БЕТФЕР®-1a

General characteristics. Structure:

Active ingredients: 1 ampoule supports 3 000 000 ME (11 mkg) or 6 000 000 ME (22 mkg), or 12 000 000 ME (44 mkg) of recombinant interferon beta 1а the person;

excipients: mannitol, albumine of human 20%.

Main physical and chemical properties: transparent yellowish slightly opalescent liquid.

Pharmacological properties:

Interferona are group of endogenous glycoproteins to which inherent immunomodulatory, antiviral and anti-proliferative properties. ^{Бетфер®-1а} - 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 ^Betfera®-1a at multiple sclerosis is studied not completely. Safety and efficiency ^{of Betfera®-1a} was estimated concerning patients with recurrent multiple sclerosis  at  introduction   in   a dose of 12 000 000 ME - 3 times a week. ^{Бетфером®-1а} 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 ^{Бетфер®-1а 6 000 000} MO in comparison with the patients receiving within 2 years of placebo, and then for the next two 2 years – ^{Бетфер®-1а 6 000 000} MO or ^{Бетфер®-1а 12 000 000} MO.

The mechanism of action ^Betfera®-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 Betfera®-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 in the same 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 not less, than 2 aggravations within 2 previous years with lack of signs of its continuous progressing current between a recurrence.

Route of administration and doses:

12 000 000 ME (44 mkg) – subcutaneously 3 times a week. To patients who badly transfer drug in this dose appoint ^{Бетфер®-1а 6 000 000} (or 2 ampoules on  3 000 000 (11 mkg)) ME subcutaneously 3 times a week. Treatment is begun under control of the doctor which has experience of treatment of multiple sclerosis. The drug is administered at the same time, it is desirable in the evening, in certain days of the week.

In an initiation of treatment ^{of Betferom®-1a} for decrease in adverse side effects it is recommended to appoint 2 400 000 ME (8,8 mkg) within the first 2 weeks of treatment, within the 3-4th week on 6 000 000 ME (22 mkg), and since 5th week and further on 12 000 000 ME (44 mkg).  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 to resume 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 by interferon beta 1а.

At the patients applying ^Betfer®-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 and to carefully follow the rules of an asepsis. 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 Betfera®-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 Betferom®-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 1, 3 and 6 month. In an initiation of treatment ^{of Betferom®-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.

At the patients receiving interferona a beta, perhaps formations of neytralizushchy antibodies. Clinical value them is not established. If insufficiently good therapeutic response to treatment ^{of Betferom®-1a} is observed and at the patient antibodies are defined, the doctor has to estimate expediency of continuation of therapy.

There is no experience of use ^{of Betfera®-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, hardening, 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, erythematic or makulopapulezny rash, a dermahemia, in some cases - a depression, suicide tendencies, depersonalization, convulsive attacks. Can be observed dysfunction of a thyroid gland (a hypothyroidism or a hyperthyroidism). Seldom – a peripheral vazodilatation, heartbeat, disturbance of a cordial rhythm that alopecia.

Reactions of hypersensitivity, change of indicators of laboratory researches (leukopenia, lymphopenia, thrombocytopenia, increase in ASAT, ALAT, γ-glutamiltransferaza and ShchF) are possible. These changes are slightly expressed, have reversible and asymptomatic character.

Interaction with other medicines:

It is necessary to be careful at simultaneous use of interferon beta 1а with drugs which have a narrow therapeutic index and which clearance considerably depends on P450 cytochrome, for example, antiepileptic drugs and antidepressants.

Interaction of interferon beta 1а 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 interferon beta 1а 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 effective adequate therapy.

Overdose:

It is not established.

Storage conditions:

In  the place protected from light at  a temperature from 2 °C to 8 °C.

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 on 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.