Teberif - Instructions For Use, Reviews, Price, Injections, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Teberif

Teberif: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Teberif

ATX code: L03AB07

Active ingredient: interferon beta-1a (Interferon beta-1a)

Manufacturer: CJSC "Biocad" (Russia)

Description and photo update: 2019-10-07

Teberif - interferon beta-1a; a drug with immunomodulatory, antiviral and antiproliferative effects for the treatment of multiple sclerosis.

Release form and composition

Dosage form - solution for subcutaneous administration: transparent, colorless [0.5 ml in syringes made of colorless glass, 1 syringe in a blister, in a cardboard box 3 or 12 packs complete with alcohol wipes (3 or 12 pcs., Respectively) and instructions for the use of Teberif].

Composition of 1 ml solution:

• active substance: recombinant human interferon beta-1a - 22 or 44 μg;
• auxiliary components: glacial acetic acid, sodium acetate trihydrate, polysorbate-20, lysine hydrochloride, water for injection.

Pharmacological properties

Pharmacodynamics

Interferons belong to the group of endogenous glycoproteins that have antiproliferative, immunomodulatory and antiviral properties.

The protein structure of recombinant human interferon beta-1a is the natural amino acid sequence of human interferon beta, obtained by genetic engineering using a Chinese hamster ovary cell culture, therefore, recombinant interferon beta-1a, like the natural protein, is glycosylated.

After a single dose of the drug within 24 hours, the serum concentration of beta-2-microglobulin and neopterin increases, as well as the serum and intracellular activity of 2 ', 5'-oligoadenylate synthetase (2', 5'OAS), during the next 2 days these indicators begin to decline gradually. The therapeutic effect on the introduction of Teberif by the subcutaneous (s / c) and intramuscular (i / m) routes is similar. After 4 consecutive s.c. injections at intervals of 48 h, the biological response remains elevated, while there are no signs of addiction.

In healthy volunteers and patients with multiple sclerosis, after SC administration of the drug, there is an increase in the level of markers of biological response (activity 2 ', 5'OAS, plasma levels of neopterin and beta-2-microglobulin). After a single subcutaneous injection of Teberif, the maximum concentration (C _max) 2 ', 5'OAS, neopterin and beta-2-microglobulin is reached within 24-48 hours, oligoadenylate synthetase 1 (OAS1) and oligoadenylate synthetase 2 (OAS2) - 24 hours, MXI - 12 hours. For most of these markers, such concentration peaks are observed after the first and sixth injections.

In patients with multiple sclerosis, the mechanism of action of Teberif is not fully understood. It has been found that the drug limits the damage to the central nervous system (demyelination process) that underlies this disease.

First episode of demyelination

Interferon beta-1a is effective in treating the first episode of demyelination, presumably due to multiple sclerosis, according to a two-year controlled clinical trial. Patients who participated in the study had at least two asymptomatic lesions on T2 weighted MRI (magnetic resonance imaging) images at least 3 mm in size, with at least one lesion being oval, infratentorial or periventricular. Any other disease that matched the present symptoms more than multiple sclerosis was excluded.

The use of the drug 44 μg 3 times a week inhibited the progression of the disease in patients with the first episode of demyelination. Compared with the placebo group, the reduction in the overall risk of progression of multiple sclerosis was 52%.

Remitting multiple sclerosis

The efficacy and safety of interferon beta-1a has been studied in patients with relapsing-remitting multiple sclerosis. The drug was administered subcutaneously in doses from 11 to 44 μg 3 times a week. It was found that at a dose of 44 μg, the drug reduces the frequency (by 30% within 2 years) and the severity of exacerbations in patients with a score of 0 to 5 on the Extended Disability Assessment Scale (EDSS) before starting treatment and with two or more episodes of exacerbations in over the past two years.

The progression of disability significantly decreased from 39% (placebo) to 30 and 27% (with the use of interferon beta-1a at a dose of 22 μg and a dose of 44 μg, respectively). After 4 years of regular use of the drug at a dose of 22 μg and a dose of 44 μg, the decrease in the number of exacerbations averaged 22 and 29%, respectively, compared with the group in which patients received placebo for 2 years, and then interferon beta-1a at a dose of 22 μg and at a dose of 44 mcg.

