Rebif^® (Solution) Instructions for Use

Instructions
Dosage forms

ATC Code

L03AB07 (Interferon beta-1a)

Active Substance

Interferon beta-1a

Interferon beta-1a (USAN)

Clinical-Pharmacological Group

Interferon. A drug used for multiple sclerosis

Pharmacotherapeutic Group

Cytokine (Interferon beta-1a)

Pharmacological Action

A recombinant human interferon produced by genetic engineering using a culture of Chinese hamster ovary cells.

The amino acid sequence in the interferon beta-1a molecule is identical to that of endogenous human interferon beta.

It has immunomodulatory, antiviral, and antiproliferative properties.

The mechanism of action in patients with multiple sclerosis is not fully understood; it has been shown that this interferon helps to limit CNS damage underlying the disease.

Indications

Outpatient treatment of patients with multiple sclerosis (to reduce the frequency and severity of exacerbations and slow the progression of disability).

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
G35	Multiple sclerosis

ICD-11 code	Indication
8A40.Z	Multiple sclerosis, unspecified

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Solution

Administered subcutaneously.

The recommended dose is 22-44 mcg three times a week at the same time (preferably in the evening), on specific days of the week, with an interval of at least 48 hours.

During the first use, it is recommended to administer a single dose of 8.8 mcg for the first 2 weeks, 22 mcg during the 3rd and 4th weeks, and starting from the 5th week and thereafter – 44 mcg.

Adverse Reactions

Flu-like symptoms headache, fever, chills, muscle and joint pain, nausea.

These symptoms are usually moderate, occur more frequently at the beginning of treatment and decrease with continued therapy.

From the digestive system rarely – diarrhea, loss of appetite, vomiting, liver damage.

From the CNS rarely – sleep disturbance, dizziness, nervousness; in isolated cases – depression, suicidal ideation, depersonalization, as well as seizures.

From the cardiovascular system rarely – peripheral vasodilation, palpitations; in isolated cases – cardiac arrhythmias.

From laboratory parameters leukopenia, lymphocytopenia, thrombocytopenia, increased levels of ALT, GGT and ALP are possible.

These changes are usually mild, reversible and asymptomatic.

Local reactions redness, swelling, skin pallor, pain (usually mild and reversible); in isolated cases, necrosis may be observed at the injection site, which usually resolves on its own.

Other rarely – skin rash, urticaria.

Contraindications

Severe depression and/or suicidal ideation; epilepsy in the absence of effect from appropriate therapy; pregnancy; lactation; children and adolescents under 16 years of age; hypersensitivity to endogenous or recombinant interferon beta, human serum albumin.

Use in Pregnancy and Lactation

Use during pregnancy and lactation is contraindicated.

Use in Hepatic Impairment

The drug should be prescribed with caution and under strict medical supervision to patients with severe hepatic insufficiency.

Use in Renal Impairment

The drug should be prescribed with caution and under strict medical supervision to patients with severe renal insufficiency.

Pediatric Use

Contraindicated in children and adolescents under 16 years of age.

Special Precautions

Use with caution in patients with depression.

Patients should be warned that they should immediately inform their doctor of any symptoms of depression and/or the appearance of suicidal ideation.

Treatment of patients with depression should be carried out under strict medical supervision and, if necessary, appropriate therapy should be prescribed.

In some cases, it may be necessary to discontinue treatment with interferon beta-1a.

Should be used with caution in patients with a history of seizures.

If seizures occur during treatment in patients who have not previously suffered from such disorders, interferon beta-1a should be discontinued, their etiology should be established, and anticonvulsant therapy should be prescribed before resuming treatment with interferon beta-1a.

In the initial stages of treatment, strict monitoring of patients with angina pectoris, congestive heart failure, and arrhythmia is necessary.

In heart disease, the development of flu-like syndrome associated with interferon beta-1a therapy may contribute to the deterioration of the patient’s condition.

The drug should be prescribed with caution and under strict medical supervision to patients with severe renal and hepatic insufficiency, as well as with severe myelosuppression.

The patient should be warned that if any of the flu-like symptoms are intense or persistent, they should inform their doctor.

In case of severe adverse reactions or their persistence for a long time, a temporary dose reduction or interruption of treatment may be allowed at the doctor’s discretion.

The patient should not independently stop treatment or change the dose.

In addition to the laboratory tests that are always performed on patients with multiple sclerosis, during treatment with interferon beta-1a, it is recommended to determine the complete and leukocyte blood count, platelet count, and conduct a biochemical blood test, including liver function tests.

