Extavia - Drug Monograph

Introduction

Extavia® (interferon beta-1b) is a disease-modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. It is a recombinant interferon beta-1b produced using bacterial fermentation techniques and is biologically equivalent to Betaseron. As an immunomodulatory agent, Extavia helps reduce the frequency of clinical exacerbations in patients with relapsing-remitting multiple sclerosis.

Mechanism of Action

Interferon beta-1b exerts its effects through binding to specific cell surface receptors, leading to the induction of various interferon-induced gene products. The drug demonstrates multiple immunomodulatory activities, including:

• Downregulation of proinflammatory cytokine production
• Inhibition of T-cell proliferation and migration
• Enhancement of suppressor T-cell function
• Reduction of antigen presentation
• Upregulation of anti-inflammatory cytokines
• Restoration of blood-brain barrier integrity

The exact mechanism by which interferon beta-1b exerts its clinical effects in multiple sclerosis remains incompletely understood but is believed to involve modulation of the immune response against central nervous system antigens.

Indications

Extavia is FDA-approved for:

• Treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations
• Patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis

Dosage and Administration

• Initial dose: 0.0625 mg (0.25 mL) subcutaneously every other day
• Titration schedule: Increase by 0.0625 mg increments every 2 weeks
• Maintenance dose: 0.25 mg (1.0 mL) subcutaneously every other day

• For subcutaneous injection only
• Rotate injection sites (arms, abdomen, hips, thighs)
• Reconstitute with supplied diluent (sodium chloride 0.54%)
• Use immediately after reconstitution (within 3 hours)

• Renal impairment: No dosage adjustment recommended
• Hepatic impairment: Use with caution; no specific dosage recommendations
• Elderly: Limited data available; use with caution
• Pregnancy: Category C; use only if potential benefit justifies potential risk
• Pediatrics: Safety and effectiveness not established

Pharmacokinetics

• Bioavailability: Approximately 50%
• Tmax: 1-8 hours post-injection
• Food effect: No significant impact

• Volume of distribution: Not fully characterized
• Protein binding: Not extensively characterized

• Primarily metabolized through proteolytic degradation
• No significant hepatic cytochrome P450 involvement

• Half-life: Approximately 8 minutes (initial phase), 4 hours (terminal phase)
• Clearance: Primarily renal
• No accumulation observed with every-other-day dosing

Contraindications

• History of hypersensitivity to interferon beta, human albumin, or any component of the formulation
• Patients with decompensated hepatic disease
• History of suicidal ideation or severe depression

Warnings and Precautions

• May cause or exacerbate depression, suicidal ideation, and other psychiatric disorders
• Monitor patients for depression; discontinue if severe depression occurs

• May cause liver injury, including elevated transaminases and rare cases of hepatic failure
• Monitor liver function tests regularly

• Serious allergic reactions, including anaphylaxis, have been reported

• Common occurrence; may include pain, erythema, swelling, and necrosis
• Proper injection technique and site rotation essential

• Cardiomyopathy and congestive heart failure reported
• Use with caution in patients with pre-existing cardiac disease

• May cause thyroid abnormalities; monitor thyroid function

• May lower seizure threshold; use with caution in patients with seizure disorders

Drug Interactions

• May affect metabolism of drugs metabolized by CYP450 enzymes

• Potential additive immunosuppressive effects

• Increased risk of liver injury when combined with other hepatotoxic agents

• May interfere with immune response to vaccines
• Avoid live vaccines during treatment

Adverse Effects

• Injection site reactions (85%)
• Flu-like symptoms (76%)
• Fever (59%)
• Headache (54%)
• Myalgia (44%)
• Chills (18%)
• Asthenia (18%)

• Depression (16%)
• Menstrual disorders (13%)
• Constipation (12%)
• Dizziness (11%)
• Elevated liver enzymes (10%)
• Leukopenia (9%)
• Anxiety (8%)

• Anaphylaxis
• Hepatic failure
• Thrombocytopenia
• Seizures
• Congestive heart failure
• Thyroid dysfunction
• Suicide attempts

Monitoring Parameters

• Complete blood count with differential
• Liver function tests
• Thyroid function tests
• Cardiac evaluation if indicated
• Psychiatric assessment
• Pregnancy test if appropriate

• CBC monthly for first 3 months, then every 3 months
• LFTs monthly for first 6 months, then every 6 months
• Thyroid function every 6 months
• Regular assessment of depression and suicidal ideation
• Injection site evaluation
• Clinical neurological assessment

Patient Education

• Demonstrate proper injection technique
• Emphasize site rotation and aseptic technique
• Review reconstitution procedure if applicable
• Provide disposal instructions for sharps

• Premedicate with NSAIDs for flu-like symptoms
• Use local measures for injection site reactions
• Time injections in the evening to sleep through side effects

• Maintain adequate hydration
• Regular follow-up with healthcare provider
• Report any mood changes or depressive symptoms
• Inform all healthcare providers of Extavia use

• Recognize signs of allergic reactions
• Report any unusual bleeding or bruising
• Monitor for signs of liver problems (jaundice, dark urine)
• Seek immediate medical attention for severe reactions

References

1. FDA Prescribing Information: Extavia (interferon beta-1b) 2. National Multiple Sclerosis Society. Disease-Modifying Therapies for MS. 2023 3. Goodin DS, et al. Neurology. 2002;59(10):1496-1506 4. Interferon Beta Multiple Sclerosis Study Group. Neurology. 1993;43(4):655-661 5. Paty DW, et al. Neurology. 1993;43(4):662-667 6. European Medicines Agency. Extavia Product Information. 2023 7. American Academy of Neurology. Practice Guidelines for MS Therapies. 2022