Hepatitis c

Hepatitis C Treatment in 2016
Amanda Noska, MD, MPH Providence VAMC & The Miriam Hospital & Immunology Center • I have no financial disclosures.
• I will be referencing trade names in addition to generic today for ease of understanding and education purposes. Learning Objectives Pharmacists• Discuss the epidemiology and immunology of hepatitis C in the United States.
• Discuss the importance of prior treatment history and liver staging in determining a HCV treatment regimen.
• Discuss current available hepatitis C treatment options.
• Describe common side effects and drug-drug interactions of directly-acting antiviral medications for HCV.
• Describe immunizations related to various types of hepatitis.
Review common side effects and therapeutic contraindications associated with hepatitis C treatment options Identify patients that may be candidates for hepatitis vaccines 1. What is the most common barrier to patients accessing hepatitis C treatment currently? a) Unstable mental health disordersb) Insurance coveragec) Drug-drug interactionsd) A life-expectancy of <1 year 2. Which of the following drugs interacts with Ledipasvir/sofosbuvir (Harvoni) to decrease serum levels of ledipasvir?a) Methadoneb) Levothyroxinec) Levetiracetamd) Omeprazole 3. Based on the ION trials, which of the following patients might be a candidate for 8 weeks of ledipasvir/sofosbuvir (Harvoni)?a) GT 1a, treatment naïve, non-cirrhotic, HCV viral load b) GT 3, treatment naïve, non-cirrhotic, HCV viral load 3 c) GT 1b, treatment naive, cirrhotic, HCV VL 2 milliond) GT 4, treatment naïve, non-cirrhotic, HCV viral load 6 4. Which of the following is among the most common noted side effect of daclatasvir(Daklinza)? a) Nauseab) Fatiguec) Skin rashd) Diarrhea 5. Which of the following measures are important to preventing morbidity associated with chronic hepatitis C?a) Weekly lab monitoringb) Vaccination against hepatitis B alonec) Vaccination against hepatitis A and Bd) Avoidance of all medications metabolized by the First described in 1989, Blood screening began in 1990. Peak prevalence occurs in those born 1945-1965. Worldwide 350,000-500,000 people die annually from HCV related Cirrhosis develops in 10-20% of patients with chronic HCV infection over 20-30 years on average, although rates vary widely (from 2% to After cirrhosis due to HCV has developed, the annual risk of developing HCC is 1-5%.
AASLD. 2015.Westbrook R, J of Hepatotogy. 2014;61:S58-68. Grebely J et al. Hepatology.2014;59:109-120. Alric L. Hepatology. 2014;60(6):Epub.

variable geographic distribution Slide courtesy of Dr. Lynn Taylor
Deaths Due to HCV Infections Now Exceed
Those Due to HIV Infection
Hepatitis C
16,600 deaths
Number of HCV-related deaths may be over 60,000 because of under-reporting on death certificates Ly KN, Xing J, Klevens RM, Jiles RB, Holmberg SD. Causes of death and characteristics of decedents with viral hepatitis, United States, 2010. Clin Infect Dis. 2014 Jan;58(1):40-9. Mahajan, IDSA 2013

Chronic HCV Infection May Lead to
Chronic Liver Disease and Liver Cancer
Hepatocellular Carcinoma
Chronic HCV
Cancer of the liver
infection can
can develop after
lead to the
years of chronic
development of
fibrous scar
tissue within
the liver
Decompensated cirrhosis: Over time, fibrosis can
Bleeding gastroesophageal progress, causing severe
scarring of the liver,
Hepatic encephalopathy restricted blood flow,
impaired liver function,
and eventually liver failure
*** Slide courtesy of Dr. Camilla Graham***
Chronic liver disease includes fibrosis, cirrhosis, and hepatic decompensation; HCC=hepatocellular carcinoma.
