Hepatitis C Virus: A Clear Role for Pharmacists

Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the United States (approximately 1.6% of Americans are infected¹), and its financial impact is vast.² This virus is insidious, starting as an easily overlooked asymptomatic infection, and three-fourths of patients fail to realize they are infected. Untreated, HCV progresses—over the course of 20 to 30 years in 75% to 85% of patients—to hepatocellular carcinoma, cirrhosis, and often, the need for liver transplantation.³ More than 15,000 people died of HCV infection in 2007.⁴ By 2035, HCV-related morbidity and mortality will increase, and experts expect 38,000 cases of end-stage liver disease (ESLD), 3200 cases requiring referral for liver transplantation, and 36,100 deaths.⁵

The Institute of Medicine has a message for the American public: health care providers and members of the general public need education about HCV infection. In addition, we need to increase HCV screening and treat HCV-infected individuals early and appropriately.⁶ Given HCV’s prevalence, pharmacists need to stay informed about HCV, its manifestations, and its treatments.

An Expensive Disease

In the United States, HCV-related care consumes $65 billion annually in direct and indirect costs, with medication, laboratory monitoring, and management of adverse effects (AEs) being most costly.³ Once ESLD develops and transplantation is needed, costs often exceed $100,000 annually.²

Usually treated with direct-acting antivirals (DAAs), HCV infection is now considered curable, but the treatment can be challenging. Pharmacists can help reduce costs by preemptively and continuously addressing AEs associated with HCV treatment. The agents traditionally used to treat HCV, peginterferon alfa and ribavirin, have many AEs. The current recommendation is to use or add DAAs, which can potentiate toxicities and create new toxicities.² Online Table 1^7-13 describes the agents currently approved for HCV and their considerations.

Table 1: Agents Used to Treat Hepatitis C Virus Infection

Agent

Considerations

Boceprevir^a

(Victrelis)

• Common side effects (>35%): fatigue, anemia, nausea, headache, shortness of breath, and taste disturbances
• To decrease side effects, reduce dose or add erythropoietin
• Potent CYP450-3A4 inhibitor
• Dosed every 7-9 hr; effective against genotype 1 only

Ledipasvir/sofosbuvir (Harvoni)

• Common AEs: fatigue and headache
• Do not administer with amiodarone or P-glycoprotein inducers

Ombitasvir/paritaprevir/ritonavir and dasabuvir (Viekira Pak) ^a

• Common AEs: fatigue, nausea, pruritus, other skin reactions (educate patients about Stevens-Johnson syndrome/toxic epidermal necrolysis), insomnia, and asthenia
• Monitor liver enzymes

Peginterferon alfa-2aa

• Common AEs: flu-like symptoms, nausea, diarrhea, dyspepsia, lack of appetite, skin irritation, alopecia, insomnia, headache, myalgia, arthralgia, dysgeusia, xerostomia, and injection site irritation
• Administer subcutaneously once weekly
• This product can cause intolerable serious AEs ; many patients refuse to continue treatment

Ribavirin

• Common AEs: anemia, sore throat, cough, shortness of breath, and rash
• Not as effective as monotherapy
• May worsen cardiac disease

Simeprevir

• Common AEs: dyspepsia, sun sensitivity, itching, and myalgia
• Effective against genotype 1 only
• Patients must report dyspnea, severe skin irritation, stomatitis, or eye irritation immediately

Sofosbuvir

• Common AEs: headache, dyspepsia, nausea, and insomnia
• Effective for any genotype; not effective as monotherapy
• Medical emergencies: depression, suicidal ideation, anxiety, emotional instability, illogical thinking, dyspnea, severe asthenia, and pallor

^{a = Require FDA-approved medication guides.AEs = adverse effects.Adapted from references 6-8, 11-13.}

The Pharmacist’s Role

High and frequent doses, cost concerns, toxic drug interactions, and AEs create the perfect breeding ground for patient nonadherence. These issues also create a clear role for pharmacists, although current HCV guidelines unfortunately do not recommend or require pharmacist involvement in the multidisciplinary team.² Online Table 2^2,3,14,15 describes key interventions for pharmacists.

