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Peginterferon alfa-2a Side Effects

For the Consumer

Applies to peginterferon alfa-2a: subcutaneous solution

Along with its needed effects, peginterferon alfa-2a may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking peginterferon alfa-2a:

More common
  • Black, tarry stools
  • chills
  • cough
  • discouragement
  • feeling sad or empty
  • fever
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • lower back or side pain
  • painful or difficult urination
  • pale skin
  • shortness of breath
  • sore throat
  • tiredness
  • trouble sleeping
  • trouble with concentrating
  • ulcers, sores, or white spots in the mouth
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Less common
  • Bone pain
  • chest pain or discomfort
  • confusion
  • constipation
  • depressed mood
  • dizziness
  • dry skin and hair
  • fainting
  • fast heartbeat
  • feeling cold
  • hair loss
  • headache
  • heart murmur
  • hives
  • hoarseness or husky voice
  • lightheadedness
  • muscle cramps and stiffness
  • pale skin
  • rapid, shallow breathing
  • slowed heartbeat
  • sneezing
  • stomach pain
  • tightness in the chest
  • troubled breathing with exertion
  • weight gain

Some side effects of peginterferon alfa-2a may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Back pain
  • blistering, crusting, irritation, itching, or reddening of the skin
  • cracked, dry, scaly skin
  • diarrhea
  • dry mouth
  • fear
  • feeling unusually cold, shivering
  • hair loss or thinning of the hair
  • muscle or joint pain
  • nervousness
  • numbness
  • pain
  • rash
  • redness
  • scarring
  • soreness
  • stinging
  • stomach pain
  • swelling
  • tenderness
  • tingling
  • ulceration
  • vomiting
  • warmth
Less common
  • Acid or sour stomach
  • belching
  • blurred vision
  • heartburn
  • indigestion
  • memory problems
  • stomach discomfort or upset
Incidence not known
  • Change of hearing
  • loss of hearing

For Healthcare Professionals

Applies to peginterferon alfa-2a: subcutaneous kit, subcutaneous solution


During hepatitis C studies, at least 1 serious side effect was reported in 10% of chronic hepatitis C (CHC) patients and 19% of CHC patients coinfected with HIV. The most common serious side effect was bacterial infection (including sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia). Other serious side effects were suicide, suicidal ideation, psychosis, aggression, anxiety, drug abuse and drug overdose, angina, hepatic dysfunction, fatty liver, cholangitis, arrhythmia, diabetes mellitus, autoimmune phenomena (e.g., hyperthyroidism, hypothyroidism, sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis), peripheral neuropathy, aplastic anemia, peptic ulcer, gastrointestinal bleeding, pancreatitis, colitis, corneal ulcer, pulmonary embolism, coma, myositis, cerebral hemorrhage, thrombotic thrombocytopenic purpura, psychotic disorder, and hallucination. The most common side effects were psychiatric reactions (including depression, insomnia, irritability, anxiety), influenza-like symptoms (such as fatigue, pyrexia, myalgia, headache, rigors), anorexia, nausea and vomiting, diarrhea, arthralgias, injection site reactions, alopecia, and pruritus. Psychiatric disorders, influenza-like syndrome (e.g., lethargy, fatigue, headache), dermatologic disorders, gastrointestinal disorders, and laboratory abnormalities (thrombocytopenia, neutropenia, anemia) were the most common reasons for discontinuation of therapy.

