomnia, dizziness, feeling of alarm, rash, a dermahemia and tachycardia, a depression, suicide tendencies, depersonalization, convulsive attacks and arrhythmia.

Reactions of hypersensitivity, change of indicators of laboratory researches (leukopenia, lymphopenia, thrombocytopenia, increase in ASAT, ALAT, γ-glutamiltransferaza and ShchF).

Interaction with other medicines:

It is necessary to be careful at simultaneous use of Betabioferona-1a with drugs which have a narrow therapeutic index and which clearance considerably depends on P450 cytochrome, anti-epileptic drugs and antidepressants. Interaction of Betabioferona-1a with GKS or AKTG was not studied, however results of clinical trials demonstrate that patients with multiple sclerosis can receive during the recurrence of a disease Betabioferon-1a in combination with GKS or AKTG. It is not compatible to myelosuppressive drugs.

Contraindications:

Hypersensitivity to natural or recombinant interferon a beta, to a seralbumin of the person or other components of drug, the period of pregnancy and feeding by a breast, a heavy depression, suicide tendencies, epilepsy in the absence of inefficient adequate therapy.

Overdose:

Cases of overdose are not described.

Storage conditions:

In  the place protected from light at a temperature from 2 °C to 8 °C. A period of validity – 2 years.

Issue conditions:

According to the recipe

Packaging:

In ampoules on 3 000 000 ME or 6 000 000 ME or 12 000 000 ME. On 5 or 10 ampoules or 5 or 10 bottles in a pack with a corrugated partition or with a polymeric insert from a film polyvinyl chloride for placement and fixing of ampoules.