AVONEX is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, or any other component of the formulation
The formerly available lyophilized vial formulation of AVONEX is contraindicated in patients with a history of hypersensitivity to albumin (human)
Warnings and Precautions1
Depression, Suicide, and Psychotic Disorders
Warning
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 physician
Details
Depression and suicide have been reported to occur with increased frequency in patients receiving AVONEX
Additionally, there have been postmarketing reports of depression, suicidal ideation, and/or development of new or worsening of other pre-existing psychiatric disorders, including psychosis
Guidance
If a patient develops depression or other severe psychiatric symptoms, cessation of AVONEX therapy should be considered
For some of these patients, symptoms of depression improved upon cessation of AVONEX
Hepatic injury
Warning
Severe hepatic injury, including cases of hepatic failure, has been reported rarely in patients taking AVONEX
Details
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
Guidance
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
Anaphylaxis and Other Allergic-Reactions
Warning
Anaphylaxis has been reported as a rare complication of AVONEX use
Signs and symptoms
Other allergic reactions have included dyspnea, orolingual edema, skin rash, and urticaria
Guidance
Discontinue AVONEX if anaphylaxis or other allergic reactions occur
Injection Site Reactions Including Necrosis
Warning
Injection site reactions, including injection site necrosis, can occur with the use of interferon beta products, including AVONEX
Details
Injection site abscesses and cellulitis and injection site necrosis have been reported in the postmarketing setting with interferon beta products, including AVONEX
Some cases required treatment with hospitalization for surgical drainage and intravenous antibiotics
Guidance
Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if injection site necrosis has occurred
Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis
For patients who continue therapy with AVONEX after injection site necrosis has occurred, avoid administration of AVONEX into the affected area until it is fully healed
If multiple lesions occur, change injection site or discontinue therapy until healing occurs
Congestive Heart Failure
Warning
Patients with pre-existing congestive heart failure should be monitored for worsening of their cardiac condition during initiation of and continued treatment with AVONEX
Details
While beta interferons do not have any known direct cardiac toxicity, during the postmarketing 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
Decreased Peripheral Blood Counts
Warning
Decreased peripheral blood counts in all cell lines, including rare pancytopenia and thrombocytopenia, have been reported from postmarketing experience in AVONEX-treated patients
Guidance
Patients should be monitored for symptoms or signs of decreased blood counts
Thrombotic Microangiopathy
Warning
Case of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported with interferon beta products, including AVONEX
Details
Cases have been reported several weeks to years after starting interferon beta products
Guidance
Discontinue AVONEX if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated
Pulmonary Arterial Hypertension
Warning
Cases of pulmonary arterial hypertension (PAH) have been reported in patients treated with interferon beta products, including AVONEX
Details
PAH has occurred in patients treated with interferon beta products in the absence of other contributory factors. Many of the reported cases required hospitalization, including one case with interferon beta in which the patient underwent a lung transplant
PAH has developed at various time points after initiating therapy with interferon beta products and may occur several years after starting treatment
Guidance
Patients who develop unexplained symptoms (e.g., dyspnea, new or increasing fatigue) should be assessed for PAH
If alternative etiologies have been ruled out and a diagnosis of PAH is confirmed, discontinue treatment and manage as clinically indicated
Seizures
Warning
Seizures have been temporally associated with the use of beta interferons in clinical trials and postmarketing safety surveillance
Details
It is not known whether these events were related to the effects of multiple sclerosis alone, to AVONEX, or to a combination of both
Autoimmune Disorders
Warning
Postmarketing reports of autoimmune disorders of multiple target organs in AVONEX-treated patients included idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis
Guidance
If AVONEX-treated patients develop a new autoimmune disorder, consider stopping the therapy
Laboratory Tests
Guidance
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
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
No changes to the well-understood safety profile of AVONEX were identified in the CHAMPIONS follow-up study out to 10 years1,2
Over the course of the entire 10-year follow-up, there were 34 serious adverse events in 25 patients, including 2 deaths (metastatic breast cancer and an automobile accident)
Serious adverse events were similar by treatment group (16 patients in the IT group and 18 patients in the DT group had serious adverse events)
No changes to the well-understood safety profile were identified in the ASSURANCE follow-up study over 15 years of use3
In placebo-controlled studies, adverse reactions observed at an incidence ≥20% on AVONEX and at least 2% more frequently on AVONEX (n=351) than placebo (n=333) were headache (58% vs 55%), flu-like symptoms (49% vs 29%), myalgia (29% vs 22%), asthenia (24% vs 18%), nausea (23% vs 19%), pain (23% vs 21%), and fever (20% vs 9%)1
