Hepatitis+C+2023+Student 2.pdf

Management of Viral Hepatitis: A Focus on Hepatitis C Monika N. Daftary, PharmD, BCPS, AAHIVP Professor & Chair Howard University College of Pharmacy Objectives To be able to explain the characteristics of direct acting antivirals for Hepatitis C infection (HCV) To be...

Management of Viral Hepatitis: A Focus on Hepatitis C Monika N. Daftary, PharmD, BCPS, AAHIVP Professor & Chair Howard University College of Pharmacy Objectives To be able to explain the characteristics of direct acting antivirals for Hepatitis C infection (HCV) To be able to explain the parameters for pre-treatment, on-treatment, and post- treatment monitoring To select preferred regimens for treatment of HCV based upon patient history, cost, and drug interactions To select appropriate HCV regimens based on special populations  Types of Viral Hepatitis Infections Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Transmission Fecal/oral Permucosal/ Permucosal/ Permucosal/ Fecal/oral Percutaneous Percutaneous Percutaneous (dependent upon HBV infection) Vaccine Yes Yes No Yes (vaccination No Availability for HBV confers protection) Treatment No Yes Yes No No Chronicity No 80-90%- neonates 60%- neonates Chronicity related No (within 6 months to HBV infection of infection) 10 x ULN and/or signs and symptoms of liver inflammation Preferred with end-stage renal disease (ESRD) Source: Zepatier [package insert]. Merck & Co Inc. Whitehouse Station, NJ. December 2021 Glecaprevir/pibrentasvir (Mavyret) NS3/4A PI (Glecaprevir) + NS5A inhibitor (Pibrentasvir) Pangenotypic GT 1-6 (ages ≥ 3 years) Dosing once daily WITH FOOD x 8 weeks If dose missed, must take within 18 hours after missed dose ADRs: headache and fatigue (10%) Contraindications in moderate-severe hepatic impairment Rare cases of liver failure Source: Mavyret [package insert]. AbbVie Inc. North Chicago, IL. June 2021. Sofosbuvir/velpatasvir (Epclusa) NS5B NT inhibitor (Sofosbuvir) + NS5A inhibitor (Velpatasvir) single tablet Pangenotypic GT 1-6 (ages ≥ 3 years) Preferred in decompensated cirrhosis Dosing: once daily x 12 weeks For decompensated cirrhosis - give with RBV ADRs: headache and fatigue (10%) Avoid or minimize acid suppressive therapy Dispense in original container Source: Epclusa [package insert]. Gilead Biosciences Inc. Foster City, CA. June 2021. PI-containing Regimens FDA Warning Dec 2019- Worsening liver disease leading to live liver failure and death in some cases for patients with CTP B or C (moderate to severe liver disease) Occurs with PI-containing regimens The following therapies are contraindicated in moderate to severe liver disease: Vosevi Mavyret Zepatier Source: FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrence-serious-liver-injury-use-hepatitis-c-medicines-mavyret-zepatier- 41 and?utm_campaign=FDA. Regimens for TE and Resistant HCV  Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) NS5B NT inhibitor (Sofosbuvir) + NS5A inhibitor (Velpatasvir) single tablet Pangenotypic GT 1-6 (ages ≥ 3 years) Preferred in decompensated cirrhosis Dosing: 400/100/100mg tablet once daily with food x 12 weeks For patients previously treated with Vosevi, give with RBV ADRs: headache, fatigue, diarrhea, and nausea (10%); asthenia, insomnia Salvage therapy Rare cases of liver failure Source: Vosevi [package insert]. Gilead Biosciences Inc. Foster City, CA. November 2019 Sofosbuvir (Sovaldi) NS5B NT Inhibitor GT 1- 4 (adults) GT 2 and 3 (ages ≥ 3 years) Used in combination with other DAAs, esp in treatment-experienced patients Dosing: 400mg one tablet daily x 12-24 weeks ADRs: Fatigue, headache, nausea, insomnia, dizziness Rare cases of liver failure Source: Sovaldi [package insert]. Gilead Biosciences Inc. Foster City, CA. March 2020. Ribavirin Directly inhibits HCV RNA- dependent RNA polymerase Minimal effect when given alone/given as adjunct Very long T1/2= 24 h (44h in HCV) Dosing: mostly weight-based (WITH FOOD) ≤75kg 1000mg/day (400mg in am 600mg pm) ≥ 75kg 1200mg/day (600mg AM/600mg PM) ADRs: Rash/pruritis, anemia, fatigue, flu-like symptoms, insomnia, anorexia Available as Rebetol, Copegus, Ribasphere Sources: 1. Copegus [package insert]. Genentech USA, Inc. South San Francisco, CA. August 2011 Rebetol [package insert]. Merck & Co Inc. Whitehouse