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Ribavirin (Ribavirin) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The primary toxicity of ribavirin is hemolytic anemia. Reductions in hemoglobin levels occurred within the first 1 to 2 weeks of oral therapy. (See WARNINGS). Cardiac and pulmonary events associated with anemia occurred in approximately 10% of patients (See WARNINGS).

Ribavirin/INTRON A Combination Therapy

In clinical trials, 19% and 6% of previously untreated and relapse patients, respectively, discontinued therapy due to adverse events in the combination arms compared to 13% and 3% in the interferon arms. Selected treatment-emergent adverse events that occurred in the US studies with ≥5% incidence are provided in TABLE 4 by treatment group. In general, the selected treatment-emergent adverse events were reported with lower incidence in the international studies as compared to the US studies with the exception of asthenia, influenza-like symptoms, nervousness, and pruritus.


TABLE 4. Selected Treatment-Emergent Adverse Events: Previously Untreated and Relapse Adult Patients
Percentage of Patients
US Previously Untreated Study US Relapse Study
24 weeks of treatment 48 weeks of treatment 24 weeks of treatment

Patients Reporting

Adverse Events 1

INTRON A

plus

Ribavirin

(N=228)

INTRON A

plus

Placebo

(N=231)

INTRON A

plus

Ribavirin

(N=228)

INTRON A

plus

Placebo

(N=225)

INTRON A

plus

Ribavirin

(N=77)

INTRON A

plus

Placebo

(N=76)

Application Site Disorders
Injection site inflammation13101214 6 8
Injection site reaction 7 9 8 9 5 3

Body as a Whole

General Disorders

Headache636366676668
Fatigue686270726053
Rigors403242394337
Fever373541403236
Influenza-like symptoms141818201313
Asthenia 9 4 9 910 4
Chest pain 5 4 9 8 6 7

Central & Peripheral

Nervous System Disorders

Dizziness171523192621
Gastrointestinal System Disorders
Nausea383546334733
Anorexia271625192114
Dyspepsia14 616 916 9
Vomiting1110 91312 8

1 Patients reporting one or more adverse events. A patient may have reported more than one adverse event within a body system/organ class category.


TABLE 4. Selected Treatment-Emergent Adverse Events: Previously Untreated and Relapse Adult Patients (continued)
Percentage of Patients
US Previously Untreated Study US Relapse Study
24 weeks of treatment 48 weeks of treatment 24 weeks of treatment

Patients Reporting

Adverse Events 1

INTRON A

plus

Ribavirin

(N=228)

INTRON A

plus

Placebo

(N=231)

INTRON A

plus

Ribavirin

(N=228)

INTRON A

plus

Placebo

(N=225)

INTRON A

plus

Ribavirin

(N=77)

INTRON A

plus

Placebo

(N=76)

Musculoskeletal System Disorders
Myalgia615764636158
Arthralgia302733362929
Musculoskeletal pain202628322228
Psychiatric Disorders
Insomnia392739302625
Irritability231932272520
Depression322536372314
Emotional lability 7 611 812 8
Concentration impaired111414141012
Nervousness 4 2 4 4 5 4
Respiratory System Disorders
Dyspnea19 918101712
Sinusitis 9 7101412 7
Skin and Appendages Disorders
Alopecia282732282726
Rash20 928 821 5
Pruritus21 919 813 4
Special Senses, Other Disorders
Taste perversion 7 4 8 4 6 5
1 Patients reporting one or more adverse events. A patient may have reported more than one adverse event within a body system/organ class category.


In addition, the following spontaneous adverse events have been reported during the marketing surveillance of ribavirin/INTRON A therapy: hearing disorder and vertigo.

Laboratory Values

Ribavirin/INTRON A Combination Therapy

Changes in selected hematologic values (hemoglobin, white blood cells, neutrophils, and platelets)during therapy are described below. (See TABLE 5).

Hemoglobin

Hemoglobin decreases among patients receiving ribavirin therapy began at Week 1, with stabilization by Week 4. In previously untreated patients treated for 48 weeks, the mean maximum decrease from baseline was 3.1 g/dL in the US study and 2.9 g/dL in the International study. In relapse patients, the mean maximum decrease from baseline was 2.8 g/dL in the US study and 2.6 g/dL in the international study. Hemoglobin values returned to pretreatment levels within 4 to 8 weeks of cessation of therapy in most patients.

Bilirubin and Uric Acid

Increases in both bilirubin and uric acid, associated with hemolysis, were noted in clinical trials. Most were moderate biochemical changes and were reversed within 4 weeks after treatment discontinuation. This observation occurs most frequently in patients with a previous diagnosis of Gilbert’s syndrome. This has not been associated with hepatic dysfunction or clinical morbidity.