According to the data of a three-year study, which studied the effect of the drug on patients with secondary progressive multiple sclerosis (3-6.5 points on the EDSS scale) with a significant progression of disability during the previous 2 years and no exacerbations during the last 8 weeks, there were no significant impact on disability, however, a decrease in the number of exacerbations by 30% was recorded.

The study also compared two groups of patients - with exacerbations and without exacerbations of the disease in the previous 2 years. In the group without exacerbations, the effect of interferon beta-1a on the progression of disability was not revealed. In the group with exacerbations of the disease at the end of the study, a decrease in the incidence of disease progression was recorded from 70% (placebo) to 57% (interferon beta-1a at a dose of 22 μg and a dose of 44 μg).

Primary progressive multiple sclerosis

In patients with primary progressive sclerosis, the effect of the drug has not been studied.

Pharmacokinetics

After intravenous administration of interferon beta-la to healthy volunteers, the concentration of the drug underwent a sharp exponential decrease, while its serum content was proportional to the dose.

After repeated sc injections of Teberif at a dose of 22 and 44 μg, C _max is noted after 8 hours, but this value varies greatly in different patients.

In the human body, interferon beta-1a is metabolized, excreted by the kidneys and liver.

After repeated sc injections of Teberif, an increase in basic pharmacokinetic parameters, such as AUC (area under the concentration-time curve) and C _max, is proportional to the increase in dose from 22 to 44 μg.

The half-life (T _½) of the drug is 50–60 hours, which correlates with the cumulation process that is observed after multiple injections of Teberif.

Indications for use

• the first episode of demyelination, which is based on an acute inflammatory process, in patients at high risk of developing clinically significant multiple sclerosis after excluding other diagnoses;
• remitting multiple sclerosis in patients with two or more exacerbations in the previous two years.

Contraindications

Absolute:

• severe depressive disorders and / or suicidal behavior;
• pregnancy;
• lactation;
• children under 12 years old;
• hypersensitivity to natural or recombinant interferon beta, as well as to any auxiliary component of Teberif.

Relative:

• myelosuppression;
• severe renal failure;
• severe hepatic impairment in history;
• active liver disease;
• the level of alanine aminotransferase (ALT) is 2.5 times higher than the upper limit of the norm;
• alcohol abuse;
• depressive conditions, including a history;
• a history of epileptic seizures, especially in patients with convulsive syndrome, not amenable to complete control with antiepileptic drugs;
• pathological changes in the thyroid gland;
• rhythm disturbances, angina pectoris;
• congestive heart failure.

Teberif, instructions for use: method and dosage

Treatment is carried out under the supervision of a medical specialist with relevant experience. Teberif is administered as a subcutaneous injection. The drug should be administered on certain days of the week with a minimum interval of 48 hours, at the same time of the day (preferably in the evening).

If the purpose of using the drug is to prevent the development of tachyphylaxis and reduce unwanted reactions, the following therapy regimen is recommended:

• 1 and 2 weeks - 8.8 mcg 3 times a week;
• 3 and 4 weeks - 22 mcg 3 times a week;
• 5 week and further - 44 mcg 3 times a week.

To reduce the severity of flu-like symptoms associated with the introduction of Teberif, it is recommended to take an antipyretic agent on the eve of each injection and within 24 hours after it.

Patients with the first episode of demyelination are prescribed 44 mcg of the drug 3 times a week.

In relapsing-remitting multiple sclerosis, adults and adolescents from 16 years of age are administered 44 mcg 3 times a week. In case of poor tolerance, a single dose is reduced to 22 μg.

The efficacy and safety of interferon beta-1a in adolescents 12-16 years old with relapsing multiple sclerosis has not yet been fully established. Therefore, it is not possible today to give precise recommendations on the dosage regimen of the drug for children of this age. Nevertheless, based on the available published data, it can be assumed that the safety profile of Teberif in adolescents 12-16 years old receiving interferon beta-1a s / c at a dose of 22 μg three times a week is similar to that in adults.

