Moderiba

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 4/5/2022
Moderiba Side Effects Center

What Is Moderiba?

Moderiba (ribavirin) is a nucleoside analogue indicated for the treatment of chronic hepatitis C (CHC) virus infection in combination with peginterferon alfa-2a in patients 5 years of age and older with compensated liver disease not previously treated with interferon alpha, and in adult CHC patients coinfected with HIV.

What Are Side Effects of Moderiba?

Common side effects of Moderiba include:

Dosage for Moderiba

The dose of Moderiba to treat CHC with HIV coinfection is 800 mg by mouth daily for a total of 48 weeks, regardless of genotype.

What Drugs, Substances, or Supplements Interact with Moderiba?

Moderiba may interact with nucleoside reverse transcriptase inhibitors and azathioprine. Tell your doctor all medications and supplements you use.

Moderiba During Pregnancy or Breastfeeding

Moderiba is not recommended for use during pregnancy; it may harm a fetus or cause fetal death. Moderiba therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Patients are instructed to use at least two forms of contraception during treatment and for 6 months after treatment has been stopped. Pregnancy testing should occur monthly during Moderiba therapy and for 6 months after therapy has stopped. It is unknown if Moderiba passes into breast milk. Because of the potential for adverse reactions in nursing infants, breastfeeding while using Moderiba is not recommended.

Additional Information

Our Moderiba (ribavirin) Tablets for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Hepatitis: How Do You Get Hepatitis A, B, and C? See Slideshow
Moderiba Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Ribavirin can cause anemia. In rare cases, this can lead to fatal heart problems. Get emergency medical attention if you have chest pain.

Call your doctor at once if you have:

  • problems with your vision;
  • severe pain in your upper stomach spreading to your back, nausea, vomiting, diarrhea;
  • new or worsening cough, fever, stabbing chest pain, wheezing, feeling short of breath;
  • severe depression, thoughts about suicide, or thoughts about hurting someone else;
  • signs of serious anemia--pale or yellowed skin, dark colored urine, confusion or weakness; or
  • other signs of low blood cell counts--fever, chills, flu-like symptoms, swollen gums, mouth sores, skin sores, easy bruising, unusual bleeding, feeling light-headed.

Ribavirin can affect growth in children. Tell your doctor if your child is not growing at a normal rate while using this medicine.

Common side effects may include:

  • nausea, vomiting, loss of appetite;
  • fever, chills or shaking;
  • low blood cell counts, anemia;
  • feeling weak or tired;
  • headache, muscle pain; or
  • mood changes, feeling anxious or irritable.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Moderiba (Ribavirin Tablets)

QUESTION

Hepatitis C virus causes an infection of the ______________. See Answer
Moderiba Professional Information

SIDE EFFECTS

Peginterferon alfa-2a in combination with ribavirin causes a broad variety of serious adverse reactions [see BOXED WARNING and WARNINGS AND PRECAUTIONS]. The most common serious or life-threatening adverse reactions induced or aggravated by ribavirin/peginterferon alfa-2a include depression, suicide, relapse of drug abuse/overdose, and bacterial infections each occurring at a frequency of less than 1%. Hepatic decompensation occurred in 2% (10/574) CHC/HIV patients [see WARNINGS AND PRECAUTIONS].

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adult Patients

In the pivotal registration trials NV15801 and NV15942, 886 patients received ribavirin for 48 weeks at doses of 1000/1200 mg based on body weight. In these trials, one or more serious adverse reactions occurred in 10% of CHC monoinfected subjects and in 19% of CHC/HIV subjects receiving peginterferon alfa-2a alone or in combination with ribavirin. 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 serious adverse reactions occurred at a frequency of less than 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.

The percentage of patients in clinical trials who experienced one or more adverse events was 98%. 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. Table 5 shows rates of adverse events occurring in greater than or equal to 5% of subjects receiving pegylated interferon and ribavirin combination therapy in the CHC Clinical Trial, NV15801.

Ten percent of CHC monoinfected patients receiving 48 weeks of therapy with peginterferon alfa-2a in combination with ribavirin 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 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 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 for 48 weeks and in 7% of patients receiving 800 mg ribavirin for 24 weeks. Ribavirin dose was reduced in 21% of patients receiving 1000 mg to 1200 mg ribavirin for 48 weeks and in 12% of patients receiving 800 mg ribavirin for 24 weeks.