TABLE 5. Selected Hematologic Values During Treatment with Ribavirin Capsules plus INTRON A: Previously Untreated and Relapse Adult Patients
Percentage of Patients
US Previously Untreated Study US Relapse Study
24 weeks of treatment 48 weeks of treatment 24 weeks of treatment

INTRON A

plus Ribavirin (N=228)

INTRON A

plus Placebo (N=231)

INTRON A

plus Ribavirin (N=228)

INTRON A

plus Placebo (N=225)

INTRON A

plus Ribavirin (N=77)

INTRON A

plus Placebo (N=76)

Hemoglobin (g/dL)
9.5-10.9 24 1 32 121 3
8.0-9.4 5 0 4 0 4 0
6.5-7.9 0 0 00.4 0 0
<6.5 0 0 0 0 0 0
Leukocytes (x109/L)
2.0-2.9 40 20 38 234526
1.5-1.9 4 1 9 2 5 3
1.0-1.40.9 0 2 0 0 0
<1.0 0 0 0 0 0 0
Neutrophils (x109/L)
1.0-1.49 30 32 31 444234
0.75-0.99 14 15 14 111618
0.5-0.74 9 9 14 7 8 4
<0.5 11 8 11 5 5 8
Platelets (x109/L)
70-99 9 11 11 14 612
50-69 2 3 2 3 0 5
30-49 00.4 00.4 0 0
<300.9 0 10.9 0 0
Total Bilirubin (mg/dL)
1.5-3.0 27 13 32 1321 7
3.1-6.00.90.4 2 0 3 0
6.1-12.0 0 00.4 0 0 0
>12.0 0 0 0 0 0 0

Postmarketing Experiences

The following adverse reactions have been identified during the post approval use of ribavirin capsules in combination with INTRON A: hearing disorder, vertigo, aplastic anemia and pure red cell aplasia. 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.

ADVERSE REACTIONS

The safety of combination ribavirin capsules/INTRON A therapy was evaluated in controlled trials of 1010 HCV-infected adults who were previously untreated with interferon therapy and were subsequently treated for 24 or 48 weeks with combination ribavirin capsules/INTRON A therapy and in 173 HCV-infected patients who had relapsed after interferon therapy and were subsequently treated for 24 weeks with combination ribavirin capsules/INTRON A therapy. (See Description of Clinical Studies.) Overall, 19% and 6% of previously untreated and relapse patients, respectively, discontinued therapy due to adverse events in the combination arms compared to 13% and 3% in the interferon arms.

The primary toxicity of ribavirin is hemolytic anemia. Reductions in hemoglobin levels occurred within the first 1 to 2 weeks of therapy (see WARNINGS). Cardiac and pulmonary events associated with anemia occurred in approximately 10% of patients treated with ribavirin capsules/INTRON A therapy. (See WARNINGS.)

The most common psychiatric events occurring in US studies of previously untreated and relapse patients treated with ribavirin capsules/INTRON A therapy, respectively, were insomnia (39%, 26%), depression (34%, 23%), and irritability (27%, 25%). Suicidal behavior (ideation, attempts, and suicides) occurred in 1% of patients. (See WARNINGS.) In addition, the following spontaneous adverse events have been reported during the marketing surveillance of ribavirin capsules/INTRON A therapy: hearing disorder and vertigo. Very rarely, combination ribavirin capsules/INTRON A therapy may be associated with aplastic anemia.

Selected treatment-emergent adverse events that occurred in the US studies with ≥5% incidence are provided in TABLE 4 by treatment group. In general, the selected treatment-emergent adverse events reported with lower incidence in the international studies as compared to the US studies with the exception of asthenia, influenza-like symptoms, nervousness, and pruritus.


TABLE 4. Selected Treatment-Emergent Adverse Events: Previously Untreated and Relapse Patients
Percentage of Patients
US Previously Untreated Study US Relapse Study
24 weeks of treatment 48 weeks of treatment 24 weeks of treatment

Patients Reporting

Adverse Events 1

INTRON A

plus

Ribavirin

capsules

(N=228)

INTRON A

plus

Placebo

(N=231)

INTRON A

plus

Ribavirin

capsules

(N=228)

INTRON A

plus

Placebo

(N=225)

INTRON A

plus

Ribavirin

capsules

(N=77)

INTRON A

plus

Placebo

(N=76)

Application Site Disorders
Injection site inflammation13101214 6 8
Injection site reaction 7 9 8 9 5 3

Body as a Whole –

General Disorders

Headache636366676668
Fatigue686270726053
Rigors403242394337
Fever373541403236
Influenza-like symptoms141818201313
Asthenia 9 4 9 910 4
Chest pain 5 4 9 8 6 7

Central & Peripheral

Nervous System Disorders

Dizziness171523192621
Gastrointestinal System Disorders
Nausea383546334733
Anorexia271625192114
Dyspepsia14 616 916 9
Vomiting1110 91312 8

1 Patients reporting one or more adverse events. A patient may have reported more than one adverse event within a body system/organ class category.


