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Xerfelan

Name: Xerfelan drug & pharmaceuticals. Xerfelan available forms, doses, prices
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Published: 2021-11-11T10:10:10+00:00

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Adverse reactions
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1 INDICATIONS AND USAGE

Xerfelan (interferon beta-1a) is indicated for the treatment of patients with relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.

Xerfelan is an interferon beta indicated for the treatment of patients with relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. (1)

2 DOSAGE AND ADMINISTRATION

For intramuscular use only
Recommended dose: 30 micrograms once a week (2.1)
Xerfelan may be titrated, starting with 7.5 micrograms for first week, to reduce flu-like symptoms (2.1)
Increase dose by 7.5 micrograms each week for next 3 weeks until recommended dose of 30 micrograms (2.1)
See patient instructions for use for complete administration instructions (2.2)
Perform first injection under the supervision of an appropriately qualified health care professional (2.2)
Analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms (2.3)

2.1 Dosing Information

Xerfelan is administered intramuscularly.

The recommended dose is 30 micrograms once a week. To reduce the incidence and severity of flu-like symptoms that may occur when initiating Xerfelan therapy at a dose of 30 micrograms, Xerfelan may be started at a dose of 7.5 micrograms and the dose may be increased by 7.5 micrograms each week for the next three weeks until the recommended dose of 30 micrograms is achieved. An AVOSTARTGRIP kit containing 3 titration devices can be used for titration and is to be used only with Xerfelan Prefilled Syringes.

¹ Dosed once a week, intramuscularly
	Xerfelan Dose¹	Recommended Dose
Week 1	7.5 micrograms	1/4 dose
Week 2	15 micrograms	1/2 dose
Week 3	22.5 micrograms	3/4 dose
Week 4+	30 micrograms	full dose

2.2 Important Administration Instructions

All Xerfelan dosage forms are single-use (injection of reconstituted solution, prefilled syringe, and prefilled autoinjector). See Patient's Instructions for Use for complete administration instructions.

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

Advise patients and caregivers to:

Rotate sites for intramuscular injections with each injection to minimize the likelihood of injection site reactions
NOT inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way
Check the injection site after 2 hours for redness, swelling, or tenderness
Contact their healthcare provider if they have a skin reaction and it does not clear up in a few days

A 25 gauge, 1” needle for intramuscular injection with Xerfelan prefilled syringe or injection of reconstituted solution 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 Xerfelan 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, syringes, prefilled syringes, or autoinjectors. Following the administration of each titrated dose, discard any remaining product.

2.3 Premedication for Flu-like Symptoms

Concurrent use of analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with Xerfelan use.

3 DOSAGE FORMS AND STRENGTHS

For injection: 30 micrograms lyophilized powder in a single-use vial
Injection: 30 micrograms per 0.5 mL solution in a single-use prefilled syringe
Injection: 30 micrograms per 0.5 mL solution in a single-use prefilled autoinjector

For Injection: 30 micrograms lyophilized powder in a single-use vial (3)
Injection: 30 micrograms per 0.5 mL solution in single-use prefilled syringe (3)
Injection: Single-use prefilled autoinjector containing 0.5 mL solution with 30 mcg (3)

4 CONTRAINDICATIONS

Xerfelan 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 lyophilized vial formulation of Xerfelan is contraindicated in patients with a history of hypersensitivity to albumin (human).

History of hypersensitivity to natural or recombinant interferon beta, albumin or any other component of the formulation (4)

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 Xerfelan if depression occurs
Hepatic Injury: monitor liver function tests; monitor patients for signs and symptoms of hepatic injury; consider discontinuation of Xerfelan if hepatic injury occurs (5.2, 5.9)
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, 5.9)
Thrombotic Microangiopathy: Cases of thrombotic microangiopathy have been reported. Discontinue Xerfelan if clinical symptoms and laboratory findings consistent with TMA occur (5.6)
Autoimmune Disorders: consider discontinuation of Xerfelan if new autoimmune disorder occurs (5.8, 5.9)

5.1 Depression, Suicide, and Psychotic Disorders

Patients treated with Xerfelan 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 Xerfelan therapy should be considered.

Depression and suicide have been reported to occur with increased frequency in patients receiving Xerfelan. 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 Xerfelan 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 Xerfelan 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 Xerfelan.

5.2 Hepatic Injury

Severe hepatic injury, including cases of hepatic failure, has been reported rarely in patients taking Xerfelan. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with Xerfelan. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. The potential risk of Xerfelan used in combination with known hepatotoxic drugs or other products should be considered prior to starting Xerfelan, or before starting hepatotoxic drugs. Patients should be monitored for signs of hepatic injury [see Warnings and Precautions (5.9)].

5.3 Anaphylaxis and Other Allergic-Reactions

Anaphylaxis has been reported as a rare complication of Xerfelan use. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria. Discontinue Xerfelan 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 Xerfelan. 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 Xerfelan. 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 ]. 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 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 Xerfelan. Cases have been reported several weeks to years after starting interferon beta products. Discontinue Xerfelan if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.

5.7 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, 4 patients receiving Xerfelan 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 Xerfelan, or to a combination of both.

5.8 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.

5.9 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 Xerfelan therapy [see Warnings and Precautions (5.2, 5.5, 5.8)]. 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.

6 ADVERSE REACTIONS

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

Depression, Suicide, and Psychotic Disorders [see Warnings and Precautions ]
Hepatic Injury [see Warnings and Precautions (5.2)]
Anaphylaxis and Other Allergic-Reactions [see Warnings and Precautions (5.3)]
Congestive Heart Failure [see Warnings and Precautions (5.4)]
Decreased Peripheral Blood Counts [see Warnings and Precautions (5.5)]
Thrombotic Microangiopathy [see Warnings and Precautions (5.6)]
Seizures [see Warnings and Precautions (5.7)]
Autoimmune Disorders [see Warnings and Precautions (5.8)]
Laboratory Tests [see Warnings and Precautions (5.9)]

The most common adverse reactions (at least 5% more frequent on Xerfelan than on placebo) were flu-like symptoms including chills, fever, myalgia, and asthenia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1-800-456-2255 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Xerfelan cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice.

Among 351 patients with relapsing forms of MS treated with Xerfelan 30 micrograms (including 319 patients treated for 6 months and 288 patients treated for greater than one year) the most commonly reported adverse reactions (at least 5% more frequent on Xerfelan than on placebo) were flu-like symptoms. Symptoms can include chills, fever, myalgia and asthenia occurring within hours to days following an injection. Most people who take Xerfelan have flu-like symptoms early during the course of therapy. Usually, these symptoms last for a day after the injection. For many people, these symptoms lessen or go away over time. The most frequently reported adverse reactions resulting in clinical intervention (for example, discontinuation of Xerfelan or the need for concomitant medication to treat an adverse reaction symptom) were flu-like symptoms and depression.

Table 2 enumerates adverse reactions that occurred with AVONEX-treated patients at an incidence of at least 2% more than that observed in the placebo-treated patients in the pooled placebo-controlled studies in patients with relapsing forms of MS [see Clinical Studies (14)].

	Placebo	Xerfelan
Adverse Reaction	(N = 333)	(N = 351)
Body as a Whole
Headache	55%	58%
Flu-like symptoms (otherwise unspecified)	29%	49%
Pain	21%	23%
Asthenia	18%	24%
Fever	9%	20%
Chills	5%	19%
Abdominal pain	6%	8%
Injection site pain	6%	8%
Infection	4%	7%
Injection site inflammation	2%	6%
Chest pain	2%	5%
Injection site reaction	1%	3%
Toothache	1%	3%

Nervous System
Depression	14%	18%
Dizziness	12%	14%

Respiratory System
Upper respiratory tract infection	12%	14%
Sinusitis	12%	14%
Bronchitis	5%	8%

Digestive System
Nausea	19%	23%

Musculoskeletal System
Myalgia	22%	29%
Arthralgia	6%	9%

Urogenital
Urinary tract infection	15%	17%
Urine constituents abnormal	0%	3%

Skin and Appendages
Alopecia	2%	4%

Special Senses
Eye disorder	2%	4%

Hemic and Lymphatic System
Injection site ecchymosis	4%	6%
Anemia	1%	4%

Cardiovascular System
Migraine	3%	5%
Vasodilation	0%	2%

Immunogenicity

Anaphylaxis and other allergic reactions have occurred in AVONEX-treated patients [see Warnings and Precautions (5.3)]. As with all therapeutic proteins, there is a potential for immunogenicity. In studies assessing immunogenicity in multiple sclerosis patients administered Xerfelan for at least 1 year, 5% (21 of 390 patients) showed the presence of neutralizing antibodies at one or more times.