For treatment to be effective and safe, patients should adhere to the following basic rules:

• apply Teberif under the supervision of an experienced doctor;
• strictly follow the instructions for the administration of the drug in order to prevent the development of necrosis. In case of development of local reactions in the area of injections, consult a doctor;
• do not interrupt therapy yourself;
• do not change the dose of the drug yourself;
• before starting treatment, warn the doctor about the intolerance of any medications (if any);
• in the course of treatment, inform the doctor about any health problems.

There are no clear recommendations on the duration of treatment. At least once every two years during the first 4 years of using Teberif, the patient's condition is assessed and a decision is made on the need to continue therapy.

Self-administered subcutaneous injection

Teberif comes in the form of a pre-filled syringe, so it can be used safely at home - on its own or with someone's help. Whenever possible, it is recommended that the first injection be given under the supervision of a qualified healthcare professional.

Drug administration rules:

1. Choose a convenient time of day, preferably in the evening before bedtime.
2. Wash hands thoroughly with soap and water.
3. Take one blister strip out of the refrigerator and keep it for several minutes so that the drug warms up to room temperature (there should be no condensation on the syringe). If it is not possible to store the drug in the refrigerator, one-time storage in a dark place at a temperature of up to 25 ° C for no more than 30 days is allowed, in this case it is necessary to mark on the packaging the date of the beginning of storage at room temperature.
4. Inspect the syringe for discoloration or precipitation in the solution, or damage to the syringe. You can only use a clear or slightly opalescent solution that does not contain impurities. If foam appears in the solution (possibly with strong shaking or shaking), you must wait until it settles.
5. Select a body site for injection. You should choose places with loose adipose tissue (fatty layer between the skin and muscle tissue), away from blood vessels, joints, nerves and places of stretching of the skin. This can be the upper outer quadrant of the buttocks, the outer surface of the shoulder, abdomen (except for the umbilical region and midline), thigh (the front surface, except for the groin and knee). Do not inject the drug into sore spots, reddened or discolored areas of the skin, or areas with nodules and lumps. To reduce discomfort and pain, you should constantly alternate injection sites and change injection points within a specific area.
6. Disinfect the injection site.
7. Take the syringe with the drug in your hand (for ease of administration, it is necessary to inject with the hand that is involved in writing), remove the protective cap from the needle.
8. Depending on the prescribed dose, if necessary, remove excess solution from the syringe by slowly pressing the syringe plunger until it reaches the desired mark on the label.
9. Gather the skin lightly into a crease with your thumb and forefinger.
10. Position the syringe perpendicular to the injection site and insert the needle into the skin at an angle of 90 ° to a depth of about 6 mm (it is selected individually depending on the body type and the thickness of the subcutaneous tissue).
11. Inject the drug by gently pressing the plunger.
12. Remove the syringe with the needle in a vertical upward motion, maintaining the same angle of inclination.
13. Apply a dry sterile cotton pad to the injection site, if necessary, cover with a plaster. Do not massage or rub the injection area.
14. Throw away the used syringe.

If the next injection is missed, the dose cannot be doubled, the drug should be administered as soon as it is remembered, and then injections should be made at intervals of at least 48 hours.

Do not stop treatment without consulting a doctor.

In case of an increase in the upper limit of the normal level of ALT, the dose of Teberif should be reduced. After its normalization, the dose can be gradually increased.

A temporary dose reduction may also be required in patients with severe flu-like symptoms.

Side effects

The most common adverse events associated with the use of interferon beta-la are due to the development of flu-like syndrome. Symptoms are usually pronounced at the beginning of treatment and subside as therapy continues. In the first six months after starting the use of Teberif, the appearance of a typical flu-like syndrome can be expected in 70% of patients.

In about 30% of cases, there are reactions at the injection site, more often it is erythema or moderate irritation.

A decrease in the number of leukocytes and an asymptomatic increase in laboratory parameters of hepatic function are also frequent.