In clinical trials, patients with chronic hepatitis B had similar side effects as CHC patients using peginterferon alfa-2a monotherapy, except for exacerbations of hepatitis. The most common or important serious side effects in the hepatitis B studies were infections (sepsis, appendicitis, tuberculosis, influenza), hepatitis B flares, thrombotic thrombocytopenic purpura, pyrexia, headache, fatigue, myalgia, alopecia, and anorexia. Therapy was discontinued most often due to laboratory abnormalities (neutropenia, thrombocytopenia, ALT elevation).[Ref]

Nervous system

Very common (10% or more): Dizziness (up to 89%), headache (up to 56%), concentration impairment
Common (1% to 10%): Vertigo, syncope, migraine, memory impairment, weakness, hypoesthesia, hyperesthesia, paresthesia, tremor, taste disturbance, somnolence, tinnitus
Uncommon (0.1% to 1%): Peripheral neuropathy, hearing loss
Rare (0.01% to 0.1%): Cerebral hemorrhage, coma, convulsions, facial palsy
Frequency not reported: Cerebral ischemia, chorea and akathisia
Postmarketing reports: Seizures, hearing impairment[Ref]

Headache (monotherapy: up to 54%; combination therapy: 43%), dizziness excluding vertigo (monotherapy: 16%; combination therapy: 14%), and memory impairment (monotherapy: 5%; combination therapy: 5%) have been reported in CHC patients.

Tinnitus was reported in up to 2% of CHC patients coinfected with HIV using peginterferon alfa-2a plus ribavirin.

A 40-year-old male coinfected with hepatitis C virus and HIV experienced chorea and akathisia coincident with peginterferon alfa-2a therapy. He was administered subcutaneous peginterferon alfa-2a 180 mcg weekly and oral ribavirin 1 g daily. At week 20 of therapy, the patient presented to the clinic complaining of irritability, difficulty in sleeping, and prominent choreiform involuntary movements with myoclonic activity of the upper and lower extremities. He was diagnosed with chorea and akathisia. He was treated with ropinirole, propranolol, and clonazepam. Peginterferon alfa-2a and ribavirin were discontinued with complete resolution of symptoms after 5 days.[Ref]


Very common (10% or more): Influenza-like signs/symptoms, fatigue/asthenia (up to 65%), pyrexia (up to 54%), fatigue (up to 51%), rigors (up to 35%), asthenia (up to 30%), pain (up to 11%), overall resistance mechanism disorders (up to 12%)
Common (1% to 10%): Fever, chills, chest pain, influenza-like illness, malaise, lethargy, shivering, hot flushes, thirst, infections (fungal, viral, bacterial), peripheral edema, flushing, earache
Rare (0.01% to 0.1%): Mucosal hyperpigmentation, otitis externa, substance overdose
Frequency not reported: Bacterial infections (e.g., sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia), infections (appendicitis, tuberculosis, influenza)[Ref]

Influenza-like signs and symptoms (fatigue/asthenia [monotherapy: 56%; combination therapy: 65%], pyrexia [monotherapy: up to 54%; combination therapy: 41%], rigors [monotherapy: 35%; combination therapy: 25%], pain [monotherapy: 11%; combination therapy: 10%]) and overall resistance mechanism disorders (monotherapy: 10%; combination therapy: 12%) have been reported in CHC patients.

The most common or important serious side effects reported during hepatitis B studies have included infections (sepsis, appendicitis, tuberculosis, influenza).

Fatigue has been reported in 24% of patients during hepatitis B studies.[Ref]


Myalgia (monotherapy: up to 37%; combination therapy: 40%), arthralgia (monotherapy: 28%; combination therapy: 22%), and back pain (monotherapy: 9%; combination therapy: 5%) have been reported in CHC patients.[Ref]

Very common (10% or more): Myalgia (up to 44%), arthralgia (up to 32%)
Common (1% to 10%): Back pain, arthritis, muscle weakness, bone pain, neck pain, musculoskeletal pain, muscle cramps
Rare (0.01% to 0.1%): Myositis
Frequency not reported: Rhabdomyolysis[Ref]


Very common (10% or more): Neutropenia (up to 40%), anemia (up to 28%), lymphopenia (up to 14%)
Common (1% to 10%): Thrombocytopenia, lymphadenopathy
Rare (0.01% to 0.1%): Pancytopenia
Very rare (less than 0.01%): Aplastic anemia, idiopathic or thrombotic thrombocytopenic purpura
Frequency not reported: Leukopenia, decreased hemoglobin, decreased absolute CD4+ cell count (without decrease in CD4+ cell percentage)
Postmarketing reports: Pure red cell aplasia[Ref]

Neutropenia (monotherapy: 21%; combination therapy: up to 40%), lymphopenia (monotherapy: 3%; combination therapy: 14%), anemia (monotherapy: 2%; combination therapy: up to 14%), and thrombocytopenia (monotherapy: 5%; combination therapy: up to 8%) have been reported in CHC patients.

