Prabhdeep Sidhu Candidate PharmD 2015 Western University of Health Sciences Mar 28, 2014.
-
Upload
elfrieda-stephanie-sherman -
Category
Documents
-
view
214 -
download
0
Transcript of Prabhdeep Sidhu Candidate PharmD 2015 Western University of Health Sciences Mar 28, 2014.
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