These data reflect the percentage of patients whose test results were considered positive for antibodies to Xerfelan using a two-tiered assay (ELISA binding assay followed by an antiviral cytopathic effect assay), and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of neutralizing activity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Xerfelan with the incidence of antibodies to other products may be misleading.

6.2 Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of Xerfelan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Menorrhagia and metrorrhagia
Rash (including vesicular rash)
Rare cases of injection site abscess or cellulitis requiring surgical intervention

8 USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm

8.1 Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Xerfelan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In pregnant monkeys given interferon beta at 100 times the recommended weekly human dose (based upon a body surface area [mg/m²] comparison), no teratogenic or other adverse effects on fetal development were observed. Abortifacient activity was evident following 3 to 5 doses at this level. No abortifacient effects were observed in monkeys treated at 2 times the recommended weekly human dose (based upon mg/m²).

8.3 Nursing Mothers

It is not known whether Xerfelan is excreted in human milk.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of Xerfelan did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.

11 DESCRIPTION

Xerfelan is a 166 amino acid glycoprotein with a molecular weight of approximately 22,500 daltons. It is produced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary cells into which the human interferon beta gene has been introduced. The amino acid sequence of Xerfelan is identical to that of natural human interferon beta.

Using the World Health Organization International Standard for Interferon, Xerfelan has a specific activity of approximately 200 million international units of antiviral activity per mg of Xerfelan determined specifically by an in vitro cytopathic effect bioassay using lung carcinoma cells (A549) and Encephalomyocarditis virus (ECM). Xerfelan 30 micrograms contains approximately 6 million international units of antiviral activity using this method. The activity against other standards is not known. Comparison of the activity of Xerfelan with other interferon betas is not appropriate, because of differences in the reference standards and assays used to measure activity.

11.1 Xerfelan Lyophilized Powder Vial

A vial of Xerfelan is a sterile, white to off-white lyophilized powder for intramuscular injection after reconstitution with supplied diluent (Sterile Water for Injection, USP). Each vial of reconstituted Xerfelan contains 30 micrograms of Xerfelan; 15 mg Albumin (Human), USP; 5.8 mg Sodium Chloride, USP; 5.7 mg Dibasic Sodium Phosphate, USP; and 1.2 mg Monobasic Sodium Phosphate, USP, in 1.0 mL at a pH of approximately 7.3.

11.2 Xerfelan Single-Use Prefilled Syringe

A prefilled syringe of Xerfelan is a sterile liquid for intramuscular injection. Each 0.5 mL of Xerfelan in a prefilled glass syringe contains 30 micrograms of Xerfelan, 0.79 mg Sodium Acetate Trihydrate, USP; 0.25 mg Glacial Acetic Acid, USP; 15.8 mg Arginine Hydrochloride, USP; and 0.025 mg Polysorbate 20 in Water for Injection, USP at a pH of approximately 4.8.

11.3 Xerfelan PEN Single-Use Prefilled Autoinjector

Xerfelan PEN is a sterile liquid for intramuscular injection in a prefilled glass syringe surrounded by an autoinjector. Each 0.5 mL (30 microgram dose) in the Xerfelan PEN contains 30 micrograms of Xerfelan, 0.79 mg Sodium Acetate Trihydrate, USP; 0.25 mg Glacial Acetic Acid, USP; 15.8 mg Arginine Hydrochloride, USP; and 0.025 mg Polysorbate 20 in Water for Injection, USP at a pH of approximately 4.8.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action by which Xerfelan exerts its effects in patients with multiple sclerosis is unknown.

12.2 Pharmacodynamics

Interferons are a family of naturally occurring proteins, produced by eukaryotic cells in response to viral infection and other biologic agents. Three major types of interferons have been defined: type I (IFN-alpha, beta, epsilon, kappa and omega), type II (IFN–gamma) and type III (IFN-lambda). Interferon-beta is a member of the type I subset of interferons. The type I interferons have considerably overlapping but also distinct biologic activities. The bioactivities of all IFNs, including IFN-beta, are induced via their binding to specific receptors on the membranes of human cells. Differences in the bioactivites induced by the three major subtypes of IFNs likely reflect differences in the signal transduction pathways induced by signaling through their cognate receptors.

Interferon beta exerts its biological effects by binding to specific receptors on the surface of human cells. This binding initiates a complex cascade of intracellular events that leads to the expression of numerous interferon-induced gene products and markers. These include 2', 5'-oligoadenylate synthetase, β₂-microglobulin, and neopterin. These products have been measured in the serum and cellular fractions of blood collected from patients treated with Xerfelan.

Clinical studies conducted in multiple sclerosis patients showed that interleukin 10 (IL-10) levels in cerebrospinal fluid were increased in patients treated with Xerfelan compared to placebo. Serum IL-10 levels maximally were increased by 48 hours after intramuscular injection of Xerfelan and remained elevated for 1 week. However, no relationship has been established between absolute levels of IL-10 and clinical outcome in multiple sclerosis.

12.3 Pharmacokinetics

Pharmacokinetics of Xerfelan in multiple sclerosis patients have not been evaluated. The pharmacokinetic and pharmacodynamic profiles of Xerfelan in healthy subjects following doses of 30 micrograms through 75 micrograms have been investigated. Serum levels of Xerfelan as measured by antiviral activity are slightly above detectable limits following a 30 microgram intramuscular dose, and increase with higher doses.

After an intramuscular dose, serum levels of Xerfelan generally peak at 15 hours post-dose (range: 6-36 hours) and then decline at a rate consistent with a 19 (range: 8-54) hour elimination half-life.

Subcutaneous administration of Xerfelan should not be substituted for intramuscular administration as there is no data establishing that subcutaneous and intramuscular administration of Xerfelan result in equivalent pharmacokinetic and pharmacodynamic parameters.

Biological response markers (e.g., neopterin and β₂-microglobulin) are induced by Xerfelan following parenteral doses of 15 micrograms through 75 micrograms in healthy subjects and treated patients. Biological response marker levels increase within 12 hours of dosing and remain elevated for at least 4 days. Peak biological response marker levels are typically observed 48 hours after dosing. The relationship of serum Xerfelan levels or levels of these induced biological response markers to the mechanisms by which Xerfelan exerts its effects in multiple sclerosis is unknown.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

Carcinogenesis: The carcinogenic potential of Xerfelan has not been tested in animals.

Mutagenesis: Interferon beta was not mutagenic when tested in an in vitro bacterial reverse mutation (Ames) test or in an in vitro cytogenetic assay in human lymphocytes.

Impairment of Fertility: In monkeys administered interferon beta by subcutaneous injection (8 to 15 doses of 1.25 mcg/kg or 50 mcg/kg) over the course of one menstrual cycle, menstrual irregularities, anovulation, and decreased serum progesterone levels were observed at the higher dose. These effects were reversible after discontinuation of drug. The no-effect dose (1.25 mcg/kg) is approximately 2 times the recommended weekly dose in humans (30 mcg) on a mg/m² basis.

14 CLINICAL STUDIES

The clinical effects of Xerfelan in patients with relapsing forms of multiple sclerosis (MS) were studied in two randomized, multicenter, double-blind, placebo-controlled studies in patients with MS (Studies 1 and 2). Safety and efficacy of treatment with Xerfelan beyond 3 years is not known.

In Study 1, 301 patients received either 30 micrograms of Xerfelan (n=158) or placebo (n=143) by intramuscular injection once weekly. Patients received injections for up to 2 years, and continued to be followed until study completion. Two hundred eighty-two patients completed 1 year on study, and 172 patients completed 2 years on study. There were 144 patients treated with Xerfelan for more than 1 year, 115 patients for more than 18 months and 82 patients for 2 years.

All patients had a definite diagnosis of multiple sclerosis of at least 1 year duration and had at least 2 exacerbations in the 3 years prior to study entry (or 1 per year if the duration of disease was less than 3 years). At entry, study participants were without exacerbation during the prior 2 months and had Kurtzke Expanded Disability Status Scale (EDSS³) scores ranging from 1.0 to 3.5. The EDSS is a scale that quantifies disability in patients with MS and ranges from 0 (normal neurologic exam) to 10 (death due to MS). Patients with chronic progressive multiple sclerosis were excluded from this study.

Disability

The primary outcome assessment was time to progression in disability, measured as an increase in the EDSS score of at least 1 point that was sustained for at least 6 months. An increase in EDSS score reflects accumulation of disability. This endpoint was used to help distinguish permanent increase in disability from a transient increase due to an exacerbation.

