With the introduction of Betaferon® No serious adverse events were detected in adult patients with cancer at a dose of up to 5.5 mg (176 million IU) 3 times a week.
hypersensitivity to natural or recombinant beta-interferon or human albumin in the anamnesis,
pregnancy,
lactation.
WITH CAUTION
For the following diseases:
heart diseases, in particular stage III–IV heart failure (according to the NYHA classification), cardiomyopathy,
depression and / or suicidal thoughts (including in the anamnesis), epileptic seizures in the anamnesis,
monoclonal gammapathy,
anemia, thrombocytopenia, leukopenia,
impaired liver function,
age up to 18 years (due to lack of sufficient application experience).
Special studies of the interaction of Betaferon® with other drugs were not carried out.
The effect of the use of Betaferon® At a dose of 0.25 mg (8 million ME) every other day, the effect on drug metabolism in patients with multiple sclerosis is unknown.
Against the background of the use of Betaferon® corticosteroids and ACTH, prescribed for up to 28 days in the treatment of exacerbations, are well tolerated. The Use Of Betaferon® at the same time with other immunomodulators, in addition to corticosteroids or ACTH has not been studied.
Interferons reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when prescribing in combination with drugs that have a narrow therapeutic index, the clearance of which largely depends on the hepatic system of cytochrome P450 (for example, antiepileptic drugs, antidepressants). Caution should be exercised when using any drugs that affect the hematopoietic system at the same time.
The following adverse events were observed with a frequency of 2% or higher than in the placebo (inactive drug) group in patients who received Betaferon during clinical trials® at a dose of 0.25 mg or 0.16 mg / m2 every other day for up to three years.
General reactions: reaction at the injection site, asthenia (weakness), a complex of flu-like symptoms, headache, fever, chills, abdominal pain, chest pain, pain of various localization, general malaise, necrosis at the injection site.
Cardiovascular system: peripheral edema, vasodilation, peripheral vascular diseases, hypertension, palpitations, tachycardia.
Digestive system: nausea, constipation, diarrhea, dyspeptic phenomena.
Blood and lymphatic system: lymphocytopenia (<1500 / mm3 ), neutropenia (<1500 / mm3), leukopenia (<3000 / mm3), lymphadenopathy.
Metabolic and alimentary disorders: an increase in the level of enzymes in the blood: ACT and ALT — 5 times from the original. Increase in body weight.
Musculoskeletal system: myasthenia gravis, arthralgia, myalgia, leg cramps.
Nervous system: hypertonicity, dizziness, insomnia, lack of coordination, restlessness, nervousness.
Respiratory system: shortness of breath.
Skin: rash, skin diseases, increased sweating, alopecia.
Urogenital system: imperative urge to urinate, frequent urination, in women-metrorrhagia (acyclic bleeding), menorrhagia (prolonged menstrual bleeding), dysmenorrhea (painful menstruation), in men-impotence, prostate diseases.
The list of side effects presented below is based on the observation of the use of Betaferon® after entering the market.
The frequency of side effects is classified as follows: very often - ≥10%, often - <10 - ≥1%, sometimes - <1 - ≥0.1%, rarely - <0.1–≥0.01% and very rarely - <0.01%.
General reactions: very often — flu-like symptoms (fever, chills, myalgia, headache or sweating)*. The frequency of these symptoms decreases over time. Rarely — general malaise, chest pain, weight loss.
Local reactions: very often — reactions at the injection site (hyperemia, local edema)* , inflammation*, pain*. Sometimes necrosis of the skin*.
Over time with continued treatment, the frequency of reactions at the injection site of the drug is usually reduced.
Blood and lymphatic system: sometimes-anemia, thrombocytopenia, leukopenia. Rarely-lymphadenopathy.
Endocrine disorders: rarely — violations of the function of the thyroid gland, hyperthyroidism, hypothyroidism.
Metabolic disorders: rarely-increased triglyceride levels.
Nervous system: sometimes-muscle hypertonus, depression. Rarely-convulsions, confusion, agitation, emotional lability, suicidal attempts, anorexia.
Cardiovascular system: sometimes-arterial hypertension. Rarely-cardiomyopathy, tachycardia, palpitations.
Respiratory organs: rarely-shortness of breath, bronchospasm.
Gastrointestinal tract: sometimes-nausea and vomiting. Rarely-pancreatitis.
Liver and biliary tract: sometimes the increase in the activity of ACT, ALT. Rarely-increased activity of gamma-glutamyltranspeptidase, bilirubin level, hepatitis.
Skin and subcutaneous tissue: sometimes-alopecia, urticaria, itchy skin, skin rashes. Rarely-discoloration of the skin, increased sweating.
Skeletal musculature: sometimes-myalgia.
Female reproductive system: rarely — violations of the menstrual cycle.
Allergic reactions: rarely-anaphylactic reactions.
* - the frequency of side effects is indicated based on the data of clinical studies.
According to the recipe.
