Composition, form of production and packaging
The solution for the infusion is slightly opalescent, light yellow in color.
1 dose (0.5 ml)
interferon beta-1a 22 Ојg (6 million IU)
- "- 44 Ојg (12 million IU)
[PRING] mannitol - 22.5 mg, benzyl alcohol - 2.5 mg, methionine - 0.06 mg, poloxamer 188 - 0.25 mg, sodium acetate buffer solution 0.01M (sodium acetate, acetic acid, sodium hydroxide (for adjustment to pH), water d / i) up to 0.5 ml.
0.5 ml - syringes with a capacity of 1 ml with a needle (1) - plastic containers (3) - packs cardboard.
0.5 ml - syringes with a capacity of 1 ml with a needle (1) - plastic containers (12) - packs of cardboard.
0.5 ml - syringe-pen capacity 1 ml (1) - plastic containers (3) - packs cardboard.
0.5 ml - syringe-pens with a capacity of 1 ml (1) - plastic containers (12) - packs of cardboard.
The solution for the infusion is slightly opalescent, light yellow in color.
3 doses (1.5 ml)
interferon beta-1a 66 Ојg (18 million IU)
- "- 132 Ојg (36 million IU)
[PRING] mannitol - 67.5 mg, benzyl alcohol - 7.5 mg, methionine - 0.18 mg, poloxamer 188 - 0.75 mg, sodium acetate buffer solution 0.01M (sodium acetate, acetic acid, sodium hydroxide (for adjustment to pH), water d / i) up to 1.5 ml.
1.5 ml - cartridges with a capacity of 3 ml (1) - plastic containers (4) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Rebif В® has immunomodulatory, antiviral and antiproliferative properties.
The protein structure of the preparation Rebif В® (interferon beta-1a recombinant human) is a natural amino acid sequence of human interferon beta, obtained by genetic engineering using the culture of Chinese hamster ovary cells.
The mechanism of action of the drug Rebif В® in the body of patients with multiple sclerosis is not fully understood. It is shown that the drug helps limit the damage to the central nervous system underlying the disease.
The mechanism of action of the drug Rebif В® in patients with multiple sclerosis is not fully understood. It is shown that the drug helps limit the damage to the central nervous system underlying the disease.
When using Rebif В® at the recommended dose, a decrease in the frequency (30% for 2 years) and the severity of exacerbations in patients with two or more exacerbations during the last 2 years and an estimate from 0 to 5 in the extended disability assessment scale (EDSS) before starting treatment. The proportion of patients with confirmed disability progression decreased from 39% (placebo) to 30% and 27% (Rebif В® 22 Ојg and 44 Ојg, respectively).
After 4 years, the mean reduction in the number of exacerbations was 22% and 29% in patients treated with Rebif В® 22 Ојg and Rebif В® 44 Ојg, respectively, compared with the group receiving 2 years of placebo, followed by Rebif В® 22 Ојg and Rebif В® 44 Ојg.
In a 3-year study in patients with secondary-progressive multiple sclerosis (3-6.5 on the EDSS scale) with a significant progression of disability during the previous 2 years and no exacerbations during the previous 8 weeks, RebifВ® had no significant effect on disability, however the frequency of exacerbations decreased by 30%. In the two groups of patients (with or without exacerbations during the previous 2 years), the effect of the drug on the progression of disability was not found in the group without exacerbations, while in the exacerbation group the proportion of patients with progression at the end of the study decreased from 70% (placebo) up to 57% (Rebif В® 22 Ојg and Rebif В® 44 Ојg).
The action of the Rebif has not been studied with primary-progressive multiple sclerosis.
Suction and distribution
When n / k or / m introduction levels of interferon beta in the blood serum are determined within 12-24 hours after the injection, regardless of the mode of administration.
After a single dose injection, 60 Ојg of C max , determined by immunological methods, is detected after 3 hours and is 6-10 IU / ml. With a 4-fold infusion of the same dose every 48 hours, a moderate cumulation of the drug occurs. After a single administration, the intracellular and serum activity of 2-5A synthetase and the serum concentration of beta 2 microglobulin and neopterin (biological response markers) increase within 24 hours, and then decrease within 2 days.
