Interferon beta-1b

Caution should be used and close monitoring considered when administering interferon beta to patients with severe renal failure.

The administration of cytokines to patients with a pre-existing monoclonal gammopathy has been associated with the development of systemic capillary leak syndrome with shock-like symptoms and fatal outcome.

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 interferon beta-1b is recommended.

Cases of pancreatitis were observed with interferon beta-1b use, often associated with hypertriglyceridaemia.

Asymptomatic elevations of serum transaminases, in most cases mild and transient, occurred very commonly in patients treated with interferon beta-1b during clinical trials. As for other beta interferons, cases of severe hepatic injury, including hepatic failure, have been reported in patients treated with interferon beta-1b. The most serious events often occurred in patients exposed to other medicinal products or substances known to be associated with hepatotoxicity or in the presence of co-morbid medical conditions (e.g. metastasising malignant disease, severe infection and sepsis, alcohol abuse).

Patients should be monitored for signs of hepatic injury. The occurrence of elevations in serum transaminases should lead to close monitoring and investigation. Withdrawal of interferon beta-1b should be considered if the levels significantly increase or if they are associated with clinical symptoms such as jaundice. In the absence of clinical evidence for liver damage, and after normalisation of liver enzymes, a reintroduction of therapy could be considered with appropriate follow-up of hepatic functions.

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 interferon beta-1b should be considered.

Interferon beta-1b should also be used with caution in patients who suffer from pre-existing cardiac disorders. 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 with interferon beta-1b.

While interferon beta-1b does not have any known direct-acting cardiac toxicity, symptoms of the flu-like syndrome associated with beta interferons may prove stressful to patients with pre-existing significant cardiac disease. During the post-marketing period very rare reports have been received of temporary worsening of cardiac status at the start of interferon beta-1b therapy in patients with pre-existing significant cardiac disease.

Cases of cardiomyopathy have been reported. If this occurs and a relationship to interferon beta-1b is suspected, treatment should be discontinued.

Extavia should be administered with caution to patients with a history of seizures, to patients receiving treatment with anti-epileptics, and in particular to patients with epilepsy who are not adequately controlled with anti-epileptics.

A large amount of data (more than 1,000 pregnancy outcomes) from interferon beta registries, national registries and post-marketing experience indicates no increased risk of major congenital anomalies, after pre-conception exposure or exposure during the first trimester of pregnancy.

However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment was likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimesters is very limited.

Based on animal data, there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated by means of the currently available data, but the data suggest no increased risk so far. If clinically needed, the use of interferon beta-1b may be considered during pregnancy.

Limited information available on the transfer of interferon beta-1b into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1b excreted in human milk are negligible. No harmful effects on the breast-fed newborn/infant are anticipated.

Interferon beta-1b can be used during breast-feeding.

Fertility

No investigations on fertility have been conducted.

No studies on the effects on the ability to drive and use machines have been performed.

Adverse events related to the central nervous system associated with the use of interferon beta-1b might influence the ability to drive and use machines in susceptible patients.