Patient Education and Treatment Strategies Implemented at a Pharmacist-Managed Hepatitis C Virus Clinic

Bonnie Kolor, Pharm.D.


Pharmacotherapy. 2005;25(9):1230-1241. 

In This Article

Management of Adverse Events

All patients treated with combination therapy experience treatment-related adverse events, and in some cases these can be considerable. Frequencies of the more commonly encountered adverse events experienced by patients undergoing treatment with combination therapy involving peginterferon alfa-2a and alfa-2b are presented in Table 2 .[54,55,56]

Patients must be educated about the adverse events associated with combination therapy, and they must be empowered to participate directly in the management of these events before therapy is begun. Management of adverse events associated with combination therapy can involve alterations in lifestyle as well as pharmacologic interventions. Interferon-based therapies are often associated with flu-like symptoms, especially in the days immediately after drug administration and in the first few weeks after the start of treatment.

Lifestyle interventions that may lessen the effects of therapy on the patient's ability to work include administration of weekly injections of peginterferon alfa at particular times during the day and at the beginning of a weekend.[66] In addition, patients should be counseled to undertake light-to-moderate exercise if possible, get enough rest, eat small meals 5-6 times during the day, and drink fluids frequently.[65,66]

Adverse events such as headache, myalgia, and fever can often be treated with acetaminophen or nonsteroidal antiinflammatory drugs taken 0.5-1 hour before injection of peginterferon alfa.[66] Other useful pharmacologic interventions are antihistamines and steroidal creams for patients experiencing pruritus, selective serotonin reuptake inhibitors for treatment of depression, and possibly epoetin alfa for treatment-induced anemia.[66,67,68]

Some patients, such as those who develop marked anemia or neutropenia, may require a temporary reduction in dosage of either peginterferon alfa or ribavirin, or lower dosages for the remainder of the recommended treatment course. In clinical trials, such reductions have been necessary for a considerable number of patients receiving combination therapy for HCV infection.[54,55,56,69] Table 3 and Table 4 provide recommended dosage reductions for peginterferon alfa-2a, peginterferon alfa-2b, and ribavirin associated with specific adverse events manifested as abnormalities in certain blood test results.[15,16,64]

Several clinical trials have addressed the effects of dosage reduction of either component of peginterferon alfa-ribavirin therapy on the efficacy of treatment.[19,56,70,71,72] The study results support the importance of adherence to the recommended therapeutic regimens, particularly for patients infected with HCV genotype 1, and especially during the earlier phases of treatment. For example, in patients infected with HCV genotype 1, adherence to 80% or more of the recommended doses of both peginterferon alfa-2b and ribavirin for more than 80% of the recommended treatment period was correlated with attainment of a sustained viral response.[19]

Results from another clinical study indicated that dosage reductions to less than 80% of the recommended regimen did not appear to affect the likelihood of achieving a sustained viral response in patients who had achieved an early virologic response.[56] Results of a study involving patients with HCV infection and cirrhosis showed that rates for both early virologic response and sustained viral response were more sensitive to early dosage reductions of ribavirin than of peginterferon alfa during the first 20 weeks of therapy. Later dosage reductions of either drug did not appear to influence sustained viral response rates in these patients who had achieved an early virologic response.

Of interest is a recent report of a clinical study involving patients with HCV infection treated with peginterferon alfa-2a monotherapy.[70] Results showed that sustained viral response rates were the same whether patients received the standard dosage of peginterferon alfa-2a 180 µg/week or 75% of the standard dosage. However, patients receiving the standard dosage were more likely to show improvement in liver histology.

Other studies have also demonstrated support for a possible antifibrotic role for peginterferon alfa or combination therapy.[71,72] The reported results support the overall benefit for patients with HCV infection receiving the full treatment regimen. Nevertheless, patients need to understand that specific types of dosage reductions—especially those of short duration or those given later in the treatment course—are not likely to dramatically affect the probability of achieving a sustained viral response. However, combination therapy should be discontinued completely in certain patients, such as those who develop severe depression or suicidal ideation.[16,56]


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