(in ter FEER on BAY ta won aye)
- rIFN beta-1a
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]:
Avonex: 30 mcg [contains albumin (human), mouse (murine) and/or hamster protein; supplied with diluent]
Avonex: 30 mcg/0.5 mL (0.5 mL) [albumin free; contains mouse (murine) and/or hamster protein; prefilled syringe]
Avonex Pen: 30 mcg/0.5 mL (0.5 mL) [albumin free; contains mouse (murine) and/or hamster protein]
Injection, solution [preservative free]:
Rebif: 22 mcg/0.5 mL (0.5 mL), 44 mcg/0.5 mL (0.5 mL) [contains albumin (human), mouse (murine) and/or hamster protein; prefilled syringe]
Rebif Rebidose: 22 mcg/0.5 mL (0.5 mL), 44 mcg/0.5 mL (0.5 mL) [contains albumin (human), mouse (murine) and/or hamster protein; autoinjector]
Injection, solution [preservative free, combination package]:
Rebif Titration Pack: 8.8 mcg/0.2 mL (6s) and 22 mcg/0.5 mL (6s) [contains albumin (human), mouse (murine) and/or hamster protein; prefilled syringe]
Rebif Rebidose Titration Pack: 8.8 mcg/0.2 mL (6s) and 22 mcg/0.5 mL (6s) [contains albumin (human), mouse (murine) and/or hamster protein; autoinjector]
Brand Names: U.S.
- Avonex Pen
- Rebif Rebidose
- Rebif Rebidose Titration Pack
- Rebif Titration Pack
Interferon beta differs from naturally occurring human protein by a single amino acid substitution and the lack of carbohydrate side chains; alters the expression and response to surface antigens and can enhance immune cell activities. Properties of interferon beta that modify biologic responses are mediated by cell surface receptor interactions; mechanism in the treatment of MS is unknown.
Onset of Action
Avonex: 12 hours (based on biological response markers)
Time to Peak
Serum: Avonex (IM): ~15 hours (range: 6-36 hours); Rebif (SubQ): 16 hours
Duration of Action
Avonex: 4 days (based on biological response markers)
Avonex: ~19 hours (range: 8-54 hours); Rebif: 69 hours
Use: Labeled Indications
US labeling: Treatment of relapsing forms of multiple sclerosis (MS) to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability
Treatment of relapsing forms of multiple sclerosis (MS) to decrease the frequency of clinical exacerbations, delay the accumulation of physical disability, reduce the requirement for steroids, reduce the number of hospitalizations, and reduce disease burden
To decrease the number and volume of active brain lesions, decrease overall disease burden, and delay onset of clinically definite MS in patients who have experienced a single demyelinating event
Hypersensitivity to natural or recombinant interferon beta, human albumin (albumin-containing formulations only), or any other component of the formulation
Documentation of allergenic cross-reactivity for interferons is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Rebif: Pregnancy; decompensated liver disease
Multiple sclerosis (MS): Note: Analgesics and/or antipyretics may help decrease flu-like symptoms on treatment days:
US labeling: 30 mcg once weekly; to decrease flu-like symptoms, may initiate once-weekly dosing with 7.5 mcg (week 1) then increase dose in increments of 7.5 mcg once weekly (weeks 2 to 4) up to recommended dose (30 mcg once weekly)
Canadian labeling: 30 mcg once weekly; to decrease flu-like symptoms, may initiate once-weekly dosing with 7.5 mcg (week 1) then increase dose in increments of 7.5 mcg once weekly (weeks 2 to 4) or once every 2 weeks (to week 7) up to recommended dose (30 mcg once weekly). In progressive relapsing MS or secondary progressive MS with recurrent neurologic dysfunction may consider increasing to 60 mcg once weekly.
SubQ (Rebif): Target dose is either 22 or 44 mcg 3 times weekly; doses should be separated by at least 48 hours:
Target dose 44 mcg 3 times weekly:
Initial: 8.8 mcg (20% of target dose) 3 times weekly for 2 weeks
Titration: 22 mcg (50% of target dose) 3 times weekly for 2 weeks
Target dose: 44 mcg 3 times weekly
Target dose 22 mcg 3 times weekly:
Initial: 4.4 mcg (20% of target dose) 3 times weekly for 2 weeks
Titration: 11 mcg (50% of target dose) 3 times weekly for 2 weeks
Target dose: 22 mcg 3 times weekly
Single demyelinating event (Canadian labeling [Rebif]; not in US labeling): SubQ:
Target dose 44 mcg 3 times weekly: Note: Analgesics and/or antipyretics prior to and for 24 hours after dosing may help decrease flu-like symptoms:
Initial: 8.8 mcg (20% of target dose) 3 times weekly for 2 weeks
Titration: 22 mcg (50% of target dose) 3 times weekly for 2 weeks
Target dose: 44 mcg 3 times weekly
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Dosing: Hepatic Impairment
There are no dosage adjustment provided in the manufacturer’s labeling; use with caution in patients with active liver disease, alcohol abuse, ALT >2.5 x ULN, or a history of significant liver disease.
