Generic Name: interferon beta-1a

Brand Names: Avonex Prefilled Syringe, Avonex, Rebif

Uses

Multiple Sclerosis (MS)

Management of relapsing-remitting MS, relapsing forms of secondary progressive MS†, and of patients at high risk of developing clinically definite MS.

Not curative, but appears to reduce the frequency of attacks or relapses and produces a beneficial effect on several magnetic resonance imaging (MRI) measures of disease activity.

Efficacy in management of primary progressive MS† not demonstrated conclusively; such use not recommended.

Dosage and Administration

General

• Administer under the supervision of qualified clinicians.
• Prior to initiating therapy, provide patient with the appropriate patient information (medication guide) provided by the manufacturer for interferon beta-1a (Avonex^® and Rebif^®) or interferon beta-1b (Betaseron^®).
• If home use is prescribed, carefully instruct patients and/or their caregivers in appropriate use; provide a puncture-resistant container for proper, safe disposal of used syringes and needles.
• Patients may feel worse or experience a temporary worsening of MS symptoms immediately following initiation of interferon beta therapy; these effects often abate with continued therapy and should not be interpreted as an indication of treatment failure.
• To minimize risk of flu-like syndrome, administer at bedtime and/or give an NSAIA (e.g., ibuprofen) or acetaminophen to prevent or partially alleviate fever and headache.

Administration

Administer by IM or sub-Q injection.

Sub-Q administration associated with higher rates of injection site reactions than IM administration.

IM Administration, Interferon Beta-1a (Avonex^®)

Administer once weekly by IM injection.

Administer IM into thigh or upper arm using a 23-gauge, 1¼-inch needle. Rotate injection sites; do not use sites that appear irritated prior to injection.

Administer Avonex^® provided in prefilled syringes as supplied; no dilution or reconstitution is necessary. Warm prefilled syringes to room temperature by removing from refrigerator about 30 minutes prior to use; do not use external heat sources (e.g., hot water) to warm syringes.

Reconstitution

Reconstitute vial containing 6.6 million units (33 mcg) of interferon beta-1a (Avonex^®) powder by adding 1.1 mL sterile water for injection to provide a solution containing 6 million units (30 mcg) of interferon beta-1a per mL. Use only the diluent supplied by manufacturer.

Swirl vial gently to ensure complete dissolution; do not shake.

Reconstituted solutions contain no preservatives; solutions preferably should be prepared immediately before use. Vials are for single use only; discard any residual solution.

Sub-Q Administration, Interferon Beta-1a (Rebif^®)

Administer 3 times weekly by sub-Q injection, on the same 3 days (e.g., Monday, Wednesday, and Friday) at least 48 hours apart each week and at the same time (preferably in the late afternoon or evening) each day.

Administer sub-Q into the abdomen (except waistline), thigh, arm, or buttocks.

To minimize risk of serious injection site reactions (e.g., necrosis), rotate injection sites and avoid sites that appear irritated, reddened, bruised, infected, or abnormal in any way.

To reduce incidence of injection site pain, warm Rebif^® prefilled syringes to room temperature by removing from refrigerator 30 minutes prior to use.

Administer Rebif^® as supplied; no dilution or reconstitution is necessary.

Rebif^® solutions contain no preservatives; discard any residual solution remaining in the syringe after single use.

Sub-Q Administration, Interferon Beta-1b (Betaseron^®)

Administer by sub-Q injection every other day.

Administer sub-Q into the abdomen (except waistline), thigh, arm, or buttocks.

To minimize risk of serious injection site reactions (e.g., necrosis), rotate injection sites and avoid sites that appear irritated, reddened, bruised, infected, or abnormal in any way.

Reconstitution

Reconstitute vial containing 9.6 million units (0.3 mg) of interferon-beta-1b (Betaseron^®) powder by attaching prefilled syringe containing 1.2 mL of 0.54% sodium chloride to the vial and slowly injecting entire contents of syringe to provide a solution containing 8 million units (0.25 mg) of interferon beta-1b per mL. Use only the diluent supplied by manufacturer.

Swirl vial gently to ensure complete dissolution; do not shake.

