General: The highest incidence of adverse reactions associated with Rebif therapy is related to flu-like syndrome. Flu-like symptoms tend to be most prominent at the initiation of therapy and decrease in frequency with continued treatment. Approximately 70% of patients treated with Rebif can expect to experience the typical interferon flu-like syndrome within the first 6 months after starting treatment. Approximately 30% of 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 interferon β-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.
Adverse Reactions by Frequency: The adverse reactions reported as follows are classified according to frequency of occurrence as follows: Very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1000 to <1/100; rare: ≥1/10,000 to <1/1000; very rare: <1/10,000.
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 mcg 3 times weekly = 398 patients; Rebif 44 mcg 3 times weekly = 727 patients) and shows the frequency of adverse reactions observed at 6-month (excess over placebo). Adverse reactions are listed as follows by frequency of occurrence and by MedDRA system organ class.
Infections and Infestations: Uncommon: Injection site abscess.
Blood and Lymphatic System Disorders: Very Common: Neutropenia, lymphopenia, leucopenia, thrombocytopenia, anemia.
Endocrine Disorders: Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism.
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, maculopapular 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 reaction mass.
Investigations: Very Common: Asymptomatic increased transaminase.
Adverse Reactions Identified During Post-Marketing Surveillance (Frequency Unknown): Infections and Infestations: Injection site infections, including cellulitis.
Immune System Disorders: Anaphylactic reactions.
Psychiatric Disorders: Suicide attempt.
Nervous System Disorders: Seizures.
Vascular Disorders: Thromboembolic events.
Hepatobiliary Disorders: Hepatitis with or without icterus.
Skin and Subcutaneous Tissue Disorders: Angioedema, urticaria, erythema multiforme, erythema multiforme-like skin reactions, hair loss.
Information Characterising Individual Serious and/or Frequently Occurring Adverse Reactions: Rebif, like other interferon β, 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 6 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 Precautions).
Adverse Reactions that Apply to the Pharmacological Class: The administration of interferons has been associated with anorexia, dizziness, anxiety, arrhythmias, vasodilation and palpitation, menorrhagia and metrorrhagia.
An increased formation of autoantibodies may occur during treatment with interferon β.