REBIF

Active material: Interferon beta-1a
When ATH: L03AB07
CCF: Interferon. Preparation, primenâemyj at rasseânnom sclerosis
ICD-10 codes (testimony): G35
When CSF: 02.12
Manufacturer: PHARMACEUTICAL INDUSTRY SERONO S. p. A. (Italy)

Pharmaceutical form, composition and packaging

The solution for the p / to the introduction slightly opalescent, light yellow.

Excipients: human serum albumin, mannitol, sodium acetate (0.01 m buffer pH 3.5).

0.5 ml – syringe 1 ml with needle (1) – Plastic containers (3) – packs cardboard.
0.5 ml – syringe 1 ml with needle (1) – Plastic containers (12) – packs cardboard.

Pharmacological action

Rekombinantny Human interferon, the resulting genetically engineered using Chinese hamster ovary cell culture. The sequence of amino acids in the molecule interferon beta-1a is identical to such endogenous human interferon beta.

Rebif^® possesses immunomodulatory, antiviral and antiproliferativnymi properties.

The mechanism of action of the drug Rebif^® in patients with multiple sclerosis is not fully understood; shows, that the drug helps limit the damage of the CENTRAL NERVOUS SYSTEM, underlying disease.

In applying the drug Rebif^® the recommended dose shown to decrease frequency (30% during 2 years) and severity of exacerbations in patients with two or more exacerbations during the last 2 years with EDSS 0-5 before treatment. The proportion of patients with a confirmed disability progression declined from 39% (placebo) to 30% (Rebif^® 22 g).

Through 4 year average decline in the number of exacerbations was 22% and 29% patients, receiving Rebif^® 22 mcg and Rebif^® 44 mcg respectively compared to patients, receiving 2 year placebo, then Rebif^® 22 mcg and Rebif^® 44 g.

The 3-year study of patients with secondary-progressive multiple sclerosis (EDSS 3-6.5) with authentic progression of disability during the preceding 2 years and the absence of complications during the preceding 8 Sun., Rebif^® had no significant effect on disablement, However, the frequency of exacerbations decreased by 30%. When you select two groups of patients (with and without exacerbations during the preceding 2 years) in the group without complications not revealed the influence of the drug on progression of disability, whereas in the group with exacerbations proportion of patients with progression at the end of the study fell from 70% (placebo) to 57 % (Rebif^® 22 mcg and Rebif^® 44 g).

Action Rebifa^® studied in primary-progressive multiple sclerosis.

Pharmacokinetics

Absorption and distribution

When s/c or/m introduction levels of interferon beta in blood serum are defined within 12 -24 hours after injection. Route of Administration Rebifa^® (n / a or / m) does not affect the level of interferon beta in blood serum. After a single injection dose 60 µg C_max, determined by immunological methods, is 6-10 Me/ml at 3 hours after injection. With 4 times the p/to the introduction of the same dose every 48 h happens to moderate accumulation of the drug. After a single injection of intracellular and serum activity of 2-5A synthetase and serum concentration of beta 2 microglobulin and neopterin (biological response markers) increased during the 24 no, and then decrease during 2 days.

Metabolism and excretion

Interferon Beta is metabolized and excreted livers and kidneys.

Testimony

-treatment of relapsing-remitting multiple sclerosis.

The drug was not effective in patients with secondary progressive multiple sclerosis in the absence of active disease.

Dosage regimen

The drug is administered s / c.

Adults and adolescents over 16 years the recommended dose of the drug is usually 44 g 3 times a week. In case of insufficient good endurance this dose Rebif^® administered at a dose of 22 g 3 times a week.

Adolescents aged 12 years before 16 years drug prescribed, usually, dose 22 g 3 times a week.

The drug should be used at the same time (preferably in the evening), on certain days of the week, at intervals of not less than 48 no.

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

At the beginning of therapy during the first 2 weeks of Rebif^® should be a dose 8.8 g (0.2 ml syringe 0.5 ml/22 mcg or 0.1 ml syringe 0.5 ml/44 mcg), during 3 and 4 of the week – dose 22 g (0.5 ml syringe 0.5 ml/22 mcg or 0.25 ml syringe 0.5 ml/44 mcg). In appointing Rebifa^® dose 44 g, beginning with 5 week injected dose 0.5 ml/44 mcg.

For convenience, the syringe marked the appropriate division. Remaining in the syringe drug is not subject to further use.