Metabolism and excretion
Interferon beta is metabolized and excreted by the liver and kidneys. The total ground clearance is about 33-55 l / h.
treatment of remitting multiple sclerosis.
The drug was not effective in patients with secondary-progressive multiple sclerosis in the absence of exacerbations.
Treatment is recommended to begin under the supervision of a doctor who has experience in the treatment of this disease.
The drug is administered sc.
Adults and adolescents over 16 years of age usually receive a recommended dose of 44 Ојg 3 times a week. In case of insufficiently good tolerability of this dose Rebif В® is prescribed in a dose of 22 mcg 3 times a week.
Adolescents aged 12 to 16 years, the drug is prescribed, usually in a dose of 22 mcg 3 times a week.
The drug should be used at the same time (preferably in the evening), on certain days of the week, with an interval of at least 48 hours.
Rebif В® can be used only if the solution of the drug is clear or slightly opalescent and if it contains no foreign particles.
For the first 2 weeks, Rebif В® should be administered at a dose of 8.8 Ојg (0.2 ml of the drug at a dosage of 0.5 ml / 22 Ојg or 0.1 ml of the drug at a dosage of 0.5 ml / 44 Ојg), for 3 and 4 weeks at a dose of 22 Ојg (0.5 ml of the drug with a dosage of 0.5 ml / 22 Ојg or 0.25 ml of the drug at a dosage of 0.5 ml / 44 Ојg). To administer the initial dose of the drug during the first 4 weeks of treatment, use syringes or cartridges, because Syringe-pens are not designed for this purpose.
With the appointment of Rebif in a dose of 44 mcg, starting at 5 weeks, inject 0.5 ml of the drug at a dosage of 0.5 ml / 44 mcg.
If necessary, to reduce influenza-like symptoms associated with the appointment of the drug Rebif В® , before the injection and within 24 hours after each injection, it is recommended to prescribe an antipyretic analgesic.
There are currently no clear recommendations on how long the treatment should be carried out. It is recommended that patients be evaluated at least every second year during the first 4 years of treatment with RebifВ®, and the decision on longer-term therapy should be taken individually by the attending physician for each patient.
The physician should inform the patient that to ensure the effectiveness and safety of treatment with Rebif В®, it is necessary:
- use Rebif В® only under the supervision of an experienced physician;
- to carefully read the instructions and follow its instructions to prevent necrosis;
- If a reaction occurs at the injection site, consult a physician;
- do not change the dose without consulting the doctor;
- Do not interrupt treatment without consulting a doctor;
- warn the doctor if there is any intolerance to any medications;
- in the course of treatment, inform the doctor of any health problems.
Rules for self-administration of the drug
Rebif В® should be a clear or slightly opalescent solution, with no visible foreign particles. If the patient has detected the presence of foreign particles in the solution or if there is any doubt as to the quality of the drug, it should not be used. In such cases, the patient should consult a doctor or nurse.
The doctor should advise the patient how to choose a possible place for injection (convenient areas are located in the upper part of the thigh or in the lower part of the abdomen). It is recommended to alternate injection sites, avoiding frequent injections in the same place. Do not administer the drug to places where there is swelling, hard nodules or pain; The patient should inform the doctor or nurse about the presence of such sites.
In case of missed injection, continue the injection, starting with the next injection on schedule. Do not administer a double dose of the drug.
The first injection of the drug is recommended to be performed under the supervision of a qualified medical professional.
1. Before carrying out the injection, wash hands thoroughly with soap and water.
2. Remove the syringe with Rebif В® from the package.
3. Wipe the skin at the injection site with an alcoholic napkin and allow the skin to dry. If alcohol partially remains on the skin, then there is a burning sensation.
4. Gently squeeze the skin around the selected place so that it is slightly raised. Pressing your wrist against the skin near the site, you should insert the needle at a right angle into the skin with a quick and firm movement. The syringe should be kept as a pencil or dart. Introduce the drug with a slow and constant pressure (press on the piston until the syringe is empty). For convenience, the corresponding slicing (graduation) is plotted on the syringe.