Effect on ability to drive vehicles and operate machinery

Adverse reactions from the CNS to interferon therapy may affect the ability to drive vehicles and operate machinery.

Drug Interactions

In humans and animals, interferons reduce the activity of cytochrome P450 isoenzymes in the liver.

Therefore, Interferon beta-1a should be used with caution concomitantly with drugs whose metabolism involves these enzymes, including anticonvulsants and some antidepressants.

A systematic study of the interaction of Interferon beta-1a with corticosteroids or ACTH has not been conducted.

Clinical trial data indicate the possibility of prescribing corticosteroids and ACTH to patients with multiple sclerosis during relapses of the disease.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Rebif^® [Merck LLC (Russia)]
Solution for subcutaneous administration 22 mcg/0.5 ml: syringes 3 or 12 pcs.

Marketing Authorization Holder

Merck LLC (Russia)

Manufactured By

Merck Serono, S.p.A. (Italy)

Pharmstandard-UfaVITA OJSC (Russia)

Dosage Form

Rebif^®

Solution for subcutaneous administration 22 mcg/0.5 ml: syringes 3 or 12 pcs.

Dosage Form, Packaging, and Composition

Solution for s.c. administration clear or slightly opalescent, from colorless to light yellow.

	1 dose (0.5 ml)
Interferon beta-1a	22 mcg (6 million IU)

Excipients : 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 (to adjust pH), water for injections) – up to 0.5 ml.

0.5 ml – syringes with a capacity of 1 ml with a needle (1) – plastic containers (3) – cardboard packs.
0.5 ml – syringes with a capacity of 1 ml with a needle (1) – plastic containers (12) – cardboard packs.

Rebif^® [Merck LLC (Russia)]
Solution for subcutaneous injection 44 mcg/0.5 ml: syringes 3 or 12 pcs.

Marketing Authorization Holder

Merck LLC (Russia)

Manufactured By

Merck Serono, S.p.A. (Italy)

Pharmstandard-UfaVITA OJSC (Russia)

Dosage Form

Rebif^®

Solution for subcutaneous injection 44 mcg/0.5 ml: syringes 3 or 12 pcs.

Dosage Form, Packaging, and Composition

Solution for s.c. injection clear or slightly opalescent, from colorless to light yellow.

	1 dose (0.5 ml)
Interferon beta-1a	44 mcg (12 million IU)

Rebif^® [Merck LLC (Russia)]
Solution for subcutaneous injection 22 mcg/0.5 ml: pen-injectors 3 or 12 pcs.

Marketing Authorization Holder

Merck LLC (Russia)

Dosage Form

Rebif^®

Solution for subcutaneous injection 22 mcg/0.5 ml: pen-injectors 3 or 12 pcs.

Dosage Form, Packaging, and Composition

Solution for s.c. injection clear or slightly opalescent, from colorless to light yellow

	1 dose. (0.5 ml)
Interferon beta-1a	22 mcg (6 million IU)

0.5 ml – pen-injectors with a capacity of 1 ml (1) – plastic containers (3) – cardboard packs.
0.5 ml – pen-injectors with a capacity of 1 ml (1) – plastic containers (12) – cardboard packs.

Rebif^® [Merck LLC (Russia)]
Solution for subcutaneous injection 44 mcg/0.5 ml: pen-injectors 3 or 12 pcs.

Marketing Authorization Holder

Merck LLC (Russia)

Dosage Form

Rebif^®

Solution for subcutaneous injection 44 mcg/0.5 ml: pen-injectors 3 or 12 pcs.

Dosage Form, Packaging, and Composition

Solution for s.c. injection clear or slightly opalescent, from colorless to light yellow.

	1 dose (0.5 ml)
Interferon beta-1a	44 mcg (12 million IU)

Rebif^® [Merck LLC (Russia)]
Solution for subcutaneous injection 66 mcg/1.5 ml: cartridges 4 pcs.

Marketing Authorization Holder

Merck LLC (Russia)

Dosage Form

Rebif^®

Solution for subcutaneous injection 66 mcg/1.5 ml: cartridges 4 pcs.

Dosage Form, Packaging, and Composition

Solution for s.c. injection clear or slightly opalescent, from colorless to light yellow.

	3 doses (1.5 ml)
Interferon beta-1a	66 mcg (18 million IU)

Excipients : 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 (to adjust pH), water for injections) – up to 1.5 ml.

1.5 ml – cartridges with a capacity of 3 ml (1) – plastic containers (4) – cardboard packs.

Rebif^® [Merck LLC (Russia)]
Solution for subcutaneous injection 132 mcg/1.5 ml: cartridges 4 pcs.