Table 2: The Pharmacist’s Role in Treating Hepatitis C Virus Infection

Role

What the Pharmacist Can Do

Encourage preventive measures

â–º Help patients adhere to the Advisory Committee on Immunization Practices’ immunization schedule for adults because patients with chronic liver disease are at increased risk of contracting other viruses.

Monitor adverse effects and recommend alternative drug regimens if necessary

â–ºKnow each agent’s adverse effects and the best ways to deal with them.

â–ºDepression is a significant and threatening problem for patients infected with HCV.

Help prescribers and patients find appropriate and cost-effective therapies

â–º HCV-infected patients can incur, on average, $64,490 in disease-related, out-of-pocket costs over a lifetime, and often more.³

â–ºTreatment costs are serious concerns for most patients and insurers; look for patient assistance programs.

Manage drug toxicity

â–ºWith treatment discontinuation rates as high as 14% (especially with peginterferon alfa and ribavirin), and new agents available, selecting nontoxic therapy is easier now.

Promote adherence

â–ºAdding first-generation direct-acting antivirals can reduce pill burden, duration of treatment, and adverse effects, but increase the likelihood of drug interaction.

â–ºPill boxes, alarms, and pocket cards are almost necessities for complex regimens. (Pocket cards are small cards that list drugs, doses, and times. View a sample template at uchc.edu/patients/health_information/medicard/pdfs/medicard.pdf).

Refer patients to providers who provide comprehensive health care

â–ºRates of HCV testing and diagnosis are poor, and many patients receive inadequate care following diagnosis.

â–ºLink HCV-infected patients to providers who deliver comprehensive HCV care.

^{Adapted from references 2, 3, 14, and 15.HCV = hepatitis C virus.}

End Note

Clearly, HCV infection burdens patients’ health and wallets, as well as the national economy. It is time to emphasize counseling for patients infected with HCV and ensure every patient speaks with a pharmacist about treatment. Pharmacists can use tracking aids (Online Figure) to ensure they cover all important issues.

Figure: Counseling Patients Infected with Hepatitis C Virus

^{HCV = hepatitis C virus.}

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.

References

• Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144(10):705-714.
• Mohammed RA, Bulloch MN, Chan J, et al. Provision of clinical pharmacist services for individuals with chronic hepatitis C viral infection. Pharmacotherapy. 2014;34(12):1341-1354.
• Razavi H, Elkhoury AC, Elbasha E, et al. Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013;57(6):2164-2170.
• Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156:271-278.
• Rein DB, Wittenborn JS, Weinbaum CM, Sabin M, Smith BD, Lesesne SB. Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States. Dig Liver Dis. 2011;43:66-72.
• Institute of Medicine. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Washington, DC: National Academies Press; 2010.
• Victrelis (boceprevir) [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc; August 2015. merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf. Accessed October 10, 2015.
• Incivek (telaprevir) [prescribing information]. Cambridge, MA: Vertex; May 2011. accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf. Accessed October 10, 2015.
• Infectious Diseases Society of America (IDSA) and American Association for the Study of Liver Diseases (AASLD), in collaboration with the International Antiviral Society—USA. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org/full-report-view. Accessed October 10, 2015.
• Harvoni (ledipasvir and sofosbuvir) tablets [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc; March 2015.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf. Accessed October 10, 2015.
• Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) [prescribing information]. North Chicago, IL: AbbVie Inc; July 2015. rxabbvie.com/pdf/viekirapak_pi.pdf. Accessed October 10, 2015.
• Pegasys (peginterferon-2α) [prescribing information]. South San Francisco, CA: Genentech USA, Inc; March 2015. gene.com/download/pdf/pegasys_prescribing.pdf. Accessed October 10, 2015.
• Copegus (ribavirin) [prescribing information]. South San Francisco, CA: Genentech USA, Inc; February 2013. gene.com/download/pdf/copegus_prescribing.pdf. Accessed October 10, 2015.
• Schafer J. Provision of clinical pharmacist services for individuals with chronic hepatitis: an alternative viewpoint. Pharmacotherapy. 2015;35:e37-e38.
• Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:1433-1444.