5. Remove the needle from the skin. Clamp the injection site with a swab.
6. Lightly massage the injection site with a dry cotton ball or gauze.
7. Discard the used syringe. The drug remaining in the syringe is not subject to further use.
Syringe pens are for single use only.
Before using the syringe pen, carefully read the instructions below.
To carry out the injection you need: a syringe-pen (make sure the integrity of its packaging); alcohol wipes.
Before the injection of syringe pen
1. Wash your hands thoroughly with soap and water.
2. Remove the syringe from the container.
3. Check the appearance of the Rebif В® preparation through the transparent control area of вЂ‹вЂ‹the pen syringe.
4. Check the expiration date on the label of the syringe pen.
Introduction of Rebif В® with a syringe pen
1. Wipe the skin at the injection site with an alcoholic napkin and allow the skin to dry. If alcohol partially remains on the skin, you can feel the burning sensation.
2. Remove the cap immediately before injection. Holding a syringe-pen in one hand by the body, remove the cap with the other hand.
3. Position the syringe handle at a right angle (90 В°) to the skin at the intended injection site, press the syringe onto the skin until you feel resistance. In this case, the limiter is retracted into the body of the syringe pen and the button on the syringe handle is unlocked.
4. While maintaining sufficient pressure of the syringe pen on the injection area, press the button with your thumb. A click will be heard indicating the start of the injection and the start of the plunger movement. Keep the syringe handle pressed on the skin for at least 10 seconds to ensure that the injection is fully completed.After the injection, the button can be released.
5. After the injection, raise the syringe pen. In this case, the limiter automatically extends and locks around the needle, providing protection against possible needle damage.
6. Check the clear control zone to make sure the piston has moved down.
7. It should be ensured that no drug remains in the syringe pen. If the solution remained in the syringe pen after the injection, then the Rebif В® preparation was not completely injected, and the patient should consult a physician.
8. The injection site should be slightly massaged with a dry cotton ball or swab.
In case of any difficulties with the use of the syringe pen, the patient should seek help from a doctor or nurse.
Used syringe pens
1. Syringe-pens are intended only for single use at a dose of 0.5 ml and should never be reused.
2. Never put a lid on the used syringe pen.
3. Immediately after the injection, discard the used syringe pen.
4. To avoid injury, never put your fingers in the hole of the safety stop that covers the needle.
Cartridges for 3 doses
Cartridges with the preparation Rebif В® are designed for reusable use together with an autoinjector.
The first injection should be carried out under the supervision of a doctor or other specialist with appropriate qualifications. The patient can use Rebif В® cartridges after the appropriate instruction is given.
How to Install a Rebif В® Cartridge
1. Wash your hands thoroughly with soap and water.
2. Immediately after the cartridge has been removed from the refrigerator, make sure that the solution in the cartridge in the package or in the autoinjector is not accidentally frozen.
3. Remove the Rebif В® cartridge from the blister package, taking off the plastic cover.
4. To install the cartridge in the injector, follow the instructions in the manual for the auto-injector.
How to enter Rebif В® in cartridges
1. The attending physician should show the patient how to set the prescribed dose in the auto injector (22 Ојg or 44 Ојg), which is also reflected in the instructions to the device. Before the injection, make sure that the dose of the drug displayed on the screen corresponds to that prescribed by the doctor.
2. Wipe the skin at the injection site with an alcoholic napkin and allow the skin to dry. If alcohol partially remains on the skin, you can feel the burning sensation.
3. Position the auto-injector on the skin at a right angle (90 В°) to the selected injection site.
4. Press the button to start the injection.
5. Wait until the end of the injection.
6. Remove the auto injector from the injection site.
7. Remove and dispose of the used needle in accordance with the instructions for the autoinjector.
8. The injection site should be slightly massaged with a dry cotton ball or gauze.
Detailed instructions for working with the autoinjector are contained in the manual that accompanies it.
If the patient decides to stop using Rebif В®
The effect of the Rebif В® preparation may not be immediately noticeable. To achieve the desired result, you should continue to administer RebifВ® regularly. You can not stop treatment yourself without consulting a doctor.
Determination of the frequency of adverse reactions: (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1/10 000 <1/1000) , very rarely (<1/10 000).
