BETAFERON

Active material: recombinant Interferon Beta-1b
When ATH: L03AB08
CCF: Interferon. Preparation, primenâemyj at rasseânnom sclerosis
ICD-10 codes (testimony): G35
When CSF: 02.12
Manufacturer: BAYER SCHERING PHARMA AG (Germany)

Pharmaceutical form, composition and packaging

Valium for drug of a solution for s / c administration in the form of dried white mass; enclosed solvent transparent, almost colourless; cooked solution of slightly opalescirujushhego to opalescirujushhego, colorless or light yellow.

Excipients: albumin human, mannitol.

Solvent: sterile r-r sodium chloride 0.54% (1.2 ml).

Glass Bottles (1) together with the solvent (syringe) – trays, plastic (5) – cardboard boxes.
Glass Bottles (1) together with the solvent (syringe) – trays, plastic (15) – cardboard boxes.
Glass Bottles (1) together with the solvent (syringe), with the needle adapter for bottles and spirit towels (2 PC.) – cardboard packaging (5) – cardboard boxes.
Glass Bottles (1) together with the solvent (syringe), with the needle adapter for bottles and spirit towels (2 PC.) – cardboard packaging (15) – cardboard boxes.

Pharmacological action

Interferon beta-1b, primenâemyj at rasseânnom sclerosis, has antiviral and immunoregulirujushhej activity. Mechanisms of action of Interferon Beta-1b in multiple sclerosis is not finally established. However it is known, the biological effect of Interferon Beta-1b is mediated by its interaction with specific receptors, those found on the surface of human cells. Binding of Interferon Beta-1b with these receptors induces the expression of a number of substances, which are considered as mediators of the biological effects of Interferon Beta-1b. The content of some of these substances were determined in the serum and blood cell fractions of patients, treated with Interferon Beta-1b. Interferon Beta-1b reduces capacity and linking the expression of receptors for gamma-interferon, strengthens their breakup. The drug improves supressornuju activity of peripheral blood mononuclear cells.

As in remittirujushhem, and in secondary progressive multiple sclerosis treatment Betaferonom reduces the frequency of (on 30%) and severity of clinical exacerbations of the disease, the number of hospitalizations and the need for treatment with steroids, as well as lengthens the duration of remission.

In patients with secondary progressive multiple sclerosis Betaferon application allows you to delay further progression of the disease and the onset of disability (incl. heavy, When patients are forced to constantly use wheelchair) for a period of up to 12 Months. This effect is observed in patients with both disease exacerbations, and without complications, as well as with any disability index (the study included patients with the assessment from the 3.0 to 6.5 extended disability scale scores for EDSS).

The results of magnetic resonance imaging (MRT) the brain of patients with remittirujushhim and secondary-progressive multiple sclerosis treatment Betaferonom showed significant positive effects of the drug on the severity of the pathological process, as well as a significant decrease in the formation of new active foci.

Pharmacokinetics

After p/to the introduction of Betaferon in the dose 0.25 mg concentrations of Interferon Beta-1b in blood serum are low or no defined. In this regard, information about the pharmacokinetics of the drug in patients with multiple sclerosis, receiving Betaferon in the recommended dose, no.

After p/to the introduction 0.5 mg drug healthy volunteers (C)_max is about 40 IU/ml achieved through 1-8 hours after injection. Absolute bioavailability Betaferon when s/to the introduction amounted to approximately 50%.

When in/with the introduction of Interferon Beta-1b RNA clearance and T_1/2 average 30 mL/min/kg and 5 h, respectively.

Introduction of Betaferon a day does not lead to increased concentrations of Interferon Beta-1b in serum, and its pharmacokinetic processes during the course of therapy, apparently, do not change.

When s/to the introduction, Betaferon in the dose 0.25 mg a day in healthy volunteers levels of biological response markers (neopterin, beta₂-microglobulin and immunosuppressive cytokine IL-10) significantly increased compared to benchmarks through 6-12 hours after the first dose of the drug. They reached a peak in 40-124 h and remained elevated during the 7-day (168 no) the study period.

