Pegasys Side Effects

Generic Name: peginterferon alfa-2a

Please note - some side effects for Pegasys may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Pegasys - for the Consumer

Pegasys

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Pegasys:

Diarrhea; dizziness; drowsiness; dry mouth; dry or irritated skin; hair thinning; headache; loss of appetite; mild flu-like symptoms (fever, chills, muscle aches, or joint pain); nausea; pain, redness, itching, or swelling at the injection site; taste changes; temporary hair loss; tiredness; trouble sleeping; vomiting; weakness.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); back pain; blisters or sores in the eyes, nose, or mouth; bloody or black, tarry stools; burning, numbness, or tingling in the arms, hands, legs, or feet; chest pain; confusion; dark urine, change in the amount of urine produced, or painful urination; difficulty hearing or hearing loss; eye pain or redness; fast, slow, or irregular heartbeat; one-sided weakness; pale stools; persistent or severe diarrhea, nausea, stomach pain, or vomiting; persistent or severe fever, chills, or sore throat; red, swollen, blistered, or peeling skin; severe or unusual tiredness or weakness; slurred speech; stomach bloating; sudden leg pain; sudden severe dizziness, fainting, headache, or vomiting; sudden shortness of breath; unusual bruising or bleeding; unusual mental or mood changes (eg, anxiety, aggressive or unusual behavior, depression, hallucinations, irritability, suicidal thoughts or behavior); unusually increased thirst; vision loss or other vision changes; weight loss; worsening psoriasis; yellowing of the eyes or skin.

Pegasys Side Effects - for the Professional

Pegasys

Pegasys alone or in combination with COPEGUS causes a broad variety of serious adverse reactions. The most common life-threatening or fatal events induced or aggravated by Pegasys and COPEGUS were depression, suicide, relapse of drug abuse/overdose, and bacterial infections, each occurring at a frequency of <1%. Hepatic decompensation occurred in 2% (10/574) of CHC/HIV patients.

In all hepatitis C studies, one or more serious adverse reactions occurred in 10% of CHC monoinfected patients and in 19% of CHC/HIV patients receiving Pegasys alone or in combination with COPEGUS. The most common serious adverse event (3% in CHC and 5% in CHC/HIV) was bacterial infection (e.g., sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia). Other SAEs occurred at a frequency of <1% and included: 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.

Nearly all patients in clinical trials experienced one or more adverse events. For hepatitis C patients, the most commonly reported adverse reactions were psychiatric reactions, including depression, insomnia, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache, and rigors. Other common reactions were anorexia, nausea and vomiting, diarrhea, arthralgias, injection site reactions, alopecia, and pruritus.

Overall 11% of CHC monoinfected patients receiving 48 weeks of therapy with Pegasys either alone or in combination with COPEGUS discontinued therapy; 16% of CHC/HIV coinfected patients discontinued therapy. The most common reasons for discontinuation of therapy were psychiatric, flu-like syndrome (e.g., lethargy, fatigue, headache), dermatologic, and gastrointestinal disorders and laboratory abnormalities (thrombocytopenia, neutropenia, and anemia).

Overall 39% of patients with CHC or CHC/HIV required modification of Pegasys and/or COPEGUS therapy. The most common reason for dose modification of Pegasys in CHC and CHC/HIV patients was for laboratory abnormalities, neutropenia (20% and 27%, respectively) and thrombocytopenia (4% and 6%, respectively). The most common reason for dose modification of COPEGUS in CHC and CHC/HIV patients was anemia (22% and 16%, respectively).

Pegasys dose was reduced in 12% of patients receiving 1000 mg to 1200 mg COPEGUS for 48 weeks and in 7% of patients receiving 800 mg COPEGUS for 24 weeks. COPEGUS dose was reduced in 21% of patients receiving 1000 mg to 1200 mg COPEGUS for 48 weeks and in 12% of patients receiving 800 mg COPEGUS for 24 weeks.

Chronic hepatitis C monoinfected patients treated for 24 weeks with Pegasys and 800 mg COPEGUS were observed to have lower incidence of serious adverse events (3% vs. 10%), Hgb <10 g/dL (3% vs. 15%), dose modification of Pegasys (30% vs. 36%) and COPEGUS (19% vs. 38%) and of withdrawal from treatment (5% vs. 15%) compared to patients treated for 48 weeks with Pegasys and 1000 mg or 1200 mg COPEGUS. On the other hand the overall incidence of adverse events appeared to be similar in the two treatment groups.

Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug. Also, the adverse event rates listed here may not predict the rates observed in a broader patient population in clinical practice.

CHC With HIV Coinfection

The adverse event profile of coinfected patients treated with Pegasys and COPEGUS in Study 6 was generally similar to that shown for monoinfected patients in Study 4 (Table 6). Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%), and mood alteration (9%).

