Pegasys (Peginterferon Alfa-2a) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

PEGASYS alone or in combination with COPEGUS causes a broad variety of serious adverse reactions (see BOX WARNING and WARNINGS). In all studies, one or more serious adverse reactions occurred in 10% of patients receiving PEGASYS alone or in combination with COPEGUS.

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 occurred at a frequency of <1%.

Nearly all patients in clinical trials experienced one or more adverse events. The most commonly reported adverse reactions were psychiatric reactions, including depression, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache, and rigors.

Overall 11% of patients receiving 48 weeks of therapy with PEGASYS either alone (7%) or in combination with COPEGUS (10%) discontinued therapy. The most common reasons for discontinuation of therapy were psychiatric, flu-like syndrome (eg, lethargy, fatigue, headache), dermatologic, and gastrointestinal disorders.

The most common reason for dose modification in patients receiving combination therapy was for laboratory abnormalities, neutropenia (20%) and thrombocytopenia (4%) for PEGASYS and anemia (22%) for COPEGUS.

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 12% in patients receiving 800 mg COPEGUS for 24 weeks.

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.

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.

The most common serious adverse event (3%) was bacterial infection (eg, 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 (eg, hyperthyroidism, hypothyroidism, sarcoidosis, systemic lupus erythematosus, rheumatoid arthritis), peripheral neuropathy, aplastic anemia, peptic ulcer, gastrointestinal bleeding, pancreatitis, colitis, corneal ulcer, pulmonary embolism, coma, myositis, and cerebral hemorrhage.

LABORATORY TEST VALUES

HEMOGLOBIN

The hemoglobin concentration decreased below 12 g/dL in 17% (median Hgb drop = 2.2 g/dL) of monotherapy and 52% (median Hgb drop = 3.7 g/dL) of combination therapy patients. Severe anemia (Hgb <10 g/dL) was encountered in 13% of patients receiving combination therapy and 2% of monotherapy recipients. Dose modification for anemia was required in 22% of ribavirin recipients treated for 48 weeks. Hemoglobin decreases in PEGASYS monotherapy were generally mild and did not require dose modification (see DOSAGE AND ADMINISTRATION: Dose Modifications).

NEUTROPHILS

Decreases in neutrophil count below normal were observed in 95% of patients treated with PEGASYS either alone or in combination with COPEGUS. Severe potentially life-threatening neutropenia (ANC <0.5 × 10⁹/L) occurred in approximately 5% of patients receiving PEGASYS either alone or in combination with COPEGUS. Seventeen percent of patients receiving PEGASYS monotherapy and 20% to 24% of patients receiving PEGASYS/COPEGUS combination therapy required modification of interferon dosage for neutropenia. Two percent of patients 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 (see DOSAGE AND ADMINISTRATION: Dose Modifications).

LYMPHOCYTES

Decreases in lymphocyte count are induced by interferon alpha therapy. Lymphopenia was observed during both monotherapy (86%) and combination therapy with PEGASYS and COPEGUS (94%). Severe lymphopenia (<0.5 × 10⁹/L) occurred in approximately 5% of monotherapy patients and 14% of combination PEGASYS and COPEGUS therapy recipients. Dose adjustments were not required by protocol. Median lymphocyte counts return to pre-treatment levels after 4 to 12 weeks of the cessation of therapy. The clinical significance of the lymphopenia is not known.

PLATELETS

Platelet counts decreased in 52% of patients treated with PEGASYS alone (median drop 45% from baseline), 33% of patients receiving combination with COPEGUS (median drop 30% from baseline). Median platelet counts return to pre-treatment levels 4 weeks after the cessation of therapy.

TRIGLYCERIDES

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 higher >/=400 mg/dL were observed in about 20% of patients.

ALT ELEVATIONS

Less than 1% of patients experienced marked elevations (5- to 10-fold above baseline) in ALT levels during treatment. 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 (see DOSAGE AND ADMINISTRATION: Dose Modifications).

THYROID FUNCTION

PEGASYS alone or in combination with COPEGUS was associated with the development of abnormalities in thyroid laboratory values, some with associated clinical manifestations. 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 (see PRECAUTIONS: Laboratory Tests).

IMMUNOGENICITY

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 of 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 these products may be misleading.

REPORTS OF SUSPECTED PEGASYS SIDE EFFECTS / ADVERSE REACTIONS

Possible Pegasys side effects / adverse reactions in 45 year old male

Reported by a pharmacist from United States on 2011-10-03

Patient: 45 year old male

Reactions: Psychotic Disorder, Diarrhoea, Rectal Haemorrhage

Adverse event resulted in: hospitalization

Suspect drug(s):
Pegasys

Other drugs received by patient: Ribasphere; Incivek

Possible Pegasys side effects / adverse reactions in 47 year old female

Reported by a physician from Cameroon on 2011-10-04

Patient: 47 year old female

Reactions: Death

Adverse event resulted in: death

Suspect drug(s):
Copegus
    Indication: Hepatitis C

Pegasys
    Indication: Hepatitis C

Possible Pegasys side effects / adverse reactions in 43 year old female

Reported by a individual with unspecified qualification from United States on 2011-10-05

Patient: 43 year old female

Reactions: Procedural Pain, Renal Disorder, Cardiac Murmur, Impaired Work Ability, Ascites, Haematuria Traumatic, Anxiety, Malaise, Mental Disorder, Depression, Thrombocytopenia, Chronic Hepatic Failure, Fluid Retention

Adverse event resulted in: hospitalization

Suspect drug(s):
Intron A
    Dosage: 10 mg;qw;
    Indication: Hepatitis C
    Start date: 2006-01-01
    End date: 2006-01-01

Pegasys
    Indication: Product Used FOR Unknown Indication

Other drugs received by patient: Ambien; Tylenol-500; Quinine; Spironolactone; Ursodiol; Fluoxetine; Ciprofloxacin