The following side effects were observed in patients with multiple sclerosis both in clinical trials and in the post-registration period (marked with *). Their frequency is classified as follows: very often - ≥ 1/10 cases, often - from ≥ 1/100 to <1/10, infrequently - from ≥ 1/1000 to <1/100, rarely - from ≥ 1/10 000 to <1/1000), very rarely - <1/10 000, unknown frequency - based on the available data, the frequency cannot be established:

• on the part of the blood and lymphatic system: very often - anemia, leukopenia, lymphopenia, thrombocytopenia, neutropenia; rarely - pancytopenia *, thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome * (is the class effect of interferons);
• from the endocrine system: infrequently - dysfunction of the thyroid gland (usually hypo- or hyperthyroidism);
• from the liver and biliary tract: very often - an asymptomatic increase in the activity of hepatic transaminases in the blood; often - a significant increase in the activity of transaminases in the blood; infrequently - hepatitis * (including with jaundice); rarely - liver failure *, autoimmune hepatitis *;
• from the gastrointestinal tract: often - diarrhea, nausea, vomiting;
• from the kidneys and urinary system: rarely - glomerulosclerosis *, nephrotic syndrome *;
• from the vascular system: infrequently - thromboembolism *;
• on the part of the skin and subcutaneous tissues: often - a rash (including erythematous and maculopapular), itching, alopecia *; infrequently - urticaria *; rarely - a skin reaction resembling erythema multiforme *, erythema multiforme *, Quincke's edema *, Stevens-Johnson syndrome *;
• from the respiratory system: infrequently - shortness of breath *; unknown frequency - pulmonary arterial hypertension (is the class effect of interferons);
• from the nervous system: very often - headache; infrequently - convulsions *; unknown frequency - transient neurological symptoms (difficulty walking, muscle spasms, muscle stiffness, hypesthesia, paresthesia) that can simulate exacerbation of multiple sclerosis *;
• mental disorders: often - insomnia, depression; rarely - suicidal attempts;
• on the part of the connective and musculoskeletal tissue: often - myalgia, arthralgia; rarely, medicinal lupus erythematosus *;
• from the immune system: rarely - anaphylactic reactions *;
• on the part of the organ of vision: infrequently - damage to the retinal vessels * ("cotton spots" on the retina, retinopathy, obstruction of the retinal vein or artery);
• general disorders and disorders at the injection site: very often - flu-like symptoms, reactions at the injection site (for example, swelling, redness, edema, bruising, inflammation); often - fatigue, fever, chills, pain at the injection site; infrequently - increased sweating *, swelling, abscess and necrosis at the injection site, infection of the injection site *; rarely - phlegmon at the injection site *.

Patients should be warned about the need to inform the attending physician about all possible side effects, even if they are not indicated in the instructions for use of Teberif. If the adverse reactions persist for a long time or are severe, the doctor may recommend temporarily reducing the dose of the drug or interrupting the treatment.

Child safety profile

Separate pharmacokinetic and clinical studies on the use of interferon beta-1a in children and adolescents have not been conducted. However, there are published data that report the use of the drug in adolescents 12-16 years old s / c 22 mcg 3 times a week. These results suggest that in this group the safety profile of Teberif is similar to that in the group of adult patients.

Class effects

Interferon treatment is associated with the following symptoms: loss of appetite, dizziness, anxiety, heart palpitations, arrhythmias, vasodilation, metrorrhagia, menorrhagia.

During the period of therapy, increased formation of antibodies is possible.

Arterial pulmonary hypertension

There are known cases of the development of pulmonary arterial hypertension in patients receiving interferon preparations, and at different stages of therapy, including several years after the start of treatment.

Overdose

To date, no case of overdose of Teberif has been reported. Patients who have injected too high a dose of the drug are advised to immediately inform their doctor. If necessary, the patient is hospitalized, closely monitored, and supportive.

special instructions

In addition to the standard laboratory tests, which are always carried out in patients with multiple sclerosis, it is recommended 1, 3 and 6 months after the start of treatment, as well as periodically, in the absence of clinical symptoms, to determine the number of platelets, to conduct a general blood test with a leukocyte formula and a biochemical blood test. including functional liver tests.