Moderate (absolute neutrophil count [ANC] 0.5 to 0.749 x 10[9]/L: 24%) and severe (ANC less than 0.5 x 10[9]/L: 5%) neutropenia was reported in patients using peginterferon alfa-2a plus ribavirin for 48 weeks.

In 1 study, CHC patients with advanced fibrosis or cirrhosis and baseline platelet counts as low as 50,000/mm3 were treated for 48 weeks. Hematologic laboratory abnormalities in the first 20 weeks included ANC less than 750/mm3 (30%), hemoglobin less than 10 g/dL (26.3%), and platelets less than 50,000/mm3 (13%).

Neutropenia (40%), anemia (14%), and thrombocytopenia (8%) have been reported during treatment with peginterferon alfa-2a plus ribavirin in CHC patients coinfected with HIV. Decrease in ANC levels below 500 cells/mm3 (monotherapy: 13%; combination therapy: 11%), decrease in platelets below 50,000/mm3 (monotherapy: 10%; combination therapy: 8%), and hemoglobin less than 10 g/dL (monotherapy: 7%; combination therapy: up to 28%) were reported in coinfected patients.

Laboratory abnormalities (thrombocytopenia, neutropenia, anemia) were among the most common reasons given for discontinuation of therapy.

The most common or important serious side effects reported during hepatitis B studies have included thrombotic thrombocytopenic purpura.[Ref]


Gastrointestinal side effects were among the most common reasons given for discontinuation of therapy.

Nausea/vomiting (monotherapy: 24%; combination therapy: 25%), diarrhea (monotherapy: 16%; combination therapy: 11%), abdominal pain (monotherapy: 15%; combination therapy: 8%), dry mouth (monotherapy: 6%; combination therapy: 4%), and dyspepsia (monotherapy: less than 1%; combination therapy: 6%) have been reported in CHC patients.

Cheilitis was reported in up to 2% of CHC patients coinfected with HIV using peginterferon alfa-2a plus ribavirin.[Ref]

Very common (10% or more): Nausea (up to 40%), diarrhea (up to 26%), nausea/vomiting (up to 25%), abdominal pain (up to 15%), vomiting (up to 13%), upper abdominal pain (up to 12%)
Common (1% to 10%): Dry mouth, dyspepsia, dysphagia, mouth ulceration, gingival bleeding, glossitis, stomatitis, flatulence, gastritis, gingivitis, cheilitis, constipation, oral candidiasis
Uncommon (0.1% to 1%): Gastrointestinal bleeding
Rare (0.01% to 0.1%): Tongue hyperpigmentation, peptic ulcer, pancreatitis
Frequency not reported: Colitis, ischemic colitis, reversible pancreatic reaction (i.e., increased amylase/lipase with or without abdominal pain)
Postmarketing reports: Tongue pigmentation[Ref]


Very common (10% or more): Insomnia (up to 36%), irritability/anxiety/nervousness (up to 33%), irritability (up to 28%), depression (up to 27%), anxiety
Common (1% to 10%): Concentration impairment, mood alteration, nightmares, aggression, emotional disorders, nervousness, decreased libido, affect lability, apathy
Uncommon (0.1% to 1%): Suicidal ideation, hallucinations
Rare (0.01% to 0.1%): Suicide, psychotic disorder
Frequency not reported: Psychosis, relapse of drug abuse/overdose, impairment of desire, sexual satisfaction affected (potentially), sexual dysfunction, mania, bipolar disorders
Postmarketing reports: Homicidal ideation[Ref]

Psychiatric side effects were among the most common reasons given for discontinuation of therapy.