As shown in Figure 1, the time to onset of sustained progression in disability was significantly longer in AVONEX-treated patients than in placebo-treated patients in Study 1 (p = 0.02). The percentage of patients progressing by the end of 2 years was 35% for placebo-treated patients and 22% for AVONEX-treated patients. This represents a 37% relative reduction in the risk of accumulating disability in the AVONEX-treated group compared to the placebo-treated group.

1 Kaplan-Meier Methodology; Disability progression was defined as at least a 1 point increase in EDSS score sustained for at least 6 months.

The distribution of confirmed EDSS change from study entry (baseline) to the end of the study is shown in Figure 2. There was a statistically significant difference between the Xerfelan and placebo groups in confirmed change for patients with at least 2 scheduled visits (p = 0.006).

Figure 1 Figure 2

Exacerbations

The rate and frequency of MS exacerbations were secondary outcomes. For all patients included in the study, irrespective of time on study, the annual exacerbation rate was 0.67 per year in the AVONEX-treated group and 0.82 per year in the placebo-treated group (p = 0.04).

Xerfelan treatment significantly decreased the frequency of exacerbations in the subset of patients who were enrolled in the study for at least 2 years (87 placebo-treated patients and 85 AVONEX-treated patients; p = 0.03; see Table 3).

MRI Results

Gadolinium (Gd)-enhanced and T2-weighted magnetic resonance imaging (MRI) scans of the brain were obtained in most patients at baseline and at the end of 1 and 2 years of treatment. Secondary outcomes included Gd-enhanced lesion number and volume, and T2-weighted lesion volume. Gd-enhancing lesions seen on brain MRI scans represent areas of breakdown of the blood brain barrier thought to be secondary to inflammation. AVONEX-treated patients demonstrated significantly lower Gd-enhanced lesion number after 1 and 2 years of treatment than placebo-treated patients (p ≤ 0.05; see Table 3). The volume of Gd-enhanced lesions showed similar treatment effects in the Xerfelan and placebo groups (p ≤ 0.03). Percentage change in T2-weighted lesion volume from study entry to Year 1 was significantly lower in AVONEX-treated than placebo-treated patients (p = 0.02). A significant difference in T2-weighted lesion volume change was not seen between study entry and Year 2 in the Xerfelan and placebo groups.

The exact relationship between MRI findings and the clinical status of MS patients is unknown. The prognostic significance of MRI findings in these studies has not been evaluated.

Summary of Effects of Clinical and MRI Endpoints in Study 1

A summary of the effects of Xerfelan on the clinical and MRI endpoints of this study is presented in Table 3.

Note: (N:, ) denotes the number of evaluable placebo and Xerfelan patients, respectively.
¹ Patient data included in this analysis represent variable periods of time on study.
² Analyzed by Mantel-Cox (logrank) test.
³ Analyzed by Mann-Whitney rank-sum test.
⁴ Analyzed by Cochran-Mantel-Haenszel test.
⁵ Analyzed by likelihood ratio test.
Endpoint	Placebo	Xerfelan	P-Value
PRIMARY ENDPOINT:

Time to sustained progression
in disability (N: 143, 158)¹	--- See Figure 1 ---		0.02²

Percentage of patients progressing
in disability at 2 years
(Kaplan-Meier estimate)¹	35%	22%

SECONDARY ENDPOINTS:
DISABILITY

Mean confirmed change in EDSS
from study entry to end of study
(N: 136, 150)¹	0.50	0.20	0.006³

EXACERBATIONS

Number of exacerbations in subset
completing 2 years (N: 87, 85)
0	26%	38%	0.03³
1	30%	31%
2	11%	18%
3	14%	7%
≥ 4	18%	7%

Percentage of patients exacerbation-
free in subset completing 2 years
(N: 87, 85)	26%	38%	0.10⁴

Annual exacerbation rate
(N: 143, 158)¹	0.82	0.67	0.04⁵
Table 3 (continued): Clinical and MRI Endpoints in Study 1
Endpoint	Placebo	Xerfelan	P-Value
MRI

Number of Gd-enhanced lesions:
At study entry (N: 132, 141)
Mean (Median)	2.3 (1.0)	3.2 (1.0)
Range	0-23	0-56

Year 1 (N: 123, 134)
Mean (Median)	1.6 (0)	1.0 (0)	0.02³
Range	0-22	0-28

Year 2 (N: 82, 83)
Mean (Median)	1.6 (0)	0.8 (0)	0.05³
Range	0-34	0-13

T2 lesion volume:
Percentage change from study
entry to Year 1 (N: 116, 123)
Median	-3.3%	-13.1%	0.02³

Percentage change from study
entry to Year 2 (N: 83, 81)
Median	-6.5%	-13.2%	0.36³

In Study 2, 383 patients who had recently experienced an isolated demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and who had lesions typical of multiple sclerosis on brain MRI, received either 30 micrograms of Xerfelan (n = 193) or placebo (n = 190) by intramuscular injection once weekly. Patients were enrolled into the study over a two-year period and followed for up to three years or until they developed a second clinical exacerbation in an anatomically distinct region of the central nervous system.

Exacerbations

In Study 2, the primary outcome measure was time to development of a second exacerbation in an anatomically distinct region of the central nervous system. Time to development of a second exacerbation was significantly delayed in AVONEX-treated compared to placebo-treated patients (p = 0.002). The Kaplan-Meier estimates of the percentage of patients developing an exacerbation within 24 months were 39% in the placebo group and 21% in the Xerfelan group. The relative rate of developing a second exacerbation in the Xerfelan group was 0.56 of the rate in the placebo group (95% confidence interval 0.38 to 0.81).

1 Kaplan-Meier Methodology

Figure 3

MRI Findings

Secondary outcomes were brain MRI measures, including the cumulative increase in the number of new or enlarging T2 lesions, T2 lesion volume at baseline compared to results at 18 months, and the number of Gd-enhancing lesions at 6 months. See Table 4 for the MRI results.

¹ P value <0.001
² P value <0.03
* P value from a Mann-Whitney rank-sum test
	Xerfelan	Placebo
CHANGE FROM BASELINE IN T2 VOLUME OF LESIONS AT 18 MONTHS:	N = 119	N = 109

Actual Change (mm³)^1* Median (25^th%, 75^th%)	28 (-576, 397)	313 (5, 1140)
Percentage Change^1* Median (25^th%, 75^th%)	1 (-24, 29)	16 (0, 53)

NUMBER OF NEW OR ENLARGING T2 LESIONS AT 18 MONTHS ^1* :	N = 132 N (%)		N = 119 N (%)

0	62 (47)	22 (18)
1-3	41 (31)	47 (40)
≥4	29 (22)	50 (42)
Mean (SD)	2.13 (3.2)	4.97 (7.7)

NUMBER OF GD-ENHANCING LESIONS AT 6 MONTHS ^2* :	N = 165 N (%)		N = 152 N (%)

0	115 (70)	93 (61)
1	27 (16)	16 (11)
>1	23 (14)	43 (28)
Mean (SD)	0.87 (2.3)	1.49 (3.1)

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Xerfelan Lyophilized Powder Vial

A vial of Xerfelan is supplied as a lyophilized powder in a single-use vial containing 33 micrograms of Xerfelan; 16.5 mg Albumin (Human), USP; 6.4 mg Sodium Chloride, USP; 6.3 mg Dibasic Sodium Phosphate, USP; and 1.3 mg Monobasic Sodium Phosphate, USP, and is preservative-free. Diluent is supplied in a single-use vial (Sterile Water for Injection, USP).

Xerfelan lyophilized vials are available in the following package configuration (NDC 59627-111-03): A package containing four Administration Dose Packs (each containing one vial of Xerfelan, one 10 mL diluent vial, two alcohol wipes, one gauze pad, one 3 mL syringe, one MICRO PIN^®* vial access pin, one 23 gauge, 1¼ inch needle, and one adhesive bandage).

Vials of Xerfelan should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Should refrigeration be unavailable, vials of Xerfelan can be stored at 25°C (77°F) for a period of up to 30 days. DO NOT EXPOSE TO HIGH TEMPERATURES. DO NOT FREEZE. Protect from light. Do not use beyond the expiration date stamped on the vial. Following reconstitution, it is recommended the product be used as soon as possible within 6 hours stored at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE RECONSTITUTED Xerfelan.

16.2 Xerfelan Single-Use Prefilled Syringe

A prefilled syringe of Xerfelan is supplied as a sterile liquid albumin-free formulation containing 30 micrograms of Xerfelan, 0.79 mg Sodium Acetate Trihydrate, USP; 0.25 mg Glacial Acetic Acid, USP; 15.8 mg Arginine Hydrochloride, USP; and 0.025 mg Polysorbate 20 in Water for Injection, USP. Each prefilled glass syringe contains 0.5 mL for Intramuscular injection.