Station, NJ. January 2020 Ribavirin Dosage Adjustments Status Dosage Adjustment Hgb ≥ 10 g/dL Normal dose Hgb < 10 g/dL 600 mg daily Hgb < 8.5 g/dL Discontinue CrCl < 50 mL/min Rebetol© is Contraindicated CrCl 30-50 mL/min Copegus©/Ribasphere© -Alternate 200mg and 400mg every other day CrCl < 30 mL/min Or HD Copegus©/Ribasphere© - 200mg daily Sources: 1. Copegus [package insert]. Genentech USA, Inc. South San Francisco, CA. August 2011 https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021511s023lbl.pdf Rebetol [package insert]. Merck & Co Inc. Whitehouse Station, NJ. January 2020 Ribavirin Contraindications Pregnancy Unstable cardiac disease COPD, asthma Renal dysfunction (Scr > 1.5 mg/dL) Hgb < 13 g/dL (male); < 12 g/dL (female) Hemoglobinopathies, sickle cell anemia Sources: 1. Copegus [package insert]. Genentech USA, Inc. South San Francisco, CA. August 2011 Rebetol [package insert]. Merck & Co Inc. Whitehouse Station, NJ. January 2020 Ribavirin Black Box Warnings Hemolytic anemia leading to worsening cardiac disease (non-fatal and fatal myocardial infarction) Avoid in cases of unstable cardiac disease Reduce dose in cases of severe anemia Teratogenicity Contraindicated in pregnant women and their partners 2 forms of contraception during treatment and up to 6 month after completion Sources: 1. Copegus [package insert]. Genentech USA, Inc. South San Francisco, CA. August 2011 Rebetol [package insert]. Merck & Co Inc. Whitehouse Station, NJ. January 2020 https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021511s023lbl.pdf Special Considerations HCV Prior-Authorization New Initially very patient Approval or Appeal ICD-10 B18.2 time consuming Prior Authorization Insurance Verified Forms and more forms Submitted DC Beneficiary Prior Formulary driven Commitment Authorization Form Process Initiated Regimen Costs Therapy/Duration Cost of Therapy (estimates as of 2019) Mavyret 8 weeks $26,400 Harvoni 12 weeks $94,500 Epclusa 12 weeks $74,760 Vosevi 12 weeks $74,760 Zepatier 12 weeks $54,600 Source: University of Washington. https://www.hepatitisc.uw.edu/page/treatment/drugs HCV/HIV Co-infection All patients with HIV should be screened for HCV Treatment of co-infected persons individualized HCV co-infection may be associated with more rapid progression of HIV and more rapid progression of fibrosis in CHC HIV patients on HAART have greater liver-related mortality Historically low response rates diminished with DAAs Drug interactions DAAs & Antiretroviral Interactions www.hcvguidelines.org Access June 20,2022 Clinically-Important Drug Interactions Statins Anticonvulsants Antiretrovirals (PIs and older NNRTIs) Oral Contraceptives (Estrogens) Rifamycins Cyclosporine St. Johns Wort Sources: Harvoni [package insert]. Gilead Biosciences Inc. Foster City, CA. March 2020. Epclusa [package insert]. Gilead Biosciences Inc. Foster City, CA. June 2021. Mavyret [package insert]. AbbVie Inc. North Chicago, IL. June 2021. Drug Interactions with Acid Reducers Acid reducers ↓ absorption/concentration of Ledipasvir and Velpatasvir Drug Class Dosing of Acid Reducers (when taken with Harvoni©) Antacids Separate by 4 hours H2 antagonists Administer WITH LDV/VEL OR separate by 12 hours Do not exceed comparable dose of 40mg famotidine twice daily Proton pump Administer WITH LDV (while fasting) inhibitors Do not exceed comparable dose of 20mg omeprazole daily Administration with VEL not recommended Sources: Harvoni [package insert]. Gilead Biosciences Inc. Foster https://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/harvoni/harvoni_pi.pdf City, CA. March 2020. Epclusa [package insert]. Gilead Biosciences Inc. Foster City, CA. June 2021. Liverpool Drug Interaction Checker for Viral Hepatitis  References 1. https://www.cdc.gov/hepatitis/resources/healthprofessionaltools/index.htm Accessed March 12, 2023. 2. Klevens RM, Liu S, Roberts H, Jiles RB, Holmberg SD. Estimating acute viral hepatitis infections from nationally reported cases. Am J Public Health. 2014;104:482-7. 3. Centers for Disease Control and Prevention (CDC). 2019 Viral Hepatitis Surveillance Report—Hepatitis C. Published May 2021. 4. Guss D, Sherigar J, Rosen P, Mohanty SR. Diagnosis and Management of Hepatitis C Infection in Primary Care Settings. J Gen Intern Med. 2018;33:551-7