Chronic Hepatitis B

In clinical trials of 48 week treatment duration, the adverse event profile of Pegasys in chronic hepatitis B was similar to that seen in chronic hepatitis C Pegasys monotherapy use, except for exacerbations of hepatitis. Six percent of Pegasys treated patients in the hepatitis B studies experienced one or more serious adverse events.

The most common or important serious adverse events in the hepatitis B studies were infections (sepsis, appendicitis, tuberculosis, influenza), hepatitis B flares, anaphylactic shock, thrombotic thrombocytopenic purpura.

The most commonly observed adverse reactions were pyrexia (54% vs. 4%), headache (27% vs. 9%), fatigue (24% vs. 10%), myalgia (26% vs. 4%), alopecia (18% vs. 2%), and anorexia (16% vs. 3%) in the Pegasys and lamivudine groups respectively.

Overall 5% of hepatitis B patients discontinued Pegasys therapy and 40% of patients required modification of Pegasys dose. The most common reason for dose modification in patients receiving Pegasys therapy was for laboratory abnormalities including neutropenia (20%), thrombocytopenia (13%), and ALT disorders (11%).

Laboratory Test Values

The laboratory test values observed in the hepatitis B trials (except where noted below) were similar to those seen in the Pegasys monotherapy hepatitis C trials.

In the hepatitis C studies, decreases in neutrophil count below normal were observed in 95% of all patients treated with Pegasys either alone or in combination with COPEGUS. Severe potentially life-threatening neutropenia (ANC <0.5 × 109/L) occurred in 5% of CHC patients and 12% of CHC/HIV patients receiving Pegasys either alone or in combination with COPEGUS. Modification of Pegasys dose for neutropenia occurred in 17% of patients receiving Pegasys monotherapy and 22% of patients receiving Pegasys/COPEGUS combination therapy. In the CHC/HIV patients 27% required modification of interferon dosage for neutropenia. Two percent of patients with CHC and 10% of patients with CHC/HIV required permanent reductions of Pegasys dosage and <1% required permanent discontinuation. Median neutrophil counts return to pre-treatment levels 4 weeks after cessation of therapy.

Decreases in lymphocyte count are induced by interferon alpha therapy. Pegasys plus COPEGUS combination therapy induced decreases in median total lymphocyte counts (56% in CHC and 40% in CHC/HIV, with median decrease of 1170 cells/mm3 in CHC and 800 cells/mm3 in CHC/HIV). In the hepatitis C studies, lymphopenia was observed during both monotherapy (81%) and combination therapy with Pegasys and COPEGUS (91%). Severe lymphopenia (<0.5 × 109/L) occurred in approximately 5% of all monotherapy patients and 14% of all combination Pegasys and COPEGUS therapy recipients. Dose adjustments were not required by protocol. The clinical significance of the lymphopenia is not known.

In CHC with HIV coinfection, CD4 counts decreased by 29% from baseline (median decrease of 137 cells/mm3) and CD8 counts decreased by 44% from baseline (median decrease of 389 cells/mm3) in the Pegasys plus COPEGUS combination therapy arm. Median lymphocyte CD4 and CD8 counts return to pre-treatment levels after 4 to 12 weeks of the cessation of therapy. CD4% did not decrease during treatment.

In the hepatitis C studies, platelet counts decreased in 52% of CHC patients and 51% of CHC/HIV patients treated with Pegasys alone (respectively median decrease of 41% and 35% from baseline), and in 33% of CHC patients and 47% of CHC/HIV patients receiving combination therapy with COPEGUS (median decrease of 30% from baseline). Moderate to severe thrombocytopenia (<50,000/mm3) was observed in 4% of CHC and 8% of CHC/HIV patients. Median platelet counts return to pre-treatment levels 4 weeks after the cessation of therapy.

In the hepatitis C studies, the hemoglobin concentration decreased below 12 g/dL in 17% (median Hgb reduction of 2.2 g/dL) of monotherapy and 52% (median Hgb reduction of 3.7 g/dL) of combination therapy patients. Severe anemia (Hgb <10 g/dL) was encountered in 13% of all patients receiving combination therapy and in 2% of CHC patients and 8% of CHC/HIV patients receiving Pegasys monotherapy. Dose modification for anemia in COPEGUS recipients treated for 48 weeks occurred in 22% of CHC patients and 16% of CHC/HIV patients.

Triglyceride levels are elevated in patients receiving alfa interferon therapy and were elevated in the majority of patients participating in clinical studies receiving either Pegasys alone or in combination with COPEGUS. Random levels ≥400 mg/dL were observed in about 20% of CHC patients. Severe elevations of triglycerides (>1000 mg/dL) occurred in 2% of CHC monoinfected patients.