Xerfelan prefilled syringes are available in the following package configuration (NDC 59627-222-05): A package containing four Administration Dose Packs (each containing one single-use syringe of Xerfelan and one 23 gauge, 1¼ inch needle), and a recloseable accessory pouch containing 4 alcohol wipes, 4 gauze pads, and 4 adhesive bandages.

Xerfelan in prefilled syringes should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Once removed from the refrigerator, Xerfelan in a prefilled syringe should be allowed to warm to room temperature (about 30 minutes). Do not use external heat sources such as hot water to warm Xerfelan in a prefilled syringe. Should refrigeration be unavailable, Xerfelan in a prefilled syringe can be stored at ≤ 25°C (77°F) for a period up to 7 days. Once the product is removed from the refrigerator, it must not be stored above 25°C (77°F). If the product has been exposed to conditions other than those recommended, DISCARD THE PRODUCT and DO NOT USE. DO NOT EXPOSE TO HIGH TEMPERATURES. DO NOT FREEZE. Protect from light. Do not use beyond the expiration date stamped on the syringe.

16.3 Xerfelan PEN Single-Use Prefilled Autoinjector

Xerfelan PEN is supplied as a sterile liquid albumin-free formulation containing 30 micrograms of Xerfelan, 0.79 mg Sodium Acetate Trihydrate, USP; 0.25 mg Glacial Acetic Acid, USP; 15.8 mg Arginine Hydrochloride, USP; and 0.025 mg Polysorbate 20 in Water for Injection, USP. Each single-use prefilled autoinjector contains 0.5 mL for intramuscular injection.

Xerfelan PEN single-use prefilled autoinjectors are available in the following package configuration (NDC 59627-333-04): A package containing four Xerfelan PEN Administration Dose Packs (each containing one Xerfelan PEN autoinjector, one 25 gauge, 5/8 inch needle and an Xerfelan PEN cover), and a recloseable accessory pouch containing 4 alcohol wipes, 4 gauze pads, and 4 adhesive bandages.

Xerfelan PEN should be stored in a 2°C to 8°C (36°F to 46°F) refrigerator. Once removed from the refrigerator, Xerfelan PEN should be allowed to warm to room temperature (about 30 minutes). Do not use external heat sources such as hot water to warm Xerfelan. Should refrigeration be unavailable, Xerfelan PEN can be stored at ≤ 25°C (77°F) for a period up to 7 days. Once the product is removed from the refrigerator, it must not be stored above 25°C (77°F). If the product has been exposed to conditions other than those recommended, DISCARD THE PRODUCT and DO NOT USE. DO NOT EXPOSE TO HIGH TEMPERATURES. DO NOT FREEZE. Protect from light. Do not use beyond the expiration date stamped on the prefilled autoinjector.

17 PATIENT COUNSELING INFORMATION

Instruct patients to carefully read the supplied Xerfelan Medication Guide and caution patients not to change the Xerfelan dose or schedule of administration without medical consultation.

Inform patients that the Prefilled Syringe tip cap of this product contains natural rubber latex which may cause allergic reactions.

Instruction on Self-injection Technique and Procedures

Provide appropriate instruction for reconstitution of Xerfelan and methods of self-injection, including careful review of the Xerfelan Medication Guide. Instruct patients in the use of aseptic technique when administering Xerfelan.

Inform patients that their healthcare provider should show them or their caregiver how to prepare and inject Xerfelan before administering the first dose. Their healthcare provider should watch the first Xerfelan injection given. Tell patients not to re-use needles or syringes and instruct patients on safe disposal procedures. Inform patients to dispose of used needles and syringes in a puncture-resistant container and instruct the patient regarding safe disposal of full containers.

Advise patients:

of the importance of rotating areas of injection with each dose to minimize the likelihood of injection site reactions. [see Choose an Injection Site section of the Medication Guide].
NOT to inject area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way
to check the injection site after 2 hours for redness, swelling, or tenderness
contact their healthcare provider if they have a skin reaction and it does not clear up in a few days

Pregnancy

Advise patients that Xerfelan should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Special Population (8.1)].

Depression

Advise patients of the symptoms of depression, suicidal ideation, or psychotic disorders as they have been reported with the use of Xerfelan and instruct patients to report them immediately to their physician [see Warnings and Precautions (5.1)].

Liver Disease

Advise patients that severe hepatic injury, including hepatic failure, has been reported during the use of Xerfelan. Advise patients of symptoms of hepatic dysfunction, and instruct patients to report them immediately to their physician [see Warnings and Precautions (5.2)].

Allergic Reactions and Anaphylaxis

Advise patients of the symptoms of allergic reactions and anaphylaxis, and instruct patients to seek immediate medical attention if these symptoms occur [see Warnings and Precautions (5.3)].

Congestive Heart Failure

Advise patients that worsening of pre-existing congestive heart failure has been reported in patients using Xerfelan. Advise patients of symptoms of worsening cardiac condition, and instruct patients to report them immediately to their physician [see Warnings and Precautions (5.4)].

Seizures

Advise patients that seizures have been reported in patients using Xerfelan. Instruct patients to report seizures immediately to their physician [see Warnings and Precautions (5.7)].

Flu-like Symptoms

Inform patients that flu-like symptoms are common following initiation of therapy with Xerfelan [see Dosage and Administration (2.3) and Adverse Reactions (6)]. Advise patients that starting with a lower dose than 30 micrograms and increasing the dose over 3 weeks reduces the incidence and severity of flu-like symptoms.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License #1697

1-800-456-2255

*MICRO PIN ^® is the trademark of B. Braun Medical Inc.

Medication Guide

Xerfelan ^® (a-vuh-necks)

(interferon beta-1a)

Injection for intramuscular use

Read this Medication Guide before you start using Xerfelan, and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about Xerfelan?

Xerfelan can cause serious side effects. Tell your healthcare provider right away if you have any of the symptoms listed below while taking Xerfelan.

Behavioral health problems including depression, suicidal thoughts or hallucinations. Some people taking Xerfelan may develop mood or behavior problems including:
- irritability (getting upset easily)
- depression (feeling hopeless or feeling bad about yourself)
- nervousness
- anxiety
- aggressive behavior
- thoughts of hurting yourself or suicide
- hearing or seeing things that others do not hear or see (hallucinations)
Liver problems, or worsening of liver problems including liver failure and death. Symptoms may include:
- nausea
- loss of appetite
- tiredness
- dark colored urine and pale stools
- yellowing of your skin or the white part of your eye
- bleeding more easily than normal
- confusion
- sleepiness
During your treatment with Xerfelan you will need to see your healthcare provider regularly and have regular blood tests to check for side effects.
Serious allergic reactions and skin reactions. Symptoms may include:
- itching
- swelling of the face, eyes, lips, tongue or throat
- trouble breathing
- anxiousness
- feeling faint
- skin rash, hives, sores in your mouth, or your skin blisters and peels

What is Xerfelan?

Xerfelan is a form of a protein called beta interferon that occurs naturally in the body. Xerfelan is a prescription medicine used to treat adults with relapsing forms of multiple sclerosis (MS). This includes people who have had their first symptoms of multiple sclerosis and have an MRI consistent with multiple sclerosis.

Xerfelan will not cure your MS but may decrease the number of flare-ups of the disease and slow the occurrence of some of the physical disability that is common in people with MS. MS is a life-long disease that affects your nervous system by destroying the protective covering (myelin) that surrounds your nerve fibers.

The way Xerfelan works in MS is not known.

It is not known if Xerfelan is safe and effective in children.

Who should not use Xerfelan?

Do not take Xerfelan if you:

are allergic to interferon beta, albumin (human), or any of the ingredients in Xerfelan. See the end of this Medication Guide for a complete list of ingredients in Xerfelan.

What should I tell my healthcare provider before using Xerfelan?

Before taking Xerfelan, tell your healthcare provider if you:

are being treated for a mental illness or had treatment in the past for any mental illness, including depression and suicidal behavior
have or had bleeding problems or blood clots
have or had low blood cell counts
have or had liver problems
have or had seizures (epilepsy)
have or had heart problems
have or had thyroid problems
have or had any kind of autoimmune disease (where the body's immune system attacks the body's own cells), such as psoriasis, systemic lupus erythematosus, or rheumatoid arthritis
drink alcohol
are pregnant or plan to become pregnant. It is not known if Xerfelan will harm your unborn baby. Tell your healthcare provider if you become pregnant during your treatment with Xerfelan.
are breastfeeding or plan to breastfeed. It is not known if Xerfelan passes into your breast milk. You and your healthcare provider should decide if you will use Xerfelan or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

How should I use Xerfelan?

