Interferon beta-1a Side Effects

Some side effects of interferon beta-1a may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to interferon beta-1a: intramuscular kit, intramuscular powder for injection, subcutaneous kit, subcutaneous solution

Get emergency medical help if you have any of these signs of an allergic reaction while taking interferon beta-1a: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• depressed mood, anxiety, trouble sleeping, restlessness, or thoughts of suicide or hurting yourself;

• easy bruising or bleeding, weakness;

• seizure (convulsions);

• numbness or tingling in your hands or feet;

• pain or burning when you urinate;

• pain, swelling, or skin changes where the injection was given;

• fever, chills, body aches, flu symptoms; or

• nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects of interferon beta-1a may include:

• headache, dizziness;

• stomach pain; or

• runny or stuffy nose.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to interferon beta-1a: intramuscular kit, intramuscular powder for injection, subcutaneous kit, subcutaneous solution

General

In general, the use of interferon beta-1a in patients with multiple sclerosis is limited. It is probable that rarely occurring adverse effects may not have been reported to date.

The most commonly reported adverse effects associated with Avonex(R) have included influenza-like and other symptoms occurring within hours to days after an injection. Symptoms have included muscle aches, fever, chills, fatigue, headache, nausea, and vomiting. The most common side effects resulting in clinical intervention (e.g., treatment discontinuation or need for treatment due to adverse effects) were influenza-like symptoms and depression.

The most commonly reported serious side effects associated with Rebif(R) have included psychiatric disorders including depression and suicidal ideation or attempt. The most common side effects have included injection site disorders, influenza-like symptoms (headache, fatigue, fever, rigors, chest pain, back pain, myalgia), abdominal pain, depression, elevated liver enzymes, and hematologic abnormalities. The most common side effects resulting in clinical intervention (e.g., treatment discontinuation or need for treatment due to adverse effects) were injection site disorders, influenza-like symptoms, depression, and elevated liver enzymes.

Nervous system

In a placebo-controlled study, four patients receiving interferon beta-1a experienced a seizure, while none receiving placebo experienced a seizure. Three of four patients had no prior seizure history. However, a causal relationship with interferon beta-1a has not been confirmed.

Seizures and extrapyramidal symptoms were reported in a 21-year-old man with a history of Tourette's syndrome and Asperger's syndrome, who was recently diagnosed with multiple sclerosis. Generalized tonic-clonic seizures occurred on days 14 and 34 following the start of therapy with interferon beta-1a 30 mcg per week. Given this patient's other neurologic conditions require a drug regimen with multiple pharmacodynamic properties, it was difficult to establish causality. A new drug regimen without interferon beta-1a has prevented seizure activity and controlled his symptoms of Tourette's syndrome.

Sudden hearing loss and tinnitus have been associated with interferon beta (the specific interferon beta was not identified in the case report). Ototoxic effects resolved 7 to 14 days after discontinuation of the drug.

Transient neurological symptoms were of limited duration, temporally related to the injections, and most prominent at the initiation of therapy. In some cases, these symptoms were associated with influenza-like syndrome.

Very common (10% or more): Headache (up to 70%), dizziness (up to 15%)
Common (1% to 10%): Hypertonia (up to 7%), seizures (up to 5%), abnormal coordination (up to 5%), migraine (up to 5%)
Frequency not reported: Sleep difficulty, muscle spasm, paresthesia, myasthenia, extrapyramidal symptoms, sudden hearing loss, tinnitus
Postmarketing reports: Rebif(R): Seizures, transient neurological symptoms (i.e., hypoesthesia, muscle spasm, paresthesia, musculoskeletal stiffness, difficulty walking) that mimic multiple sclerosis exacerbations

Other

Very common (10% or more): Influenza-like symptoms (up to 59%), fatigue (up to 41%), fever (up to 28%), asthenia (up to 24%), pain (up to 23%), chills/rigors (up to 19%)
Common (1% to 10%): Chest pain (up to 8%), abdominal pain (up to 8%), infection (up to 7%), malaise (up to 5%), toothache (up to 3%)
Rare (less than 0.1%): Avonex(R): Chills and shaking following injection (at least 1 case)

A register nurse reported to the manufacturer that a 48-year-old female patient with stage 4 non-small cell lung cancer with metastases discontinued Avonex(R) due to chills, shaking, and difficulty breathing following injection. The registered nurse reported the lung cancer was not related to Avonex(R); however, causality for the other events was not assessed. Avonex(R) was discontinued prior to the patient's death due to lung cancer.