Women with fertile potential

Women of reproductive age should use reliable methods of contraception during treatment. Patients who are planning a pregnancy or become pregnant while using the drug should inform their attending physician about this to consider canceling Teberif. Patients with a high relapse rate should be weighed against the risk of severe relapse due to drug withdrawal due to pregnancy and a possible increase in the likelihood of spontaneous abortion if the drug is continued.

Thrombotic microangiopathy (TMA)

Cases of thrombotic microangiopathy development have been reported during drug therapy. It manifested itself with thrombotic / thrombocytopenic purpura or hemolytic uremic syndrome, up to death. Was registered in different periods of treatment - from several weeks to several years from the beginning of the use of interferon beta-1a. In this regard, it is recommended to monitor the early symptoms of these complications: newly emerging cases of hypertension, decreased renal function, fever, thrombocytopenia, disorders of the central nervous system (for example, paresis or confusion).

If TMA is suspected, tests for platelets and serum lactate dehydrogenase (LDH), blood tests to assess renal function are indicated. According to the test results, a decrease in the number of platelets and an increase in serum LDH activity caused by hemolysis and schizocytes in a blood smear are possible. If the diagnosis is confirmed, treatment with Teberif is stopped and appropriate treatment is urgently prescribed, if necessary, a plasma transfusion is made.

Dysfunction of the kidneys and urinary system

There are known cases of the development of nephrotic syndrome with various nephropathies, including focal segmental glomerulosclerosis, membrane glomerulopathy and membranoproliferative glomerulonephritis. Violations developed both during the period of treatment with interferon beta-1a, and several years after its termination. It is recommended to pay attention to the possible appearance of early signs, such as impaired renal function, proteinuria, edema, especially in patients at high risk of developing kidney disease.

If nephrotic syndrome is detected, Teberif is canceled and appropriate treatment is immediately prescribed.

Liver dysfunction

In clinical trials, cases of asymptomatic increase in the activity of hepatic transaminases, especially ALT, have been reported. At the same time, in 1–3% of patients, the level exceeded the upper limits of the norm (ULN) by 5 or more times.

If there are no clinical symptoms, the ALT should be monitored before the appointment of Teberif, after 1, 3 and 6 months, then periodically throughout the entire period of treatment.

If the ALT activity is 5 times higher than the VGN, the dose of the drug should be reduced until it is normalized, after which a gradual increase in the dose is allowed.

Patients with liver disease (including a history) and an initially elevated ALT level require caution and more careful monitoring.

In case of the appearance of any clinical symptom indicating a functional impairment of the liver, or jaundice, the administration of Teberif should be discontinued.

All interferons beta have the potential to cause severe liver damage, including acute liver failure. Severe disorders are usually noted in the first six months of treatment. To date, neither risk factors nor the mechanism of these conditions have been identified.

Cardiovascular diseases

At the initial stage of therapy, careful monitoring of patients with cardiovascular diseases, such as rhythm disturbances, congestive heart failure, angina pectoris, is required in order to detect possible deterioration in time.

Flu-like symptoms associated with the use of interferon beta-1a can be a serious burden for patients with heart disease.

Diseases of the thyroid gland

Against the background of drug therapy, it is possible to develop or aggravate existing pathological changes in the thyroid gland.

Before starting treatment and every 6-12 months during therapy, it is recommended to assess the state of the thyroid gland, especially if signs of thyroid dysfunction appear.

Depression and suicidal ideation

In patients with multiple sclerosis taking interferon, depressive and suicidal states are observed with an increased frequency.

Patients should be warned to immediately inform their doctor of any signs of depression and / or suicidal thoughts.

In patients with depression, the use of Teberif is possible only under close medical supervision. In some cases, it may be necessary to cancel the drug.

Injection site necrosis

There are isolated cases of necrosis at the injection site. This risk can be minimized by strict adherence to the rules of asepsis when injecting the drug and the constant change of the injection site. Physicians should periodically evaluate the patient's technique for self-administration of Teberif.

