Avonex kit avonex pen Kit

AVONEX is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

AVONEX is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, or any other component of the formulation [see Warnings and Precautions (5.3)].

The formerly available lyophilized vial formulation of AVONEX is contraindicated in patients with a history of hypersensitivity to albumin (human).

The following serious adverse reactions are discussed in more detail in other sections of labeling:

1. Depression, Suicide, and Psychotic Disorders [see Warnings and Precautions (5.1)]
2. Hepatic Injury [see Warnings and Precautions (5.2)]
3. Anaphylaxis and Other Allergic-Reactions [see Warnings and Precautions (5.3)]
4. Injection Site Reactions Including Necrosis [see Warnings and Precautions (5.4)]
5. Congestive Heart Failure [see Warnings and Precautions (5.5)]
6. Decreased Peripheral Blood Counts [see Warnings and Precautions (5.6)]
7. Thrombotic Microangiopathy [see Warnings and Precautions (5.7)]
8. Pulmonary Arterial Hypertension [see Warnings and Precautions (5.8)]
9. Seizures [see Warnings and Precautions (5.9)]
10. Autoimmune Disorders [see Warnings and Precautions (5.10)]
11. Laboratory Tests [see Warnings and Precautions (5.11)]

• 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, 5.10)

• Injection Site Reactions: Do not administer AVONEX into affected area until fully healed; if multiple lesions occur, change injection site or discontinue AVONEX until healing of skin lesions (5.4).

• Anaphylaxis and Other Allergic-Reactions: Discontinue if occurs (5.4)

• Congestive Heart Failure: monitor patients with pre-existing significant cardiac disease for worsening of cardiac symptoms (5.5)

• Decreased Peripheral Blood Counts: monitor complete blood count (5.6, 5.10)

• Thrombotic Microangiopathy: Cases of thrombotic microangiopathy have been reported. Discontinue AVONEX if clinical symptoms and laboratory findings consistent with TMA occur (5.7)

• Pulmonary Arterial Hypertension: Cases of pulmonary arterial hypertension (PAH) have been reported in patients treated with interferon beta products, including AVONEX. Discontinue AVONEX if PAH is diagnosed (5.8)

• Autoimmune Disorders: consider discontinuation of AVONEX if new autoimmune disorder occurs (5.10, 5.11) 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 postmarketing 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 (5.10)]. 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 Injection Site Reactions Including Necrosis

Injection site reactions, including injection site necrosis, can occur with the use of interferon beta products, including AVONEX. In controlled clinical trials, injection site reactions (e.g., injection site pain, bruising or erythema) occurred in 18% of patients receiving AVONEX and 13% in the placebo group. These reactions included injection site inflammation (6%), injection site pain (8%), injection site mass (<1%), nonspecific reactions.

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.

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. 5.5 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 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. In some cases, these events have been temporally related to the administration of AVONEX. In some of these instances recurrence upon rechallenge was observed. 5.6 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. 5.7 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 AVONEX. Cases have been reported several weeks to years after starting interferon beta products. Discontinue AVONEX if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated. 5.8 Pulmonary Arterial Hypertension

Cases of pulmonary arterial hypertension (PAH) have been reported in patients treated with interferon beta products, including AVONEX. 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.

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. 5.9 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. 5.10 Autoimmune Disorders

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. If AVONEX-treated patients develop a new autoimmune disorder, consider stopping the therapy. 5.11 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, 5.6, 5.10)]. 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.

AVONEX dosage forms (prefilled syringe and prefilled autoinjector) are single-dose. See Patient's Instructions for Use for complete administration instructions.

The first AVONEX injection should be performed under the supervision of an appropriately qualified healthcare professional. If patients or caregivers are to administer AVONEX, train them in the proper intramuscular injection technique and assess their ability to inject intramuscularly to ensure the proper administration of AVONEX.

Advise patients and caregivers to:

1. Rotate injection sites with each administration to minimize the likelihood of injection site reactions, including necrosis or localized infection [see Warnings and Precautions (5.4)]
2. NOT inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way
3. Check the injection site after 2 hours for redness, swelling, or tenderness
4. Contact their healthcare provider if they have a skin reaction and it does not clear up in a few days

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

A 25 gauge, 1” needle for intramuscular injection with AVONEX prefilled syringe may be substituted for the 23 gauge, 1 ¼” needle by the healthcare provider, if deemed appropriate. A 25 gauge, 5/8” needle specific to the prefilled autoinjector is supplied with the AVONEX PEN^® Administration Dose Pack. DO NOT use any other needle with the autoinjector.

Use safe disposal procedures for needles and syringes. DO NOT re-use needles, prefilled syringes, or autoinjectors. Following the administration of each titrated dose, discard any remaining product.

1. Injection: 30 micrograms per 0.5 mL clear, colorless solution in a single-dose prefilled syringe
2. Injection: 30 micrograms per 0.5 mL clear, colorless solution in a single-dose prefilled autoinjector