Psychiatric

Very common (10% or more): Depression (up to 25%)
Common (1% to 10%): Somnolence (up to 5%)
Frequency not reported: Suicidal ideation, suicide attempt, suicide, anhedonia, psychotic thoughts, mood disturbances, hypersexuality, aggressive behavior, panic attacks
Postmarketing reports: Avonex(R): Depression, suicidal ideation, development of new or worsening of other preexisting psychiatric disorders (including psychosis); Rebif(R): Suicide

Data from the SPECTRIMS (Secondary Progressive Efficacy Trial of Interferon beta-1a in MS) study suggest that depression is not a side effect of interferon beta-1a.

A case reported to the manufacturer pertained to a 62-year-old female patient on Avonex(R) for multiple sclerosis who was hospitalized for 2 to 3 days due to attempting suicide by overdosing on alprazolam. Treatment is unknown and the patient recovered. Avonex(R) therapy was not discontinued. Upon follow-up, the patient's neurologist confirmed hospitalization due to suicide attempt, but indicated she had overdosed on Valium (R). No further information was provided and the neurologist did not assess causality.

Local

Injection site reactions were reported more frequently by patients receiving Rebif(R) than in patients receiving Avonex(R) (83% vs. 28%, p less than 0.001) during the EVIDENCE Trial (EVidence of Interferon Dose-response: European North American Comparative Efficacy) where efficacy and safety of interferon beta-1a (Rebif[R]) 44 mcg subcutaneously three times weekly was compared against interferon beta-1a (Avonex[R]) 30 mcg intramuscularly once weekly in patients with relapsing-remitting multiple sclerosis (n=667).

Very common (10% or more): Injection site reaction (up to 92%), inflammation at site of subcutaneous injection (up to 52%)
Common (1% to 10%): Injection site pain (up to 8%), injection site inflammation (up to 6%), injection site necrosis (up to 4%)
Frequency not reported: Subcutaneous injection sites: Injection site necrosis, injection site atrophy, injection site edema, injection site hemorrhage
Postmarketing reports: Avonex(R): Rare cases of injection site abscess or cellulitis requiring surgical intervention; Rebif(R): Injection site abscesses, injection site infections (including cellulitis and necrosis requiring debridement, systemic antibiotic treatment, and/or grafting)

Hematologic

Altered leukocyte counts were reported more frequently by patients receiving Rebif(R) than in patients receiving Avonex(R) (11% vs. 5%, p=0.003) during the EVIDENCE Trial (EVidence of Interferon Dose-response: European North American Comparative Efficacy) where efficacy and safety of interferon beta-1a (Rebif[R]) 44 mcg subcutaneously three times weekly was compared against interferon beta-1a (Avonex[R]) 30 mcg intramuscularly once weekly in patients with relapsing-remitting multiple sclerosis (n=667).

Very common (10% or more): Leukopenia (up to 36%), lymphadenopathy (up to 12%)
Common (1% to 10%): Thrombocytopenia (up to 8%), injection site ecchymosis (up to 6%), anemia (up to 5%)
Postmarketing reports: Avonex(R): Decreased peripheral blood counts in all cell lines (including rare pancytopenia, thrombocytopenia); Rebif(R): Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), pancytopenia

Musculoskeletal

Very common (10% or more): Myalgia (up to 29%), back pain (up to 25%), skeletal pain (up to 15%)
Common (1% to 10%): Arthralgia (up to 9%)

Hepatic

Very common (10% or more): Elevated SGPT (up to 27%), elevated SGOT (up to 17%)
Common (1% to 10%): Abnormal hepatic function (up to 9%), bilirubinemia (up to 3%)
Frequency not reported: Jaundice, symptoms of liver dysfunction
Postmarketing reports: Avonex(R): Hepatic injury (including hepatic failure, elevated serum hepatic enzyme levels); Rebif(R): Rare cases of severe liver dysfunction (including hepatic failure requiring liver transplantation)

Symptoms of liver dysfunction appeared from 1 to 6 months following the initiation of therapy.

