Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.


AVONEX should be administered with caution to patients with previous or current depressive disorders, in particular to those with antecedents of suicidal ideation (see section 4.3).
Depression and suicidal ideation are known to occur in increased frequency in the multiple sclerosis population and in association with interferon use. Patients 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 and treated appropriately. Cessation of therapy with AVONEX should be considered (see also sections 4.3 and 4.8).

AVONEX should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their epilepsy is not adequately controlled with anti-epileptics (see sections 4.5 and 4.8).

Caution should be used and close monitoring considered when administering AVONEX to patients with severe renal and hepatic failure and to patients with severe myelosuppression.

Thrombotic microangiopathy (TMA): Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of Avonex is recommended.

Nephrotic Syndrome: Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative glomerulonephritis (MPGN) and membranous glomerulopathy (MGN) have been reported during treatment with interferon-beta products. Events were reported at various time points during treatment and may occur after several years of treatment with interferon-beta. Periodic monitoring of early signs or symptoms, e.g. oedema, proteinuria and impaired renal function is recommended, especially in patients at higher risk of renal disease. Prompt treatment of nephrotic syndrome is required and discontinuation of treatment with Avonex should be considered.

Hepatic injury including elevated serum hepatic enzyme levels, hepatitis, autoimmune hepatitis and hepatic failure has been reported with interferon beta in post-marketing (see section 4.8). In some cases, these reactions have occurred in the presence of other medicinal products that have been associated with hepatic injury. The potential of additive effects from multiple medicinal products or other hepatotoxic agents (e.g. alcohol) has not been determined. Patients should be monitored for signs of hepatic injury and caution exercised when interferons are used concomitantly with other medicinal products associated with hepatic injury.

Patients with cardiac disease, such as angina, congestive heart failure or arrhythmia, should be closely monitored for worsening of their clinical condition during treatment with AVONEX.
Flu-like symptoms associated with AVONEX therapy may prove stressful to patients with underlying cardiac conditions.

Laboratory abnormalities are associated with the use of interferons. Therefore, in addition to those laboratory tests normally required for monitoring patients with MS, complete and differential white blood cell counts, platelet counts, and blood chemistry, including liver function tests, are recommended during AVONEX therapy. Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts.

Patients may develop antibodies to AVONEX. The antibodies of some of those patients reduce the activity of interferon beta-1a in vitro (neutralising antibodies). Neutralising antibodies are associated with a reduction in the in vivo biological effects of AVONEX and may potentially be associated with a reduction of clinical efficacy. It is estimated that the plateau for the incidence of neutralising antibody formation is reached after 12 months of treatment. Recent clinical studies with patients treated up to three years with AVONEX suggest that approximately 5% to 8% develop neutralising antibodies.

The use of various assays to detect serum antibodies to interferons limits the ability to compare antigenicity among different products.

In post marketing experience, cases of injection site necrosis have been reported (see section 4.8). To minimise the risk of injection site reactions, patients should be advised to use an aseptic injection technique and 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 accompanied by swelling or drainage of fluid from the injection site, the patient should be advised to speak with their doctor. Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis. For patients who continue therapy with AVONEX after injection site necrosis has occurred, avoid administration of AVONEX into the affected area until it is fully healed. If multiple lesions occur, change injection site, or discontinue therapy until healing occurs.

Effects on Driving

4.7     Effects on ability to drive and use machines

No studies on the effects of AVONEX on the ability to drive and use machines have been performed. Central nervous system-related adverse reactions may have a minor influence on the ability to drive and use machines in susceptible patients (see section 4.8).