Testimony

-clinically isolated syndrome (KEES) (a single clinical episode demyelination, allows you to suggest multiple sclerosis, subject to the deletion of the alternative diagnoses) with a sufficient degree of inflammatory process for appointment/SCS – to ease the transition into clinically reliable multiple sclerosis (KDRS) in patients with a high risk of KDRS. There is no universally accepted definition of high risk. According to a study of high-risk patients are KDRS development monoochagovym KEYS (clinical manifestations 1 hearth in the CNS) and ≥ T2-pockets and/or MRI contrast dye nakaplivajushhim centers. Patients with mnogoochagovym KEYS (clinical manifestations >1 hearth in the CNS) belong to the high risk of KDRS regardless of the number of hearths in MRI;

remittirujushhij-multiple sclerosis – to reduce the frequency and severity of exacerbations of multiple sclerosis among outpatients (ie. patients, able to walk without assistance) with a history of at least two exacerbations of the disease over the past 2 year and the subsequent complete or incomplete restoration of neurological symptoms;

-secondary-progressive multiple sclerosis with active disease, characterized by exacerbations or marked worsening of neurologic function within 2 the last years – to reduce the frequency and severity of exacerbations, as well as for slowing the progression of the disease.

Dosage regimen

Betaferonom treatment should start under the supervision of a physician, with experience treating this disease.

Currently remains unresolved the question of duration of treatment Betaferonom. In clinical studies, the duration of therapy in patients with remittirujushhim and secondary-progressive multiple sclerosis has reached 5 and 3 years respectively. Duration of therapy is a doctor.

The recommended dose of Betaferon 0.25 mg (8 million. ME), which is contained in 1 ml solution prepared, Enter n/a in a day.

The patient should be informed, that in case of injection, the drug should enter immediately, as soon as he remembers it. Following injection makes through 48 no.

Terms of preparation of the solution

1. Packaging, containing the vials and syringes with solvent.

For dissolution liofilizirovannogo powder for injection using the attached syringe ready with the solvent and the needle.

2. Packaging, containing vials, syringes with solvent, with the needle adapter for bottles and alcohol swabs.

For dissolution liofilizirovannogo powder for injection using the enclosed syringe ready with the solvent and the adapter with the needle for vial. 1.2 mL of solvent (sodium chloride solution 0.54%) injected into the vial with Betaferonom. Powder must dissolve completely without shaking. Before using, inspect ready solution. If there are particles or change color solution cannot be applied. IN 1 ml solution contains 0.25 mg (8 million. ME) Interferon Beta-1b.

The drug should enter n/a immediately after preparation solution. If the injection is delayed, the solution should be stored in the refrigerator and used within 3 no. Do not freeze.

Side effect

Below are side effects, observed with frequency on 2% and higher, than placebo, patients, during controlled clinical trials received Betaferon in the dose 0.25 mg / m² or 0.16 mg / m² a day for a period of up to 3 years.

From the body as a whole: reaction at the injection site, asthenia, complex of flu-like symptoms, headache, fever, chills, abdominal pain, chest pain, general malaise, necrosis at the injection site, pain of various localization.

Cardio-vascular system: peripheral edema, vasodilation, arterial hypertension, Peripheral Vascular Disease, palpitation, tachycardia.

From the digestive system: nausea, constipation, diarrhea, AST and ALT rise in 5 time from initial level, dyspepsia.

From the hematopoietic system: lymphocytes <1500/l, Neutrophils <1500/l, leukocytes <3000/l, lymphadenopathy.

Metabolism: weight gain.

On the part of the musculoskeletal system: myasthenia, myalgia, arthralgia, leg cramps.

CNS: gipertonus, dizziness, insomnia, incoordination, anxiety, nervousness.

The respiratory system: breathlessness.

Dermatological reactions: rash, skin diseases, increased perspiration, alopecia.

From the urinary system: peremptory craving to urination, frequent urination.

On the part of the reproductive system: metrorragija (acyclic bleeding), menorragii, dysmenorrhoea, males – impotence, prostate disease.

The following side effects are based on postmarketingovyh observations of the use of Betaseron, systems are grouped and presented authorities with the following frequency of occurrence: Often (≥10%), relatively common (<10% – ≥1%), infrequently (<1% – ≥0.1%), rarely (<0.1% – ≥0.01%), rarely (<0.01%).

Common reactions: Often – flu-like symptoms (fever, chills, mialgii, headache, increased perspiration), the frequency of these symptoms declined over time; rarely – general malaise, chest pain.

From the hematopoietic system: infrequently – leukopenia, anemia, thrombocytopenia; rarely – lymphadenopathy.

