ADVERSE REACTIONS
Peginterferon alfa-2a in combination with ribavirin tablets 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 peginterferon alfa-2a and ribavirin tablets were depression, suicide, relapse of drug abuse/overdose, and bacterial infections, each occurred 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 receiving peginterferon alfa-2a alone or in combination with ribavirin tablets. 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 peginterferon alfa-2a in combination with ribavirin tablets 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 peginterferon alfa-2a and/or ribavirin tablets therapy. The most common reason for dose modification of peginterferon alfa-2a 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 ribavirin tablets in CHC and CHC/HIV patients was anemia (22% and 16%, respectively).
Peginterferon alfa-2a dose was reduced in 12% of patients receiving 1000 mg to 1200 mg ribavirin tablets for 48 weeks and in 7% of patients receiving 800 mg ribavirin tablets for 24 weeks. Ribavirin tablet dose was reduced in 21% of patients receiving 1000 mg to 1200 mg ribavirin tablets for 48 weeks and in 12% of patients receiving 800 mg ribavirin tablets for 24 weeks.
Chronic hepatitis C monoinfected patients treated for 24 weeks with peginterferon alfa-2a and 800 mg ribavirin tablets were observed to have lower incidence of serious adverse events (3% vs. 10%), hemoglobin <10 g/dL (3% vs. 15%), dose modification of peginterferon alfa-2a (30% vs. 36%) and ribavirin tablets (19% vs. 38%), and of withdrawal from treatment (5% vs. 15%) compared to patients treated for 48 weeks with peginterferon alfa-2a and 1000 mg or 1200 mg ribavirin tablets. 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 Occurring in ≥5% of Patients in Chronic Hepatitis C Clinical Trials (Study NV15801 )
Body System
|
CHC Combination Therapy Study NV15801
|
|
Peginterferon alfa-2a 180 mcg + 1000 mg or 1200 mg Ribavirin Tablets 48 week
|
Interferon alfa-2b + 1000 mg or 1200 mg Ribavirin Capsules 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 Pyrexia Rigors Pain |
65 41 25 10 |
68 55 37 9 |
Gastrointestinal
Nausea/vomiting Diarrhea Abdominal pain Dry mouth Dyspepsia |
25 11 8 4 6 |
29 10 9 7 5 |
Hematologic
Lymphopenia Anemia Neutropenia Thrombocytopenia |
14 11 27 5 |
12 11 8 <1 |
Metabolic and Nutritional
Anorexia Weight decrease |
24 10 |
26 10 |
Musculoskeletal, Connective Tissue and Bone
Myalgia Arthralgia Back pain |
40 22 5 |
49 23 5 |
Neurological
Headache Dizziness (excluding vertigo) Memory impairment |
43 14 6 |
49 14 5 |
Psychiatric
Irritability/Anxiety/Nervousness Insomnia Depression Concentration impairment Mood alteration |
33 30 20 10 5 |
38 37 28 13 6 |
Resistance Mechanism Disorders
Overall |
12 |
10 |
Respiratory, Thoracic and Mediastinal
Dyspnea Cough Dyspnea exertional |
13 10 4 |
14 7 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 peginterferon alfa-2a and ribavirin tablets 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 ribavirin tablets and peginterferon alfa-2a 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 reactions have been identified and reported during post-approval use of peginterferon alfa-2a following adverse therapy: dehydration, hearing impairment, hearing loss, and serious skin reactions (see WARNINGS: Hypersensitivity).
|
REPORTS OF SUSPECTED RIBAVIRIN SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Ribavirin. The information is not vetted and should not be considered as verified clinical evidence.
Possible Ribavirin side effects / adverse reactions in 56 year old male
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-04
Patient: 56 year old male weighing 88.0 kg (193.6 pounds)
Reactions: Drug Interaction, DRY Skin, Sinus Bradycardia, Cardiac Disorder, Long QT Syndrome, Palpitations, International Normalised Ratio Decreased, Chest Pain, Hypertension, Skin Warm, Oxygen Saturation Decreased, Influenza Like Illness
Adverse event resulted in: hospitalization
Suspect drug(s):
PEG-Intron
Dosage: 150 mg;qw
Indication: Product Used FOR Unknown Indication
Start date: 2011-08-10
Amitriptyline HCL
Indication: Product Used FOR Unknown Indication
End date: 2011-08-10
Ribavirin
Dosage: 600 mg;bid;po
Administration route: Oral
Indication: Product Used FOR Unknown Indication
Start date: 2011-08-09
PEG-Intron
Indication: Product Used FOR Unknown Indication
Start date: 2011-08-09
End date: 2011-08-09
Trazodone Hydrochloride
Indication: Product Used FOR Unknown Indication
End date: 2011-08-10
Other drugs received by patient: Colace; Metoprolol Tartrate; Lovenox; Oxycontin; Nexium
Possible Ribavirin side effects / adverse reactions in 65 year old male
Reported by a physician from Japan on 2011-10-04
Patient: 65 year old male
Reactions: Glomerulonephritis Membranous, Ascites
Adverse event resulted in: hospitalization
Suspect drug(s):
Ribavirin
Dosage: po
Administration route: Oral
Indication: Hepatitis C
Start date: 2009-03-01
End date: 2010-07-01
PEG-Intron
Dosage: sc
Indication: Hepatitis C
Start date: 2009-03-01
End date: 2010-07-01
Possible Ribavirin side effects / adverse reactions in 65 year old female
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-04
Patient: 65 year old female
Reactions: Weight Decreased, White Blood Cell Count Decreased, Dyspnoea, Fatigue, Cystitis, Fall
Adverse event resulted in: hospitalization
Suspect drug(s):
Ribavirin
Indication: Hepatitis C
Start date: 2011-08-01
PEG-Intron
Indication: Hepatitis C
Start date: 2011-08-01
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