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OVERVIEW OF HEPATITIS B AND C MANAGEMENT
toxicities, which may emerge on therapy while maintaining
efficacy.
Both pegIFN products approved for use in the U.S.,
pegINF alpha-2b and pegINF alpha-2a, have demonstrated
superior efficacy to standard interferon plus
ribavirin. 13 These products are similar in that both
drugs have added various polyethylene glycol side
chains to the parent molecule to increase the duration
of pharmacologic activity. It is important to note that
there are differences with respect to dosing, frequency,
and how each product is combined with ribavirin.
PegINF alpha-2b is given, in combination with ribavirin,
as a weight-based dose of 1.5 mcg/kg, while a
fixed dose of 180 mcg is used with pegINF alpha-2a.
Both are given as weekly subcutaneous injections.
Standard INF alphacon-1 is also approved for treatment
in HCV in a fixed dosage given subcutaneously
three times weekly alone or in combination with
ribavirin. Adverse reactions to INF products are common
and may lead to patient intolerance as well as
reduced efficacy due to the need for dose reductions.
Commonly experienced side effects attributable to
INF include flulike symptoms, myelosuppression
(anemia, neutropenia, and/or thrombocytopenia),
psychiatric adverse effects, injection-site reactions,
alopecia, anorexia, and sleep abnormalities. 14 Toxicities
generally associated with ribavirin include hemolytic
anemia, fatigue, dermatologic reactions, and precipitation
of gout. Ribavirin is also an abortifacient and
is carcinogenic and teratogenic. As a result, adequate
contraception must be present with female patients as
well as female partners of male patients who are of
childbearing age and should be continued for 6 months
following treatment cessation. 15
Monitoring and Follow-up: Duration of therapy
and disease monitoring are dependent on HCV
genotype, with genotype 1 generally requiring a
longer course of therapy. In genotype 1–infected
patients started on pegIFN/ribavirin, quantitative
HCV-RNA is measured at baseline and at 12 weeks
after treatment (see FIGURE 1). Patients with an EVR
should continue treatment for a total of 48 weeks
and then be assessed for an ETR. HCV-RNA testing
is repeated 24 weeks following treatment cessation
to determine presence of an SVR. If partial EVR is
attained at Week 12 (HCV-RNA reduction of ≥2
log), treatment should be continued for an additional
12 weeks. A negative HCV-RNA test at 24 weeks
means treatment should be continued for a total of
48 weeks. If no response is seen after 12 or 24 weeks,
then treatment should be discontinued as the benefit
is unlikely. In genotype 2 or 3 patients, HCV-
RNA is not assessed until 24 weeks of therapy are
complete. 13 If HCV-RNA is not detected, then assessment
for SVR is performed at 48 weeks. If HCV is
still detectable, treatment failure has occurred. Efficacy
defined by attainment of SVR is roughly 75%
for genotypes 2 and 3 and 50% for genotype 1. 13
Ongoing monitoring for both INF and ribavirin
toxicity is indicated during treatment. Baseline CBC,
serum creatinine, transaminases, thryoid-stimulating
hormone (TSH), and pregnancy testing should be assessed
at baseline. TSH should be monitored every 12 weeks
on therapy, while other chemistries may be assessed
monthly for the first 12 weeks, then every 2 months
until the end of treatment unless specific toxicity issues
warrant more frequent visits. Specific dosage reductions
or treatment cessation for ribavirin is necessary with the
development of anemia and or severe renal failure. 15
Dosage reductions of pegIFN may also be necessary
with elevated liver enzymes or renal insufficiency.
Patient Counseling
Pharmacists play an important role in the care of patients
infected with viral hepatitis. The pharmacist may provide
medication counseling and follow-up to ensure
adherence or identify problems (e.g., drug toxicities)
that emerge during therapy. All patients should be
counseled to abstain from alcohol and avoid OTC drugs
or supplements that may be hepatotoxic (e.g., high
doses of acetaminophen). Counseling should include
strategies to minimize disease prevention, such as use
of barrier contraceptive methods or avoidance of highrisk
behaviors. Immunization against HBV also plays
a key role in primary prevention of HBV infection, and
hepatitis B vaccination may be provided directly by
pharmacists in many states.
REFERENCES
1. Centers for Disease Control and Prevention. Hepatitis B: FAQs for health professionals.
www.cdc.gov/hepatitis/HBV/HBVfaq.htm#overview. Accessed October
2, 2009.
2. Marcellin P. Hepatitis B and hepatitis C in 2009. Liver Int. 2009;29(supp1):1-8.
3. Liaw YF. Natural history of chronic hepatitis B virus infection and long-term
outcome under treatment. Liver Int. 2009;29(supp1):100-107.
4. Corey RL. Update on pharmacotherapy of chronic Hepatitis B and C. In:
Richardson M, Chant C, Cheng JW, et al, eds. Pharmacotherapy Self-Assessment
Program. 6th ed. Gastroenterology and Nutrition. Lenexa, KS: American College
of Clinical Pharmacy; 2009:1-20.
5. Intron A [package insert]. Kenilworth, NJ: Schering-Plough; 2008.
6. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology.
2009;50(3):661-662.
7. Jenh AM, Thio CL, Pham PA. Tenofovir for the treatment of hepatitis B virus.
Pharmacother. 2009;29(10):1212-1227.
8. Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008;359:1486-1500.
9. Liaw YF, Leung N, Kao JH, et al. Asian-Pacific consensus statement on the management
of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2(3):263-283.
10. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C
virus infection in the United States, 1999 through 2002. Ann Intern Med.
2006;144:705-714.
11. Centers for Disease Control and Prevention. Hepatitis C: FAQs for health
professionals. www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section1. Accessed September
7, 2009.
12. Kowdley KV. Hepatitis C. In: Floch MH, Floch NR, Kowdley KV, et al, eds.
Netter’s Gastroenterology. Carlstadt, NJ: Icon Learning Systems; 2005.
13. Ghany MG, Strader DB, Thomas D, et al. AASLD practice guideline: diagnosis,
management, and treatment of hepatitis C: an update. Hepatology.
2009;49:1335-1373.
14. Peg-intron [package insert]. Kenilworth, NJ: Schering-Plough; 2009.
15. Copegus [package insert]. Nutley, NJ: Roche Laboratories; 2009.
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U.S. Pharmacist • December 2009 • www.uspharmacist.com