Dosing: Adjustment for Toxicity
Autoimmune disorder development: Consider discontinuing treatment.
Depression or other severe psychiatric symptoms: Consider discontinuing treatment.
ALT >5 x ULN: Temporarily discontinue therapy or consider dose reduction until ALT normalizes, then may consider retitration of dose.
Symptomatic (eg, jaundice): Discontinue immediately.
Leukopenia: May require temporary discontinuation or dose reduction until resolution.
Avonex: Reconstitute with 1.1 mL of diluent (SWFI) and swirl gently to dissolve. Do not shake. The reconstituted product contains no preservative and is for single-use only; discard unused portion.
The first injection should be administered under the supervision of a health care professional.
Avonex: Administer IM; rotate injection site; do not inject into area where skin is irritated, red, bruised, scarred, or infected. Two hours after injection, examine site for redness, swelling, or tenderness. Discard any unused portion.
Rebif: Administer SubQ at the same time of day on the same 3 days each week (eg, Mon, Wed, Fri), preferably in the late afternoon or evening; doses should be at least 48 hours apart; rotate injection site; do not inject into area where skin is irritated, red, bruised, or scarred. Discard any unused portion.
Prefilled syringe or pen: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Allow to warm to room temperature prior to use (do not use external heat source). If refrigeration is not available, product may be stored at ≤25°C (77°F) for up to 7 days.
Vial: Store unreconstituted vial at 2°C to 8°C (36°F to 46°F). If refrigeration is not available, may be stored at 25°C (77°F) for up to 30 days; do not freeze. Protect from light. Following reconstitution, use immediately, but may be stored up to 6 hours at 2°C to 8°C (36°F to 46°F); do not freeze.
Rebif: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from heat and light. Allow to warm to room temperature prior to use (do not use external heat source). Refrigeration is preferred; however, if needed, may be stored at 2°C to 25°C (36°F to 77°F) for up to 30 days.
Theophylline Derivatives: Interferons may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Monitor therapy
Adverse reactions reported as a composite of both commercially-available products. Spectrum and incidence of reactions is generally similar between products, but consult individual product labels for specific incidence.
Central nervous system: Headache (58% to 70%), fatigue (33% to 41%), depression (18% to 25%), pain (23%), chills (19%), dizziness (14%)
Gastrointestinal: Nausea (23%), abdominal pain (8% to 22%)
Genitourinary: Urinary tract infection (17%)
Hematologic & oncologic: Leukopenia (28% to 36%), lymphadenopathy (11% to 12%)
Hepatic: Increased serum ALT (20% to 27%), increased serum AST (10% to 17%)
Immunologic: Antibody development (neutralizing; significance not known; Rebif: 24% to 31%; Avonex: 5%)
Local: Injection site reaction (3% to 92%)
Neuromuscular & skeletal: Myalgia (25% to 29%), back pain (23% to 25%), weakness (24%), skeletal pain (10% to 15%), rigors (6% to 13%)
Ophthalmic: Visual disturbance (7% to 13%)
Respiratory: Flu-like symptoms (49% to 59%), sinusitis (14%), upper respiratory tract infection (14%)
Miscellaneous: Fever (20% to 28%)
1% to 10%:
Cardiovascular: Chest pain (5% to 8%), vasodilation (2%)
Central nervous system: Hypertonia (6% to 7%), migraine (5%), ataxia (4% to 5%), drowsiness (4% to 5%), malaise (4% to 5%), seizure (1% to 5%), suicidal tendencies (4%)
Dermatologic: Erythematous rash (5% to 7%), maculopapular rash (4% to 5%), alopecia (4%), hyperhidrosis (4%), urticaria
Endocrine & metabolic: Thyroid disease (4% to 6%)
Gastrointestinal: Xerostomia (1% to 5%), toothache (3%)
Genitourinary: Urinary frequency (2% to 7%), urinary incontinence (2% to 4%), urine abnormality (3%)
Hematologic & oncologic: Thrombocytopenia (2% to 8%), anemia (3% to 5%)
Hepatic: Hyperbilirubinemia (2% to 3%)
