The salient safety issue of ribavirin is hemolytic anemia occurring within the first weeks of therapy. The hemolytic anemia associated with ribavirin therapy may result in deterioration of cardiac function and/or worsening of pre-existing cardiac disease.
4). Use of Ribavirin in combination with direct antiviral agents (DAA) Based on the review of safety data derived from clinical studies in adults with DAA in combination with ribavirin, the most frequent adverse reactions identified as associated with ribavirin were anaemia, nausea, vomiting, asthenia, fatigue, insomnia, cough, dyspnoea, pruritus and rash.
Except anaemia, the majority of these adverse reactions were not serious and resolved without treatment discontinuation. Use of Ribavirin in combination with interferon alfa-2a or peginterferon alfa-2a The adverse events listed in this section are reported in clinical trials and/or as adverse drug reactions from spontaneous reports primarily when ribavirin was used in combination with interferon alfa-2a or peginterferon alfa-2a.
Adverse events reported in patients receiving ribavirin in combination with interferon alfa-2a are essentially the same as for those reported for ribavirin in combination with peginterferon alfa-2a. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Refer also to the SmPC of the medicinal products that are used in combination with ribavirin for additional undesirable effects reported with these products. Chronic Hepatitis C The most frequently reported adverse events with ribavirin in combination with peginterferon alfa-2a 180 μg were mostly mild to moderate in severity, Most of them were manageable without the need for discontinuation of therapy.
Chronic hepatitis C in prior non-responder patients Overall, the safety profile for ribavirin in combination with peginterferon alfa-2a in prior non-responder patients was similar to that in naive patients. In a clinical trial of non-responder patients to prior pegylated interferon alfa-2b/ribavirin, which exposed patients to either 48 or 72 weeks of treatment, the frequency of withdrawal for adverse events or laboratory abnormalities from peginterferon alfa-2a treatment and ribavirin treatment was 6% and 7%, respectively, in the 48 week arms and 12% and 13%, respectively, in the 72 week arms.
Similarly, for patients with cirrhosis or transition to cirrhosis, the frequencies of withdrawal from peginterferon alfa-2a treatment and ribavirin treatment were higher in the 72-week treatment arms (13% and 15%) than in the 48-week arms (6% and 6%).
Patients who withdrew from previous therapy with pegylated interferon alfa-2b/ribavirin because of haematological toxicity were excluded from enrolling in this trial. In another clinical trial, non-responder patients with advanced fibrosisis or cirrhosis (Ishak score of 3 to 6) and baseline platelet counts as low as 50,000/mm3 were treated for 48 weeks.
4). Chronic Hepatitis C and Human Immunodeficiency Virus Co-infection In HIV-HCV co-infected patients, the clinical adverse event profiles reported for peginterferon alfa-2a, alone or in combination with ribavirin, were similar to those observed in HCV mono-infected patients.
For HIV-HCV patients receiving Ribavirin and peginterferon alfa-2a combination therapy other undesirable effects have been reported in ≥1% to ≤2% of patients: hyperlactacidaemia/lactic acidosis, influenza, pneumonia, affect lability, apathy, pharyngolaryngeal pain, cheilitis, acquired lipodystrophy and chromaturia.
Peginterferon alfa-2a treatment was associated with decreases in absolute CD4+ cell counts within the first 4 weeks without a reduction in CD4+ cell percentage. The decrease in CD4+ cell counts was reversible upon dose reduction or cessation of therapy.
The use of peginterferon alfa-2a had no observable negative impact on the control of HIV viraemia during therapy or follow-up. Limited safety data are available in co-infected patients with CD4+ cell counts ≤ 200/μl. (see peginterferon alfa-2a SmPC).
Table 4 shows the undesirable effects reported in patients who have received ribavirin primarily in combination with peginterferon alfa-2a or interferon alfa-2a. Table 4 Undesirable Effects Reported with Ribavirin primarily in combination with Peginterferon alfa-2a for HCV Patients Body system Very Common ≥1 /10 Common ≥1 /100 to < 1 /10 Uncommo n ≥1 /1000 to < 1 /100 Rare ≥1 /10,000 to < 1 /1000 Very rare <1/10,000 Frequenc y not known* Infections and infestations Upper respiratory infection, bronchitis, oral candidiasis, herpes simplex Lower respiratory tract infection, pneumonia, urinary tract infection, skin infection Endocarditis , Otitis externa Blood and Anaemia, Thrombocyto Pancytopeni Aplastic Pure red lymphatic system disorders neutropenia penia, lymphadenop athy a anaemia cell aplasia Immune system disorders Sarcoidosis, thyroiditis Anaphylaxis , systemic lupus erythematos us, rheumatoid arthritis idiopathic or thromboti c thromboc ytopenic purpura Liver and renal graft rejection, Vogt- Koyanagi- Harada disease Endocrine disorders Hypothyroidi sm, hyperthyroidi sm Diabetes Metabolism and Nutrition Disorders Anorexia Dehydratio n Psychiatric disorders Depression , insomnia Mood alteration, emotional disorders, anxiety, aggression, nervousness, libido decreased Suicidal ideation, hallucinatio ns, anger Suicide, psychotic disorder Mania, bipolar disorders, homicidal ideation Nervous system disorders Headache, dizziness, concentrati on impaired Memory impairment, […]