ADVERSE REACTIONS
PEGASYS in combination with COPEGUS causes a broad variety of serious adverse reactions (see BOXED WARNING and WARNINGS).
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 (see WARNINGS: Hepatic Failure).
In all 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. 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.
Ten percent of CHC monoinfected patients receiving 48 weeks of therapy with PEGASYS 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%), hemoglobin <10g/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.
Table 4 Adverse Reactions Occurringin ≥5% of Patients in Chronic Hepatitis C Clinical Trials (Study NV15801 ) | CHC Combination Therapy Study NV15801 |
|---|
| Body System | PEGASYS 180 µg +
1000 mg or 1200 mg
COPEGUS
48 week | Intron A +
1000 mg or 1200 mg
REBETOL®
48 week |
|---|
| N=451 | N=443 |
|---|
| % | % |
|---|
| Application Site Disorders | | |
| Injection site reaction | 23 | 16 |
| Endocrine Disorders | | |
| Hypothyroidism | 4 | 5 |
| Flu-like Symptoms and Signs | | |
| Fatigue/Asthenia | 65 | 68 |
| Pyrexia | 41 | 55 |
| Rigors | 25 | 37 |
| Pain | 10 | 9 |
| Gastrointestinal | | |
| Nausea/Vomiting | 25 | 29 |
| Diarrhea | 11 | 10 |
| Abdominal pain | 8 | 9 |
| Dry mouth | 4 | 7 |
| Dyspepsia | 6 | 5 |
| Hematologic
| | |
| Lymphopenia | 14 | 12 |
| Anemia | 11 | 11 |
| Neutropenia | 27 | 8 |
| Thrombocytopenia | 5 | <1 |
| Metabolic and Nutritional | | |
| Anorexia | 24 | 26 |
| Weight decrease | 10 | 10 |
| Musculoskeletal, Connective Tissue and Bone | | |
| Myalgia | 40 | 49 |
| Arthralgia | 22 | 23 |
| Back pain | 5 | 5 |
| Neurological | | |
| Headache | 43 | 49 |
| Dizziness (excluding vertigo) | 14 | 14 |
| Memory impairment | 6 | 5 |
| Psychiatric | | |
| Irritability/Anxiety/Nervousness | 33 | 38 |
| Insomnia | 30 | 37 |
| Depression | 20 | 28 |
| Concentration impairment | 10 | 13 |
| Mood alteration | 5 | 6 |
| Resistance Mechanism Disorders | | |
| Overall | 12 | 10 |
| Respiratory, Thoracic and Mediastinal | | |
| Dyspnea | 13 | 14 |
| Cough | 10 | 7 |
| Dyspnea exertional | 4 | 7 |
| Skin and Subcutaneous Tissue | | |
| Alopecia | 28 | 33 |
| Pruritus | 19 | 18 |
| Dermatitis | 16 | 13 |
| Dry skin | 10 | 13 |
| Rash | 8 | 5 |
| Sweating increased | 6 | 5 |
| Eczema | 5 | 4 |
| Visual Disorders | | |
| Vision blurred | 5 | 2 |
Common Adverse Reactions in CHC With HIV Coinfection
The adverse event profile of coinfected patients treated with PEGASYS and COPEGUS in Study NR15961 was generally similar to that shown for monoinfected patients in Study NV15801 ( Table 4). Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%), and mood alteration (9%).
Laboratory Test Values
Anemia due to hemolysis is the most significant toxicity of ribavirin therapy. Anemia (hemoglobin <10 g/dL) was observed in 13% of all COPEGUS and PEGASYS combination-treated patients in clinical trials. The maximum drop in hemoglobin occurred during the first 8 weeks of initiation of ribavirin therapy (see DOSAGE AND ADMINISTRATION: Dose Modifications).
Postmarketing Experience
The following adverse reactions have been identified and reported during post-approval use of PEGASYS therapy: dehydration, hearing impairment, hearing loss, serious skin reactions (see WARNINGS: Hypersensitivity), and serous retinal detachment.
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REPORTS OF SUSPECTED COPEGUS SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Copegus. The information is not vetted and should not be considered as verified clinical evidence.
Possible Copegus 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):
Pegasys
Indication: Hepatitis C
Copegus
Indication: Hepatitis C
Possible Copegus side effects / adverse reactions in 44 year old male
Reported by a physician from Germany on 2011-10-05
Patient: 44 year old male weighing 84.0 kg (184.8 pounds)
Reactions: Haemorrhoids, Anal Haemorrhage
Adverse event resulted in: hospitalization
Suspect drug(s):
Victrelis
Dosage: 2400 mg, qd
Indication: Hepatitis C
Start date: 2011-08-25
Pegasys
Dosage: 180 mcg, qw
Indication: Hepatitis C
Start date: 2011-07-28
Copegus
Dosage: 1200 mg, qd
Indication: Hepatitis C
Start date: 2011-07-28
Possible Copegus side effects / adverse reactions in 42 year old male
Reported by a physician from France on 2011-10-07
Patient: 42 year old male
Reactions: Deafness
Adverse event resulted in: disablity
Suspect drug(s):
Pegasys
Indication: Product Used FOR Unknown Indication
Copegus
Administration route: Oral
Indication: Product Used FOR Unknown Indication
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