1. Highleyman L. Hepatitis C Support Project. http://www.hcvadvocate.org/hepatitis/factsheets_pdf/Fibrosis.pdf. Accessed August 18, 20112. Bataller R et al. J Clin Invest. 2005;115:209-218; 3. Medline Plus. http://www.nlm.nih.gov/medlineplus/enxy.article/000280.htm. Accessed August 28, 2012; 4. Centers for Disease Control and 12 http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm. Accessed May 8, 2012.
CDC and ACIP Vaccine Schedule: http://www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule.pdf HAV/HCV Co-infection Acute hepatitis A infection + chronic HCV can be devastating. In a prospective study by Vento, 432 patients with chronic hepatitis C (183 with cirrhosis) were observed over a 7-year period. – Of the 17 patients with concurrent HAV infection, seven (41.4%) developed fulminant hepatitis and 6 patients died (35.3%).
Vento S. J of Viral Hepatitis. 2002; 7(S1):7-8.
Hepatitis A Vaccination Two doses required Havrix:1440 ELISA Units (1 ml) IM with a booster dose (1440 units) at 6+ months after the primary immunization VAQTA : 50 units (1 ml) IM with a booster dose (50 units) given at 6-18 months after primary immunization. HBV/HCV Co-infection 7-20 million people worldwide are co-infected with HBV/HCV. Patients with HBV/HCV coinfection have an increased risk for cirrhosis, hepatocellular carcinoma (HCC) and even death.
Potthoff A, Manns MP, Wedemeyer H. Expert Opin on Pharmacotherapy. 2010;11(6):919-28. Hepatitis B Immunization – Immunocompetent hosts: • 1 ml/dose for 3 total doses administered at 0, 1, and 6 – Immunocompromised hosts: • 20 mcg/ml: administer 2 ml per dose at 0, 1, 2 and 6 Recombivax HB: – Immunocompromised hosts: • 40 mcg/ml: administer 1 ml per dose at 0, 1, and 6 months Twinrix: Hepatitis A and B vaccine Hepatitis A and recombinant hepatitis B inactivated vaccine – Hepatitis A virus antigen 720 ELISA units and hepatitis B surface ag 20 mcg/mL (1 ml) – Contains aluminum, trace amounts of neomycin, and some Given as 1 mL intramuscular injections at 0, 1, and 6 months – Hep A component is ½ that of the Hep A vaccine alone, so it may be less immunogenic after 1 dose.
– Hep B component is likewise ½ that of the Hep B vaccine alone, so it may be less immunogenic after a single dose.
– Should not be used as post-exposure prophylaxis.

Developing a HCV Vaccine: Hepatitis C is highly variable even among strains HCV mutates quickly The vaccine likely needs to be specific to only one genotype Utilization of the T cell response is critical to viral clearance Hepatitis C Vaccine • Simian adenovirus vector (ChAd3) + modified vaccinia Ankara vector (MVA) that encodes NS3, NS4, NS5A and NS5B proteins of Hepatitis C genotype 1b • HCV specific T-cells are induced ChAd3, then boosted by MVA, to generate high levels of CD8+ and CD4+ HCV- specific T cells that target multiple HCV antigens • Sustained memory cells and effector T cells are then • T-cell memory evolves over time to produce anti-HCV • So far appears to produce a "durable, broad, sustained and balanced T-cell response to [HCV]… associated with viral Swadling et al. Science Translational Medicine. 2014; 6(261):261.

FIRST IFN-Free Therapy FDA-approved
Nucleotide Analogue Inhibitor of HCV NS5B polymerase enzyme
Effective for treatment-naives + pts who failed prior IFN treatment, cirrhotics, decompensated cirrhotics Slide courtesy of Dr. Lynn Taylor Multiple Validated Drug Targets
MIR 122 Inhibitors
Membraneous web (Preclin)
- MIravirsen
Viral enzyme
Viral enzyme
Viral enzyme
Active site
Replication complex
Active site
Graphic courtesy of Dr John Link,
Slide courtesy of Dr. Camilla Graham.
Ahmed A, Felmlee DJ. Viruses. 2015 Dec 18;7(12):6716-29.