Irritability/anxiety/nervousness (monotherapy: 19%; combination therapy: 33%), insomnia (monotherapy: 19%; combination therapy: 30%), depression (monotherapy: 18%; combination therapy: 20%), concentration impairment (monotherapy: 8%; combination therapy: 10%), and mood alteration (monotherapy: 3%; combination therapy: 5%) have been reported in CHC patients.

Affect lability and apathy were reported in up to 2% of CHC patients coinfected with HIV using peginterferon alfa-2a plus ribavirin.

Impairment of desire, sexual satisfaction affected (potentially), and sexual dysfunction have been reported with peginterferon alfa-2a plus ribavirin in male patients.[Ref]


Dermatologic side effects were among the most common reasons given for discontinuation of therapy.

Alopecia (monotherapy: up to 23%; combination therapy: 28%), pruritus (monotherapy: 12%; combination therapy: 19%), dermatitis (monotherapy: 8%; combination therapy: 16%), dry skin (monotherapy: 4%; combination therapy: 10%), increased sweating (monotherapy: 6%; combination therapy: 6%), rash (monotherapy: 5%; combination therapy: 8%), and eczema (monotherapy: 1%; combination therapy: 5%) have been reported in CHC patients.

Lipodystrophy acquired was reported in up to 2% of CHC patients coinfected with HIV using peginterferon alfa-2a plus ribavirin.

Skin disorders associated with combination therapy have included lichenoid eruptions and maculopapular rashes.[Ref]

Very common (10% or more): Alopecia (up to 28%), pruritus (up to 25%), dermatitis (up to 16%), rash (up to 16%), dry skin (up to 13%)
Common (1% to 10%): Increased sweating, eczema, psoriasis, urticaria, skin disorder, photosensitivity reaction, night sweats, herpes simplex, lipodystrophy acquired
Uncommon (0.1% to 1%): Skin infection
Very rare (less than 0.01%): Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, erythema multiforme
Frequency not reported: Lichenoid eruptions, maculopapular rashes, drug-induced Sweet's syndrome
Postmarketing reports: Serious skin reactions[Ref]


Injection site reactions (monotherapy: 22%; combination therapy: 23%) have been reported in CHC patients.

Skin disorders associated with combination therapy have included cutaneous necrosis at peginterferon alfa-2a injection sites.[Ref]

Very common (10% or more): Injection site reactions (up to 28%)
Frequency not reported: Cutaneous necrosis at injection sites, hyperpigmentation around/over injection sites[Ref]


Very common (10% or more): Elevated ALT (up to 27%)
Common (1% to 10%): Hepatic decompensation
Uncommon (0.1% to 1%): Hepatic dysfunction
Rare (0.01% to 0.1%): Hepatic failure, fatty liver, cholangitis
Frequency not reported: Elevated ALT occasionally associated with hyperbilirubinemia, exacerbations of hepatitis, hepatitis B flares, increased bilirubin[Ref]

Transient ALT elevations reported during hepatitis B therapy. ALT elevation greater than 10-fold higher than the upper limit of normal was reported in 12% and 18% during treatment and 7% and 12% posttreatment in HBeAg-negative and HBeAg-positive patients, respectively.

Hepatic decompensation has been reported in 2% of CHC patients coinfected with HIV.

The most common or important serious side effects reported during hepatitis B studies have included hepatitis B flares.[Ref]


Very common (10% or more): Anorexia (up to 27%), weight decrease (up to 16%), decreased appetite (up to 16%)
Common (1% to 10%): Hyperlactacidemia/lactic acidosis
Uncommon (0.1% to 1%): Dehydration, diabetes mellitus
Rare (0.01% to 0.1%): Diabetic ketoacidosis
Frequency not reported: Elevated triglycerides, electrolyte disturbance (hypokalemia, hypocalcemia, hypophosphatemia), hyperglycemia, hypoglycemia[Ref]

Anorexia (monotherapy: up to 17%; combination therapy: 24%) and weight decrease (monotherapy: 4%; combination therapy: 10%) have been reported in CHC patients.