Duration of treatment the doctor determines individually.

Side effect

Flu-like symptoms: about 40% (during the during the first 6 months of treatment) – headache, fever, chills, muscle and joint pain, nausea. These manifestations are usually moderately expressed, There are more frequent at the beginning of treatment and reduced for continuing treatment (the patient should be informed, that if any of these symptoms or pronounced is constant, You should inform your doctor; You can assign a analgeziruty drug or temporarily change the dose Rebifa^®).

Local reactions: There may be redness, swelling, Blanching of the skin, soreness (usually expressed slightly and are reversible); in a few cases – necrosis at the injection site (usually goes away on its own); rarely – injection site infection, While in the affected area there is skin elasticity, swelling and soreness.

From the digestive system: rarely – include diarrhea, loss of appetite, nausea, vomiting, želtušnost′.

CNS: rarely – sleep disturbance, dizziness, nervousness.

Cardio-vascular system: rarely – dilation of blood vessels, palpitations.

Allergic reactions: in exceptional cases, there may be a serious allergic reaction. If immediately after the injection occurred shortness of breath, hives, feeling weak or dizzy, requires immediate medical advice.

On the side laboratory parameters: possible leukopenia, lymphopenia, thrombocytopenia, increased ALT, GGT, Alkaline phosphatase. These changes are usually minor, asymptomatic and reversible.

On the part of the endocrine system: possible – Hyper- or hypothyroidism without pronounced clinical symptoms (may require additional inspection).

Other: rarely – rash, infringements/menstrual cycle changes.

Contraindications

-severe depression and/or suicidal ideas;

-epilepsy in the absence of the effect of the use of appropriate therapy;

- Pregnancy;

- Lactation;

- Children up to age 12 years (efficacy and safety of the drug studied not enough);

-increased sensitivity to endogenous or recombinase Beta Interferon, human albumin albumin or to other components of the drug.

Pregnancy and lactation

Application of Rebif^® Pregnancy and lactation (breast-feeding) contraindicated.

Women of childbearing age must use effective contraception. Given the potential risk to the fetus, When planning a pregnancy or during pregnancy, occurring during treatment, the patient should be sure to inform your doctor to decide on the continuation of (lifting) therapy.

Data about the allocation of interferon beta-1a in breast milk are not available. Given the likelihood of serious adverse reactions in infants, If necessary, use during lactation should stop breastfeeding.

Cautions

The caution should appoint drug patients with depression. Such patients during treatment Rebifom^® requires careful medical supervision and conditions, to ensure the provision of the necessary assistance. In some cases, may require discontinuation of treatment with interferon beta.

Patients should be warned about, that they should immediately inform the attending doctor about any symptoms of depression and/or the emergence of suicidal ideas.

There is also a need to be careful in appointing interferon beta-1a in patients, who have previously experienced convulsions, patients, receiving anti preparations, especially, If they are not effective enough. If you encounter during treatment with Rebif^® seizures in patients, earlier without such violations, You must cancel the Rebif^®, to establish the etiology of seizures and appoint the anticonvulsant therapy before, than resume treatment Rebifom^®.

In the early stages of treatment with interferon beta-1a must be strict monitoring of patients, suffering from heart disease, such as angina, congestive heart failure and rhythm disturbances. This observation should be aimed at the early identification of possible deterioration. Heart diseases flu-like symptoms, associated with therapy with interferon beta-1a, can complicate the condition of patients.

There are few reports about the development of necrosis at the injection site. To minimize the risk of necrosis aseptic compliance is necessary when performing the injections and constant change seats injection. If the violation of the integrity of the skin with expiration fluid in injection , the patient must consult a physician before, than keep a drug. With multiple skin lesions should stop the drug to their healing. When a single defeat possible continuation therapy Rebifom^®, provided, that defeat expressed moderately.

In clinical trials, there was an increase in liver transaminaz, particularly ALT. In the absence of symptoms, you should determine the level of ALT in plasma pre-treatment Rebifom^® and repeating through 1, 3 and 6 months and periodically for continuing treatment. It is necessary to reduce the dose of the drug, If the ALT level exceeds the 5 times VGN, and gradually increase the dose after its normalization. Use caution when assigning interferon beta-1a in patients with liver failure in history, with signs of liver disease, with signs of alcohol abuse, ALT level in 2.5 times higher than VGN. Therapy should be discontinued if the appearance of jaundice or other symptoms of liver dysfunction.