Keeping it Straight A 56 yo M with diabetes mellitus, peptic ulcer disease due to NSAIDS with prior upper GI bleed, opioid use disorder in remission, tobacco dependence, and chronic hepatitis C genotype 1a, fibrosis stage 2, HCV viral load 2.6 million, presents for evaluation to your office. Pt's EGD last month shows no active upper GI bleeding and well-healed peptic ulcers. He has never been treated for chronic hepatitis C before, presents today to discuss his treatment options. Pt has no known mental health disorders, is stably housed, and hasn't used injection drugs in over 10 years, stable on methadone. Provided the patient has no drug-drug interactions… Which of the following directly-acting antivirals is the best option for treatment? 1. Ledipasvir 90 mg/sofosbuvir 400 mg (HARVONI) x 8 weeks 2. Sofobuvir 400 mg (SOVALDI) + weight- based ribavirin x 12 weeks 3. Paritepravir 150 mg/ritonavir 100 mg/ombitasvir 25 mg + dasabavir 250 mg BID (VIEKIRA PAK) twice daily + weight-based ribavirin x 8 weeks 4. Daclatasvir 60 mg (DAKLINZA) + Sofosbuvir 400 mg (SOVALDI) x 24 weeks Case #1 continued This patient's med list includes:omeprazole 40 mg dailylevothyroxine 125 mcg dailylevetiracetam 1000 mg twice dailymethadone 90 mg daily What changes would you suggest to the patient's provider regarding this patient's medications prior to treatment initiation? 1. Suggest an alternate anti-convulsant 2. Reduce omeprazole to 20 mg daily if clinically feasible and advise the patient to take the drug at the same time as Ledipasvir/Sofosbuvir(Harvoni) 3. Increase the levothyroxine 4. Reduce the pt's methadone dose 5. No changes needed here Genotype 1: C-EDGE 382 patients received 12 weeks of elbasvir 50 mg + grazoprevir 100 mg (ZEPATIER) for genotype 1 HCV.
– 50% genotype 1a– 41% genotype 1b C-EDGE (12 wks Zepatier): SVR12
GT 1a, non-C, naïve
GT 1b, non-C, naïve
Genotype 1: C-WORTHY 74 patients, treatment-naïve, non-cirrhotic, included both HCV mono-infected and HIV/HCV co-infected patients who received 12 weeks of elbasvir 50 mg + grazoprevir 100 mg (ZEPATIER) without ribavirin.
C-WORTHY (12 weeks Zepatier):
GT 1a, non-C, naïve
GT 1b, non-C, naïve
Genotype 1: C-EDGE, Cirrhotic pts Presence or absence of compensated cirrhosis does not appear to alter the efficacy of the elbasvir 50 mg/grazoprevir 100 mg (ZEPATIER) regimen.
92 (22%) patients in the trial had Metavir F4 disease consistent with cirrhosis.
SVR12 was 97% (90/92) in cirrhotic patients with GT 1 disease.
Baseline NS5A Resistance-associated variants (RAVs) significantly reduce rates of SVR12 with a 12-week course of the elbasvir 50 mg/grazoprevir 100 mg (ZEPATIER) regimen in NS5A RAVs were identified at baseline in 12% (19/154) of GT 1a patients enrolled in the C-EDGE study.
