Prabhdeep Sidhu
Candidate PharmD 2015
Western University of Health Sciences
Mar 28, 2014
Objectives
 Discuss epidemiology of Hepatitis C
 Explain testing and diagnosis
 Describe current treatments
 Explain new medication Sovaldi
 Identify place in treatment
 Compare Sovaldi with other treatment plans
Patient Case
 AJ is 45 year old male African American patient who
got diagnosed with Hepatitis C genotype 2. AJ has a
past medical history of DM and is taking metformin
and glipizide. Pt also has a history of IVDU and
stopped using drugs 5 years ago. Pt is experiencing
fatigue and low in energy from past few months.
Resident physician wants to start AJ on Sovaldi and
asking for pharmacist’s receommendation.
Hepatitis C
 Symptoms
 Acute

Mostly asymptomatic
 Chronic
 Persistent fatigue
 Nausea
 Poor appetite
 Transmission
 Caused by infection with Hepatitis C virus
 Spread through exposure to infected blood
 Sharing needles to inject drugs
 Blood transfusions (before 1992)
Hepatitis C
 Approximately 3.2 million people infected with HCV
 Risk groups
 Injection drug users
 Recipient of blood products prior to 1992
 Chronic haemodialysis patients
 Persons with HIV infection
 Children born to HCV infected mothers
Testing Recommendations
 Persons born from 1945 through 1965
 Persons injecting illegal drugs
 Recipients of blood transfusions prior to 1992
 Long term haemodialysis patients
 Persons with HIV infection
Diagnosis
 Screening tests for antibody to HCV
 RNA polymerase chain reaction
 Quantitative test to detect amount of virus
Current Treatments
 For genotype 1 (duration varies on treatment response)
 Peg interferon and Ribavirin
 Plus Boceprevir or Telaprevir
 For genotype 2 or 3 ( 24 weeks)
 Peg interferon Plus Ribavirin
Sovaldi (Sofosbuvir)
 Nucleotide analogue inhibitor of hepatitis C virus
NS5B polymerase enzyme
 400 mg tablet
 Once daily
 Approved Dec 2013
Mechanism of Action
 HCV NS5B RNA dependent RNA polymerase
 Essential for viral replication
 Sovaldi is a prodrug which undergoes intracellular
metabolism to active form uridine analog triphospahte
 Gets incorporated into viral RNA and acts as a chain
terminator
Pharmacokinetics
Parameters Sofosbuvir
Absorption
Tmax – 0.5 to 2 hrs
Distribution
61% to 65% protein bound
Metabolism
Extensively metabolised
Excretion
Primarily renal (80%)
Elimination
Half-life
Parent compound 0.4 hours
Active metabolites 27 hours
Adverse Effects
 Common
 Rash (18%)
 Diarrhea (12%)
 Nausea (34%)
 Anemia (6%)
 Serious
 Pancytopenia (<1%)
 Increased bilirubin levels (3%)
 Depression (<1%)
Monitoring
 Detect viral load
 Improvement in signs and symptoms of Hepatitis C
 In female patients and female partners of male
patients, perform pregnancy test before initiating
treatment and monthly thereafter, and for 6 months
after discontinuing treatment
CI and DDI
 CI
 Pregnancy – Category B
 DDI
 Carbamazepine
 Fosphenytoin
 Oxcarbazepine
 Phenytoin
 Rifampin
 St. John’s wort
Place in treatment
 Genotype 1
 Sovaldi + Peg interferon + Ribavirin for 12 weeks
 Genotype 2
 Sovaldi + Ribavirin for 12 weeks
 Genotype 3
 Sovaldi + Ribavirin for 24 weeks
Treatment comparison
 NEUTRINO trial – single group open label trial
Outcome
Sovaldi + Ribavirin +
Peg- inerferon for 12
weeks (N= 327)
SVR in Genotype 1
HCV RNA < 25IU/ml
89%
Anemia
23%
Leukopenia
5%
Thrombocytopenia
1%
Treatment comparison
 FISSION trial – randomized open label active- control
groups
Outcome
Sovaldi +
Ribavirin for 12
weeks (N = 256)
Peg- interferon +
Ribavirin for 24
weeks (N = 243)
SVR in Genotype 2
HCV RNA <
25IU/ml
67%
67%
Anemia
9%
14%
Leukopenia
0%
4%
Thrombocytopenia
0%
7%
Treatment comparison
 Cost
 Peg- interferon + Ribavirin for 24 weeks = 23,002
 Sovaldi + Ribavirin for 12 weeks = 101, 195
Pros &Cons
 Pros  Oral Administration
 Once daily dosing
 Shorter treatment duration
 Cons –
 Increase in cost of treatment
 Long term data not available
Recommendation for AJ
 Peg-interferon 180 mcg once weekly for 24 weeks
 Ribavirin 400 mg twice daily for 24 weeks
References
 Hepatitis C information for health professionals. Retrieved on Mar 24,
2014 from http://www.cdc.gov/hepatitis/HCV/index.htm
 Sovaldi Lexi-comp
http://online.lexi.com.proxy.westernu.edu/lco/action/doc/retrieve/docid/patch_f/4884323
Accessed on Mar 27, 2014.
 Lawitz E. et al. Sofosbuvir for previously untreated chronic hepatitis C
infection. The New England Journal of Medicine 2013; 368:1878-1887
Thank You
Questions