TABLE 4. Selected Treatment-Emergent Adverse Events: Previously Untreated and Relapse Patients (continued)
Percentage of Patients
US Previously Untreated Study US Relapse Study
24 weeks of treatment 48 weeks of treatment 24 weeks of treatment

Patients Reporting

Adverse Events 1

INTRON A

plus

Ribavirin

capsules

(N=228)

INTRON A

plus

Placebo

(N=231)

INTRON A

plus

Ribavirin

capsules

(N=228)

INTRON A

plus

Placebo

(N=225)

INTRON A

plus

Ribavirin

capsules

(N=77)

INTRON A

plus

Placebo

(N=76)

Musculoskeletal System Disorders
Myalgia615764636158
Arthralgia302733362929
Musculoskeletal pain202628322228
Psychiatric Disorders
Insomnia392739302625
Irritability231932272520
Depression322536372314
Emotional lability 7 611 812 8
Concentration impaired111414141012
Nervousness 4 2 4 4 5 4
Respiratory System Disorders
Dyspnea19 918101712
Sinusitis 9 7101412 7
Skin and Appendages Disorders
Alopecia282732282726
Rash20 928 821 5
Pruritus21 919 813 4
Special Senses, Other Disorders
Taste perversion 7 4 8 4 6 5
1 Patients reporting one or more adverse events. A patient may have reported more than one adverse event within a body system/organ class category.


Laboratory Values

Changes in selected hematologic values (hemoglobin, white blood cells, neutrophils, and platelets) during combination ribavirin capsules/INTRON A treatment are described below (see TABLE 5).

Hemoglobin

Hemoglobin decreases among patients on combination therapy began at Week 1, with stabilization by Week 4. In previously untreated patients treated for 48 weeks the mean maximum decrease from baseline was 3.1 g/dL in the US study and 2.9 g/dL in the International study. In relapse patients the mean maximum decrease from baseline was 2.8 g/dL in the US study and 2.6 g/dL in the International study. Hemoglobin values returned to pretreatment levels within 4 to 8 weeks of cessation of therapy in most patients.

Neutrophils

There were decreases in neutrophil counts in both the combination ribavirin capsules/INTRON A and INTRON A plus placebo dose groups. In previously untreated patients treated for 48 weeks the mean maximum decrease in neutrophil count in the US study was 1.3x 109/L and in the International study was 1.5 x 109/L. In relapse patients the mean maximum decrease in neutrophil count in the US study was 1.3 x 109/L and in the International study was 1.6 x 109/L. Neutrophil counts returned to pretreatment levels within 4 weeks of cessation of therapy in most patients.

Platelets

In both previously untreated and relapse patients mean platelet counts generally remained in the normal range in all treatment groups, however, mean platelet counts were 10% to 15% lower in the INTRON A plus placebo group than the ribavirin capsules/INTRON A group. Mean platelet counts returned to baseline levels within 4 weeks after treatment discontinuation.

Thyroid Function

Of patients who entered the previously untreated (24 and 48 week treatment) and relapse (24 week treatment) studies without thyroid abnormalities, approximately 3% to 6% and 1% to 2%, respectively, developed thyroid abnormalities requiring clinical intervention.

Bilirubin and Uric Acid

Increases in both bilirubin and uric acid, associated with hemolysis, were noted in clinical trials. Most were moderate biochemical changes and were reversed within 4 weeks after treatment discontinuation. This observation occurs most frequently in patients with a previous diagnosis of Gilbert’s syndrome. This has not been associated with hepatic dysfunction or clinical morbidity.


TABLE 5. Selected Hematologic Values During Treatment with Ribavirin Capsules plus INTRON A: Previously Untreated and Relapse Patients
Percentage of Patients
US Previously Untreated Study US Relapse Study
24 weeks of treatment 48 weeks of treatment 24 weeks of treatment

INTRON A

plus Ribavirin (N=228)

INTRON A

plus Placebo (N=231)

INTRON A

plus Ribavirin (N=228)

INTRON A

plus Placebo (N=225)

INTRON A

plus Ribavirin (N=77)

INTRON A

plus Placebo (N=76)

Hemoglobin (g/dL)
9.5-10.9 24 1 32 121 3
8.0-9.4 5 0 4 0 4 0
6.5-7.9 0 0 00.4 0 0
<6.5 0 0 0 0 0 0
Leukocytes (x109/L)
2.0-2.9 40 20 38 234526
1.5-1.9 4 1 9 2 5 3
1.0-1.40.9 0 2 0 0 0
<1.0 0 0 0 0 0 0
Neutrophils (x109/L)
1.0-1.49 30 32 31 444234
0.75-0.99 14 15 14 111618
0.5-0.74 9 9 14 7 8 4
<0.5 11 8 11 5 5 8
Platelets (x109/L)
70-99 9 11 11 14 612
50-69 2 3 2 3 0 5
30-49 00.4 00.4 0 0
<300.9 0 10.9 0 0
Total Bilirubin (mg/dL)
1.5-3.0 27 13 32 1321 7
3.1-6.00.90.4 2 0 3 0
6.1-12.0 0 00.4 0 0 0
>12.0 0 0 0 0 0 0



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: 2008-01-17

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