Infection: Infection (7%)
Local: Pain at injection site (8%), bruising at injection site (6%), inflammation at injection site (6%), tissue necrosis at injection site (1% to 3%)
Neuromuscular & skeletal: Arthralgia (9%)
Ophthalmic: Eye disease (4%), xerophthalmia (1% to 3%)
Respiratory: Bronchitis (8%)
<1%, postmarketing, and/or case reports: Abnormal gait, abnormal healing, abnormal hepatic function tests, abscess, abscess at injection site, amnesia, anaphylaxis, angioedema, anxiety, arteritis, arthritis, ascites, autoimmune hepatitis, basal cell carcinoma, Bell's palsy, bloody stools, breast fibroadenosis, cardiac arrhythmia, cardiac failure, cardiomyopathy, cellulitis, cellulitis at injection site, clumsiness, cold and clammy skin, colitis, confusion, conjunctivitis, constipation, contact dermatitis, dehydration, depersonalization, dermal ulcer, diaphoresis, diverticulitis, drug dependence, dyspnea, dysuria, ecchymoses, emotional lability, emphysema, epididymitis, erythema, erythema multiforme, eye pain, facial edema, facial paralysis, fibrocystic breast changes, fibrosis at injection site, furunculosis, gallbladder disease, gastritis, gastrointestinal hemorrhage, genital pruritus, gingival hemorrhage, gingivitis, gynecomastia, hematuria, hemolytic-uremic syndrome, hemoptysis, hemorrhage, hepatic failure, hepatic injury, hepatic neoplasm, hepatitis, hepatomegaly, hepatotoxicity (idiosyncratic) (Chalasani 2014), hernia, hiccups, hyperesthesia, hypermenorrhea, hypersensitivity reaction at injection site, hyperthyroidism, hyperventilation, hypoglycemia, hypokalemia, hypomagnesemia, hypotension, hypothyroidism, immune thrombocytopenia, increased appetite, increased coagulation time, increased libido, increased thirst, intestinal obstruction, intestinal perforation, labyrinthitis, laryngitis, leukorrhea, lipoma, lump in breast, lupus erythematosus, menopause, myasthenia, neoplasm, nephrolithiasis, neurological signs and symptoms (transient; may mimic multiple sclerosis exacerbations), nevus, nocturia, orolingual edema, orthostatic hypotension, osteonecrosis, otalgia, palpitations, pancytopenia, paresthesia, pelvic inflammatory disease, penile disease, pericarditis, periodontal abscess, periodontitis, peripheral ischemia, peripheral vascular disease, petechia, Peyronie disease, pharyngeal edema, pneumonia, polyuria, postmenopausal bleeding, proctitis, prostatic disease, pruritus, psychiatric disturbance (new or worsening; including suicidal ideation), psychoneurosis, pulmonary embolism, pulmonary hypertension (Govern 2015; Health Canada Nov. 2, 2016), pyelonephritis, renal pain, retinal vascular disease, seborrhea, sepsis, severe weakness (transient), skin blister, skin discoloration, skin photosensitivity, skin rash, spider telangiectasia, Stevens-Johnson syndrome, synovitis, tachycardia, telangiectasia, testicular disease, thromboembolism, thrombotic thrombocytopenic purpura, tongue disease, urethral pain, urinary retention, urinary urgency, uterine fibroids, uterine hemorrhage, vaginal hemorrhage, vascular disease, vesicular eruption, vitreous opacity, vomiting
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Allergic reactions, including anaphylaxis, have been reported. Some reactions may occur after prolonged use. Discontinue therapy if anaphylaxis or other allergic reactions occur.
• Autoimmune disorders: Autoimmune disorders including idiopathic thrombocytopenia, hyper- and hypothyroidism and rarely autoimmune hepatitis have been reported. Consider discontinuation of treatment if patient develops a new autoimmune disorder.
• Bone marrow suppression: Pancytopenia (rare), leukopenia, and thrombocytopenia have been reported. Monitor blood counts at 1, 3, and 6 months post therapy initiation and periodically thereafter. Events may recur with rechallenge.
• Flu-like symptoms: Associated with a high incidence of flu-like adverse effects; use of analgesics and/or antipyretics on treatment days may be helpful.