In HCV/HIV coinfected patients, fasting levels ≥400 mg/dL were observed in up to 36% of patients receiving either Pegasys alone or in combination with COPEGUS. Severe elevations of triglycerides (>1000 mg/dL) occurred in 7% of coinfected patients.

Chronic Hepatitis C

One percent of patients in the hepatitis C trials experienced marked elevations (5- to 10-fold above the upper limit of normal) in ALT levels during treatment and follow-up. These transaminase elevations were on occasion associated with hyperbilirubinemia and were managed by dose reduction or discontinuation of study treatment. Liver function test abnormalities were generally transient. One case was attributed to autoimmune hepatitis, which persisted beyond study medication discontinuation.

Chronic Hepatitis B

Transient ALT elevations are common during hepatitis B therapy with Pegasys. Twenty-five percent and 27% of patients experienced elevations of 5 to 10 × ULN and 12% and 18% had elevations of >10 × ULN during treatment of HBeAg negative and HBeAg positive disease, respectively. Flares have been accompanied by elevations of total bilirubin and alkaline phosphatase and less commonly with prolongation of PT and reduced albumin levels. Eleven percent of patients had dose modifications due to ALT flares and <1% of patients were withdrawn from treatment.

ALT flares of 5 to 10 × ULN occurred in 13% and 16% of patients, while ALT flares of >10 × ULN occurred in 7% and 12% of patients in HBeAg negative and HBeAg positive disease, respectively, after discontinuation of Pegasys therapy.

Pegasys alone or in combination with COPEGUS was associated with the development of abnormalities in thyroid laboratory values, some with associated clinical manifestations. In the hepatitis C studies, hypothyroidism or hyperthyroidism requiring treatment, dose modification or discontinuation occurred in 4% and 1% of Pegasys treated patients and 4% and 2% of Pegasys and COPEGUS treated patients, respectively. Approximately half of the patients, who developed thyroid abnormalities during Pegasys treatment, still had abnormalities during the follow-up period.

Chronic Hepatitis C

Nine percent (71/834) of patients treated with Pegasys with or without COPEGUS developed binding antibodies to interferon alfa-2a, as assessed by an ELISA assay. Three percent of patients (25/835) receiving Pegasys with or without COPEGUS, developed low-titer neutralizing antibodies (using an assay with a sensitivity of 100 INU/mL).

Chronic Hepatitis B

Twenty-nine percent (42/143) of hepatitis B patients treated with Pegasys for 24 weeks developed binding antibodies to interferon alfa-2a, as assessed by an ELISA assay. Thirteen percent of patients (19/143) receiving Pegasys developed low-titer neutralizing antibodies (using an assay with a sensitivity of 100 INU/mL).

The clinical and pathological significance of the appearance of serum neutralizing antibodies is unknown. No apparent correlation of antibody development to clinical response or adverse events was observed. The percentage of patients whose test results were considered positive for antibodies is highly dependent on the sensitivity and specificity of the assays.

Additionally, the observed incidence of antibody positivity in these assays may be influenced by several factors including sample timing and handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Pegasys with the incidence of antibodies to other products may be misleading.

The following adverse reactions have been identified and reported during post-approval use of Pegasys therapy: dehydration, hearing impairment, hearing loss, and serious skin reactions. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting or (3) strength of causal connection to Pegasys.

Side Effects by Body System

General

During hepatitis C studies, one or more serious side effects were 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, and pneumonia (3% CHC, 5% CHC/HIV). Other serious side effects have included 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 in less than 1% of patients.

The most common side effects have included psychiatric reactions, (including depression, insomnia, irritability, and anxiety), flu-like symptoms (such as fatigue, pyrexia, myalgia, headache, rigors), anorexia, nausea and vomiting, diarrhea, arthralgias, injection site reactions, alopecia, and pruritus. Psychiatric, flu-like syndrome, dermatologic, and gastrointestinal disorders and laboratory abnormalities (thrombocytopenia, neutropenia, and anemia) were the most common reasons for discontinuation of therapy.

Immunologic

Immunologic side effects have included bacterial infections (e.g., sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia), autoimmune phenomena (e.g., hyperthyroidism, hypothyroidism, sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis), and the development of binding antibodies to peginterferon alfa-2a. Alpha interferons have been associated with the development or exacerbation of autoimmune disorders, including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus. The most common or important serious side effects reported during hepatitis B studies have included infections (sepsis, appendicitis, tuberculosis, influenza).

Psychiatric

Psychiatric side effects have included irritability/anxiety/nervousness (19% monotherapy, 33% combination therapy), depression (18% monotherapy, 20% combination therapy), concentration impairment (8% monotherapy, 10% combination therapy), and mood alteration (3% monotherapy, 5% combination therapy). Suicidal ideation, suicide, psychosis, aggression, psychotic disorder, and relapse of drug abuse and drug overdose have been reported.