Your healthcare provider should show you how to prepare and measure your dose of Xerfelan and how to inject your Xerfelan before you use Xerfelan for the first time.
Your healthcare provider or nurse should watch the first Xerfelan injection you give yourself.
Xerfelan is given once a week by injection into the muscle (intramuscular injection).
Inject Xerfelan exactly as your healthcare provider tells you.
Your healthcare provider will tell you how much Xerfelan to inject and how often to inject Xerfelan. Do not inject more than your healthcare provider tells you to.
If you miss a dose, you should take your next dose as soon as you remember. You should continue your regular schedule the following week. Do not take Xerfelan 2 days in a row.
Do not change your dose unless your healthcare provider tells you to.
Change (rotate) your injection site you choose with each injection. This will help decrease the chance that you will have an injection site reaction.
Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.
Xerfelan comes as a:
- Vial with freeze-dried (lyophilized) powder
- Prefilled syringe (can be used with the AVOSTARTGRIP titration kit)
- Single-Use Prefilled Autoinjector Pen (AVONEX PEN^®)

Your healthcare provider will decide which one is best for you. See the Instructions for Use at the end of this Medication Guide for detailed instructions for preparing and injecting your dose of Xerfelan.

Always use a new, unopened Xerfelan vial, prefilled syringe, or single-use prefilled autoinjector pen for each intramuscular injection.

What are the possible side effects of Xerfelan?

Xerfelan can cause serious side effects including:

See “What is the most important information I should know about Xerfelan?”
Heart problems, including heart failure. While Xerfelan is not known to have any direct effects on the heart, a few patients who did not have a history of heart problems developed heart muscle problems or congestive heart failure after taking Xerfelan. If you already have heart failure, Xerfelan may cause your heart failure to get worse. Call your healthcare provider right away if you have worsening symptoms of heart failure such as shortness of breath or swelling of your lower legs or feet while using Xerfelan.
- Some people using Xerfelan may have other heart problems including:
  - low blood pressure
  - fast or abnormal heart beat
  - chest pain
  - heart attack or a heart muscle problem (cardiomyopathy)
Blood problems. Xerfelan can affect your bone marrow and cause low red and white blood cell, and platelet counts. In some people, these blood cell counts may fall to dangerously low levels. If your blood cell counts become very low, you can get infections and problems with bleeding and bruising.
Seizures. Some patients have had seizures while taking Xerfelan, including patients who have never had seizures before.
Infections. Some people who take Xerfelan may get an infection. Symptoms of an infection may include:
- fever
- chills
- pain or burning with urination
- urinating often
- bloody diarrhea
- coughing up mucus
Thyroid problems. Some people taking Xerfelan develop changes in their thyroid function. Symptoms of thyroid changes include:
- problems concentrating
- feeling cold or hot all the time
- weight changes (gain or loss)
- skin changes

Tell your healthcare provider right away if you have any of the symptoms listed above.

The most common side effects of Xerfelan include:

Flu-like symptoms. Most people who take Xerfelan have flu-like symptoms early during the course of therapy. Usually, these symptoms last for a day after the injection. You may be able to manage these flu-like symptoms by taking over-the-counter pain and fever reducers. For many people, these symptoms lessen or go away over time. Symptoms may include:
- muscle aches
- fever
- tiredness
- chills

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Xerfelan?

Store Xerfelan in the refrigerator at 36°F to 46°F (2°C to 8°C).
Do not freeze Xerfelan. Do not use Xerfelan that has been frozen.
Do not store Xerfelan above 77°F (25°C).
Keep Xerfelan away from light.
Do not use Xerfelan past the expiration date.
If you cannot refrigerate your Xerfelan vials, you can store your Xerfelan vials at 77°F (25°C) for up to 30 days. After mixing, the Xerfelan solution should be used immediately, within 6 hours when stored refrigerated at 36°F to 46°F (2°C to 8°C).
If you cannot refrigerate your Xerfelan PEN and Xerfelan prefilled syringes, you can store your Xerfelan PEN and Xerfelan prefilled syringes up to 77°F (25°C) for up to 7 days.

Keep Xerfelan vials, prefilled syringes, pens and all other medicines out of the reach of children.

General advice about the safe and effective use of Xerfelan

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Xerfelan for a condition for which it was not prescribed. Do not give Xerfelan to other people, even if they have the same symptoms that you have, it may harm them.

This Medication Guide summarizes the most important information about Xerfelan. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about Xerfelan that is written for healthcare professionals.

What are the ingredients in Xerfelan?

Active ingredient: Xerfelan

Inactive ingredients:

Vial with freeze-dried (lyophilized) powder: albumin (human), sodium chloride, dibasic sodium phosphate, and monobasic sodium phosphate.
Single-Use Prefilled Syringe: sodium acetate trihydrate, glacial acetic acid, arginine hydrochloride, polysorbate 20 in water for injection.
Single-Use Prefilled Autoinjector Pen: sodium acetate trihydrate, glacial acetic acid, arginine hydrochloride, polysorbate 20 in water for injection.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License #1697

1-800-456-2255

Revised: 03/2016

Instructions for Use

Xerfelan PEN ^® (a-vuh-necks) (pen)

(interferon beta-1a)

injection for intramuscular use

single-use prefilled autoinjector pen

Read the Instructions for Use before you start using Xerfelan and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Your healthcare provider should show you or your caregiver how to prepare the dose of Xerfelan and how to inject your Xerfelan PEN the right way before Xerfelan PEN is used for the first time. Your healthcare provider or nurse should watch you inject the dose of Xerfelan the first time Xerfelan PEN is used.

Preparing the Xerfelan PEN:

Find a well lit, clean, flat work surface like a table and collect all the supplies you will need to give yourself or receive an injection.
Take 1 Xerfelan PEN Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting the Xerfelan dose to allow it to reach room temperature. Do not use external heat sources such as hot water to warm the Xerfelan PEN.
Check the expiration date printed on the Xerfelan PEN, Xerfelan PEN Administration Dose Pack carton, and the outer carton. Do not use the Xerfelan PEN past the expiration date.
Wash your hands with soap and water.

Supplies you will need to give the Xerfelan PEN injection:

1 Xerfelan Administration Dose Pack that contains:
- 1 Xerfelan PEN
- a 25 gauge, 5/8 inch long sterile needle
- 1 Xerfelan PEN cover
1 alcohol wipe
1 gauze pad
1 adhesive bandage
a puncture resistant container for disposal of used Xerfelan PEN and needle

Identifying parts of the Xerfelan PEN.

Single-Use Administration Dose Pack Contents – Xerfelan PEN, Supplied Needle and Xerfelan PEN Cover

(Figure A)

Preparing the Xerfelan PEN injection:

Step 1: Hold the Xerfelan PEN with the white tamper-evident cap (cap) pointing up. Check that the cap is intact and has not been removed. If the cap has been removed or is not tightly attached, do not use it, throw it away and get a new Xerfelan PEN.	(Figure B)
Step 2: With your other hand, grasp the cap and bend it at a 90° angle until the cap snaps off. After the cap comes off, you will see the glass tip of the syringe. Do not touch the glass tip of the syringe.	(Figure C) (Figure D)
Step 3: Place the Xerfelan PEN down on a flat work surface.
Step 4: Pull off the sterile foil from the needle cover. Only use the needle that comes with your Xerfelan PEN.	(Figure E)
Step 5: Hold the Xerfelan PEN with the glass syringe tip pointing up. Press the needle onto the Xerfelan PEN glass syringe tip.	(Figure F)
Step 6: Gently turn the needle clockwise until it is firmly attached. If the needle is not firmly attached, it may leak, and you may not get your full dose of Xerfelan.	(Figure G)
Do not remove the plastic cover from the needle.	(Figure H)
Step 7: Hold the body of the Xerfelan PEN in 1 hand with the needle and needle cover pointing away from you and other people. Do not remove the plastic cover from the needle.	(Figure I)
Step 8: Using your other hand, hold onto the injector shield (grooved area) tightly and quickly pull up on the injector shield until the injector shield covers the needle all the way. The plastic needle cover will “pop” off after the injector shield has been fully extended.	(Figure J)
When the injector shield is extended the right way, you will see a small blue rectangular area next to the oval medication display window.	(Figure K)
Step 9: Check the oval medication display window and make sure the Xerfelan is clear and colorless. You might see air bubbles in the oval display window. This is normal and will not affect your dose. Do not use Xerfelan PEN if the liquid is colored, cloudy, or contains any lumps or particles. Throw away the Xerfelan PEN and get a new one, then repeat steps 1 to 9.	(Figure L)

Giving the Xerfelan injection:

Your healthcare provider should show you or your caregiver how to prepare the dose of Xerfelan and how to inject your Xerfelan PEN the right way before Xerfelan PEN is used for the first time. Your healthcare provider or nurse should watch you inject the dose of Xerfelan the first time Xerfelan PEN is used.
Inject your Xerfelan PEN exactly as your healthcare provider has shown you.
Xerfelan PEN is injected into the muscle (intramuscularly).
Xerfelan PEN should be injected into the upper, outer thigh.
Change (rotate) injection sites for each dose. Do not use the same injection site for each injection.
Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.
Do not push down on the injector shield and the blue activation button at the same time until you are ready to give your injection.