Fulminant liver failure occurring 7 weeks after the start of Rebif(R) therapy that required a liver transplantation has been reported in a patient who was also receiving nefazodone.

Asymptomatic elevation of hepatic transaminases has been reported, and in some patients has occurred upon rechallenge with Avonex(R).

Asymptomatic abnormalities of liver enzymes have been reported more frequently in patients receiving Rebif(R) compared with the patients receiving Avonex(R) (18% vs. 10%, p=0.002) during the EVIDENCE Trial (EVidence of Interferon Dose-response: European North American Comparative Efficacy) where efficacy and safety of interferon beta-1a (Rebif[R]) 44 mcg subcutaneously three times weekly was compared against interferon beta-1a (Avonex[R]) 30 mcg intramuscularly once weekly in patients with relapsing-remitting multiple sclerosis (n=667).

Gastrointestinal

Very common (10% or more): Nausea (up to 23%), abdominal pain (up to 22%)
Common (1% to 10%): Dry mouth (up to 5%)
Frequency not reported: Gastrointestinal upset (i.e., nausea, diarrhea, dyspepsia)

Cardiovascular

Common (1% to 10%): Vasodilation (up to 2%)
Postmarketing reports: Avonex(R): Congestive heart failure (CHF), cardiomyopathy, cardiomyopathy with CHF

CHF, cardiomyopathy, and cardiomyopathy with CHF have been reported in patients without prior known history to these events. In some cases recurrence was observed upon rechallenge.

Hypersensitivity

Frequency not reported: Anaphylaxis, other allergic reactions (including dyspnea, orolingual edema, skin rash, urticaria)

Respiratory

Very common (10% or more): Upper respiratory tract infection (up to 14%), sinusitis (up to 14%)
Common (1% to 10%): Bronchitis (up to 8%)
Rare (less than 0.1%): Avonex(R): Difficulty breathing following injection (at least 1 case)

A register nurse reported to the manufacturer that a 48-year-old female patient with stage 4 non-small cell lung cancer with metastases discontinued Avonex(R) due to chills, shaking, and difficulty breathing following injection. The registered nurse reported the lung cancer was not related to Avonex(R); however, causality for the other events was not assessed. Avonex(R) was discontinued prior to the patient's death due to lung cancer.

Genitourinary

Very common (10% or more): Urinary tract infection (up to 17%)
Common (1% to 10%): Micturition frequency (up to 7%), urinary incontinence (up to 4%), abnormal urine constituents (up to 3%)
Rare (less than 0.1%): Menstrual disorders (at least 1 case)
Postmarketing reports: Avonex(R): Menorrhagia, metrorrhagia

Ocular

Very common (10% or more): Rebif(R): Abnormal vision (up to 13%)
Common (1% to 10%): Avonex(R): Eye disorder (4%); Rebif(R): Xerophthalmia (up to 3%)
Rare (less than 0.1%): Retinopathy (at least 1 case), exacerbation of Susac syndrome retinopathy (at least 1 case)
Postmarketing reports: Rebif(R): Retinal vascular disorders (i.e., retinopathy, cotton wool spots or obstruction of retinal artery or vein)

A 48-year-old female with relapsing-remitting multiple sclerosis experienced retinopathy coincident with interferon beta-1a therapy. Five months prior to presenting with blurry vision in the inferonasal quadrant of her right eye, the patient began interferon beta-1a 44 mcg subcutaneously three times per week. Dilated fundus examination showed cotton wool spots in the maculae of each eye. Therapy with interferon beta-1a was discontinued. Six weeks later a follow-up fundoscopic examination showed complete resolution of her cotton wool spots. Four years later, she remained without any symptoms and without recurrence of retinal findings.