Hyperlactacidemia/lactic acidosis was reported in up to 2% of CHC patients coinfected with HIV using peginterferon alfa-2a plus ribavirin.[Ref]


Dyspnea (monotherapy: 4%; combination therapy: 13%), cough (monotherapy: 4%; combination therapy: 10%), and exertional dyspnea (monotherapy: less than 1%; combination therapy: 4%) have been reported in CHC patients.

Pneumonia, influenza, and pharyngolaryngeal pain were reported in up to 2% of CHC patients coinfected with HIV using peginterferon alfa-2a plus ribavirin.[Ref]

Very common (10% or more): Cough (up to 19%), dyspnea (up to 15%)
Common (1% to 10%): Pharyngitis, exertional dyspnea, epistaxis, nasopharyngitis, sinus congestion, nasal congestion, rhinitis, sore throat, bronchitis, upper respiratory tract infection, pulmonary congestion, chest tightness, pneumonia, influenza, pharyngolaryngeal pain
Uncommon (0.1% to 1%): Wheezing
Rare (0.01% to 0.1%): Interstitial pneumonitis (including fatalities), pulmonary embolism
Frequency not reported: Lower respiratory tract infection[Ref]


Examples of autoimmune phenomena include hyperthyroidism, hypothyroidism, sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis, immune thrombocytopenic purpura, thyroiditis, psoriasis.

Sarcoidosis was reported in a 65-year-old man at the 7th month of therapy. Most of the symptoms improved over the next 3 months after discontinuation of therapy.[Ref]

Common (1% to 10%): Development of neutralizing anti-interferon antibodies
Uncommon (0.1% to 1%): Sarcoidosis
Rare (0.01% to 0.1%): Systemic lupus erythematosus, rheumatoid arthritis
Frequency not reported: Autoimmune phenomena, development of binding antibodies to peginterferon alfa-2a, Vogt-Koyanagi-Harada disease
Postmarketing reports: Liver graft rejection, renal graft rejection

Alpha interferons:
-Frequency not reported: Development or exacerbation of autoimmune disorders (including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, systemic lupus erythematosus)[Ref]


Common (1% to 10%): Tachycardia, palpitations
Uncommon (0.1% to 1%): Hypertension
Rare (0.01% to 0.1%): Myocardial infarction, congestive heart failure, cardiomyopathy, angina, arrhythmia, atrial fibrillation, pericarditis, supraventricular tachycardia, endocarditis, vasculitis
Frequency not reported: Peripheral ischemia[Ref]


Blurred vision (monotherapy: 4%; combination therapy: 5%) has been reported in CHC patients.[Ref]

Common (1% to 10%): Blurred vision, eye pain, eye inflammation, xerophthalmia
Uncommon (0.1% to 1%): Retinal hemorrhage
Rare (0.01% to 0.1%): Optic neuropathy, papilledema, retinal vascular disorder, retinopathy, corneal ulcers
Very rare (less than 0.01%): Vision loss
Postmarketing reports: Serous retinal detachment[Ref]


Hypothyroidism (monotherapy: 3%; combination therapy: 4%) has been reported in CHC patients.

Common (1% to 10%): Hypothyroidism, hyperthyroidism, clinically significant abnormal thyroid laboratory values
Uncommon (0.1% to 1%): Thyroiditis


Chromaturia was reported in up to 2% of CHC patients coinfected with HIV using peginterferon alfa-2a plus ribavirin.[Ref]

Common (1% to 10%): Impotence, chromaturia[Ref]


Uncommon (0.1% to 1%): Hepatic neoplasm
Frequency not reported: Malignant hepatic neoplasm


Rare (0.01% to 0.1%): Anaphylaxis
Frequency not reported: Anaphylactic shock

Anaphylactic shock has been reported during hepatitis B studies.


Rare (0.01% to 0.1%): Renal insufficiency


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Some side effects of peginterferon alfa-2a may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.