Summary of safety profile: 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 six 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 white blood cells (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.
List of adverse reactions: The adverse reactions presented have been identified from clinical studies as well as from post-marketing reports (an asterisk [*] indicates adverse reactions identified during post-marketing surveillance). The following definitions apply to the frequency terminology used hereafter: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), frequency not known (cannot be estimated from the available data).
Blood and the lymphatic system disorders: Very common: Neutropenia, lymphopenia, leukopenia, thrombocytopenia, anaemia. Rare: Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome* (class label for interferon beta products), pancytopenia*.
Endocrine disorders: Uncommon: Thyroid dysfunction, most often presenting as hypothyroidism or hyperthyroidism.
Immune system disorders: Rare: Anaphylactic reactions*.
Hepatobiliary disorders: Very common: Asymptomatic transaminase increase. Common: Severe elevations in transaminases. Uncommon: Hepatitis with or without icterus*. Rare: Hepatic failure*, autoimmune hepatitis*.
Psychiatric disorders: Common: Depression, insomnia. Rare: Suicide attempt*.
Nervous system disorders: Very common: Headache. Uncommon: Seizures*. Frequency not known: Transient neurological symptoms (i.e. hypoesthesia, muscle spasm, paraesthesia, difficulty in walking, musculoskeletal stiffness) that may mimic multiple sclerosis exacerbations*.
Eye disorders: Uncommon: Retinal vascular disorders (i.e. retinopathy, cotton wool spots, obstruction of retinal artery or vein)*.
Vascular disorders: Uncommon: Thromboembolic events*.
Respiratory, thoracic and mediastinal disorders: Uncommon: Dyspnoea*. Frequency not known: Pulmonary arterial hypertension* (class label for interferon beta products, see Pulmonary arterial hypertension as follows).
Gastrointestinal disorders: Common: Diarrhoea, vomiting, nausea.
Skin and subcutaneous tissue disorders: Common: Pruritus, rash, erythematous rash, maculo-papular rash, alopecia*. Uncommon: Urticaria*. Rare: Quincke's oedema (angio-oedema)*, erythema multiforme*, erythema multiforme-like skin reactions*, Stevens Johnson syndrome*.
Musculoskeletal and connective disorders: Common: Myalgia, arthralgia. Rare: Drug-induced lupus erythematosus*.
Renal and urinary disorders: Rare: Nephrotic syndrome*, glomerulosclerosis*.
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 mass, injection site abscess, injection site infections*, increased sweating*. Rare: Injection site cellulitis*.
Class effects: The administration of interferons has been associated with anorexia, dizziness, anxiety, arrhythmias, vasodilation and palpitation, menorrhagia and metrorrhagia.
An increased formation of auto-antibodies may occur during treatment with interferon beta.
Pulmonary arterial hypertension: Cases of pulmonary arterial hypertension (PAH) have been reported with interferon beta products. Events were reported at various time points including up to several years after starting treatment with interferon beta.