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Managing Side Effects of Medications for HCV

Managing Side Effects of Medications for HCV . Nursing Inservice Rajwant Minhas, FH Resident HIV/AIDS Rotation May 2012. Objectives. Be aware of common side effects of: Peginterferon alfa (PegIFN) Ribavirin (RBV) Boceprevir (BOC) Telaprevir (TVR)

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Managing Side Effects of Medications for HCV

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  1. Managing Side Effects of Medications for HCV Nursing Inservice Rajwant Minhas, FH Resident HIV/AIDS Rotation May 2012

  2. Objectives • Be aware of common side effects of: • Peginterferon alfa (PegIFN) • Ribavirin (RBV) • Boceprevir (BOC) • Telaprevir (TVR) • Name 3 most common side effects more frequent in triple therapy arm vs. Standard of care (SOC) • Understand how to manage common side effects of HCV therapy

  3. Hepatitis C Overview • A chronic liver disease caused by the hepatitis C virus (HCV) • Most common cause of chronic liver disease and cirrhosis • Canada: ~242,500 individuals are infected • ~ 21% unaware of infection & remain undiagnosed • Many are asymptomatic Public Health Agency of Canada: Hepatitis C Available from: http://www.phac-aspc.gc.ca/hepc/index-eng.php

  4. Signs and Symptoms NDDIC. Available from: http://digestive.niddk.nih.gov/ddiseases/pubs/hepc_ez/ • Most people are asymptomatic until the virus causes liver damage, which can take 10 or more years to happen • Others have one or more of the following symptoms: • Jaundice • Longer time to control bleeding, easy bruising • Ascites, ankle edema • Fever • Nutritional: loss of appetite, blood-sugar disorders • GI: indigestion, diarrhea, nausea, abdominal discomfort • GU: light-colored stools, dark yellow urine • Skin: itchiness • Aches: flu-like illness, joint pain, muscle aches, general weakness, fatigue

  5. HCV Overview Protective protein shell • Single stranded RNA Virus • Replicates in cytoplasm of hepatocytes • 6 known genotypes Fatty envelope 2 viral envelope glycoproteins: E1&E2 Available from: http://www.med-ars.it/galleries/virus_4.htm

  6. Natural History of HCV Infection If the virus can still be detected in the body 6 months after becoming infected Chen SL, Int.J.Med.Sci.2006,3

  7. Natural History of HCV Infection • HCV can cause acute and chronic hepatitis • Acute process: Self-limited • Rarely causes hepatic failure, usually leads to chronic infection • Chronic HCV infection: Often follows a progressive course over many years • Can ultimately result in: • Cirrhosis • Hepatocellular carcinoma (HCC) • Need for liver transplantation Chen SL, Int.J.Med.Sci.2006,3

  8. Risk Factors for HCV Infection • Blood transfusion before 1992 • IV drug use • High risk sexual activity • Solid organ transplantation from an infected donor • Occupational exposure • Hemodialysis • Household exposure • Birth to an infected mother • Intranasal cocaine use Chen SL, Int.J.Med.Sci.2006,3

  9. Risk Factors for Developing Chronic HCV Infection • Age at time of infection > 25 years • Male gender • No jaundice or symptoms during acute infection • African American race • HIV infection • Immunosuppression Chen SL, Int.J.Med.Sci.2006,3

  10. Risk Factors for Advanced Progression of Liver Fibrosis • Alcohol consumption • Age at time of infection > 40 years • Male gender • Degree of inflammation and fibrosis on liver biopsy • Coinfection with HIV or HBV • Comorbid disease Chen SL, Int.J.Med.Sci.2006,3

  11. Monitoring of On-therapy Response to PegIFN + RBV EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264

  12. Goals of Therapy • Eradicate HCV infection • Endpoint of therapy: Sustained virological response (SVR) • Once obtained, SVR usually = cure of infection in >99% of patients • Patients without cirrhosis: SVR is generally associated with resolution of disease • Patients with cirrhosis: Remain at risk of life-threatening complications • particularly, HCC may occur even after eradication of viral infection Ghany et al. AASLD Practice Guidelines. Hepatology 54, No.4, 2011

  13. HCV Treatment • Not treated unless it becomes chronic • Drugs slow or stop the virus from damaging the liver • Peginterferon: Weekly shots • Ribavirin: PO daily • Treatment lasts from 24 to 48 weeks • 48 wks (HCV genotypes 1,4,5 and 6) • 24 wks (HCV genotypes 2 and 3) Has been the standard of care (SOC) 2 major advances: Development of direct-acting antiviral agents (DAA) Ghany et al. AASLD Practice Guidelines. Hepatology 54, No.4, 2011

  14. Protease Inhibitors • Boceprevir (BOC) • Telaprevir (TVR) • HCV nonstructural protein 3/4A (NS3/4A) serine protease inhibitors