Cardio-vascular system: infrequently – arterial hypertension; rarely – cardiomyopathy, tachycardia, heartbeat.

On the part of the endocrine system: rarely – thyroid dysfunction, hyperthyroidism, gipotireoz.

CNS: infrequently – Muscle hypertonicity, depression; rarely – convulsions, confusion, excitation, emotional lability, suicide attempts.

The respiratory system: rarely – breathlessness, bronchospasm.

From the digestive system: infrequently – nausea, vomiting, increasing the activity level of the ACT, GOLD; rarely – raising cium and GGT activity, pancreatitis, anorexia.

On the part of the musculoskeletal system: infrequently – mialgii.

On the part of the reproductive system: rarely – menstrual irregularities.

Allergic reactions: rarely – anaphylactic reactions.

Local reactions: Often – hyperemia, local swelling, inflammation, pain; infrequently – skin necrosis (over time, with continued treatment, the frequency of reactions at the injection of the drug usually decreases).

Dermatological reactions: infrequently – alopecia, hives, itch, rash; rarely – livor, increased perspiration.

Other: elevated triglycerides.

Contraindications

- Pregnancy;

- Lactation (breast-feeding);

-hypersensitivity to natural or recombinase beta-interferonu or human albumin in history.

FROM caution the drug should be used in patients with heart disease (incl. in heart failure functional class III-IV NYHA classification, when cardiomyopathy), with anemia, thrombocytopenia, anaemia in unknown, gammapatii, When depression and suicidal thoughts in history, When seizures pripadkah in history, hepatic dysfunction, as well as patients under the age of 18 years (due to the lack of sufficient experience with the drug in a given age group).

Pregnancy and lactation

Betaferon is contraindicated for use in pregnancy and lactation (breast-feeding).

Unknown, whether to Betaferon damage to the foetus in the application during pregnancy and whether drug impact on human reproduction. In controlled clinical trials in patients with multiple sclerosis there were cases of spontaneous abortion.

IN experimental studies from rhesus monkeys human Interferon Beta-1b has provided embriotoksicescoe effect, and in higher doses caused an increase in the frequency of abortions.

Unknown, is allocated whether Interferon Beta-1b with breast milk. Given the theoretical possibility of serious side effects in infants, breastfed, If necessary, the use of Betaferon in the lactation period must stop breastfeeding.

Women of childbearing age during therapy should use Betaferonom adequate contraceptive methods. In the case of pregnancy during treatment Betaferonom or when planning a pregnancy, it is recommended that you stop the drug.

Cautions

The product contains human albumin, so there is very little risk of transmitting viral diseases. The theoretical risk of transmission of Creutzfeldt-Jakob disease also is highly unlikely to occur.

In addition to standard laboratory tests, appointed in the conduct of patients with multiple sclerosis, before therapy Betaferonom, as well as regularly during the treatment it is recommended to carry out a detailed analysis of blood, including determination of Leukocyte formula, the number of platelets and blood biochemical analysis, and check the function of the liver (eg, activity of ACT, ALT and GGT). When managing patients with anemia, thrombocytopenia, leukopenia (single or combined) may require closer monitoring detailed analysis of blood, including determination of the number of red blood cells, leukocytes, platelet and leukocyte formula.

In rare cases, against the backdrop of Betaferon observed the development of pancreatitis, in most cases, is associated with the presence of hypertriglyceridemia.

Clinical studies have shown, Betaferonom therapy can often lead to increased liver transaminaz bessimptomnomu, which in most cases is expressed slightly and is transitory.

As with the treatment of other beta-interferons, severe liver injury (including hepatic failure) When applying Betaferon are rare. The most severe cases have been observed in patients, -exposed gepatotoksicnah drugs or substances, as well as in certain related diseases (eg, malignant diseases with metastasis, severe infections and sepsis, alcohol abuse).

During treatment Betaferonom liver function should be monitored (including an assessment of the clinical picture). Raising transaminaz in the serum requires careful monitoring and surveys. The increase in transaminaz in the serum, or signs of liver damage (eg, želtuhi) the drug should be discontinued. In the absence of clinical signs of liver damage or after the normalization of the level of liver enzymes may resume Betaferonom therapy with monitoring of liver function.