Chronic hepatitis C monoinfected patients treated for 24 weeks with peginterferon alfa-2a and 800 mg ribavirin were observed to have lower incidence of serious adverse events (3% vs. 10%), hemoglobin less than 10 g/dL (3% vs. 15%), dose modification of peginterferon alfa-2a (30% vs. 36%) and ribavirin (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. On the other hand, the overall incidence of adverse events appeared to be similar in the two treatment groups.

Table 5 : Adverse Reactions Occurring in greater than or equal to 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 weeks
N=451%
interferon alfa-2b + 1000 mg or 1200 mg ribavirin capsules 48 weeks
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
*Severe hematologic abnormalities (lymphocyte less than 500 cells/mm³; hemoglobin less than 10 g/dL; neutrophil less than 750 cells/mm³; platelet less than 50,000 cells/mm³).

Pediatric Patients

In a clinical trial with 114 pediatric subjects (5 to 17 years of age) treated with peginterferon alfa-2a alone or in combination with ribavirin, dose modifications were required in approximately one-third of subjects, most commonly for neutropenia and anemia. In general, the safety profile observed in pediatric subjects was similar to that seen in adults. In the pediatric study, the most common adverse events in subjects treated with combination therapy peginterferon alfa-2a and ribavirin for up to 48 weeks were influenza-like illness (91%), upper respiratory tract infection (60%), headache (64%), gastrointestinal disorder (56%), skin disorder (47%), and injection-site reaction (45%). Seven subjects receiving combination peginterferon alfa-2a and ribavirin treatment for 48 weeks discontinued therapy for safety reasons (depression, psychiatric evaluation abnormal, transient blindness, retinal exudates, hyperglycemia, type 1 diabetes mellitus, and anemia). Severe adverse events were reported in 2 subjects in the peginterferon alfa-2a plus ribavirin combination therapy group (hyperglycemia and cholecystectomy).

Table 6 : Percentage of Pediatric Subjects with Adverse Reactions* During First 24 Weeks of Treatment by Treatment Group and for 24 Weeks Post-treatment (in at Least 10% of Subjects )

System Organ Class Study NV17424
peginterferon alfa-2a 180 mcg/1.73 m² x BSA + ribavirin tablets 15 mg/kg
(N=55)%
peginterferon alfa-2a 180 mcg/1.73 m² x BSA + Placebo**
(N=59)%
General disorders and administration site conditions
Influenza like illness 91 81
Injection site reaction 44 42
Fatigue 25 20
Irritability 24 14
Gastrointestinal disorders
Gastrointestinal disorder 49 44
Nervous system disorders
Headache 51 39
Skin and subcutaneous tissue disorders
Rash 15 10
Pruritus 11 12
Musculoskeletal, connective tissue and bone disorders
Musculoskeletal pain 35 29
Psychiatric disorders
Insomnia 9 12
Metabolism and nutrition disorders
Decreased appetite 11 14
*Displayed adverse drug reactions include all grades of reported adverse clinical events considered possibly, probably, or definitely related to study drug.
**Subjects in the peginterferon alfa-2a plus placebo arm who did not achieve undetectable viral load at week 24 switched to combination treatment thereafter. Therefore, only the first 24 weeks are presented for the comparison of combination therapy with monotherapy.

In pediatric subjects randomized to combination therapy, the incidence of most adverse reactions was similar for the entire treatment period (up to 48 weeks plus 24 weeks follow-up) in comparison to the first 24 weeks, and increased only slightly for headache, gastrointestinal disorder, irritability and rash. The majority of adverse reactions occurred in the first 24 weeks of treatment.

Growth Inhibition in Pediatric Subjects [see WARNINGS AND PRECAUTIONS].

Pediatric subjects treated with peginterferon alfa-2a plus ribavirin combination therapy showed a delay in weight and height increases with up to 48 weeks of therapy compared with baseline. Both weight for age and height for age z-scores as well as the percentiles of the normative population for subject weight and height decreased during treatment. At the end of 2 years follow-up after treatment, most subjects had returned to baseline normative curve percentiles for weight (64th mean percentile at baseline, 60th mean percentile at 2 years post-treatment) and height (54th mean percentile at baseline, 56th mean percentile at 2 years post-treatment). At the end of treatment, 43% (23 of 53) of subjects experienced a weight percentile decrease of more than 15 percentiles, and 25% (13 of 53) experienced a height percentile decrease of more than 15 percentiles on the normative growth curves. At 2 years post-treatment, 16% (6 of 38) of subjects were more than 15 percentiles below their baseline weight curve and 11% (4 of 38) were more than 15 percentiles below their baseline height curve.