Reconstituted solutions contain no preservatives; solutions preferably should be prepared immediately before use. Vials are for single use only; discard any residual solution.

Dosage

Available as interferon beta-1a or interferon beta-1b; dosage and potency expressed in terms of international units (IU, units) or mg.

Each mg of interferon beta-1a is approximately equivalent to 200 million units (for Avonex^®) and 270 million units (for Rebif^®); each mg of interferon beta-1b is approximately equivalent to 32 million units (for Betaseron^®).

Adults

Relapsing-remitting MS

Interferon beta-1a (Avonex^®)

IM

6 million units (30 mcg) once weekly. Safety and efficacy of Avonex^® given for >3 years not established.

Interferon beta-1a (Rebif^®)

Sub-Q

Gradually titrate dosage over a 4-week period to 6 million units (22 mcg) or 12 million units (44 mcg) 3 times weekly using the schedule in Table 1.

Interferon beta-1b (Betaseron^®)

Sub-Q

Gradually titrate dosage over a 6-week period to 8 million units (0.25 mg) every other day using the schedule in Table 2.

Safety and efficacy of interferon beta-1b (Betaseron^®) given for >3 years not established.

Prescribing Limits

Adults

IM

Safety of interferon beta-1a (Avonex^®) dosages >12 million units (60 mcg) once weekly not established.

Special Populations

Hepatic Impairment

Consider decreasing dosages if serum ALT concentrations >5 times ULN.

Discontinue therapy if hepatic transaminase (AST, ALT) concentrations >10 times ULN (with or without jaundice or other clinical symptoms of liver dysfunction) or if the serum bilirubin >5 times ULN.

When concentrations return to normal, interferon beta therapy may be restarted at a 50% dose reduction, if clinically appropriate.

Geriatric Patients

Titrate dosage, usually initiating therapy at the low end of the dosage range due to possible age-related decreases in hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.

Cautions

Contraindications

• Known hypersensitivity to natural or recombinant interferon beta or any other component of the formulations.
• Administration of preparations containing albumin human in patients with known hypersensitivity to albumin. (See Albumin Sensitivity under Cautions.)

Warnings/Precautions

Warnings

Depression and Suicide

Possible depression, suicidal ideation, and suicide; use with caution in patients with depression or other mood disorders, conditions that are common in individuals with MS.

If depression or other severe psychiatric symptoms occur during therapy, monitor closely and consider discontinuing therapy.

Hepatotoxicity

Serious hepatic injury including autoimmune hepatitis and possibly severe, fulminant hepatic failure requiring liver transplantation reported.

Use with caution in patients with active liver disease, alcohol abuse, increased serum ALT concentrations (>2.5 times ULN), or history of clinically important liver disease.

Use with caution in patients receiving concomitant therapy with other drugs associated with hepatic injury; use caution when other drugs are added to an existing interferon beta treatment regimen. (See Specific Drugs under Interactions.)

Perform liver function tests prior to initiation of therapy and at regular intervals (e.g., 1, 3, 6 months) and then periodically thereafter in the absence of clinical symptoms.

Possible asymptomatic elevation of hepatic transaminases.

Injection Site Necrosis

Potentially severe injection site necrosis possible following sub-Q administration, sometimes requiring dermal debridement or skin grafting. Has not been reported to date following IM administration.

If injection site necrosis occurs, reevaluate patient’s understanding and use of aseptic technique and proper procedures for self-administration. Whether to discontinue therapy following a single site of necrosis depends on the extent of necrosis.

Sensitivity Reactions

Hypersensitivity Reactions

Possible anaphylaxis or anaphylactoid reactions.

If acute, serious hypersensitivity reactions occur, discontinue immediately and initiate appropriate therapy.

Albumin Sensitivity

Some formulations (e.g., Avonex^® powder for injection, Betaseron^®, Rebif^®) contain albumin human; contraindicated in sensitive patients.

Antibody Formation

Possible development of binding or neutralizing antibodies to interferon beta following long-term therapy.

General Precautions

Cardiovascular Effects

Possible cardiomyopathy with or without CHF; use with caution in patients with cardiac disease or history of any cardiac condition.