Rebif^®, like other interferons beta, can potentially cause serious violations of the liver, up to acute liver failure. The mechanism of these States is unknown, specific risk factors have been identified.

In addition to laboratory samples, which are always held in patients with multiple sclerosis, during treatment with interferon beta-1a recommended every 1, 3 and 6 Months, define full and leikocitarnuu blood formula, content of platelets, as well as biochemical blood analysis, including the functional liver samples.

Patients, receiving Rebif^®, sometimes develop or exacerbated by thyroid dysfunction. It is recommended to study thyroid function prior to treatment and, If the revealed violations, every 6-12 Months. Patients, receiving interferons beta, the formation of neutralizing antibodies. The clinical significance of them is not installed. If there is not enough good therapeutic response to treatment Rebifom^® and the patient identifies antibodies, the physician must evaluate the appropriateness of the continuation of therapy.

Use caution when prescribing the drug to patients with renal insufficiency and mielosupressiei.

Use in Pediatrics

Effectiveness and safety of drug Rebif^® in children aged 12 years It has not been studied.

Effects on ability to drive vehicles and management mechanisms

Adverse reactions from the CNS to the therapy with interferons can affect the ability to drive and technology.

The physician must inform the patient About, that, in order to ensure the effectiveness and safety of drugs treatment Rebif^® necessary:

— apply Rebif^® only under the supervision of an experienced doctor;

-to prevent necrosis, carefully read the instruction manual carefully and follow its instructions;

— When an reactions at the injection site should consult with a physician;

-do not change the dose of the drug without the consent of a doctor;

-do not interrupt treatment without the consent of a doctor;

-notify the physician, If you have an intolerance to any medicines;

-during the treatment to inform your doctor about any health violations.

Rules of self injection s/c

Since Rebif^® available in a pre-filled syringe to the p/to the introduction, the patient can safely apply it at home, as yourself, and when outside help. If possible, the first injection should be done under the supervision of a qualified medical professional.

1. Before the injections should be carefully wash hands with SOAP and water.

2. In accordance with the recommendations of the physician should choose the site for injection (convenient sites are located in the upper part of the thigh or lower abdomen). It is recommended to alternate seats injection, avoiding frequent introduction of one and the same place.

3. Not to introduce the drug in those places, where felt swelling, solid nodules or pain. The patient should inform your doctor or nurse about the availability of such sites.

4. Get a syringe with a drug Rebif^® from packaging.

5. Clean the skin at the injection alcohol cloth. Let the skin dry. If alcohol partly remain on the skin, the burning sensation is felt.

6. Gently squeeze the skin around the chosen location so, to slightly raise. Pinning his wrist to the skin near the site, You should insert the needle at a right angle to the skin fast and strong motion. Hold the syringe like a pencil or DART. Enter the drug a slow and constant pressure (Press the plunger until, until the syringe is empty).

7. Hold the swab the injection site. Remove the needle from the skin.

8. Gently rub the injection site with a dry cotton ball or gauze. Throw the used syringe in place for waste.

In the case of injections, should continue to introduction, starting with the next injection on schedule. Do not enter a double dose of this medication.

Overdose

In case of overdose, the patient should be hospitalized for observation and spending if necessary maintenance therapy.

Currently no cases of overdose not described. However, in the case of overdose (increase the amount or frequency of introduction of disposable per week) the patient should immediately inform your doctor.

Drug Interactions

Special clinical study on Rebif drug interactions^® with other drugs, not carried out. However it is known, that humans and animals interferons reduce the activity of isoenzymes of cytochrome P450 system in the liver. Therefore should be cautious appoint Rebif^® simultaneously with drugs, have a narrow therapeutic index, the ground which depends largely on the activity of this enzyme system, eg, with protivosudorojnami means and some antidepressants.

The systematic study of the interaction of the drug Rebif^® with korticosteroidami or ACTG not conducted. Clinical studies indicate that patients with multiple sclerosis Rebifa^® and corticosteroids or ACTH during acute illness.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in its original packaging in the dark place at a temperature between 2° c to 8° c; Do not freeze. Shelf life – 2 year.

Keep out of the reach of children.

Transported at a temperature from 2° to 8° c.

In the absence of the ability to store in the refrigerator product can be stored at a temperature of no higher than 25° c for not more 30 days. Then it must be again put in the fridge and use up to the expiry date.