- 58% (11/19) achieved SVR12 compared to - 99% (133/135) SVR12 in patients without RAVs Recommendation: Patients should be tested for RAVS to NS5A inhibitors before beginning treatment. Genotype 1: ION Trials ION-1: Ledipasvir 90 mg/sofosbuvir 400 mg (HARVONI) 865 treatment-naïve patients, including pts with cirrhosis. – SVR12 was 97-99% overall in all groups
– There was no significant difference in SVR12 based on:
• Use of RBV• HCV genotype 1 subtype • Length of treatment (12 vs. 24 week regimens) – 16% of subjects had cirrhosis • SVR12 was 97% in cirrhotic patients
Genotype 1: ION Trials ION-3: Ledipasvir 90 mg/sofosbuvir 400 mg (Harvoni) 647 treatment-naïve patients, non-cirrhotic only – There were lower relapse rates in patients receiving 8 weeks of ledipasvir/sofosbuvir(Harvoni) who had baseline HCV RNA levels below 6 million IU/mL (2%; 2 of 123) Genotype 1: PEARL-IV, SAPPHIRE-1, SAPPHIRE-I: Paritaprevir 150 mg/ ritonavir 100 mg/ ombitasvir 25 mg + Dasabavir 250 mg BID x 12 wks (VIEKIRA PAK) + weight-based ribavirin 322 treatment-naïve, non-cirrhotic patients with genotype 1a – SVR12 was 95% with 12 weeks of Viekira pak and ribavirin– Virologic failure was higher in GT1a (7 of the 8 failures were GT PEARL-IV:305 treatment-naïve, non-cirrhotic patients with genotype 1a – This trial provided the rationale for recommendation to use ribavirin with all GT1a disease if using Viekira pak Genotype 1: PEARL-IV, SAPPHIRE-1, PEARL-IV:305 treatment-naïve, non-cirrhotic patients with genotype 1a – This trial provided the rationale for recommendation to use ribavirin with all GT1a disease if using Viekira pak PEARL-IV: Viekira pak for GT1a
+/- RBV: SVR12
GT1a, naïve, non-C, no RBV
GT1a, naïve, non-C, +RBV
Genotype 1: PEARL-IV, SAPPHIRE-1, TURQUOISE-II: Paritaprevir 150 mg/ ritonavir 100 mg/ ombitasvir 25 mg + Dasabavir 250 mg BID x 12 wks (Viekira pak) + weight-based ribavirin261 treatment-naïve and -experienced patients with genotype 1a and cirrhosis. TURQUOISE-II (Viekira pak + RBV
12 vs. 24wks): SVR12
GT1, 12 wks, all pts
GT1, 24 wks, all pts
Due to at least 2 cases of CTP class A compensated cirrhotic patients dying or requiring liver transplant after receipt of Viekira pak or Technivie, this regimen is now contraindicated in patients with Child Turcotte Pugh (CTP) class B or C hepatic
impairment (decompensated liver disease).
Genotype 1: OPTIMIST-1 OPTIMIST-1: 310 treatment-naïve and -experienced patients without cirrhosisSimeprevir 150 mg (OLYSIO) and sofosbuvir 400 mg (SOVALDI) in chronically infected patients with HCV genotype 1 OPTIMIST 1: SIM + SOF for GT1,
OPTIMIST-1: SIM + SOF for GT1,
8 vs. 12 weeks: SVR12
Treatment-naive vs. -exp'd: SVR12
SIM + SOF x 8 wks
SIM + SOF x 12 wks
SIM + SOF, naïve, 12 wks
SIM + SOF, exp'd, 12 wks
Genotype 1: OPTIMIST -2 Simeprevir 150 mg (OLYSIO) and sofosbuvir 400 mg (SOVALDI) in chronically infected patients with HCV genotype 1 OPTIMIST-2:103 treatment-naïve and -experienced patients with cirrhosis OPTIMIST-2: SIM + SOF x 12 weeks,
Cirrhotic patients, Treatment-naive
and experienced: SVR12
SIM + SOF overall
SIM + SOF, cirrhotic,
SIM + SOF, cirrhotic,
Genotype 1: ALLY-1 ALLY-1: Daclatasvir 60 mg daily (DACLINZA) + sofosbuvir 400 mg daily (SOVALDI) + weight-based RBV in 60 patients with advanced cirrhosis ALLY-1: DAC + SOF + RBV x 12 weeks
for cirrhotic pts- SVR12
Therefore 24 weeks of treatment is recommended for GT1a with cirrhosis, although the SVR12 remains unclear in this A 65 yo M with history of anemia of chronic disease, GERD, asthma, CAD and chronic hepatitis C genotype 2, fibrosis stage 3, HCV viral load 4 million, presents for evaluation. Pt is interested in treatment. Pt's anemia has been thoroughly evaluated and appears to be anemia of chronic disease. His last hemoglobin was 9.5. He denies having ever had any bleeding, melena, BRBPR, hematemesis, epistaxis or hemoptysis. Meds: albuterol inhaler as neededomeprazole 20 mg dailymetoprolol tartrate 100 mg dailylisinopril 10 mg daily aspirin 325 mg dailysimvastatin 10 mg daily Which of the following is a contraindication to the use of ribavirin in this patient? 1. Drug-drug interaction 2. Hemoglobin baseline 3. Coronary artery 4. Patient's HCV Genotype 2: FISSION, VALENCE, Sofosbuvir 400 mg daily (SOVALDI) and weight-based ribavirin FISSION: 499 treatment-naïve pts with GT 2 or 3, randomized to daily PEG- IFN/RBV x 24 wks vs. Sofosbuvir 400 mg daily (SOVALDI) + RBV x 12 weeks.
