Section 04 · Monograph
Interferon beta-1a
Reviewed Nov 2026FDA label
Avonex / RebifInterferon
- Forms
- Avonex IM: 30mcg/0.5mL | Rebif SC: 22, 44mcg
- Dose
- weekly (Avonex) or 3x/wk (Rebif)
- MOA
- Immunomodulatory, ↓T-cell activation
Indications
- Treatment of relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease (both Avonex IM and Rebif SC formulations)FDA-labeled
Mechanism of Action
- The mechanism(s) by which interferon beta-1a (Avonex and Rebif) exerts its therapeutic effects in MS is unknown, per FDA labeling
- Interferon beta-1a is produced by recombinant DNA technology using genetically engineered Chinese hamster ovary cells, and is glycosylated, matching the amino acid sequence of natural human interferon beta
- Interferon beta binds to specific cell-surface receptors, initiating a cascade of intracellular signaling that leads to immunomodulatory effects thought to underlie its clinical benefit in relapsing MS
Full Dosing
Adult / usual
- Avonex (IM): 30 mcg intramuscularly once weekly
- Avonex titration to reduce flu-like symptoms: Week 1 = 7.5 mcg (1/4 dose); Week 2 = 15 mcg (1/2 dose); Week 3 = 22.5 mcg (3/4 dose); Week 4 onward = 30 mcg full dose
- Avonex: first injection should be given under supervision of a healthcare professional; rotate IM injection sites (thigh or upper arm)
- Rebif (SC): target maintenance dose is 22 mcg or 44 mcg given subcutaneously three times weekly, on the same 3 days each week (e.g., Mon/Wed/Fri), at least 48 hours apart, preferably in late afternoon/evening
- Rebif titration (22 mcg target): Weeks 1-2 = 4.4 mcg TIW; Weeks 3-4 = 11 mcg TIW; Week 5+ = 22 mcg TIW
- Rebif titration (44 mcg target): Weeks 1-2 = 8.8 mcg TIW; Weeks 3-4 = 22 mcg TIW; Week 5+ = 44 mcg TIW
- Concurrent analgesics/antipyretics on treatment days may help ameliorate flu-like symptoms (both formulations)
Renal
- Geriatric patients (Rebif): use caution and consider starting at the low end of dosing given greater likelihood of decreased hepatic, renal, or cardiac function
Contraindications
- History of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation
Drug Interactions
- No specific formal drug-drug interaction studies are described in the Avonex or Rebif prescribing information
- Use caution with concomitant hepatotoxic drugs or alcohol given the risk of hepatic injury with interferon beta
- Patients should inform prescribers of all concomitant medications given lack of formal interaction data
Adverse Effects
- Flu-like symptoms (chills, fever, myalgia, asthenia) — very common with both formulations, typically within hours of injection, often diminishing with continued therapy
- Injection site reactions, including injection site necrosis: Avonex (IM) — abscess/cellulitis/necrosis reported postmarketing; Rebif (SC) — injection site reactions in 89-92% (vs 39% placebo), with necrosis in 1-3% of Rebif-treated patients, some requiring debridement or skin grafting
- Hepatic injury — severe liver injury and rare hepatic failure (including transplantation with Rebif) reported
- Depression and suicidality — reported with increased frequency versus placebo (Avonex: 4% vs 1% for suicidal tendency in one trial)
- Headache, asthenia, myalgia, abdominal pain
- Hematologic abnormalities — leukopenia, lymphopenia, thrombocytopenia, rare pancytopenia (Rebif pancytopenia: 5.5/1000 subject-years vs 1.2/1000 placebo)
- Seizures reported temporally associated with use, including in patients without prior seizure history
- Anaphylaxis and other hypersensitivity reactions (rare)
- Thrombotic microangiopathy (TMA), including TTP/HUS, sometimes fatal, weeks to years after initiation
- Pulmonary arterial hypertension (PAH), sometimes years after starting therapy
- Cardiac events — congestive heart failure, cardiomyopathy reported postmarketing
- Autoimmune disorders — drug-induced lupus, autoimmune hepatitis, thyroid dysfunction, idiopathic thrombocytopenia
- Neutralizing antibody formation (Rebif: 24-31% of patients), which may reduce efficacy
Monitoring Parameters
- Complete blood count with differential and platelet count at baseline and periodically (Rebif specifies 1, 3, and 6 months post-initiation, then periodically)
- Liver function tests (ALT/SGPT, AST, bilirubin) at baseline and periodically; consider dose reduction if SGPT exceeds 5x ULN (Rebif)
- Thyroid function tests periodically, especially in patients with history of thyroid dysfunction
- Monitor for new or worsening depression and suicidal ideation
- Inspect injection sites regularly for erythema, swelling, tenderness, or necrosis; rotate sites
- Assess for signs/symptoms of TMA (thrombocytopenia, new-onset hypertension, fever, neurologic symptoms, renal impairment) and PAH (dyspnea, fatigue) throughout treatment
- Cardiac monitoring in patients with pre-existing cardiac disease
Pregnancy & Lactation
- Pregnancy: large population-based cohort studies (including Nordic cohorts) have not shown a clear increased risk of major birth defects with interferon beta exposure in early pregnancy; data on low birth weight/miscarriage risk have been inconsistent across studies
- Animal reproduction studies at high doses showed abortifacient activity; interferon beta may cause fetal harm based on animal data
- Advise patients to notify their healthcare provider if pregnancy occurs or is planned during treatment
- Lactation: limited published literature describes low levels of interferon beta-1a in human milk; no data on effects on milk production; weigh developmental/health benefits of breastfeeding against potential infant exposure and maternal clinical need for therapy