warnings and cautions
5 WARNINGS AND PRECAUTIONS Depression, Suicide, and Psychotic Disorders: advise patients to immediately report any symptoms of depression, suicidal ideation, and/or psychosis; consider discontinuation of AVONEX if depression occurs ( 5.1 ) Hepatic Injury: monitor liver function tests; monitor patients for signs and symptoms of hepatic injury; consider discontinuation of AVONEX if hepatic injury occurs ( 5.2 , 5.8 ) Anaphylaxis and Other Allergic-Reactions: Discontinue if occurs ( 5.3 ) Congestive Heart Failure: monitor patients with pre-existing significant cardiac disease for worsening of cardiac symptoms ( 5.4 ) Decreased Peripheral Blood Counts: monitor complete blood count ( 5.5 , 5.8 ) Autoimmune Disorders: consider discontinuation of AVONEX if new autoimmune disorder occurs ( 5.7 , 5.8 ) 5.1 Depression, Suicide, and Psychotic Disorders Patients treated with AVONEX and their caregivers should be advised to report immediately any symptoms of depression, suicidal ideation, and/or psychosis to their prescribing physicians. If a patient develops depression or other severe psychiatric symptoms, cessation of AVONEX therapy should be considered. Depression and suicide have been reported to occur with increased frequency in patients receiving AVONEX. In Study 1, the incidence of depression was similar in placebo-treated and in AVONEX-treated patients, but suicidal tendency was seen more frequently in AVONEX-treated patients (4% in AVONEX group vs. 1% in placebo group). In Study 2, there was a greater incidence of depression in AVONEX-treated patients than in placebo-treated patients (20% in AVONEX group vs. 13% in placebo group) [see Clinical Studies ( 14 ) ]. Additionally, there have been post-marketing reports of depression, suicidal ideation, and/or development of new or worsening of other pre-existing psychiatric disorders, including psychosis. For some of these patients, symptoms of depression improved upon cessation of AVONEX. 5.2 Hepatic Injury Severe hepatic injury, including cases of hepatic failure, has been reported rarely in patients taking AVONEX. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with AVONEX. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential risk of AVONEX used in combination with known hepatotoxic drugs or other products (e.g., alcohol) should be considered prior to starting AVONEX, or before starting hepatotoxic drugs. Patients should be monitored for signs of hepatic injury [see Warnings and Precautions ( 5.8 ) ]. 5.3 Anaphylaxis and Other Allergic-Reactions Anaphylaxis has been reported as a rare complication of AVONEX use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria. Discontinue AVONEX if anaphylaxis or other allergic reactions occur. 5.4 Congestive Heart Failure Patients with pre-existing congestive heart failure should be monitored for worsening of their cardiac condition during initiation of and continued treatment with AVONEX. While beta interferons do not have any known direct cardiac toxicity, during the post-marketing period cases of congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure have been reported in patients without known predisposition to these events, and without other etiologies being established. In some cases, these events have been temporally related to the administration of AVONEX. In some of these instances recurrence upon rechallenge was observed. 5.5 Decreased Peripheral Blood Counts Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia, have been reported from postmarketing experience in AVONEX-treated patients [see Adverse Reactions ( 6.2 ) ]. In some cases, platelet counts were below 10,000/microliter. Some cases recurred with rechallenge [see Adverse Reactions ( 6.2 ) ]. Patients should be monitored for symptoms or signs of decreased blood counts. 5.6 Seizures Seizures have been temporally associated with the use of beta interferons in clinical trials and postmarketing safety surveillance. In the two placebo-controlled studies in multiple sclerosis (Studies 1 and 2), 4 patients receiving AVONEX experienced seizures, while no seizures occurred in the placebo group [see Clinical Studies ( 14 ) ]. Three of these 4 patients had no prior history of seizure [see Adverse Reactions ( 6.1 ) ]. It is not known whether these events were related to the effects of multiple sclerosis alone, to AVONEX, or to a combination of both. 5.7 Autoimmune Disorders Post-marketing reports of autoimmune disorders of multiple target organs in AVONEX-treated patients included idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis. If AVONEX-treated patients develop a new autoimmune disorder, consider stopping the therapy. 5.8 Laboratory Tests 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 during AVONEX therapy [see Warnings and Precautions ( 5.2 , 5.5 , 5.7 ) ]. Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts. Thyroid function should be monitored periodically. If patients have or develop symptoms of thyroid dysfunction (hypo- or hyperthyroidism), thyroid function tests should be performed according to standard medical practice.