4

BETASERON used in combination with known hepatotoxic drugs or other products (eg, alcohol) prior to BETASERON

administration, or when adding new agents to the regimen of patients already on BETASERON.

Monitor patients for

signs and symptoms of hepatic injury. Consider discontinuing BETASERON if serum transaminase levels significantly

increase, or if they are associated with clinical symptoms such as jaundice.

Asymptomatic elevation of serum transaminases is common in patients treated with BETASERON. In controlled clinical

trials, elevations of SGPT to greater than five times baseline value were reported in 12% of patients receiving

BETASERON (compared to 4% on placebo), and increases of SGOT to greater than five times baseline value were

reported in 4% of patients receiving BETASERON (compared to 1% on placebo), leading to dose-reduction or

discontinuation of treatment in some patients

[see Adverse Reactions (

6.1

)]

. Monitor liver function tests

[see Warnings

and Precautions (5.11)].

5.2 Anaphylaxis and Other Allergic Reactions

Anaphylaxis has been reported as a rare complication of BETASERON use. Other allergic reactions have included

dyspnea, bronchospasm, tongue edema, skin rash and urticaria

[see Adverse Reactions (

6.1

)]

. Discontinue BETASERON

if anaphylaxis occurs.

5.3 Depression and Suicide

Depression and suicide have been reported to occur with increased frequency in patients receiving interferon beta

products, including BETASERON.

Advise patients to report any symptom of depression and/or suicidal ideation to their

healthcare provider. If a patient develops depression, discontinuation of BETASERON therapy should be considered.

In randomized controlled clinical trials, there were three suicides and eight suicide attempts among the 1532 patients on

BETASERON compared to one suicide and four suicide attempts among 965 patients on placebo.

5.4 Congestive Heart Failure

Monitor patients with pre-existing congestive heart failure (CHF) for worsening of their cardiac condition during initiation

of and continued treatment with BETASERON. While beta interferons do not have any known direct-acting cardiac

toxicity, cases of CHF, cardiomyopathy, and cardiomyopathy with CHF have been reported in patients without known

predisposition to these events, and without other known etiologies being established. In some cases, these events have

been temporally related to the administration of BETASERON. Recurrence upon rechallenge was observed in some

patients. Consider discontinuation of BETASERON if worsening of CHF occurs with no other etiology.

5.5 Injection Site Necrosis and Reactions

Injection site necrosis (ISN) was reported in 4% of BETASERON-treated patients in controlled clinical trials (compared

to 0% on placebo)

[see Adverse Reactions (

6.1

)]

. Typically, ISN occurs within the first four months of therapy, although

postmarketing reports have been received of ISN occurring over one year after initiation of therapy. The necrotic lesions

are typically 3 cm or less in diameter, but larger areas have been reported. Generally the necrosis has extended only to

subcutaneous fat, but has extended to the fascia overlying muscle. In some lesions where biopsy results are available,

vasculitis has been reported. For some lesions, debridement, and/or skin grafting have been required. In most cases

healing was associated with scarring.

Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis. For patients who

continue therapy with BETASERON after injection site necrosis has occurred, avoid administration of BETASERON into

the affected area until it is fully healed. If multiple lesions occur, discontinue therapy until healing occurs.