Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the 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 are also common.


The majority of adverse reactions observed with interferon 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, see section 4.4), 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* (see section 4.4), 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 products, see below Pulmonary arterial hypertension)

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* (see section 4.4) 
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*
Frequency not known:    Panniculitis (occurred in the injection site) 
Paediatric population

No formal clinical trials or pharmacokinetic studies have been conducted in children or adolescents. Limited safety data suggest that the safety profile in children and adolescents (2 to 17 years old) receiving Rebif 22 micrograms or 44 micrograms three times weekly is similar to that seen in adults.

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.


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/