FISSION: SOF + RBV vs. PEG-
IFN + RBV for GT 2- SVR12
PEG-IFN + RBV
POSITRON: 278 interferon-ineligible or unwilling, treatment-naïve and treatment-experienced GT2 and GT3 pts randomized to 12 weeks Sofosbuvir (SOVALDI) + RBV vs. placebo x 12 weeks. - SVR12 was 93% (101/109) among GT2s Genotype 2: FISSION, VALENCE, VALENCE: 419 treatment-naïve and treatment-experienced patients with HCV genotype 2 or 3. GT 2 patients received 12 weeks of sofosbuvir 400 mg daily (SOVALDI) + RBV versus • SVR12 for GT2 was 97% (31/32) for SOF + RBV x12 The overall SVR12 was 94% in a pooled analysis of all 3 trials with SOF/RBV x 12 weeks (for GT 2) • Patients with cirrhosis tended to do worse in all 3 • Thus therapy was extended to 16 weeks in pts with cirrhosis (despite limited data) A 45 yo M w/ a seizure disorder, hypothyroidism, and treatment-experienced hepatitis C genotype 3 without cirrhosis (null response to PEG-IFN + RBV after 12 weeks), presents for treatment. His provider decides to treat him with 12 weeks of daclatasvir(DAKLINZA) + sofosbuvir (SOVALDI). Which of the following drug-drug interactions are you most concerned about? 1. Carbamazepine2. Pantoprazole3. Levothyroxine4. Levetiracetam5. Omeprazole Genotype 3: ALLY-3 Trial ALLY-3: 101 treatment-naïve patients with and without cirrhosis, daclatasvir 60 mg daily (Daklinza) + sofosbuvir 400 mg daily (Sovaldi) x 12 weeks (no ribavirin) This data suggests that cirrhotic patients might benefit from extension of therapy to 24 weeks. ALLY-3: DAC + SOF x 12 weeks for
Genotype 3
GT3, non-C, naïve GT3, Cirrhotic, naïve
Genotype 3: ALLY-3 Trial Daclatasvir + Sofosbuvir + RBV x 12 vs. 16 weeks in those with cirrhosis: – SVR12 rates were 88% (15/17) for those in the 12 – SVR12 of 89% (16/18) in the 16 week arm Genotype 3: BOSON Trial 592 patients total, both treatment-naïve and treatment-experienced (IFN-eligible ONLY) 196 received sofosbuvir 400 mg daily (SOVALDI) and RBV for 16 weeks 199 received sofosbuvir 400 mg daily (SOVALDI) and RBV for 24 weeks197 received sofosbuvir 400 mg daily (SOVALDI) + PEG-IFN/RBV for 12 weeks BOSON: SOF + RBV for Genotype 3
BOSON Trial: SOF + RBV compared
(Cirrhotic vs. non-Cirrhotic)
to SOF + RBV + PEG-IRN x 12 weeks
SOF + RBV x
SOF + RBV x
SOF + RBV x
SOF + RBV x
16 wks, non-C 24 wks, non-C
SOF + PEG-IFN+ RBV x 12 wks
SOF + RBV x 12 wks
Genotype 3: VALENCE Trial 250 treatment-naïve (42%) and -experienced (58%) subjects with genotype 3 (cirrhotic (n=45) and non-cirrhotic (n=100)) received sofosbuvir 400 mg daily (SOVALDI) plus weight-based RBV x 24 weeks.