Closely monitor patients with history of cardiac disease (e.g., angina, arrhythmia, CHF) for worsening of their clinical condition during initiation and continued treatment with interferon beta.

Seizures

Possible seizures; use with caution in patients with preexisting seizure disorders.

If patients with no prior history of seizures develop seizures during therapy, establish an etiologic basis and institute appropriate anticonvulsant therapy prior to considering resumption of therapy.

Hematologic Effects

Decreased peripheral blood cell counts in all cell lines, including rare pancytopenia and thrombocytopenia, reported.

Use with caution in patients with myelosuppression and in those receiving drugs that may be myelosuppressive. (See Specific Drugs under Interactions.)

Perform CBCs, platelet counts, and appropriate blood chemistry tests prior to initiation of therapy and periodically thereafter.

Other Autoimmune Disorders

Possible development of idiopathic thrombocytopenia, hyperthyroidism, hypothyroidism, or autoimmune hepatitis; monitor patients for manifestations and perform appropriate tests when necessary.

Infectious Complications

Some formulations (e.g., Avonex^® powder for injection, Betaseron^®, Rebif^®) contain albumin human; theoretical risk for transmission of human viruses and Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).

Specific Populations

Pregnancy

Category C.

Pregnancy registry for Rebif^® at 877-447-3243 or http://www.rebifprenancyregistry.com and for Avonex^® at 800-456-2255.

Lactation

Not known whether interferon beta is distributed into milk; discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution. Adjust dosage in patients with hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Flu-like symptoms, local effects at the injection site.

Interactions

No formal drug interaction studies to date.

Because of the potential for hepatic injury associated with interferon beta-1a and beta-1b, use caution when another agent is added to an existing interferon beta regimen. (See Hepatic Effects under Cautions.)

Has been used concomitantly with corticosteroids, corticotropin (ACTH), antidepressants, and/or oral contraceptives in clinical studies without unusual adverse effects.

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Bioavailability of interferon beta-1b (Betaseron^®) following sub-Q administration is approximately 50%.

Elimination

Half-life

Elimination half-life of interferon beta-1a (Avonex^®) following a single IM dose is 10 hours.

Plasma half-life of interferon beta-1a (Rebif^®) following a single sub-Q dose is approximately 69 hours.

Stability

Storage

Parenteral

Injection

Interferon beta-1a (Avonex^®) prefilled syringes: 2–8°C. After removing from refrigerator, warm to room temperature (about 30 minutes) and use within 12 hours. Protect from heat and light; do not freeze.

Interferon beta-1a (Rebif^®) prefilled syringes: 2–8°C (may be stored at up to 25°C for up to 30 days). Protect from heat and light; do not freeze.

Powder for Injection

Interferon beta-1a (Avonex^®) lyophilized powder: 2–8°C (may be stored at 25°C for up to 30 days). Following reconstitution, store for up to 6 hours at 2–8°C. Protect from heat and light; do not freeze.

Interferon beta-1b (Betaseron^®) lyophilized powder: 25°C (may be exposed to 15–30°C). Following reconstitution, store at 2–8°C and use within 3 hours. Do not freeze.

Actions

• Has complex antiviral, antineoplastic, and immunomodulating activities.
• Mechanisms of action in the treatment of MS have not been fully elucidated, but may involve immunomodulating effects, including anti-inflammatory effects.

Advice to Patients

• Provide patient a copy of the medication guide and advise patient of the importance of reading this information each time a new or refill prescription is dispensed.
• Importance of taking interferon beta exactly as prescribed. Advise patients not to change interferon beta preparations during a single regimen of therapy without consulting their clinician.
• Risk of developing depression and suicidal ideation. Importance of notifying clinician immediately if symptoms of depression occur.
• Potential for temporary worsening of symptoms immediately following initiation of therapy; advise patients that these symptoms often abate with continued therapy and should not be interpreted as an indication of treatment failure.
• If patient or caregiver is to administer interferon beta, provide careful instructions on proper administration methods (including aseptic technique) and proper disposal of used needles and syringes.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.
• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions June 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.