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

Hematologic

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

Hematologic side effects have included neutropenia (21% monotherapy, 27% combination therapy), thrombocytopenia (5% monotherapy, 5% combination therapy), lymphopenia (3% monotherapy, 14% combination therapy), anemia (2% monotherapy, 11% combination therapy), aplastic anemia, thrombotic thrombocytopenic purpura, and cerebral hemorrhage. Neutropenia (40%), anemia (14%), and thrombocytopenia (8%) have been reported during treatment with peginterferon alfa-2a plus ribavirin in CHC patients coinfected with HIV. The most common or important serious side effects reported during hepatitis B studies have included thrombotic thrombocytopenic purpura.

Other

Other side effects commonly reported have included fever and chills. Flu-like signs and symptoms have been reported and have included fatigue/asthenia (56% monotherapy, 65% combination therapy), pyrexia (37% to 54% monotherapy, 41% combination therapy), rigors (35% monotherapy, 25% combination therapy), and pain (11% monotherapy, 10% combination therapy). Anorexia (16% to 17% monotherapy, 24% combination therapy) and overall resistance mechanism disorders (10% monotherapy, 12% combination therapy) have been reported. Fatigue has been reported in 24% of patients during hepatitis B studies. Sarcoidosis has been reported in a 65-year-old man at the seventh month of therapy. Most of the symptoms improved over the next three months following discontinuation of therapy.

Gastrointestinal

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

Gastrointestinal side effects have included nausea and vomiting (24% monotherapy, 25% combination therapy), diarrhea (16% monotherapy, 11% combination therapy), abdominal pain (15% monotherapy, 8% combination therapy), dry mouth (6% monotherapy, 4% combination therapy), dyspepsia (less than 1% monotherapy, 6% combination therapy), peptic ulcer, gastrointestinal bleeding, pancreatitis, and colitis.

Nervous system

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.

Nervous system side effects have included headache (27% to 54% monotherapy, 43% combination therapy), insomnia (19% monotherapy, 30% combination therapy), dizziness (excluding vertigo; 16% monotherapy, 14% combination therapy), concentration impairment (8%), memory impairment (5% monotherapy, 5% combination therapy), peripheral neuropathy, hallucination, and coma. At least one case of chorea and akathisia has been reported. Hearing impairment and hearing loss have been reported during postmarketing experience, although a direct causal relationship has not been established.

Dermatologic

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

Dermatologic side effects have included alopecia (18% to 23% monotherapy, 28% combination therapy), pruritus (12% monotherapy, 19% combination therapy), dermatitis (8% monotherapy, 16% combination therapy), increased sweating (6% monotherapy, 6% combination therapy), rash (5% monotherapy, 8% combination therapy), dry skin (4% monotherapy, 10% combination therapy), and eczema (1% monotherapy, 5% combination therapy). Skin disorders associated with combination therapy have included lichenoid eruptions and maculopapular rashes. At least one case of drug-induced Sweet's syndrome has been reported.

Hepatic

Hepatic side effects have included elevated ALT (occasionally associated with hyperbilirubinemia), hepatic dysfunction, fatty liver, cholangitis, and exacerbations of hepatitis. 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.

Cardiovascular

Cardiovascular side effects have included angina, arrhythmia, and endocarditis.

Metabolic

Elevated triglyceride levels have been reported in patients receiving alfa interferons, including peginterferon alfa-2a.

Metabolic side effects have included weight decrease (4% monotherapy, 10% combination therapy), elevated triglycerides, and diabetes mellitus. Dehydration has been reported during postmarketing experience.

Ocular

Ocular side effects have included blurred vision (4% monotherapy, 5% combination therapy) and corneal ulcers. Serious retinal detachment has been reported during postmarketing experience.

Respiratory

Respiratory side effects have included dyspnea (4% monotherapy, 13% combination therapy), cough (4% monotherapy, 10% combination therapy), and exertional dyspnea (less than 1% monotherapy, 4% combination therapy). Pneumonia, interstitial pneumonitis, and pulmonary embolism have been reported.

Musculoskeletal

Musculoskeletal side effects have included myalgia (26% to 37% monotherapy, 40% combination therapy), arthralgia (28% monotherapy, 22% combination therapy), back pain (9% monotherapy, 5% combination therapy), and myositis.

Local

Local side effects have included injection site reactions (22% monotherapy, 23% combination therapy). Skin disorders associated with combination therapy have included cutaneous necrosis at peginterferon alfa-2a injection sites. Hyperpigmentation around/over the injection sites has been reported.

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