VALENCE Trial: SOF + RBV x 24 wks
for Tx-naive and -exp'd, Cirrhotic and
non-C Genotype 3
Cirrhosis had no significant impact on overall SVR12. Genotype 3: C-SWIFT Trial 40 patients with GT 3, treatment-naïve, with and without cirrhosis, randomized to 8 versus 12 weeks of triple therapy with elbasvir 50 mg/grazoprevir 100 mg (ZEPATIER) + sofosbuvir 400 mg daily (SOVALDI).
C-SWIFT: Zepatier + Sovaldi (8 vs. 12 wks)
for Genotype 3
12 weeks, Cirrhotic
Genotype 4: SYNERGY Trial 21 patients with GT4, both treatment-naïve and - experienced, both cirrhotic and non-cirrhotic, randomized to 12 weeks of ledipasvir 90 mg/sofosbuvir 400 mg (HARVONI) • 60% were treatment-naïve • 43% had advanced fibrosis (F3 or F4) Overall SVR12 was 100% for all 20 patients.
Genotype 4: PEARL-1 Trial PEARL-I:86 treatment-naïve GT4 patients, non-cirrhotic received 12 weeks of the daily fixed-dose combination of paritaprevir 150 mg/ritonavir 100 mg/ombitasvir 25 mg (TECHNIVIE) +/- RBV PEARL-1: 12 weeks Technivie +/- RBV
for Genotype 4 (12 wks, Tx-naïve,
Genotype 4: AGATE-I and –II Trials AGATE-1:
120 treatment-naïve and -experienced patients with GT4 + cirrhosis
- 12 versus 16 weeks of paritaprevir/ritonavir/ombitasvir (TECHNIVIE) + RBV- SVR12 was 96% in the 12 week Technivie + RBV - SVR12 was 100% in the 16 week Technivie + RBV arm AGATE-II:
100 treatment-naïve and -experienced non-cirrhotic GT4 patients received 12
weeks of paritaprevir/ritonavir/ombitasvir (TECHNIVIE )+ RBV - Overall SVR12 was 94% for 12 weeks of TECHNIVIE + RBV AGATE-II:
60 treatment-naïve and -experienced GT4 patients with cirrhosis
12 versus 24 weeks of paritaprevir/ritonavir/ombitasvir (TECHNIVIE) + RBV
- SVR12 was 97% for 12 weeks of PrO + RBV in cirrhotic pts Genotype 4: C-EDGE Trial 66 treatment-naïve GT4 patients, with and without cirrhosis, received elbasvir 50 mg/grazoprevir 100 mg (ZEPATIER) x 12 weeks • 6 were cirrhotic (9.1%)• 28 were co-infected with HIV (42.4%)• 10 also received RBV• 56 did not receive RBV - Overall SVR12 was 97% (64/66) regardless of status of cirrhosis or coinfection - 1 treatment failure - Baseline RAVs did not impact SVR12 rates Genotype 4: NEUTRINO Trial 28 treatment-naïve patients with GT4 with and without cirrhosis received 12 weeks of sofosbuvir 400 mg daily (SOVALDI) + PEG-IFN 2a + RBV - SVR12 was 96% (27/28)- The one treatment failure was in a cirrhotic pt Important to carefully consider the patient's baseline comorbidities.
- If you have to stop RBV, you have to stop treatment.
- Pts with prior CVA, CAD, COPD, etc… may be risky candidates due to anemia
and low oxygen carrying capacity that can result Avoid ribavirin in pts w/ anemia or thalassemia
- Anyone with hemoglobin <11.0 should not receive RBV- Particularly problematic in women (Pregnancy category X); 2 forms of contraception needed Ribavirin needs to be dosed according to renal function.
