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Medicine information : REBIF Injection
| Drug class description : | Cytokines |
| Generic Name : | Interferon beta-1a |
| Drug description : | Solution for injection. Clear to opalescent solution, with a 3.4 to 4.4 pH and 250 mOsm/l to 450 mOsm/l osmolarity. |
| Presentation : | Each pre-filled syringe (0.5 ml) contains 44 micrograms (12 million IU*) of Interferon beta-1a**. Excipients: 0.5 ml water for injection, 27.3 mg mannitol, 4 mg human serum albumin. * measured by cytopathic effect (CPE) bioassay against the in-house IFN beta-1a standard which is calibrated against the current international NIH standard (GB-23-902-531). ** produced in Chinese Hamster Ovary Cells (CHO-K1) by recombinant DNA technology. |
| Indications : | Rebif is indicated for the treatment of relapsing multiple sclerosis. In clinical trials, this was characterised by two or more acute exacerbations in the previous two years. Efficacy has not been demonstrated in patients with secondary progressive multiple sclerosis without ongoing relapsing activity. |
| Adult Dosage : | Rebif is available in three strengths: 8.8 micrograms, 22 micrograms and 44 micrograms. The recommended posology of Rebif is 44 micrograms given three times per week by subcutaneous injection. Rebif 22 micrograms, also given three times per week by subcutaneous injection, is recommended for patients who cannot tolerate the higher dose in view of the treating specialist. Treatment should be initiated under supervision of a physician experienced in the treatment of the disease. For patients initiating treatment with Rebif, Rebif 8.8 micrograms and Rebif 22 micrograms are available in a package that corresponds to the patient needs for the first month of therapy. At the present time, it is not known for how long patients should be treated. Safety and efficacy with Rebif have not been demonstrated beyond 4 years of treatment. It is recommended that patients should be evaluated at least every second year in the 4-year period after initiation of treatment with Rebif and a decision for longer-term treatment should then be made on an individual basis by the treating physician. |
| Child Dosage : | There is no experience with Rebif in children under 16 years of age with multiple sclerosis and therefore Rebif should not be used in this population. |
| Contra Indications : | Interferon beta-1a is contraindicated in patients with a known hypersensitivity to natural or recombinant interferon beta, human serum albumin, or any other component of the formulation. Interferon beta-1a is contraindicated in pregnant patients (See Interactions), patients with severe depressive disorders and/or suicidal ideation, and in epileptic patients with a history of seizures not adequately controlled by treatment (See Special Precautions and Adverse Reactions). |
| Special Precautions : | Patients should be informed of the most common adverse reactions associated with interferon beta administration, including symptoms of the flu-like syndrome (See Adverse Reactions). These symptoms tend to be most prominent at the initiation of therapy and decrease in frequency and severity with continued treatment. Interferons should be used with caution in patients with depression. Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients treated with Interferon beta-1a should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy with Interferon beta-1a and treated appropriately. Cessation of therapy with Interferon beta-1a should be considered (See Contraindications, and Adverse Reactions). Caution should be exercised when administering Interferon beta-1a to patients with pre-existing seizure disorders. For patients without a pre-existing seizure disorder who develop seizures during therapy with Interferon beta-1a, an aetiological basis should be established and appropriate anti-convulsant therapy instituted prior to resuming Interferon beta-1a treatment (see also Contraindications, and Adverse Reactions). Patients with cardiac disease, such as angina, congestive heart failure or arrhythmia, should be closely monitored for worsening of their clinical condition during initiation of therapy with Interferon beta-1a. Symptoms of the flu-like syndrome associated with Interferon beta-1a therapy may prove stressful to patients with cardiac conditions. Injection site necrosis (ISN) has been reported in patients using Rebif (See Adverse Reactions). To minimise the risk of injection site necrosis patients should be advised to: - use an aseptic injection technique - rotate the injection sites with each dose. The procedure for the self-administration by the patient should be reviewed periodically especially if injection site reactions have occurred. If the patient experiences any break in the skin, which may be associated with swelling or drainage of fluid from the injection site, the patient should be advised to consult with their physician before continuing injections with Rebif. If the patient has multiple lesions, Rebif should be discontinued until healing has occurred. Patients with single lesions may continue provided that the necrosis is not too extensive. Patients should be advised about the abortifacient potential of interferon beta (See Interactions). In clinical trials with Rebif, asymptomatic elevations of hepatic transaminases (particularly alanine aminotransferase (ALT)) were common and 1-3% of patients developed elevations of hepatic transaminases above 5 times the upper limit of normal (ULN). Dose reduction of Rebif should be considered if ALT rises above 5 times the ULN, and gradually re-escalated when enzyme levels have normalized. Rebif should be initiated with caution in patients with a history of significant liver disease, clinical evidence of active liver disease, alcohol abuse or increased serum ALT >2.5 times ULN). Serum ALT levels should be monitored prior to the start of therapy, at months 1, 3 and 6 on therapy and periodically thereafter in the absence of clinical symptoms. Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (See Adverse Reactions). Rebif, like other interferons beta, has a potential for causing severe liver injury (See Adverse Reactions) including acute hepatic failure. The mechanism for the rare symptomatic hepatic dysfunction is not known. No specific risk factors have been identified. Laboratory abnormalities are associated with the use of interferons. The overall incidence of these is slightly higher with Rebif 44 than Rebif 22 micrograms. Therefore, in addition to those laboratory tests, normally required for monitoring patients with multiple sclerosis, and in addition to liver enzyme monitoring, complete and differential blood cell counts and platelet counts are also recommended during Rebif therapy. These should be more frequent when initiating Rebif 44 micrograms. Patients being treated with Rebif may occasionally develop new or worsening thyroid abnormalities. Thyroid function testing is recommended at baseline and if abnormal, every 6-12 months following initiation of therapy. If tests are normal at baseline, routine testing is not needed but should be performed if clinical findings of thyroid dysfunction appear (See Adverse Reactions). Caution should be used, and close monitoring considered when administering Interferon beta-1a to patients with severe renal and hepatic failure and to patients with severe myelosuppression. Serum neutralising antibodies against Interferon beta-1a may develop. The precise incidence of antibodies is as yet uncertain. Clinical data suggest that after 24 to 48 months of treatment with Rebif 44 micrograms, approximately 13 to 14% of patients develop persistent serum antibodies to Interferon beta-1a. The presence of antibodies has been shown to attenuate the pharmacodynamic response to Interferon beta-1a (Beta-2 microglobulin and neopterin). Although the clinical significance of the induction of antibodies has not been fully elucidated, the development of neutralising antibodies is associated with reduced efficacy on clinical and MRI variables. If a patient responds poorly to therapy with Rebif, and has neutralising antibodies, the treating physician should reassess the benefit/risk ratio of continued Rebif therapy. The use of various assays to detect serum antibodies and differing definitions of antibody positivity limits the ability to compare antigenicity among different products. Only sparse safety and efficacy data are available from non-ambulatory patients with multiple sclerosis. |
| Interactions : | No interaction studies have been performed with Rebif (Interferon beta-1a) in humans. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants. The interaction of Rebif with corticosteroids or ACTH has not been studied systematically. Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses. Pregnancy and lactation Because of the potential hazards to the foetus, Rebif is contraindicated in pregnancy (See Ontraindications). There are no studies of Interferon beta-1a in pregnant women. At high doses, in monkeys, abortifacient effects were observed with other interferons. It cannot be excluded that such effects will be observed in humans. Women of childbearing potential receiving Rebif have to use effective contraception during treatment. Patients planning for pregnancy and those becoming pregnant should be informed of the potential hazards of interferons to the foetus and Rebif should be discontinued. It is not known whether Rebif is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made either to discontinue nursing or to discontinue Rebif therapy. |
| Adverse Reactions : | a) General description Approximately 40% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first six months after starting treatment. Most patients will also experience reactions at the injection site, predominantly mild inflammation or erythema. Asymptomatic increases in laboratory parameters of hepatic function and decreases in WBC are also common. The majority of adverse reactions observed with IFN-beta-1a are usually mild and reversible, and respond well to dose reductions. In case of severe or persistent undesirable effects, the dose of Rebif may be temporarily lowered or interrupted, at the discretion of the physician. b) Adverse reactions by frequency The adverse reactions reported below are classified according to frequency of occurrence as follows: Very Common > 1/10 Common 1/100 - 1/10 Uncommon 1/1000 - 1/100 Rare 1/10 000 - 1/ 1000 Very Rare <1/10000 Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Adverse reactions identified in clinical studies: the data presented is obtained from pooled clinical studies in multiple sclerosis (placebo=824 patients; Rebif 22 micrograms TIW= 398 patients; Rebif 44 micrograms TIW= 727 patients) and shows the frequency of adverse reactions observed at six-month (excess over placebo). Blood and lymphatic system disorders - Common: Neutropenia, lymphopenia, leucopenia, thrombocytopenia, anemia. Endocrine Disorders - Uncommon: Thyroid dysfunction (elevated T3, T4, reduced TSH). Psychiatric disorders - Common: Depression, insomnia. Nervous system disorders - Very common: Headache. Gastrointestinal disorders - Common: Diarrhoea, vomiting, nausea. Skin and subcutaneous tissue disorders - Common: Pruritus, rash, erythematous rash, maculo-papular rash. Musculoskeletal and connective tissue disorders - Common: Myalgia, arthralgia. General disorders and administration site conditions - Very Common: Injection site inflammation, injection site reaction, influenza-like symptoms. Common: Injection site pain, fatigue, rigors, fever. Uncommon: Injection site necrosis, injection site abscess, injection site mass. Investigations - Very Common: Asymptomatic transaminase increase. Adverse reactions identified during post-marketing surveillance. Immune system disorders Very rare: Anaphylactic reaction. Psychiatric disorders - Very rare: Suicide attempt. Nervous system disorders - Very rare: Seizures. Vascular disorders - Very rare: Thromboembolic events. Hepatobiliary disorders - Rare: Hepatitis with or without icterus. Skin and subcutaneous tissue disorders - Very rare: Angioedema, urticaria, erythema multiforme, erythema multiforme-like skin reactions, hair loss. c) Information characterising individual serious and/or frequently-occurring adverse reactions. Rebif, like other interferons beta, has a potential for causing severe liver injury. The mechanism for the rare symptomatic hepatic dysfunction is not known. The majority of the cases of severe liver injury occurred within the first six months of treatment. No specific risk factors have been identified. Treatment with Rebif should be stopped if icterus or other clinical symptoms of liver dysfunction appear (See Special Precautions). d) Adverse reactions that apply to the pharmacological class The administration of interferons has been associated with anorexia, dizziness, anxiety, arythmias, vasodilation and palpitation, menorrhagia and metrorrhagia. An increased formation of autoantibodies may occur during treatment with interferon beta. |
| Manufacturer : | Serono |
| Drug Availability : | (POM) |
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