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.

Hepatic injury

Elevated serum hepatic transaminase levels, hepatitis, autoimmune hepatitis and rare cases of severe hepatic failure have been reported with interferon beta medicinal products. Elevations in hepatic enzymes have been observed with the use of Plegridy. Patients should be monitored for signs of hepatic injury (see section 4.8).

Depression

Plegridy should be administered with caution to patients with previous depressive disorders (see section 4.3).
Depression occurs with 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 Plegridy should be considered (see section 4.8).

Hypersensitivity reactions
Serious hypersensitivity reactions including cases of anaphylaxis have been reported as a rare complication of treatment with interferon beta, including Plegridy. Patients should be advised to discontinue Plegridy and seek immediate medical care if they experience signs and symptoms of anaphylaxis or severe hypersensitivity . Treatment with Plegridy should not be restarted (see section 4.8).
(see section 4.8).

Injection site reactions

Injection site reactions, including injection site necrosis, have been reported with the use of subcutaneous interferon beta. To minimise the risk of injection site reactions patients should be instructed in the use of an aseptic injection technique. 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. One patient treated with Plegridy in clinical trials experienced an injection site necrosis. Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis (see section 4.8).

Decreased peripheral blood counts

Decreased peripheral blood counts in all cell lines, including rare pancytopenia and severe thrombocytopenia, have been reported in patients receiving interferon beta. Cytopenias, including rare severe neutropenia and thrombocytopenia, have been observed in patients treated with Plegridy. Patients should be monitored for symptoms or signs of decreased peripheral blood counts (see section 4.8).

Renal and urinary disorders

Nephrotic syndrome (class effects)
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 Plegridy should be considered.

Severe renal impairment

Caution should be used when administering Plegridy to patients with severe renal impairment.
Thrombotic microangiopathy (TMA) (class effects)

Cases of TMA, 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 Plegridy is recommended.


Laboratory abnormalities
Laboratory abnormalities are associated with the use of interferons. In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis, complete blood and differential blood cell counts, platelet counts, and blood chemistries, including liver function tests (e.g. aspartate aminotransferase (AST), alanine aminotransaminase (ALT) are recommended prior to initiation and at regular intervals following introduction of Plegridy therapy and then periodically thereafter in the absence of clinical symptoms.

Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts.

Hypothyroidism and hyperthyroidism have been observed with the use of interferon beta products. Regular thyroid function tests are recommended in patients with a history of thyroid dysfunction or as clinically indicated.

Seizure

Plegridy 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 section 4.8).

Cardiac disease

Worsening of cardiac disease has been reported in patients receiving interferon beta. The incidence of cardiovascular events was similar between Plegridy (125 micrograms every 2 weeks) and placebo treatment groups (7% in each group). No serious cardiovascular events were reported in patients who received Plegridy in the ADVANCE study. Nevertheless, patients with pre-existing significant cardiac disease, such as congestive heart failure, coronary artery disease or arrhythmia should be monitored for worsening of their cardiac condition, particularly during initiation of treatment.

Immunogenicity

Patients may develop antibodies to Plegridy. Data from patients treated up to 2 years with Plegridy suggests that less than 1% (5/715) developed persistent-neutralising antibodies to the interferon beta-1a portion of peginterferon beta-1a. Neutralising antibodies have the potential to reduce clinical efficacy. However, the development of antibodies against the interferon moiety of peginterferon beta-1a had no discernible impact on safety or clinical efficacy, although the analysis was limited by the low immunogenicity incidence.

Three percent of patients (18/681) developed persistent antibodies to the PEG moiety of peginterferon beta- 1a. In the clinical study conducted, the development of antibodies against the PEG moiety of peginterferon beta-1a had no discernible impact on safety, or clinical efficacy (including annualised relapse rate, MRI lesions, and disability progression).

Hepatic impairment

Caution should be used and close monitoring considered when administering Plegridy to patients with severe hepatic impairment. 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 (see sections 4.8 and 5.2).

Sodium content

This medicinal product contains less than 1 mmol (23 mg) sodium , that is to say it is essentially “sodium- free”.




Effects on Driving

4.7    Effects on ability to drive and use machines

Plegridy has no or negligible influence on the ability to drive and use machines.