Introduction
Betaseron (interferon beta-1b) is a recombinant interferon medication used primarily in the management of relapsing forms of multiple sclerosis. It belongs to the class of biologic response modifiers and was one of the first disease-modifying therapies approved for MS treatment in the United States (1993).
Mechanism of Action
Betaseron exerts its therapeutic effects through multiple immunomodulatory mechanisms. As a recombinant interferon beta-1b, it binds to specific cell surface receptors, triggering intracellular signaling cascades that:
- Downregulate pro-inflammatory cytokine production
- Upregulate anti-inflammatory cytokines
- Reduce T-cell activation and migration across the blood-brain barrier
- Inhibit antigen presentation
- Modulate expression of matrix metalloproteinases
These actions collectively reduce the frequency and severity of inflammatory attacks on the central nervous system in multiple sclerosis patients.
Indications
- Relapsing-remitting multiple sclerosis (to reduce frequency of clinical exacerbations)
- Secondary progressive multiple sclerosis (in patients with active disease)
- First clinical episode with MRI features consistent with MS (to delay progression to clinically definite MS)
Dosage and Administration
Standard dosing: 0.25 mg (8 million IU) subcutaneously every other day Administration:- Reconstitute with 1.2 mL of diluent provided
- Administer subcutaneously in arms, abdomen, hips, or thighs
- Rotate injection sites to minimize lipoatrophy
- Preferably administer at bedtime to minimize flu-like symptoms
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution
- Elderly: Limited data available
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability approximately 50% following subcutaneous administration Distribution: Volume of distribution approximately 2.45 L/kg; poorly crosses blood-brain barrier Metabolism: Primarily metabolized intracellularly and in renal tubular cells Elimination: Half-life approximately 8 minutes to 4.3 hours; primarily renal eliminationContraindications
- Hypersensitivity to interferon beta-1b, natural interferon, or any component
- History of suicidal ideation or severe depression
Warnings and Precautions
Black Box Warning:- Depression and suicidal ideation
- Hepatic injury including elevated transaminases and hepatic failure
- Anaphylaxis and other allergic reactions
- Decreased peripheral blood counts
- Cardiomyopathy
- Seizures
- Autoimmune disorders including thyroid disorders
- Injection site reactions including necrosis
Drug Interactions
- Theophylline: Interferon beta may decrease clearance
- Other myelosuppressive drugs: Additive bone marrow suppression
- Hepatotoxic drugs: Increased risk of liver injury
- Live vaccines: Theoretical risk of increased adverse reactions
Adverse Effects
Very common (>10%):- Injection site reactions (85%)
- Flu-like symptoms (76%)
- Fever (59%)
- Headache (43%)
- Pain (35%)
- Asthenia (35%)
- Depression
- Elevated liver enzymes
- Leukopenia
- Anemia
- Thyroid dysfunction
- Menstrual disorders
- Anaphylaxis
- Hepatic failure
- Suicidal ideation
- Cardiomyopathy
- Seizures
- Injection site necrosis
Monitoring Parameters
Baseline:- Complete blood count with differential
- Liver function tests
- Thyroid function tests
- ECG in patients with cardiac risk factors
- Depression screening
- CBC monthly for 3 months, then every 3 months
- LFTs monthly for 6 months, then every 6 months
- Thyroid function every 6 months
- Regular assessment of depression symptoms
- Injection site evaluation
- Clinical assessment of MS disease activity
Patient Education
- Proper injection technique and site rotation
- Management of flu-like symptoms (symptomatic treatment, timing of doses)
- Recognition of injection site reactions
- Importance of adherence to monitoring schedule
- Signs of depression to report immediately
- Pregnancy planning and contraception requirements
- Storage and handling instructions
- Disposal of used needles and syringes
References
1. IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. Neurology. 1993;43(4):655-661. 2. Goodin DS, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2002;58(2):169-178. 3. Betaseron® [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 2021. 4. Rice GP, et al. The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-1b. Neurology. 1999;52(6):1277-1279. 5. Calabresi PA, et al. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL. Neurology. 2007;69(14):1391-1403. 6. National Multiple Sclerosis Society. Disease Modifying Therapies for MS. 2023. 7. European Medicines Agency. Betaseron EPAR product information. 2022.