REBIF

Clinical safety rating: caution

Comprehensive clinical and safety monograph for REBIF (REBIF).

How it works

Interferon beta-1a binds to type I interferon receptors, activating the JAK-STAT signaling pathway, which leads to expression of interferon-responsive genes. This results in modulation of immune responses, including reduction of pro-inflammatory cytokines, enhancement of anti-inflammatory cytokines, inhibition of T-cell activation and proliferation, and decreased blood-brain barrier permeability.

What the body does with it

Metabolism	Metabolized via proteolytic degradation to amino acids and small peptides; no specific cytochrome P450 involvement.
Excretion	Renal (primarily via glomerular filtration and catabolism) and hepatic metabolism; <5% excreted unchanged in urine.
Half-life	Terminal half-life approximately 50 hours (range 28-75 hours) after subcutaneous administration, supporting every-other-day dosing.
Protein binding	Approximately 30-40% bound to albumin and other serum proteins.
Volume of Distribution	Approximately 0.55-0.72 L/kg, indicating distribution primarily into extracellular fluid.
Bioavailability	Approximately 40-50% after subcutaneous injection (absolute bioavailability).
Onset of Action	Clinical effects (reduction in relapse rate and MRI activity) observed within 3-6 months of initiating subcutaneous therapy; time not applicable for acute effects.
Duration of Action	Duration of action is sustained over the dosing interval (48 hours); immunomodulatory effects persist with regular administration.

Classification & Brands

Action Class

Interferons

Dosing & administration

Subcutaneous injection, 22 mcg (0.5 mL) or 44 mcg (0.5 mL) three times per week, at least 48 hours apart.

Dosage form	SYRINGE
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment; use with caution.
Liver impairment	No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment; use with caution.
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years; no approved dosing.
Geriatric use	No specific dose adjustment; limited data in elderly, consider age-related renal/hepatic function decline and use with caution.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for REBIF (REBIF).

Breastfeeding	Unknown if excreted in human milk. M/P ratio not available. Due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue drug, considering importance of drug to mother.
Teratogenic Risk	Pregnancy category C. First trimester: No increased risk of major congenital anomalies based on limited human data; animal studies show fetal harm at high doses. Second and third trimesters: Potential for reversible decreases in platelet counts and thyroid function abnormalities in neonates exposed in utero. Risk of spontaneous abortion may be increased.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of hypersensitivity to interferon beta or any component of the formulation","Pregnancy (Rebif may cause fetal harm)"]

Clinical Precautions

Precautions

["Hepatic injury including severe hepatitis and hepatic failure","Depression and suicide risk","Injection site necrosis","Anaphylaxis and allergic reactions","Leukopenia and thrombocytopenia","Seizures","Congestive heart failure","Thyroid dysfunction","Nephrotic syndrome"]

Clinical Tips & Counseling

Drug interactions

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REBIF

Clinical safety rating: caution

Comprehensive clinical and safety monograph for REBIF (REBIF).

How it works

What the body does with it

Metabolism	Metabolized via proteolytic degradation to amino acids and small peptides; no specific cytochrome P450 involvement.
Excretion	Renal (primarily via glomerular filtration and catabolism) and hepatic metabolism; <5% excreted unchanged in urine.
Half-life	Terminal half-life approximately 50 hours (range 28-75 hours) after subcutaneous administration, supporting every-other-day dosing.
Protein binding	Approximately 30-40% bound to albumin and other serum proteins.
Volume of Distribution	Approximately 0.55-0.72 L/kg, indicating distribution primarily into extracellular fluid.
Bioavailability	Approximately 40-50% after subcutaneous injection (absolute bioavailability).
Onset of Action	Clinical effects (reduction in relapse rate and MRI activity) observed within 3-6 months of initiating subcutaneous therapy; time not applicable for acute effects.
Duration of Action	Duration of action is sustained over the dosing interval (48 hours); immunomodulatory effects persist with regular administration.

Classification & Brands

Action Class

Interferons

Dosing & administration

Subcutaneous injection, 22 mcg (0.5 mL) or 44 mcg (0.5 mL) three times per week, at least 48 hours apart.

Dosage form	SYRINGE
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment; use with caution.
Liver impairment	No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment; use with caution.
Pediatric use	Safety and efficacy not established in pediatric patients under 18 years; no approved dosing.
Geriatric use	No specific dose adjustment; limited data in elderly, consider age-related renal/hepatic function decline and use with caution.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for REBIF (REBIF).

Breastfeeding	Unknown if excreted in human milk. M/P ratio not available. Due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue drug, considering importance of drug to mother.
Teratogenic Risk	Pregnancy category C. First trimester: No increased risk of major congenital anomalies based on limited human data; animal studies show fetal harm at high doses. Second and third trimesters: Potential for reversible decreases in platelet counts and thyroid function abnormalities in neonates exposed in utero. Risk of spontaneous abortion may be increased.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of hypersensitivity to interferon beta or any component of the formulation","Pregnancy (Rebif may cause fetal harm)"]