  15. Peginterferon EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264 • 2 pegylated IFN-a molecules: • Pegylated IFN-alfa2a and pegylated IFN-alfa2b • Different pharmacokinetics • Difference in efficacy is still debated • Pegasys: PegIFN alfa-2a • Pegeteron: RBV 200 mg capsules + PegIFN alfa-2b powder for Solution • Victrelis Triple: BOC 200 mg capsules + RBV 200 mg capsules + PegIFN alfa-2b powder

  16. Peginterferon Alfa Side Effects Headache, fatigue, depression, insomnia, dizziness Hair loss Flu like signs Blurry vision, change in thinking clearly Injection site reaction N, V, anorexia, diarrhea Small meals help Anemia, neutropenia, thrombocytopenia EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264 Victrelis triple product monograph. Merck 2011

  17. How to Manage Side Effects? EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264

  18. When to Reduce or Stop PegIFN? EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264

  19. Ribavirin (RBV) EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264 • Synthetic nucleoside analogue • Recommended dose: 800-1400 mg daily based upon patient weight divided in 2 doses with food (Victrelis Triple monograph) • Dose depends on product used • Risk of teratogenicity contraception required for 6 months beyond treatment

  20. Boceprevir (BOC) • Indication is specifically for adults with CHC genotype 1 with: • Compensated liver disease including cirrhosis • Previously untreated • Who have failed previous IFN and RBV therapy • Regimen: 4-week lead-in PegIFN/RBV, then add boceprevir 800 mg PO TID (ie q7-9hr) with food • Duration of treatment: Depends on HCV-RNA levels at treatment wks 8, 12 and 24 Ghany et al. AASLD Practice Guidelines. Hepatology 54, No.4, 2011

  21. Boceprevir (VICTRELIS) Side Effects Headache, dizziness Alopecia Anemia and neutropenia Dysgeusia, dry mouth Insomnia Thrombocytopenia Anemia (<100g/L): 49% in BOC group vs. 29% SOC <85 g/L: 9% Fatigue, chills N, V, D, ↓ in appetite Irritability Underlined: most common in triple therapy Boceprevir capsules [package insert]. Merck & Co., Inc.; 2011.

  22. How to Manage Side Effects? EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264

  23. Management of Anemia Nelson, D et al. HCV Clinical Management CBC pretreatment, q 2 wks until tx week 8, then monthly Primary strategy: RBV dose reductions Hgb <100 g/L: ↓ in dosage or interruption of RBV is recommended Hgb <85 g/L: discontinue all therapy If RBV is permanently dced, BOC or TVR also must be D/C Do not reduce PI dose to manage anemia Once RBV dose reduction has been tried, erythropoietin can be considered TVR: RBV dose reductions; if inadequate consider d/c TVR

  24. Management of Anemia/Neutropenia EASL Clinical Practice Guidelines. J. of Hepatology vol. 55, 245-264 Use of growth factors helpful in limiting treatment dose reductions Recombinant erythropoietin: To maintain or ↑ Hgb levels (to avoid RBV dose reductions or interruptions) No clear evidence indicating that neutropenia during pegylated IFN-a and RBV therapy, a common event in cirrhotic patients, has an adverse effect No evidence that G-CSF ↓ the rate of infections and/or ↑ SVR rates

  25. RBV Dose Reduction Victrelis product monograph. Merck 2011

  26. VICTRELIS TRIPLE • Boceprevir PO 200 mg capsule • Ribavirin PO 200 mg capsule • Peginterferon alfa-2b SC • Powder for solution in REDIPEN single dose delivery system • 80 mcg/0.5 mL • 100 mcg/0.5 mL • 120 mcg/0.5 mL • 150 mcg/0.5 mL • Indicated for treatment of CHC genotype 1 infection in >18 years with: • Compensated liver disease including cirrhosis who are previously untreated or who have failed previous therapy Victrelis product monograph. Merck 2011

  27. Pharmacare CoverageSpecial Authority for BOC

  28. Telaprevir (TVR) • Recommended dose: 750 mg with food (not low-fat) TID (q 7-9 hrs) + PegIFN alfa + weight-based RBV • Duration: 12 weeks followed by an additional 12-36 weeks of PegIFN alfa and RBV Ghany et al. AASLD Practice Guidelines. Hepatology 54, No.4, 2011

  29. Telaprevir (TVR) • Due to high rates of early viral suppression and • Low rates of relapse after therapy cessation • Therapy could be shortened to 24 weeks in patients who have a rapid virologic response (RVR) Ghany et al. AASLD Practice Guidelines. Hepatology 54, No.4, 2011

  30. Telaprevir Side Effects Anemia Fatigue T12PR: Hgb <100 g/L: 36% vs. 14% SOC group Hgb <85 g/L: 9% Taste changes Rash Pruritus Anal or rectal problems: hemorrhoids, discomfort, itching or burning around or near the anus N, V, D Telaprevir tablets [package insert] Vertex Pharmaceuticals Incorporated; 2011.

  31. TVR: Rash Management Nelson, D et al. HCV Clinical Management

  32. TVR: Rash Management Nelson, D et al. HCV Clinical Management

  33. THANK YOU! Questions?

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