5

Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if

injection site necrosis has occurred.

In controlled clinical trials, injection site reactions occurred in 78% of patients receiving BETASERON with injection site

necrosis in 4%. Injection site inflammation (42%), injection site pain (16%), injection site hypersensitivity (4%), injection

site necrosis (4%), injection site mass (2%), injection site edema (2%) and nonspecific reactions were significantly

associated with BETASERON treatment.

The incidence of injection site reactions tended to decrease over time.

Approximately 69% of patients experienced injection site reactions during the first three months of treatment, compared

to approximately 40% at the end of the studies.

5.6 Leukopenia

In controlled clinical trials, leukopenia was reported in 18% of patients receiving BETASERON (compared to 6% on

placebo), leading to a reduction of the dose of BETASERON in some patients

[see Adverse Reactions (

6.1

)]

. Monitoring

of complete blood and differential white blood cell counts is recommended. Patients with myelosuppression may require

more intensive monitoring of complete blood cell counts, with differential and platelet counts.

5.7 Thrombotic Microangiopathy

Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic

syndrome, some fatal, have been reported with interferon beta products, including BETASERON. Cases have been

reported several weeks to years after starting interferon beta products. Discontinue BETASERON if clinical symptoms

and laboratory findings consistent with TMA occur, and manage as clinically indicated.

5.8 Flu-like Symptom Complex

In controlled clinical trials, the rate of flu-like symptom complex for patients on BETASERON was 57%

[see Adverse

Reactions (

6.1

)]

. The incidence decreased over time, with 10% of patients reporting flu-like symptom complex at the end

of the studies. The median duration of flu-like symptom complex in Study 1 was 7.5 days

[see Clinical Studies (

14

)]

.

Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with BETASERON

use.

5.9 Seizures

Seizures have been temporally associated with the use of beta interferons in clinical trials and postmarketing safety

surveillance. It is not known whether these events were related to a primary seizure disorder, the effects of multiple

sclerosis alone, the use of beta interferons, other potential precipitants of seizures (eg, fever), or to some combination of

these.

5.10 Drug-induced Lupus Erythematosus

Cases of drug-induced lupus erythematosus have been reported with some interferon beta products, including

BETASERON. Signs and symptoms of drug-induced lupus reported in BETASERON-treated patients have included rash,

serositis, polyarthritis, nephritis, and

Raynaud’s phenomenon

. Cases have occurred with positive serologic testing

(including positive anti-nuclear and/or anti-double-stranded DNA antibody testing). If BETASERON-treated patients

develop new signs and symptoms characteristic of this syndrome, BETASERON therapy should be stopped.

5.11 Monitoring for Laboratory Abnormalities

In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis, complete blood and

differential white blood cell counts, platelet counts and blood chemistries, including liver function tests, are recommended