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Ribavirin (Ribavirin) - Side Effects and Adverse Reactions

 
 



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 1)

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 2

Lymphopenia 
Anemia 
Neutropenia 
Thrombocytopenia


14
11
27
5

12 
11

<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

1 Described as study 4 in the peginterferon alfa-2a package insert.
2 Severe hematologic abnormalities(lymphocyte <0.5 x 109/L; hemoglobin <10 g/dL; neutrophil <0.75 x 109/L; platelet <50 x 109/L).

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



See index of all Ribavirin side effect reports >>

Drug label data at the top of this Page last updated: 2010-07-29

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