A 23-year-old male was diagnosed with multiple sclerosis. About 4 months later, following peripheral vision loss in his left eye, he was started on oral prednisone (short course) and subcutaneous interferon beta-1a. His visual symptoms improved. Three months later peripheral vision loss in his right eye developed, but resolved following a week of prednisone. Signs of retinopathy were found during testing 15 months after interferon beta-1a was started. After additional tests, the diagnosis was changed to Susac syndrome and interferon beta-1a was discontinued. Two weeks after the drug was stopped, the patient showed dramatic improvement of the retinopathy, suggesting interferon beta-1a may have exacerbated the retinal findings of Susac syndrome.

Dermatologic

Common (1% to 10%): Erythematous rash (up to 7%), maculopapular rash (up to 5%), alopecia (up to 4%)
Rare (less than 0.1%): Severe urticaria (at least 1 case), calcified subcutaneous nodules (at least 1 case), psoriasis (at least 1 case), periungual and nail alterations (at least 1 case)
Postmarketing reports: Avonex(R): Rash (including vesicular rash); Rebif(R): Erythema multiforme, Stevens-Johnson syndrome

A 30-year-old woman developed severe widespread urticaria within 30 minutes of her second dose of interferon beta-1a. The patient had suspended therapy with interferon beta-1a due to pregnancy, and reinitiated her treatment 18 months later. Patient underwent prick and intradermal tests with 0.03 mL of the drug diluted in normal saline, starting with a concentration of 1:1000. She had a positive response to the most diluted concentration of the drug.

A 24-year-old female with multiple sclerosis experienced a 12-month history of subcutaneous nodules coincident with Rebif(R) therapy. These lesions became apparent during the early stages of pregnancy at which time she was taking a break from therapy. Prior to pregnancy, she had received 3 years of subcutaneous treatment, requiring injections of Rebif(R) 44 mcg three times weekly. The site of injection had included the thighs, abdomen, upper arms, and buttocks, although her preferred site of injection was the abdomen. The examination showed multiple 5 to 10 mm diameter firm subcutaneous nodules in a bandlike distribution across the lower abdomen, below the umbilicus. The subcutaneous nodules stayed palpable after 18 months. No further cutaneous adverse events developed once the site of injection was rotated without preference.

Immunologic

Very common (10% or more): Rebif(R): Detection of serum neutralizing antibodies (NAb) (up to 31%)
Common (1% to 10%): Avonex(R): Detection of serum NAb (up to 5%)
Rare (less than 0.1%): Exacerbation or induction of severe dermatomyositis (at least 1 case), subacute cutaneous lupus erythematosus (at least 1 case)
Postmarketing reports: Avonex(R): Autoimmune disorders of multiple target organs (including idiopathic thrombocytopenia, hyperthyroidism, hypothyroidism, rare cases of autoimmune hepatitis); Rebif(R): Drug-induced lupus erythematosus, autoimmune hepatitis

The clinical significance of the presence of NAb is unknown. A small preliminary study suggests that switching these patients to alternate interferon beta preparations may not be clinically beneficial.

Subacute cutaneous lupus erythematosus was confirmed in a 43-year-old white man with a long history of multiple sclerosis. He had received interferon beta-1a 3 million international units weekly for 5 months and listed no family history of autoimmune diseases.

Autoimmune hepatitis in a 38-year-old female treated with Avonex(R) has been reported to occur after 24 months of treatment.

Neutralizing antibodies developed in up to 31% receiving Rebif(R) and up to 5% of patients receiving Avonex(R) during the EVIDENCE Trial (EVidence of Interferon Dose-response: European North American Comparative Efficacy) where efficacy and safety of interferon beta-1a (Rebif[R]) 44 mcg subcutaneously three times weekly was compared against interferon beta-1a (Avonex[R]) 30 mcg intramuscularly once weekly in patients with relapsing-remitting multiple sclerosis (n=667).

Endocrine

Common (1% to 10%): Thyroid disorder (up to 6%)

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