Figure M

Step 10: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose. Do not touch this area again before giving the injection.	(Figure N)
Step 11: Place the Xerfelan PEN on the injection site.	(Figure O)
Step 12: Hold the body of the Xerfelan PEN at a 90º angle to the injection site, and make sure you can see the windows.	(Figure P)
Step 13: Keeping your fingers away from the blue activation button, firmly push the body of the Xerfelan PEN down against the thigh to release the safety lock. Do not lift the Xerfelan PEN off of the injection site. Check to make sure the safety lock has been released. You will know the safety lock is released when the small blue rectangular area above the oval medication display window is gone.	(Figure Q) (Figure R)
Step 14: Continue to firmly maintain pressure and push down on the Xerfelan PEN against the injection site, then push down on the blue activation button with your thumb. Keep the Xerfelan PEN pushed down against the injection site and slowly count to 10. You will hear a “click” when the injection starts. If you do not hear a “click”, your injection was not given the right way. If this happens, make sure that the injector shield is extended, the safety lock is completely released, and that you are firmly maintaining pressure and pushing down against the injection site. Press the blue activation button with your thumb again. If you still do not hear a “click”, call Biogen Idec Inc. at 1-800-456-2255.	(Figure S)
Step 15: After you count to 10, pull the Xerfelan PEN straight out of the skin. Use the gauze pad to apply pressure to the injection site for a few seconds or rub gently in a circular motion. If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.	(Figure T)
Step 16: Check the circular display window on the Xerfelan PEN to make sure that it is yellow. This is to be sure that you have been given your full dose. If you did not receive your full dose of Xerfelan, throw away the Xerfelan PEN and call your doctor. Do not re-use the Xerfelan PEN.	(Figure U)
STEP 17: Do not hold the Xerfelan PEN cover with your hands. Place the Xerfelan PEN cover on a flat work surface. Line up the exposed needle with the hole of the Xerfelan PEN cover, and insert directly into the opening.	(Figure V)
STEP 18: Firmly press the Xerfelan PEN down until you hear a “click” to seal the needle. You may need to hold both hands around the Xerfelan PEN body to snap the Xerfelan PEN cover into place.	(Figure W)

After the Xerfelan injection:

Throw away the used Xerfelan PENS and needles in a sharps container or some type of hard plastic or metal container with a screw cap such as a detergent bottle or coffee can. Check with your healthcare provider about the right way to throw away the container. There may be local or state laws about how to throw away used Xerfelan PENS and needles. Do not throw away used Xerfelan PENS and needles in household trash or recycling bins.
After 2 hours, check the injection site for redness, swelling or tenderness. If you have a skin reaction and it does not clear up in a few days, contact your healthcare provider.

General information about the safe and effective use of Xerfelan PEN

Always use a new Xerfelan PEN and needle for each injection. Do not re-use your Xerfelan PEN or needle.
Do not share your Xerfelan PEN or needles.
Keep Xerfelan PEN and needles out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

1-800-456-2255

Revised: 08/2015

41610-02

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Instructions for Use

Xerfelan ^® (a-vuh-necks)

(interferon beta-1a)

injection for intramuscular use

single-use prefilled syringe

Supplies you will need for the Xerfelan injection:

1 Xerfelan Administration Dose Pack that contains:
- 1 Xerfelan prefilled syringe
- 23 gauge, 1¼ inch long sterile needle
1 alcohol wipe
1 gauze pad
1 adhesive bandage
a puncture resistant container for disposal of used syringes and needles

Preparing the dose of Xerfelan:

Find a well lit, clean, flat work surface like a table and collect all the supplies you will need to give yourself or receive an injection.
Take 1 Xerfelan Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting the Xerfelan dose to allow it to reach room temperature. Do not use external heat sources such as hot water to warm the Xerfelan prefilled syringe.
Check the expiration date printed on Xerfelan prefilled syringe, Xerfelan prefilled syringe Administration Dose Package carton, and the outer carton. Do not use Xerfelan prefilled syringe past the expiration date.
Wash your hands with soap and water.

Identifying parts of the Xerfelan prefilled syringe :

Preparing the Xerfelan injection:

Step 1: Hold the Xerfelan prefilled syringe with the cap pointing down and with the 0.5 mL mark at eye level. Check the syringe: The syringe should not have any cracks or damage. Check that the cap is intact and has not been removed. The amount of liquid in the syringe should be at or very close to the 0.5 mL mark. Xerfelan should look clear, colorless, and should not have any particles in it. Do not use the Xerfelan prefilled syringe if: the syringe is cracked or damaged the solution is cloudy, colored, or has lumps or particles in it the cap has been removed or is not tightly attached or there is not enough liquid in the syringe Do not use that syringe. Get a new syringe. Contact MS ACTIVESOURCE at 1-800-456-2255.	(Figure A)
Step 2: With 1 hand, hold the Xerfelan prefilled syringe right under the cap and with the cap pointing up. Make sure you are holding the Xerfelan prefilled syringe by the ridged part, directly under the cap.	(Figure B)
Step 3: With the other hand, grasp the cap and bend it at a 90º angle until the cap snaps off.	(Figure C) (Figure D)
Step 4: Open the sterile needle package and take out the covered needle. Hold the Xerfelan prefilled syringe with the glass syringe tip pointing up. Press the needle on the Xerfelan prefilled syringe glass tip.	(Figure E)
Step 5: Gently turn the needle forward (clockwise) until it is tight and firmly attached. If the needle is not firmly attached, it may leak and you may not get your full dose of Xerfelan. Do not remove the plastic cover from the needle.	(Figure F)

Giving the Xerfelan injection:

Your healthcare provider should show you or a caregiver how to prepare and inject the dose of Xerfelan before Xerfelan prefilled syringe is used for the first time. Your healthcare provider or nurse should watch you inject the dose of Xerfelan the first time Xerfelan prefilled syringe is used.
Inject your Xerfelan exactly as your healthcare provider has shown you.
Xerfelan is injected into the muscle (intramuscularly).
Xerfelan should be injected into the thigh or upper arm.
Change (rotate) your injection sites for each dose. Do not use the same injection site for each injection.
Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.

Step 6: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose. Do not touch this area again before giving the injection.	(Figure G) (Figure H)
Step 7: Pull the protective cover straight off the needle. Do not twist the cover off.	(Figure I)
Step 8: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90 degree angle, through the skin and into the muscle. Once the needle is in, let go of the skin.	(Figure J)

Step 9: Slowly push the plunger down until the syringe is empty.	(Figure K)
Step 10: Pull the needle out of the skin. Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion. If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.	(Figure L)

After the Xerfelan injection:

Do not recap the needle. Recapping the needle can lead to a needle stick injury.
Throw away the used Xerfelan prefilled syringes and needles in a sharps container or some type of hard plastic or metal container with a screw cap such as a detergent bottle or coffee can. Check with your healthcare provider about the right way to throw away the container. There may be local or state laws about how to throw away used Xerfelan prefilled syringes and needles. Do not throw away used Xerfelan prefilled syringes and needles in household trash or recycling bins.
After 2 hours, check the injection site for redness, swelling or tenderness. If you have a skin reaction and it does not clear up in a few days, contact your healthcare provider.

General information about the safe and effective use of Xerfelan

Always use a new Xerfelan prefilled syringe and needle for each injection. Do not re-use your Xerfelan prefilled syringe or needles.
Do not share your Xerfelan prefilled syringe or needles.
Keep the Xerfelan prefilled syringe and needles out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

U.S. License # 1697

1-800-456-2255

Revised: 08/2014

41611-02

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Instructions for Use

AVOSTARTGRIP ^® Titration Kit

Use with Xerfelan ^® (interferon beta-1a) Prefilled Syringe Only

Preparing the Xerfelan Prefilled Syringe:

Find a well lit, clean, flat work surface like a table and collect all the supplies you will need to give yourself or receive an injection.
Take 1 Xerfelan Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting the Xerfelan dose to allow it to reach room temperature. Do not use external heat sources such as hot water to warm the Xerfelan prefilled syringe.
Check the expiration date printed on the Xerfelan prefilled syringe, Xerfelan prefilled syringe Administration Dose Package carton, and the outer carton. Do not use the Xerfelan prefilled syringe past the expiration date.
Wash your hands with soap and water.