Betaferon® contains human albumin, so there is very little risk of transmission of viral diseases. The theoretical risk of transmission of Creutzfeldt-Jakob disease is also considered extremely unlikely.
Changes in laboratory parameters. In addition to standard laboratory tests prescribed for the management of patients with multiple sclerosis, before starting therapy with Betaferon® and regularly during treatment, it is recommended to conduct a complete blood count, including differential count, platelet count and blood chemistry, and liver function test (for example, activity ACT, ALT and GGT). In the management of patients with anemia, thrombocytopenia, leukopenia (single or combined) may require more careful monitoring of the deployed blood tests, including determination of the number of erythrocytes, leukocytes, platelets, and leukocyte formula.
Gastrointestinal disorders. In rare cases, against the background of the use of Betaferon® the development of pancreatitis was observed, in most cases associated with the presence of hypertriglyceridemia.
Disorders of the liver and biliary tract. Clinical studies have shown that Betaferon therapy® it can often lead to an asymptomatic increase in hepatic transaminases, which in most cases is expressed slightly and is transient.
As with the treatment of other beta-interferons, severe liver damage (including liver failure) with the use of Betaferon® rarely observed. The most severe cases were observed in patients exposed to hepatotoxic drugs or substances, as well as in some concomitant diseases (for example, malignant diseases with metastasis, severe infections and sepsis, alcohol abuse).
When treated with Betaferon® it is necessary to monitor liver function (including the assessment of the clinical picture). An increase in the level of transaminases in the blood serum requires careful monitoring and examination. With a significant increase in transaminases in the blood serum or the appearance of signs of liver damage (for example, jaundice), the drug should be discontinued. In the absence of clinical signs of liver damage or after normalization of the level of liver enzymes, it is possible to resume therapy with Betaferon® with monitoring of liver function.
Endocrine disorders. Patients with thyroid dysfunction are recommended to check thyroid function (thyroid hormones, TSH) regularly, and in other cases-according to clinical indications.
Diseases of the cardiovascular system. Betaferon® it is necessary to apply with caution in patients with heart diseases, in particular with stage III–IV heart failure according to the NYHA classification, since such patients were not included in clinical studies.
If on the background of treatment with Betaferon® cardiomyopathy develops and it is assumed that this is due to the use of the drug, then treatment with Betaferon® it should be stopped.
Diseases of the nervous system. Patients should be informed that the side effect of Betaferon® there may be depression and suicidal thoughts, if they occur, you should immediately consult a doctor.
In two controlled clinical trials involving 1,657 patients with secondary progressive multiple sclerosis, there were no significant differences in the frequency of depression and suicidal thoughts when using Betaferon® or a placebo. However, caution should be exercised when prescribing Betaferon® patients with a history of depressive disorders and suicidal thoughts. If such phenomena occur against the background of treatment, it should be considered whether it is advisable to cancel Betaferon®.
Betaferon® it is necessary to apply with caution in patients with a history of epileptic seizures.
General disorders and the state of the injection site. Serious allergic reactions may occur (rare, but acute and severe, such as bronchospasm, anaphylaxis, and urticaria).
If there are signs of damage to the integrity of the skin (for example, fluid leakage from the injection site), the patient should consult a doctor before he continues to perform injections of Betaferon®.
In patients treated with Betaferon®, cases of necrosis at the injection site have been observed (see "Side effects"). Necrosis can be extensive and spread to the muscle fascia, as well as adipose tissue and, as a result, lead to the formation of scars. In some cases, the removal of dead areas or, less often, skin grafting is required. The healing process can take up to 6 months.
With the appearance of multiple foci of necrosis, treatment with Betaferon® it should be stopped until the damaged areas are completely healed. In the presence of a single focus, if the necrosis is not too extensive, the use of Betaferon® it can be continued, since in some patients, the healing of the dead area at the injection site occurred against the background of the use of Betaferon®.
In order to reduce the risk of developing a reaction and necrosis at the injection site, patients should be recommended:
- carry out injections, strictly observing the rules of asepsis,
- change the injection site every time,
- administer the drug strictly subcutaneously.
Periodically, you should monitor the correctness of performing independent injections, especially when local reactions occur.
Neutralizing antibodies. As with the treatment of any other drugs with a protein content, when using Betaferon® there is a possibility of antibody formation. In a number of controlled clinical trials, blood serum was analyzed every 3 months to detect the development of antibodies to Betaferon®. In these studies, it was shown that neutralizing antibodies to interferon beta-lb developed in 23-41% of patients, which was confirmed by at least two subsequent positive laboratory test results. In 43-55% of these patients, subsequent laboratory tests revealed a stable absence of antibodies to interferon beta-1b.
The presence of neutralizing antibodies has not been shown to significantly affect clinical outcomes, including MRI data. The development of neutralizing activity was not associated with the appearance of any adverse reactions.
The decision to continue or discontinue therapy should be based on indicators of the clinical activity of the disease, and not on the status of neutralizing activity.