• Hepatic effects: Rare cases of severe hepatic injury, including cases of hepatic failure requiring transplantation, have been reported in patients receiving interferon beta-1a; risk may be increased by ethanol use or concurrent therapy with hepatotoxic drugs. Some reports indicate symptoms began after 1 to 6 months of treatment. Transaminase elevations may be asymptomatic. Use with caution in patients with active or a history of liver disease, alcohol abuse, or increased serum ALT (>2.5 times ULN) at baseline. Obtain liver function tests at 1, 3, and 6 months post therapy initiation and periodically thereafter. Treatment should be suspended immediately if jaundice or symptoms of hepatic dysfunction occur. Consider dose reductions or temporary discontinuation if ALT >5 times ULN.
• Injection site reactions: Severe injection site reactions have occurred, including pain, erythema, edema, cellulitis, abscess, and necrosis. Necrosis may occur at single and multiple sites. Some reactions have occurred ≥2 years after initiation; reactions typically resolve with conservative treatment (antibiotics or surgical intervention may be required). Patient and/or caregiver competency in injection technique should be confirmed and periodically re-evaluated.
• Neuropsychiatric disorders: Interferons have been associated with psychiatric adverse events (psychosis, depression, suicidal behavior/ideation) in patients with and without previous psychiatric symptoms; use with caution in patients with depression. Patients exhibiting symptoms of depression or other severe psychiatric symptoms should be closely monitored and discontinuation of therapy should be considered.
• Thrombotic microangiopathy: Cases of thrombotic microangiopathy manifesting as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) (some fatal) have been reported (Hunt 2014; Mahe 2013; Rebif Canadian product labeling 2016). Some cases may occur after several years of therapy. Monitor for new onset hypertension, thrombocytopenia, or impaired renal function; discontinuation of therapy and prompt treatment may be necessary if TTP/HUS are confirmed.
• Cardiovascular disease: Use with caution in patients with preexisting cardiovascular disease. Rare cases of new-onset cardiomyopathy and/or HF have been reported. In a scientific statement from the American Heart Association, interferon has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate/major) (AHA [Page 2016]).
• Hepatic impairment: Use with caution in patients with hepatic impairment or in those who abuse alcohol.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
• Thyroid dysfunction: Thyroid abnormalities may develop with use; may worsen pre-existing thyroid conditions. Monitor thyroid function tests every 6 months or as clinically necessary.
• Chronic progressive MS: Safety and efficacy have not been established for this use.
Dosage form specific issues:
• Albumin: Some formulations contain albumin, which may carry a remote risk of transmitting Creutzfeldt-Jakob or other viral diseases. Interferon beta-1a formulations that contain albumin are contraindicated in albumin-sensitive patients.
• Latex: The packaging (prefilled syringe tip cap) may contain latex.
Thyroid function tests, CBC with differential, transaminase levels, blood chemistries, symptoms of autoimmune disorders, signs/symptoms of psychiatric disorder (including depression and/or suicidal ideation), signs/symptoms of new onset/worsening cardiovascular disease, signs/symptoms of thrombotic microangiopathy (new-onset hypertension, thrombocytopenia, renal impairment)
Avonex: Frequency of monitoring for patients receiving Avonex has not been specifically defined; in clinical trials, monitoring was at 6-month intervals.
Rebif: CBC and liver function testing at 1-, 3-, and 6 months, then periodically thereafter. Thyroid function every 6 months (in patients with pre-existing abnormalities and/or clinical indications).
Pregnancy Risk Factor
Adverse events have not been observed in animal reproduction studies; however, the possibility of adverse effects cannot be ruled out. Preliminary data from the Avonex pregnancy registry (published in abstract) do not show an increased risk of adverse fetal events when exposure occurs during pregnancy (Richman 2012; Tomczyk 2013); however, other studies have reported conflicting results. Until additional information is available, consideration should be given to discontinuing treatment if a woman becomes pregnant, or 1 month prior to becoming pregnant in women with mild disease (Coyle 2012; Houtchens 2013; Lu 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience flu-like symptoms, nausea, vomiting, abdominal pain, muscle pain, joint pain, back pain, fatigue, or dry mouth. Have patient report immediately to prescriber signs of infection, signs of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (bruising or bleeding; loss of strength and energy; dark urine or jaundice; pale skin; change in amount of urine passed; vision changes; change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance; or fever), signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria, black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of thyroid problems (change in weight without trying, anxiety, feeling restless, feeling very weak, hair thinning, depression, neck swelling, difficulty focusing, inability handling heat or cold, menstrual changes, tremors, or sweating), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe injection site reaction, polyuria, angina, tachycardia, seizures, severe dizziness, passing out, or loss of strength or energy (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
More about interferon beta-1a
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- Drug class: interferons