CrCl >50, no dose adjustment CrCl 30-50: Alternate 200 mg and 400 mg every other dayCrCl <30: 200 mg once dailyESRD: 200 mg once daily Ribavirin's half-life is very long.
Capsule, single dose; 44 hours in HCV pts Tablet: 120-170 hours www.uptodate.com, Ribavirin Drug Information, 2015. Barriers to Treatment • Insurance coverage is the major barrier to treatment access. • Drug-drug interactions (esp. antacids with • Provider misconceptions• Competing interests at patient level Multidisciplinary team approach Involvement of a multidisciplinary team (including specialty-trained HCV pharmacists, RNs, social workers and counselors) improves HCV-related outcomes and overall SVR rates. Nurse practitioners and MDs/DOs can work in common to provide high-quality care to pts living with hepatitis C, and outcomes are equivalent.
Chopra A, Klein PL, Drinnan T, Lee SS. Liver Int. 2013 Feb;33 Suppl 1:30-4.
Manos MM, Ho CK, Murphy RC, Shvachko VA. Patient. 2013;6(1):23-34.
Backus L, Belperio PS, Shahoumian TA, Mole LA. J Clin Gastroenterol. 2015 Apr;49(4):329-35.
Role of Pharmacists in Improving • Careful evaluation for drug-drug interactions• Adherence checks: Evaluation of refill records• Counselling regarding possible side effects of • Continuity of care for hospitalized patients• Evaluation for proper dose and frequency of • Expertise in pharmacology; best therapies and dose adjustments for folks with renal disease, etc.
H2 Blockers and Proton Pump Inhibitors with H2 blockers
H2 blocker may be administered at the
same time with LED/SOF OR 12 hours apart
Famotidine 40mg BID
from LED/SOF at a dose that does not
Ranitidine 150mg BID
exceed doses comparable to famotidine
Tagamet 800mg BID
Proton Pump Inhibitors
PPI doses comparable to omeprazole 20mg or lower can be administered at the same Omeprazole 20mg daily
time with LED/SOF under fasting conditions.
Prevacid 30mg daily
Aciphex 20mg daily
Protonix 40mg daily
Nexium 20 to 40mg daily (try
to stay with lower dose if
possible)
*** Slide courtesy of Dr. Camilla Graham***
Ritonavir: Drug-Drug Interactions • Phenobarbital, phenytoin, oxcarbazepine• Amiodarone• Quetiapine• Efavirenz• Atorvastatin, simvastatin• Many, many others • Check for drug-drug interactions, then double- Common Side Effects Sofosbuvir (NS5B Polymerase inhibitor): Neutropenia (<1%-17%) Insomnia (15-25%) Irritability (10-13%) Flu-like symptoms (6-16%) Pruritus (11-27%) Skin rash (8-18%) Increased Lipase (<2%) Increased CPK (1-2%) Increased serum bilirubin (3%) Severe depression (<1%) Suicidal ideation (<1%) Common Side Effects Ledipasvir (NS5A Inhibitor): Daclatasvir (NS5A inhibitor):
Fatigue (14%)
Increased CPK (1%) Weakness (18-31%) Irritability (8%) Increased lipase (2%) Skin rash (including blistering skin disease, Depression (<5%) angioedema) (<1%) Nausea (6-9%)Diarrhea (3-7%)Increased lipase (<9%)Elevated bilirubin (<3%) Common Side Effects Paritepravir/ritonavir/ombitasvir + Dasabuvir:
Fatigue (34%)
Headache (44%)
Insomnia (5-26%)
Skin reaction/rash (7-24%)
Pruritus (7-18%)
Anemia (11-29%)
Increased serum bilirubin (15-54%)
Weakness (4-14%)
Muscle spasm (21%)
Cough (11-32%)
Irritability (10%)
Icterus (10%)
Dyspnea (<1%)
Hepatic failure/liver decompensation (in pt's with underlying cirrhosis- FDA issued a
safety alert on 10/22/15)
Hypersensitivity reaction (<1%)