Patients should see a doctor if they detect skin lesions with fluid and swelling at the injection site. If multiple skin lesions appear, it is recommended to cancel the drug before they heal. If the lesion is single and moderate, therapy can be continued.

Neutralizing antibodies

Approximately 13-14% of patients receiving a dose of 44 mcg and 24% of patients receiving a dose of 22 mcg, after 1-2 years of using Teberif, neutralizing antibodies to interferon beta-1a are found in the blood serum. This is associated with a decrease in the effectiveness of the therapy, which is confirmed by clinical parameters and MRI studies.

The full clinical significance of such a phenomenon as the production of neutralizing antibodies has not been sufficiently studied to date. Presumably, this is due to the reaction to the presence of various forms of interferon beta.

In case of insufficiently good response to the administration of Teberif, due to the persistent presence of neutralizing antibodies, it is necessary to consider the feasibility of continuing therapy.

The ability to compare the immunogenicity of different drugs is limited by the use of different methods for detecting and characterizing antibodies in serum.

Other forms of multiple sclerosis

Limited data are available on the safety and efficacy of Teberif in non-ambulatory patients with multiple sclerosis. The use of the drug for the treatment of primary progressive multiple sclerosis has not been studied, so it is not prescribed for this disease.

Influence on the ability to drive vehicles and complex mechanisms

Teberif can cause side effects that can negatively affect the speed of reactions and the ability to concentrate. The degree of restrictions on the performance of potentially hazardous activities is determined individually.

Application during pregnancy and lactation

During pregnancy, it is contraindicated to start treatment with the drug. Interferon beta-1a has been reported to promote spontaneous abortion.

There is no data on the excretion of the drug in breast milk, but it is assumed that there is a risk of serious side effects in newborns. In this regard, it is recommended to stop feeding the baby if the woman needs treatment with interferon beta-1a.

Pediatric use

Teberif is not used to treat children under the age of 12, since the data on its use in this age group are very limited.

The efficacy and safety of interferon beta-1a in adolescents 12-16 years old with relapsing multiple sclerosis has not yet been fully established. It is not possible today to give precise recommendations on the dosage regimen for children of this age. Nevertheless, based on the available published data, it can be assumed that the safety profile of Teberif in adolescents 12-16 years old receiving interferon beta-1a s / c at a dose of 22 μg three times a week is similar to that in adults.

With impaired renal function

Patients with severe renal failure should use Teberif with caution.

For violations of liver function

It is required to observe precautions when treating the drug in patients with active liver disease, severe hepatic failure in history, high ALT levels (2.5 times higher than ULN), as well as alcohol abusers.

Use in the elderly

There is no information about changes in the pharmacokinetics of interferon beta-1a in elderly patients.

Drug interactions

Special controlled studies to study the interactions of interferon beta-1a with other medications have not been conducted. However, it is known for sure that in the body of animals and humans, interferons reduce the activity of cytochrome-P450-dependent liver enzymes. In this regard, it is recommended to use with caution other drugs with a narrow therapeutic index, the clearance of which largely depends on the cytochrome P450 system of the liver, including antiepileptic drugs and some antidepressants.

According to clinical studies, patients with multiple sclerosis during exacerbations of the disease can be simultaneously prescribed adrenocorticotropic hormone (ACTH) or corticosteroids.

Analogs

The analogues of Teberif are: Betaferon, Genfaxon, Infibeta, Rebif, SinnoVex, Interferon beta1-B, etc.

Terms and conditions of storage

Store in a dark place with a temperature of 2-8 ° C. Keep out of the reach of children. Do not freeze.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Teberife

The drug appeared on the pharmaceutical market relatively recently, so there are no reviews about Teberif. This tool is a complete domestic analogue of the Italian drug Rebif, reviews of which are positive. In this regard, in specialized forums, patients mainly try to find out about the effectiveness and portability of Teberif, however, messages from users who are already receiving treatment with this drug are not found at the moment.

The price of Teberif in pharmacies

The price of Teberif for a pack of 3 syringes with a solution for subcutaneous administration at a dose of 22 mcg is approximately 8300 rubles.

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!