Patients with dysfunction of the thyroid gland, it is recommended to regularly check the thyroid function (thyroid hormones, TSH), and in other cases – as clinically indicated.

Betaferon should be used with caution in patients with heart disease, in particular, in heart failure III stage IV by the NYHA classification, because such patients were not included in the clinical studies.

If during treatment Betaferonom developing cardiomyopathy and assumes, that is associated with the use of the drug, treatment Betaferonom should stop.

Patients should be informed, that side effect of Betaferon can be depression and suicidal thoughts, When you see that, you should immediately consult your doctor.

In two controlled clinical trials involving 1657 patients with secondary-progressive multiple sclerosis found no reliable differences in the incidence of depression and suicidal thoughts when applying Betaseron or placebo. Nevertheless, caution should be exercised in the appointment of Betaseron patients with depressive disorders and suicidal thoughts in history. Upon the occurrence of such phenomena in the face of treatment, should consider the desirability of the abolition of the Betaseron.

Betaferon should be used with caution in patients with epileptic in history.

You may experience serious allergic reactions (few, but in terms of acute and severe, such as bronchospasm, Anaphylaxis and urticaria).

When signs of damage to the integrity of the skin (eg, expiration fluid from an injection site) the patient should consult a physician before, than he would continue injecting Betaseron.

Patients, treated with Betaferon, There had been cases of necrosis at the injection site. Necrosis may be extensive and distributed on the muscle fascia, as well as adipose tissue and, Consequently, result in scarring. In some cases, you must remove dead sites or, less often, skin transplantation. The healing process can take up to 6 months.

When you see multiple foci of necrosis Betaferonom treatment should stop until complete healing of the damaged sites. If one of the hearth, If necrosis is not too extensive, use of Betaferon can be continued, because some patients healing omertvevshego plot in the injection took place against the background of the use of Betaseron.

To reduce the risk of reactions and injection site necrosis in patients should be encouraged to carry out injection, strictly aseptically, each time change the injection site, Enter the drug strictly n/a.

You should periodically monitor the proper execution of separate injection, especially when you see the local reactions.

As with the treatment of any other drugs with protein, in the application there is the possibility of Betaseron antibodies. In several controlled clinical trials produced serum analysis every 3 months to detect the development of antibodies to Betaferonu. In these studies it has been shown, that neutralizing antibodies to Interferon Beta-1b has evolved from 23-41% patients, that was confirmed by at least two consecutive positive results of laboratory tests. In 43-55% of these patients in subsequent laboratory studies revealed a stable lack antibodies to Interferon Beta-1b.

Not been proven, that the presence of neutralizing antibodies to any significantly affects the clinical results, including MRI data. With the development of neutralizing activity not associated by the occurrence of any adverse reactions.

The decision to continue or discontinue therapy should be based on the indicators of clinical disease activity, rather than on status of neutralizing activity.

Application of cytokines in patients with unknown gammapatiej sometimes accompanied by systemic capillary permeability increases with the development of the shock, and fatal.

Use in Pediatrics

Systematic study of the efficacy and safety of Betaferon from children and adolescents up to 18 years not performed.

Effects on ability to drive vehicles and management mechanisms

Special studies have not been conducted. Adverse effects of the central nervous system can affect the ability to drive and operate moving mechanisms. In this regard, it should be used with caution in potentially hazardous activities, require attention.

Overdose

When you introduce Betaferon in the dose 5.5 mg (176 Million International Units) 3 times a week adult patients with cancer found no severe adverse reactions.

Drug Interactions

Unknown effect of Betaseron on the metabolism of drugs in patients with multiple sclerosis in applying the drug in a dose 0.25 mg (8 million. ME) in one day.

Against the backdrop of Betaferon GKS and ACTH, appointed for a period of up to 28 days when treating exacerbations, transferred nicely.

Use of Betaferon simultaneously with other immunomodulators (In addition to CORTICOSTEROIDS or ACTH) It has not been studied.

Interferons reduce the activity of microsomal liver enzymes p 450 system in humans and animals. Use caution when assigning Betaferon in combination with drugs, have a narrow therapeutic index, the ground which depends largely on the activity of these enzymes (incl. antiepileptic drugs, antidepressants).

You should also use caution while applying any medications, affecting the blood.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 25 ° C; Do not freeze. Shelf life liofilizirovannogo powder – 2 year, Solvent – 3 year.