Adverse reactions noted in clinical trials
The summarized data obtained in clinical studies in patients with multiple sclerosis during the first 6 months of treatment compared with placebo are summarized below.
Infections and invasions: infrequently - postinjection abscess.
From the hemopoietic system: very often - neutropenia, lymphopenia, leukopenia, thrombocytopenia, anemia.
From the endocrine system: infrequently - hypo- or hyperthyroidism.
From the nervous system: very often - a headache.
Mental disorders: often - depression, insomnia.
From the skin and subcutaneous tissues : often - itching, rash (including erythematous and maculopapular).
From the osteomuscular and connective tissue: often - myalgia, arthralgia.
Common reactions: very often - influenza-like symptoms; often fatigue, chills, fever. Flu-like symptoms (headache, fever, chills, muscle and joint pains, nausea) are observed in approximately 70% of patients during the first 6 months of treatment and decrease with continued therapy.
Local reactions: very often - inflammation at the injection site, reactions at the injection site (eg, bruising, swelling, redness); often - pain at the injection site;infrequently - necrosis at the injection site. Reactions at the injection site are observed in approximately 30% of patients, are usually not very pronounced and are reversible.
From the side of laboratory indicators: very often - an asymptomatic increase in the concentration of transaminases in the blood; often - significant (> 5 times higher than UGN) increase in the concentration of transaminases in the blood.
Adverse reactions observed during post-registration follow-up
The frequency of these reactions is unknown, most likely from "infrequently" to "very rare".
Infections and infestations: infection at the injection site, incl. inflammation of the subcutaneous tissue.
From the coagulation system: thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome.
On the part of the nervous system: convulsions, transient neurological symptoms (hypoesthesia, muscle spasms, paresthesia, difficulty walking, stiff muscles) that can mimic the aggravation of multiple sclerosis.
From the cardiovascular system: thromboembolic disorders.
From the respiratory system: shortness of breath.
Mental disorders: attempted suicide.
From the side of the organ of vision: damage to the retinal vessels (ie, retinopathy, "cotton spots" on the retina, artery obstruction or retinal vein).
From the skin and subcutaneous tissues: erythema multiforme and similar skin reactions, Stevens-Johnson syndrome, alopecia.
Allergic reactions: Quincke's edema, hives, anaphylactic reactions.
From the liver and biliary tract: liver failure, hepatitis (with jaundice or without it).
If side effects are maintained for a long time or if serious adverse reactions develop, at the discretion of the doctor, a temporary reduction in the dose of the drug or interruption of treatment is allowed.
The patient should inform the doctor of any adverse reactions.
- severe depressive disorders and / or suicidal ideation;
- epilepsy in the absence of effect from the application of appropriate therapy;
- children's age till 12 years;
- Hypersensitivity to natural or recombinant interferon beta, to other components of the drug.
PREGNANCY AND LACTATION
The use of Rebif В® during pregnancy and lactation (breastfeeding) is contraindicated.
Women of childbearing age should use effective means of contraception. Given the potential risk to the fetus, when planning a pregnancy or during pregnancy, which set against the background of the treatment, the patient should be sure to inform your doctor to decide on the abolition of therapy.
Data on the allocation of interferon beta-1a in breast milk are not available. Given the likelihood of serious adverse reactions in infants, breastfeeding should be discontinued, if necessary, use during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution and under strict medical supervision should be prescribed to patients with severe renal insufficiency.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution and under strict medical supervision should be prescribed to patients with severe hepatic insufficiency.
APPLICATION FOR CHILDREN
Contraindicated in children under 12 years.
In adolescents aged 12 to 16 years of drug administered usually at a dose of 22 mg 3 times a week.
Precautions should be prescribed to patients with depression. Such patients during treatment with Rebif requires careful medical supervision and conditions to ensure the provision of adequate assistance. In some cases, it may require discontinuation of treatment with interferon beta.
Patients should be warned that they should immediately inform the doctor about any symptoms of depression and / or emergence of suicidal ideation.
