Rebif - Drug Monograph

Introduction

Rebif (interferon beta-1a) is a disease-modifying therapy used for the treatment of relapsing forms of multiple sclerosis (MS). It is a recombinant form of human interferon beta, a naturally occurring protein that modulates the immune system. Rebif is administered via subcutaneous injection and has been shown to reduce the frequency of clinical exacerbations and delay the accumulation of physical disability in MS patients.

Mechanism of Action

Rebif exerts its therapeutic effects through multiple immunomodulatory mechanisms. As a recombinant interferon beta-1a, it binds to specific cell surface receptors, leading to the activation of multiple interferon-induced genes. This results in:

• Downregulation of pro-inflammatory cytokines
• Upregulation of anti-inflammatory cytokines
• Inhibition of T-cell activation and proliferation
• Reduction of blood-brain barrier permeability
• Modulation of antigen presentation

These actions collectively reduce inflammatory activity in the central nervous system, thereby decreasing the frequency and severity of MS relapses.

Indications

Rebif is FDA-approved for:

• Treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease

Dosage and Administration

• Initiation: 8.8 mcg subcutaneously three times weekly
• Titration: Increase to 22 mcg three times weekly after 2 weeks
• Maintenance: 44 mcg three times weekly thereafter

• Administer subcutaneously in the arms, thighs, abdomen, or buttocks
• Rotate injection sites to minimize local reactions
• Preferably administered in the evening to minimize flu-like symptoms
• Prefilled syringes and autoinjectors are available

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution; no specific dosage recommendations
• Elderly: Limited data available; use clinical judgment
• Pregnancy: Category C; use only if potential benefit justifies potential risk

Pharmacokinetics

• Bioavailability: Approximately 40% following subcutaneous administration
• Tmax: 16 hours post-dose

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

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

• Half-life: Approximately 69 hours
• Clearance: Primarily renal filtration and proteolytic degradation
• No established pharmacokinetic differences based on age, gender, or race

Contraindications

• History of hypersensitivity to natural or recombinant interferon beta, human albumin, or other components
• Patients with current depressive disorders or suicidal ideation (relative contraindication)
• History of autoimmune disorders other than multiple sclerosis
• Decompensated hepatic disease

Warnings and Precautions

• Monitor patients for depression and suicidal ideation
• Discontinue therapy if severe depression occurs

• Monitor liver function tests regularly
• Cases of severe hepatic injury, including hepatic failure, have been reported

• Serious allergic reactions have occurred
• Have appropriate medical support available

• Caution in patients with pre-existing cardiac disease
• Monitor for cardiomyopathy and arrhythmias

• Use with caution in patients with pre-existing seizure disorders

• Cases of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome reported

• May exacerbate pre-existing autoimmune conditions

Drug Interactions

• May affect metabolism of drugs metabolized by CYP450 enzymes

• Avoid concurrent use with other immunosuppressive agents

• Increased risk of hepatic toxicity when used with other hepatotoxic agents

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

Adverse Effects

• Injection site reactions (redness, pain, swelling)
• Flu-like symptoms (fever, chills, myalgia, fatigue)
• Headache
• Elevated liver enzymes

• Depression
• Insomnia
• Anemia
• Leukopenia
• Thyroid abnormalities
• Nausea
• Arthralgia

• Hepatic failure
• Anaphylaxis
• Suicidal ideation
• Seizures
• Thrombotic microangiopathy
• Autoimmune disorders

Monitoring Parameters

• Complete blood count with differential
• Liver function tests
• Thyroid function tests
• Pregnancy test if applicable
• Depression screening
• Cardiac evaluation if indicated

• CBC monthly for first 3 months, then every 3 months
• LFTs monthly for first 6 months, then every 3 months
• Thyroid function every 6 months
• Regular depression assessment
• Clinical evaluation for injection site reactions
• Neurological assessment for disease progression

Patient Education

• Proper injection technique and site rotation
• Storage requirements (refrigerate at 2-8°C)
• Do not freeze or shake the medication

• Premedication with NSAIDs for flu-like symptoms
• Proper injection site care to minimize reactions
• Report any signs of depression or suicidal thoughts
• Monitor for signs of hepatic dysfunction (jaundice, dark urine)

• Importance of adherence to prescribed regimen
• Regular follow-up with healthcare provider
• Avoidance of live vaccines
• Report any new symptoms or health changes

• Discuss family planning with healthcare provider
• Use effective contraception during treatment

References

1. FDA Prescribing Information for Rebif (2023) 2. Multiple Sclerosis Therapy Consensus Group Guidelines (2022) 3. Clinical Trials.gov: Rebif clinical studies 4. European Medicines Agency: Rebif product information 5. Neurology clinical practice guidelines for MS management (2023) 6. Journal of Neurology: Interferon beta-1a efficacy and safety data 7. Therapeutic Advances in Neurological Disorders: Long-term Rebif studies 8. Cochrane Database of Systematic Reviews: Interferon therapy for MS