Immune disorders. The use of cytokines in patients with monoclonal gammapathy was sometimes accompanied by a systemic increase in capillary permeability with the development of shock and death.
Use in children. Systematic study of the efficacy and safety of Betaferon® in children and adolescents under 18 years of age, it was not carried out.
Influence on the ability to drive a car and work with mechanisms No special studies were conducted. Adverse events from the central nervous system can affect the ability to drive a car and work with mechanisms, In this regard, it is necessary to be careful when engaging in potentially dangerous activities that require increased attention.
The active substance of the drug Betaferon® (interferon beta-1b) has antiviral and immunoregulatory activity. The mechanisms of action of interferon beta-1b in multiple sclerosis have not been definitively established. However, it is known that the biological effect of interferon beta-1b is mediated by its interaction with specific receptors that are found on the surface of human cells. The binding of interferon beta-1b to these receptors induces the expression of a number of substances that are considered as mediators of the biological effects of interferon beta-1b. The content of some of these substances was determined in the serum and blood cell fractions of patients receiving interferon beta-1b. Interferon beta-1b reduces the binding capacity and expression of gamma-interferon receptors, increases their decay. In addition, interferon beta-1b increases the suppressor activity of peripheral blood mononuclear cells
After the recommended dose of 0.25 mg, the concentration of interferon beta-1b in the blood is low or not determined at all.
After p / c administration of 0.5 mg of Betaferon® healthy volunteers Cmax In plasma, it is about 40 IU / ml 1-8 hours after injection. In this study, the absolute bioavailability of Betaferon® with the n / a administration-about 50%. When used in / in, the clearance and T 1/2 the preparation of the serum-an average of 30 ml / min/kg and 5 h, respectively.
Introduction of Betaferon® after a day, it does not lead to an increase in the level of the drug in the blood plasma, its pharmacokinetic parameters also do not change during the course of therapy.
When using Betaferon n/a® at a dose of 0.25 mg every other day in healthy volunteers, the levels of markers of biological response (neopterin, beta2- microglobulin and immunosuppressive cytokine IL-10) were significantly increased compared to baseline values 6-12 hours after the first dose of the drug. Cmax It was reached after 40-124 hours and remained elevated during the 7-day (168 h) study period.
At a temperature not exceeding 25 °C.
Keep out of reach of children.
| Lyophilizate for preparation of solution for injection | 1 fl. |
| active substance: | |
| interferon beta-1b | 0.3 mg |
| (corresponds to 9.6 million IU) | |
| excipients: human albumin, mannitol | |
| 1 ml of the prepared solution contains 0.25 mg (8 million IU) of recombinant interferon beta-1b | |
| 1 ml of an aqueous solvent for the preparation of a solution for injection contains 5.4 mg of sodium chloride |
Lyophilized powder for the preparation of a solution for injection. In vials, complete with solvent in syringes or vials with or without alcohol wipes, in a box of 5 or 15 sets.
Contraindicated in pregnancy. However, it is not known whether Betaferon is capable of® to cause damage to the fetus in the treatment of pregnant women or can affect reproductive function of a man. In controlled clinical trials, cases of spontaneous abortion have been reported in patients with multiple sclerosis. In studies in rhesus macaques, human interferon beta-1b had an embryotoxic effect and at higher doses caused an increase in the frequency of abortions. Women of reproductive age should use adequate methods of contraception during treatment with this drug. In case of pregnancy during treatment with Betaferon® or when planning a pregnancy, discontinuation of treatment should be recommended.
It is not known whether interferon beta-1b is excreted in breast milk. Given the potential for serious adverse reactions in infants who are breastfed, you should stop breastfeeding or discontinue the drug.
P/c, every other day.
Treatment With Betaferon® it should be started under the supervision of a doctor who has experience in the treatment of multiple sclerosis.
Currently, the question of the duration of therapy with Betaferon remains unresolved®. In clinical studies, the duration of treatment in patients with remitting and secondary-progressive multiple sclerosis reached 5 and 3 years, respectively. The duration of the course is determined by the doctor.
Preparation of the injection solution
A. Packaging of the drug containing vials and pre-filled syringes: to dissolve the lyophilized interferon beta-lb powder for injection, use the supplied ready-made syringe with solvent and needle.
B. Packaging of the drug containing vials, pre-filled syringes, an adapter for a bottle with a needle and alcohol wipes: to dissolve the lyophilized interferon beta-lb powder for injection, use the supplied ready-made syringe with a solvent and an adapter for a bottle with a needle.
In a bottle with Betaferon® enter 1.2 ml of solvent (0.54% sodium chloride solution). The powder should dissolve completely without shaking. Before use, you should inspect the finished solution, in the presence of particles or a change in the color of the solution, it can not be used.
1 ml of the prepared solution contains the recommended dose of Betaferon® - 0.25 mg (8 million ME).
If the injection was not made in due time, then it is necessary to introduce the drug as soon as possible. The next injection is made after 48 hours.
L03AB08 Interferon beta-1b