Supplies you will need for the Xerfelan injection:

1 Xerfelan Administration Dose Pack that contains:
- 1 Xerfelan prefilled syringe
- 23 gauge, 1¼ inch long sterile needle
1 alcohol wipe
1 gauze pad
1 adhesive bandage
a puncture resistant container for disposal of used syringes and needles

Identifying parts of the Xerfelan prefilled syringe :

Preparing the Xerfelan injection:

Step 1: Hold the Xerfelan prefilled syringe with the cap pointing down and with the 0.5 mL mark at eye level. Check the syringe: The syringe should not have any cracks or damage. Check that the cap is intact and has not been removed. The amount of liquid in the syringe should be at or very close to the 0.5 mL mark. Xerfelan should look clear, colorless, and should not have any particles in it. Do not use the Xerfelan prefilled syringe if: the syringe is cracked or damaged the solution is cloudy, colored, or has lumps or particles in it the cap has been removed or is not tightly attached or there is not enough liquid in the syringe Do not use that syringe. Get a new syringe. Contact MS ACTIVESOURCE at 1-800-456-2255.	(Figure A)
Step 2: With 1 hand, hold the Xerfelan prefilled syringe right under the cap and with the cap pointing up. Make sure you are holding the Xerfelan prefilled syringe by the ridged part, directly under the cap.	(Figure B)
Step 3: With the other hand, grasp the cap and bend it at a 90º angle until the cap snaps off.	(Figure C) (Figure D)
Step 4: Open the sterile needle package and take out the covered needle. Hold the Xerfelan prefilled syringe with the glass syringe tip pointing up. Press the needle on the Xerfelan prefilled syringe glass tip.	(Figure E)
Step 5: Gently turn the needle forward (clockwise) until it is tight and firmly attached. If the needle is not firmly attached, it may leak and you may not get your full dose of Xerfelan. Do not remove the plastic cover from the needle.	(Figure F)

Using the Xerfelan prefilled syringe with the AVOSTARTGRIP titration kit:

Your Xerfelan dose may be titrated over 3 weeks by using Xerfelan prefilled syringe with the AVOSTARTGRIP titration kit. The AVOSTARTGRIP is used for giving the week 1, 2, and 3 (¼, ½, ¾) injections.
- Week 1: ¼ dose (white device)
- Week 2: ½ dose (yellow device)
- Week 3: ¾ dose (purple device)
- Week 4: a full dose
The 3 AVOSTARTGRIP devices are for single-use only with the Xerfelan prefilled syringe. Do not re-use the Xerfelan prefilled syringe and AVOSTARTGRIP devices.
You must prepare the Xerfelan prefilled syringe and needle before you put it into the AVOSTARTGRIP device. Follow steps 1 to 5 above to prepare the Xerfelan prefilled syringe.

Identifying the parts of AVOSTARTGRIP titration kit :

(Figure G)

AVOSTARTGRIP has a “collar” on top of the device that will stop the syringe from injecting a full dose. The “collar” makes sure that you do not get the full dose of Xerfelan.

(Figure H)

Attaching the AVOSTARTGRIP device:

Step 6: Choose the right AVOSTARTGRIP titration device for your weekly dose. Week 1 Injection: Choose the white device to give ¼ dose.	(Figure I)
Week 2 Injection: Choose the yellow device to give ½ dose.	(Figure J)
Week 3 Injection: Choose the purple device to give ¾ dose.	(Figure K)
Step 7: Put the right AVOSTARTGRIP device on a flat surface with the door open.	(Figure L)
Step 8: Line up the Xerfelan prefilled syringe over the AVOSTARTGRIP device with the plunger pointing to the left and the needle pointing to the right.	(Figure M)
Step 9: Push the Xerfelan prefilled syringe down into the AVOSTARTGRIP device until both ends “snap” into place.	(Figure N)
Step 10: Using two fingers, push the door down until it closes over the Xerfelan prefilled syringe. You will hear a “snap” when the door is closed the right way. Do not open door after it is closed.	(Figure O)
Step 11: Check to make sure that the Xerfelan prefilled syringe is in the AVOSTARTGRIP device the right way and that the door is tightly closed.

Giving the Xerfelan injection:

Your healthcare provider should show you or a caregiver how to prepare and inject the dose of Xerfelan before Xerfelan prefilled syringe is used for the first time. Your healthcare provider or nurse should watch you inject the dose of Xerfelan the first time Xerfelan prefilled syringe is used.
Inject your Xerfelan exactly as your healthcare provider has shown you.
Xerfelan is injected into the muscle (intramuscularly).
Xerfelan should be injected into the thigh or upper arm.
Change (rotate) your injection sites for each dose. Do not use the same injection site for each injection.
Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.

Step 12: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose. Do not touch this area again before giving the injection.	(Figure P)	(Figure Q)
Step 13: Pull the protective cover straight off the needle. Do not twist the cover off.	(Figure R)
Step 14: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90º angle, through the skin and into the muscle. Once the needle is in, let go of the skin.	(Figure S)
Step 15: Make sure that you push the plunger all the way down until it touches the collar.	(Figure T)
Step 16: Pull the needle out of the skin. Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion. If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.	(Figure U)

After the Xerfelan injection:

Do not recap the needle. Recapping the needle can lead to a needle stick injury.

Throw away the used Xerfelan prefilled syringes, AVOSTARTGRIP devices, and needles in a sharps container or some type of hard plastic or metal container with a screw cap such as a detergent bottle or coffee can. Check with your healthcare provider about the right way to throw away the container. There may be local or state laws about how to throw away used Xerfelan prefilled syringes, AVOSTARTGRIP devices, and needles. Do not throw away used Xerfelan prefilled syringes, AVOSTARTGRIP devices, and needles in household trash or recycling bins.
After 2 hours, check the injection site for redness, swelling or tenderness. If you have a skin reaction and it does not clear up in a few days, contact your healthcare provider.

General information about the safe and effective use of Xerfelan

Always use a new Xerfelan prefilled syringe, AVOSTARTGRIP device, and needle for each injection. Do not re-use your Xerfelan prefilled syringe, AVOSTARTGRIP device, or needles.
Do not share your Xerfelan prefilled syringe, AVOSTARTGRIP device, or needles.
Keep the Xerfelan prefilled syringe, AVOSTARTGRIP device, and needles out of the reach of children.
You can use the table below to keep track of your weekly injections.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised 09/2016

Manufactured for:

Biogen Inc.

250 Binney Street

Cambridge, MA 02142 USA

1-800-456-2255

I11073-05

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Instructions for Use

Xerfelan ^® (a-vuh-necks)

(interferon beta-1a)

lyophilized powder for intramuscular injection

single-use vial

Read the Instructions for Use before you start using Xerfelan and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

Supplies you will need for the Xerfelan injection :

1 Xerfelan Administration Dose Pack that contains:
- 1 vial of Xerfelan (white to off-white powder or cake)
- 10 mL diluent vial (Sterile Water for Injection, USP)
- a 3 mL syringe
- 1 MICRO PIN^® (vial access pin)
- 23 gauge, 1¼ inch long sterile needle
- 2 alcohol wipes
- 1 gauze pad
- 1 adhesive bandage
a puncture resistant container for disposal of used syringes, needles, and MICRO PIN

Preparing the Xerfelan dose:

Find a well-lit, clean, flat work surface like a table and collect all the supplies you will need to give yourself or receive an injection.
Take 1 Xerfelan Administration Dose Pack out of the refrigerator about 30 minutes before you plan on injecting the Xerfelan dose to allow it to reach room temperature.
Before you start to prepare the injection, check the expiration date on the Xerfelan and diluent vials. Do not use Xerfelan or diluent past the expiration date printed on the label.
Wash your hands with soap and water.