Thirty-eight of the 114 subjects enrolled in the long-term follow-up study, extending up to 6 years posttreatment. For most subjects, post-treatment recovery in growth at 2 years post-treatment was maintained to 6 years post-treatment.

Common Adverse Reactions In CHC With HIV Coinfection (Adults)

The adverse event profile of coinfected patients treated with peginterferon alfa-2a/ribavirin in Study NR15961 was generally similar to that shown for monoinfected patients in Study NV15801 (Table 5). Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%), and mood alteration (9%).

Laboratory Test Abnormalities

Adult Patients

Anemia due to hemolysis is the most significant toxicity of ribavirin therapy. Anemia (hemoglobin less than 10 g/dL) was observed in 13% of all ribavirin 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].

Table 7 : Selected Laboratory Abnormalities During Treatment with Ribavirin in Combination with Either Peginterferon alfa-2a or Interferon alfa-2b

Laboratory Parameter Peginterferon alfa-2a + Ribavirin 1000/1200 mg 48 wks
(N=887)
Interferon alfa-2b + Ribavirin 1000/1200 mg 48 wks
(N=443)
Neutrophils (cells/mm³)
1,000 <1,500 34% 38%
500 <1,000 49% 21%
<500 5% 1%
Platelets (cells/mm³)
50,000 - <75,000 11% 4%
20,000 - <50,000 5% <1%
<20,000 0 0
Hemoglobin (g/dL)
.9 9. - .5 8. 11% 11%
<8.5 2% <1%

Pediatric Patients

Decreases in hemoglobin, neutrophils and platelets may require dose reduction or permanent discontinuation from treatment [see DOSAGE AND ADMINISTRATION]. Most laboratory abnormalities noted during the clinical trial returned to baseline levels shortly after discontinuation of treatment.

Table 8 : Selected Hematologic Abnormalities During First 24 Weeks of Treatment by Treatment Group in Previously Untreated Pediatric Subjects

Laboratory Parameter Peginterferon alfa-2a 180 mcg/1.73 m² x BSA + Ribavirin tablets 15 mg/kg
(N=55)
Peginterferon alfa-2a 180 mcg/1.73 m² x BSA + Placebo*
(N=59)
Neutrophils (cells/mm³)
1,000 - <1,500 31% 39%
750 - <1,000 27% 17%
500 - <750 25% 15%
<500 7% 5%
Platelets (cells/mm³)
75,000 - <100,000 4% 2%
50,000 - <75,000 0% 2%
<50,000 0% 0%
Hemoglobin (g/dL)
8.5 - <10 7% 3%
<8.5 0% 0%
*Subjects in the peginterferon alfa-2a plus placebo arm who did not achieve undetectable viral load at week 24 switched to combination treatment thereafter. Therefore, only the first 24 weeks are presented for the comparison of combination therapy with monotherapy.

In patients randomized to combination therapy, the incidence of abnormalities during the entire treatment phase (up to 48 weeks plus 24 weeks follow-up) in comparison to the first 24 weeks increased slightly for neutrophils between 500 and 1,000 cells/mm and hemoglobin values between 8.5 and 10 g/dL. The majority of hematologic abnormalities occurred in the first 24 weeks of treatment.

Postmarketing Experience

The following adverse reactions have been identified and reported during post-approval use of peginterferon alfa-2a/ribavirin combination therapy. 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.

Blood And Lymphatic System disorders

Pure red cell aplasia

Ear And Labyrinth Disorders

Hearing impairment, hearing loss

Eye Disorders

Serous retinal detachment

Immune Disorders

Liver and renal graft rejection

Metabolism And Nutrition Disorders

Dehydration

Skin And Subcutaneous Tissue Disorders

Stevens-Johnson Syndrome (SJS)

Toxic epidermal necrolysis (TEN)

Read the entire FDA prescribing information for Moderiba (Ribavirin Tablets)

© Moderiba Patient Information is supplied by Cerner Multum, Inc. and Moderiba Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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