You must also be careful in appointing interferon beta-1a to patients who have previously been observed seizures, patients receiving antiepileptic drugs, especially if they are not sufficiently effective. If there during treatment with Rebif В®seizures in patients who have not previously suffered from these disorders, it is necessary to cancel the Rebif В® , establish the etiology of seizures and assign anticonvulsant therapy before resuming treatment Rebif.
In the early stages of treatment with interferon beta-1a requires strict monitoring of patients suffering from cardiovascular diseases such as angina, congestive heart failure and cardiac arrhythmias. This observation should be directed to the timely identification of possible states of deterioration. In diseases of the heart flu-like symptoms associated with interferon therapy beta-1a may aggravate the condition of patients.
There are few reports about the development of necrosis at the site of injection. To minimize the risk of strict adherence to aseptic necrosis of the rules is necessary in the performance of the injection and the constant change of the injection sites. If there is damage to the skin with swelling and fluid release at the injection site, the patient should consult a physician before continuing administration of the drug. When multiple skin lesions should abolish drug before healing. When a single lesion may continued therapy with Rebif В® , provided that the lesion is moderately expressed.
In clinical trials, there was an increase in liver enzymes, particularly ALT. In the absence of clinical symptoms need to monitor plasma levels of ALT before therapy drug Rebif В®and repeated after 1, 3 and 6 months, as well as periodically during the further treatment. It is necessary to reduce the dose if ALT levels exceeding 5 times ULN, and gradually increase the dose after normalization. Care must be taken when assigning interferon beta-1a patients with severe hepatic insufficiency history with evidence of liver disease, alcohol abuse characteristics, ALT 2.5 times the ULN. Therapy should be discontinued if jaundice or other symptoms of liver dysfunction.
Rebif В® , as well as other interferon betas may potentially cause serious disorders of the liver, up to acute liver failure. The mechanism of these conditions is unknown, the specific risk factors have been identified.
In addition to laboratory tests, which are always carried out in patients with multiple sclerosis, it is recommended in the 1st, 3rd and 6th month of starting therapy with Rebif В® , and periodically, the absence of clinical symptoms in the course of further treatment spend a common clinical blood tests, blood leukocyte formula, platelet count, and to carry out a biochemical blood, including liver function tests.
In patients receiving Rebif В®Sometimes develop or worsen thyroid dysfunction. It is recommended to carry out a study of thyroid function immediately before the start of treatment and in case of violations - every 6-12 months from the date of its commencement. If prior to treatment thyroid function is normal, periodic studies of its functions are not required, but their conduct is necessary for the appearance of clinical signs of thyroid dysfunction
in patients receiving interferon beta, the formation of neutralizing antibodies. The clinical significance of not established. If there is not enough good therapeutic response to therapy with Rebif В® , and it is associated with a stable presence of neutralizing antibodies, your doctor should evaluate the advisability of continuing interferon therapy.
Caution should be exercised when administering the drug to patients with severe renal insufficiency, and myelosuppression.
Use in Pediatrics
The safety profile in adolescents aged 12 to 16 years of age receiving Rebif В® at a dose of 22 mg n / a 3 times per week is similar to the profile of adult patients.
Impact on the ability to drive vehicles and manage mechanisms
Adverse reactions from the CNS to the ongoing interferon therapy may affect the ability for transportation vehicles and equipment management.
With the introduction of more than prescribed, dose the patient should immediately notify your doctor.
If necessary, in the case of an overdose the patient should be hospitalized for further observation and supportive care.
Specific clinical studies of drug interactions Rebif В® with other drugs have not been performed.
It is known that in humans and animal interferons decrease the activity of cytochrome P450 isoenzymes in liver. It should therefore be used with caution Rebif В®simultaneously with drugs having a narrow therapeutic index, the clearance of which largely depends on the activity of the enzyme system, such as some anticonvulsants and antidepressants.
A systematic study of drug interaction Rebif В®with ACTH or corticosteroids is not performed. Data from clinical studies indicate the possibility of multiple sclerosis patients receiving drug Rebif В® and ACTH or corticosteroids during exacerbations of the disease.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of the reach of children at a temperature of 2 В° to 8 В° C; Do not freeze. Shelf life - 2 years.
Transported at a temperature of from 2 В° to 8 В° C.