(Figure A)

Preparing the Xerfelan dose:

Step 1: Pull off the cap from the vial of Xerfelan and the vial of diluent.	(Figure B)
Step 2: Wipe the rubber stopper on each vial with an alcohol wipe.	(Figure C)
Step 3: Open the sterile package and take out the MICRO PIN. Hold the syringe with the tip pointing up. Push the MICRO PIN down onto the top of the syringe. Turn the MICRO PIN counterclockwise until it is tight and firmly attached. Do not over-tighten the MICRO PIN, it can make it hard to remove.	(Figure D)
Step 4: Pull straight up on the MICRO PIN cover to remove it, and save the cover for later. Do not twist the MICRO PIN cover when you are removing it.	(Figure E)
Step 5: Pull down the syringe plunger until the rubber tip reaches the 1.1 mL mark.	(Figure F)
Step 6: Push the MICRO PIN down through the center of the rubber stopper of the diluent vial.	(Figure G)
Step 7: Push the plunger all the way in. This puts air into the diluent vial.	(Figure H)
Step 8: Keep the MICRO PIN in the vial. Turn the diluent vial and syringe upside down and slowly pull the plunger down until the rubber tip reaches the 1.1 mL mark on the syringe. If there are air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top. If you still see air bubbles, slowly push the plunger up until the bubbles come out through the needle. Check to make sure there is still 1.1 mL of diluent in the syringe.	(Figure I) (Figure J)
Step 9: Slowly pull the MICRO PIN out of the diluent vial's rubber stopper.	(Figure K)
Step 10: Push the MICRO PIN through the center of the rubber stopper of the Xerfelan vial. If the rubber stopper of the Xerfelan vial falls into the vial, do not use the Xerfelan. Throw away the Xerfelan vial and get a new one, then repeat steps 1 to 10.	(Figure L)
Step 11: Slowly push the plunger all the way in. This puts the diluent into the vial of Xerfelan. Do not remove the syringe. Do not aim the stream of diluent directly on the Xerfelan powder or push the plunger down too fast. If you aim the stream of diluent directly on the Xerfelan powder or push the plunger down too fast, the Xerfelan may foam and make it hard to withdraw the Xerfelan into the syringe.	(Figure M)
Step 12: Gently swirl the Xerfelan vial until the powder in the vial is dissolved. Do not shake the Xerfelan vial. Check the Xerfelan vial to make sure that all of the Xerfelan is dissolved. Xerfelan should look clear to slightly yellow in color after mixing and should not have any particles in it. Do not use Xerfelan if it looks cloudy, is colored any color other than slightly yellow, or has any lumps or particles in it. Do not use that vial. Get a new vial. Contact MS ACTIVESOURCE at 1-800-456-2255.	(Figure N)
Step 13: Turn the Xerfelan vial and syringe upside down and slowly pull the plunger down until the rubber tip reaches the 1 mL mark on the syringe. If there are large bubbles in the syringe, slowly push the plunger all the way in to push the Xerfelan solution back into the vial, then repeat Step 13. If there are small air bubbles, tap the syringe gently a few times to let any air bubbles rise to the top. If you still see air bubbles, slowly push the plunger up until the bubbles come out through the needle.	(Figure O) (Figure P)
Step 14: Pull the MICRO PIN and syringe out of the Xerfelan vial's rubber stopper.	(Figure Q)
Step 15: Put the cover back on the MICRO PIN and turn it clockwise to remove the MICRO PIN from the syringe.	(Figure R) (Figure S)
Step 16: Open the sterile needle package and take out the covered needle. Hold the syringe with the tip pointing up. Push the needle onto the syringe and turn it forward (clockwise) until it is tight and firmly attached. If the needle is not firmly attached, it may leak and you may not get your full dose of Xerfelan. Do not remove the plastic cover from the needle.	(Figure T)

Giving the Xerfelan injection:

Your healthcare provider should show you or a caregiver how to prepare and inject the dose of Xerfelan before Xerfelan is used for the first time. Your healthcare provider or nurse should watch you inject the dose of Xerfelan the first time Xerfelan is used.
Inject your Xerfelan exactly as your healthcare provider has shown you.
Xerfelan is injected into the muscle (intramuscularly).
Xerfelan should be injected into the thigh or upper arm.
Change (rotate) your injection sites. Do not use the same site for each injection.
Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or scarred in any way.

Step 17: Choose an injection site and wipe the skin with an alcohol wipe. Let the injection site dry before injecting the dose. Do not touch this area again before giving the injection.	(Figure U) (Figure V)
Step 18: Pull the protective cover straight off the needle. Do not twist the cover off.	(Figure W)
Step 19: With 1 hand, stretch the skin out around the injection site. With the other hand, hold the syringe like a pencil. Use a quick dart-like motion and insert the needle at a 90 degree angle, through the skin and into the muscle. Once the needle is in, let go of the skin.	(Figure X)
Step 20: Slowly push the plunger in until the syringe is empty.	(Figure Y)
Step 21: Pull the needle out of the skin. Press down on the injection site with the gauze pad for a few seconds or rub gently in a circular motion. If you see blood after you press the injection site for a few seconds, wipe it off with gauze and apply an adhesive bandage.	(Figure Z)

After the Xerfelan injection:

Do not recap the needle. Recapping the needle can lead to a needle stick injury.
Throw away empty Xerfelan and diluent vials, used syringes, needles, and MICRO PINS in a sharps container or some type of hard plastic or metal container with a screw cap such as a detergent bottle or coffee can. Check with your healthcare provider about the right way to throw away the container. There may be local or state laws about how to throw away the used syringes and needles. Do not throw away the used syringes and needles in household trash or recycling bins.
After 2 hours, check the injection site for redness, swelling or tenderness. If you have a skin reaction and it does not clear up in a few days, contact your healthcare provider.

General information about the safe and effective use of Xerfelan

Always use a new syringe and needle for each injection. Do not re-use your syringe or needles.
Do not share your syringes or needles.
Keep the Xerfelan vials, syringes, and needles out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Biogen Inc.

Cambridge, MA 02142 USA

1-800-456-2255

MICRO PIN ^® is the trademark of B. Braun Medical Inc.

Revised: 08/2015

41612-02

Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure

Principal Display Panel - 30 mcg Carton Label

NDC 59627-333-04

Xerfelan Pen ^®

(interferon beta-1a)

Injection

30 mcg/0.5 mL Single-Use Prefilled Autoinjector

For Intramuscular Injection

Once a Week

Principal Display Panel - 30 mcg Carton Label

NDC 59627-222-05

Xerfelan ^®

(interferon beta-1a)

Injection

30 mcg/0.5 mL Single-Use Prefilled Syringe

For Intramuscular Injection

Once a Week

Principal Display Panel - 30 mcg Carton Label

NDC 59627-111-03

Xerfelan ^®

(interferon beta-1a)

Injection

30 mcg Single-Use Lyophilized Powder Vial

For Intramuscular Injection

Once a Week

Principal Display Panel - 30 mcg Tray Lid Label

NDC 59627-111-04

Xerfelan ^® (interferon beta-1a)

30 mcg Single-Use Lyophilized Powder Vial

For Intramuscular Injection

Principal Display Panel - Carton Label

NDC 59627-003-04

Xerfelan PEN®

(interferon beta-1a)

Injection

30 mcg/0.5 mL

Single-Use Prefilled Autoinjector

For Intramuscular Injection

Contents:

4 Xerfelan Pen Administration Dose Packs

Dispense with enclosed Medication Guide

Rx only

Biogen Idec _®

Principal Display Panel - Carton Label

NDC 59627-002-05

AVONEX® Prefilled Syringe

(interferon beta-1a)

Injection

30 mcg Prefilled Syringe

For intramuscular injection

Contents:

4 Xerfelan Administration Dose Packs

Dispense with enclosed Medication Guide

Rx only

Biogen Idec _®

Principal Display Panel - Carton Label

NDC 59627-001-03

AVONEX®

(interferon beta-1a)

Injection

30 mcg

For Intramuscular Injection

Contents:

4 Xerfelan Administration Dose Packs

Dispense with enclosed Medication Guide

Rx only

Biogen Idec _®

Xerfelan pharmaceutical active ingredients containing related brand and generic drugs:

Interferon Beta-1a

Xerfelan available forms, composition, doses:

Injectable; Injection; Interferon Beta-1a 12 MIU / 0.5 ml

Xerfelan destination | category:

Human:
Antineoplastic agents
Antivirals
Immunological chemotherapy
Interferons

Xerfelan Anatomical Therapeutic Chemical codes:

L03AB07 - Interferon beta

Xerfelan pharmaceutical companies:

Landsteiner Scientific

References

Dailymed."AVONEX (INTERFERON BETA-1A) KIT AVONEX PEN (INTERFERON BETA-1A) INJECTION, SOLUTION AVONEX (INTERFERON BETA-1A) INJECTION, POWDER, LYOPHILIZED, FOR SOL". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Xerfelan?

Depending on the reaction of the Xerfelan after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Xerfelan not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Xerfelan addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

Review

sdrugs.com conducted a study on Xerfelan, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Xerfelan consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.