1. What is the most common barrier to patients accessing hepatitis C treatment currently? a) Unstable mental health disordersb) Insurance coveragec) Drug-drug interactionsd) A life-expectancy of <1 year 1. What is the most common barrier to patients accessing hepatitis C treatment currently? a) Unstable mental health disordersb) Insurance coveragec) Drug-drug interactionsd) A life-expectancy of <1 year 2. Which of the following drugs interacts with Ledipasvir/sofosbuvir to decrease serum levels of ledipasvir?a) Methadoneb) Levothyroxinec) Levetiracetamd) Omeprazole 2. Which of the following drugs interacts with Ledipasvir/sofosbuvir to decrease serum levels of ledipasvir?a) Methadoneb) Levothyroxinec) Levetiracetamd) Omeprazole 3. Based on the ION trials, which of the following patients might be a candidate for 8 weeks of ledipasvir/sofosbuvir?a) GT 1a, treatment naïve, non-cirrhotic, HCV viral load b) GT 3, treatment naïve, non-cirrhotic, HCV viral load 3 c) GT 1b, treatment naive, cirrhotic, HCV VL 2 milliond) GT 4, treatment naïve, non-cirrhotic, HCV viral load 6 3. Based on the ION trials, which of the following patients might be a candidate for 8 weeks of ledipasvir/sofosbuvir?a) GT 1a, treatment naïve, non-cirrhotic, HCV viral load b) GT 3, treatment naïve, non-cirrhotic, HCV viral load 3 c) GT 1b, treatment naive, cirrhotic, HCV VL 2 milliond) GT 4, treatment naïve, non-cirrhotic, HCV viral load 6 4. Which of the following is among the most common noted side effect of daclatasvir? a) Nauseab) Fatiguec) Skin rashd) Diarrhea 4. Which of the following is among the most common noted side effect of daclatasvir? a) Nauseab) Fatiguec) Skin rashd) Diarrhea 5. Which of the following measures are important to preventing morbidity associated with chronic hepatitis C?a) Weekly lab monitoringb) Vaccination against hepatitis B alonec) Vaccination against hepatitis A and Bd) Avoidance of all medications metabolized by the 5. Which of the following measures are important to preventing morbidity associated with chronic hepatitis C?a) Weekly lab monitoringb) Vaccination against hepatitis B alonec) Vaccination against hepatitis A and Bd) Avoidance of all medications metabolized by the World Health Organization. 2009. Retrieved online at: http://hepcbc.ca/wp-content/uploads/2012/08/GlobalDist_HCV_genotypes.jpg, Retrieved 6/15/15. AASLD. Recommendations for testing, managing and treating hepatitis C. Retrieved online at: http://www.hcvguidelines.org/full-report/when-and-whom-initiate-hcv-therapy, Retrieved 6/15/15. CDC. Hepatitis C. Retrieved online at: http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#section1, Retrieved 7/30/15. Afdhal et al. The new paradigm of hepatitis C therapy: integration of oral therapies into best practices. J Viral Hepat. 2013 Nov; 20(11): 745–760.
McNamara B, Losikoff P, Huguenin L, Macalino G, Rich J, Gregory SH. Increasing hepatitis C prevalence and associated risk behaviors among Incarcerated young adults. J Urban Health. 2013; 91(2): 376-82. Stockman LJ, Guilfoye SM, Benoit AL, Vergeront JM, Davis JP. Rapid hepatitis C testing among persons at increased risk for infection– Wisconsin, 2012-2013. MMWR Morb Mortal Wkly Rep. 2014 Apr 11; 63(14): 309-11. CDC. Use of enhanced surveillance for hepatitis C virus infection to detect a cluster among young injection-drug users--new York, November 2004-April 2007. MMWR Morb Mortal Wkly Rep. 2008 May 16;57(19):517-21.
CDC. Hepatitis C virus infection among adolescents and young adults:Massachusetts, 2002-2009. MMWR MorbMortal Wkly Rep. 2011 May 6;60(17):537-41.
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