Prabhdeep SidhuCandidate PharmD 2015Western University of Health Sciences Mar 28, 2014

ObjectivesDiscuss epidemiology of Hepatitis CExplain testing and diagnosisDescribe current treatmentsExplain new medication SovaldiIdentify place in treatmentCompare Sovaldi with other treatment plans

Patient CaseAJ 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 CSymptoms

Acute Mostly asymptomatic

Chronic Persistent fatigue Nausea Poor appetite

TransmissionCaused by infection with Hepatitis C virusSpread through exposure to infected bloodSharing needles to inject drugsBlood transfusions (before 1992)

Hepatitis CApproximately 3.2 million people infected

with HCVRisk groups

Injection drug usersRecipient of blood products prior to 1992Chronic haemodialysis patientsPersons with HIV infectionChildren born to HCV infected mothers

Testing RecommendationsPersons born from 1945 through 1965Persons injecting illegal drugsRecipients of blood transfusions prior to 1992Long term haemodialysis patientsPersons with HIV infection

DiagnosisScreening tests for antibody to HCVRNA polymerase chain reactionQuantitative test to detect amount of virus

Current TreatmentsFor genotype 1 (duration varies on treatment

response)Peg interferon and RibavirinPlus 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 enzyme400 mg tabletOnce dailyApproved Dec 2013

Mechanism of ActionHCV NS5B RNA dependent RNA polymerase Essential for viral replicationSovaldi is a prodrug which undergoes

intracellular metabolism to active form uridine analog triphospahte

Gets incorporated into viral RNA and acts as a chain terminator

PharmacokineticsParamete

rsSofosbuvir

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 EffectsCommon

Rash (18%)Diarrhea (12%)Nausea (34%)Anemia (6%)

SeriousPancytopenia (<1%)Increased bilirubin levels (3%)Depression (<1%)

MonitoringDetect viral loadImprovement in signs and symptoms of

Hepatitis CIn 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 DDICI

Pregnancy – Category B

DDICarbamazepineFosphenytoinOxcarbazepinePhenytoinRifampinSt. John’s wort

Place in treatmentGenotype 1

Sovaldi + Peg interferon + Ribavirin for 12 weeks

Genotype 2Sovaldi + Ribavirin for 12 weeks

Genotype 3Sovaldi + Ribavirin for 24 weeks

Treatment comparisonNEUTRINO trial – single group open label

trial

Outcome Sovaldi + Ribavirin + Peg- inerferon for 12 weeks (N= 327)

SVR in Genotype 1HCV RNA < 25IU/ml

89%

Anemia 23%

Leukopenia 5%

Thrombocytopenia 1%

Treatment comparisonFISSION 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 2HCV RNA < 25IU/ml

67% 67%

Anemia 9% 14%

Leukopenia 0% 4%

Thrombocytopenia

0% 7%

Treatment comparisonCost

Peg- interferon + Ribavirin for 24 weeks = 23,002

Sovaldi + Ribavirin for 12 weeks = 101, 195

Pros &Cons Pros -

Oral AdministrationOnce daily dosing Shorter treatment duration

Cons – Increase in cost of treatmentLong term data not available

Recommendation for AJPeg-interferon 180 mcg once weekly for 24

weeksRibavirin 400 mg twice daily for 24 weeks

ReferencesHepatitis 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