Dr Daniel Ching. Associate Professor Catherine Stedman. 7:00-8:00 Abbvie Breakfast Session. Rheumatologist Timaru Public Hospital Timaru

Transcription

1 Dr Daniel Ching Rheumatologist Timaru Public Hospital Timaru Associate Professor Catherine Stedman Gastroenterologist Clinical Pharmacologist Christchurch Hospital University of Otago 7:00-8:00 Abbvie Breakfast Session

2 HEPATITIS C: Cure in the Community Catherine Stedman Associate Professor of Medicine, University of Otago, Christchurch Gastroenterology Department, Christchurch Hospital Patients who achieve sustained virological response 12 weeks after end of treatment (SVR12) have substantially improved qualities of life, including physical, emotional, and social health. 1 *Cure is defined as undetectable HCV RNA 12 weeks after completion of treatment 1 American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. Available at

3 This meeting was initiated and funded by AbbVie Ltd for the purpose of enhancing medical knowledge and scientific exchange. The views and opinions expressed in the following presentation are those of the presenter and do not necessarily reflect those of AbbVie Ltd. AbbVie Limited does not endorse the use of unregistered products or of products outside of their registered indications. Please refer to the Data Sheets for licensed indications. These can be accessed at through an AbbVie representative or through AbbVie Medical Information on AbbVie Ltd, Wellington. NZ-HCV August

4 Disclosures I am a member of Advisory Boards for AbbVie, Gilead Sciences, Janssen, and MSD. The opinions expressed are my own. 4

5 A brighter future for your patients with Hepatitis C achieving cure in General Practice TOPIC What is hepatitis C and who should be tested? 5 Why should we treat hepatitis C? 5 How to assess patients for treatment 5 What is the treatment and how is it prescribed? 5 How to manage side effects and drug interactions 5 Questions? 5 TIME 5

6 What is hepatitis C? Hepatitis C is a blood-borne virus that causes inflammation of the liver. Hepatitis C infection is often asymptomatic and undiagnosed, and acute infections clear spontaneously in 25% of patients. Chronic infection can damage the liver, and progress to fibrosis, cirrhosis, liver failure, hepatocellular carcinoma, and death. In most patients with chronic HCV, the virus also causes negative effects beyond the liver, including cardiovascular, renal, metabolic, neurological, and immune diseases. 1 Australian Government. National Hepatitis C Resource Manual 2nd Edition. Department of Health; Canberra; Bowden DS et al. Chronic hepatitis C virus infection: genotyping and its clinical role. Future Microbiol. 2006;1(1):

7 Chronic hepatitis C in New Zealand In NZ, more than 50,000 people are estimated to have chronic infection with the hepatitis C virus (HCV). Of these only around 40% have been diagnosed. People who are undiagnosed may not yet be experiencing symptoms, or they may have mild or non-specific symptoms such as fatigue, nausea, or depression. Without treatment, the virus can cause liver cancer, liver failure, and death. HCV has been shown to double the risk of all-cause mortality. Early diagnosis and treatment can prevent many of these complications. Gane E, et al. NZ Med J 2014;127(1407): Cacoub P, etal. Ther Adv Infect Dis 2016 Feb; 3(1):3-14. Ministry of Health. Hepatitis C

8 Proportion of HCV +ve tests (%) Total Viremic Infected (2013) Age of NZ patients with chronic HCV Ministry of Health Ministry of Health modeling HCV Pilots ,000 Median age at diagnosis 7,000 = 47 years Duration of infection >25 years 6, Wellington BoP 5, , ,000 2, , Age (years) Age (years) Hepatitis Foundation of NZ. Report; Nov Gane E, et al. NZ Med J 2014;127(1407):

9 Hepatitis C 7 key questions for age cohort 1. Have you ever injected drugs? 2. Have you received a blood transfusion prior to 1992? 3. Have you ever been in prison? 4. Have you ever had jaundice or abnormal liver function? 5. Have you ever lived in or received health care in South East Asia, India, Middle East, or Eastern Europe? 6. Have you ever received a tattoo or body piercing using unsterile equipment? 7. Does your mother or any household member have HCV? Anyone with a history of jaundice or abnormal liver function should consider a test, particularly if they also have other risk factors. 9

10 How to test for hepatitis C? HCV Antibody test HCV antibodies indicate exposure to virus. Test remains positive after virus cleared or cured; some false positives. HCV RNA test (PCR) Positive viral load confirms current HCV: acute or chronic. Test patients who are: antibody positive previously treated but not tested in past 5 years, previous acute hepatitis (i.e. jaundice or ALT >10x ULN). HCV Genotype (and Subtype) Genotype determines eligibility for treatment with funded drugs. Retest if no genotype result within past 5 years (old assays misclassified genotypes 1 and 6, and were unable to subtype 20% of GT1). Gane, Stedman. NZ Society of Gastroenterology HCV Treatment Guidelines Available at: Accessed December

11 Genotype distribution among NZ patients with chronic HCV 6130 patients genotyped at LabPlus ( ) 0.5% 1% GT1a GT1b GT2 35% 45% GT3 GT4 GT6 56% have genotype 1 7% 12% VIEKIRA PAK and VIEKIRA PAK-RBV are licensed only for genotype 1. Gane E, et al. NZ Med J 2014;127(1407):61 74 AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; 10: May

12 A brighter future for your patients with Hepatitis C achieving cure in General Practice TOPIC What is hepatitis C and who should be tested? 5 Why should we treat hepatitis C? 5 How to assess patients for treatment 5 What is the treatment and how is it prescribed? 5 How to manage side effects and drug interactions 5 Questions? 5 TIME 12

13 Ageing cohort with increasing disease severity Ministry of Health HCV Pilot in Bay of Plenty and Wellington: 788 Fibroscans 11% have established cirrhosis 23% have at least severe fibrosis Unsuccessful scan, 12% Cirrhosis, 11% Severe fibrosis, 12% Mild fibrosis, 65% Most of the remaining patients (F0-F2) would be suitable for treatment in the community, according to local Guidelines. Hepatitis Foundation of NZ. Report; Nov Gane, Stedman. NZ Society of Gastroenterology HCV Treatment Guidelines

14 # transplants per annum # HCCs per year Increasing disease burden from chronic hepatitis C Liver Transplants (ANZLTR) Liver Cancer (NZLTU) HCV HBV NASH ALD Other th Australian and New Zealand Liver Transplant Registry. Accessed July

15 Median age at death (years) Chronic hepatitis C reduces life expectancy Premature death (<65 years) and median age at death among all deaths, NYC ( ) 1 25% died prematurely yrs 64% died prematurely 60 yrs 20 0 HCV has been shown to double the rate of all-cause mortality 2 HCV negative HCV infected (All deaths = 619,254) (All deaths = 13,307) 1. Pinchoff J, et al. Clin Infect Dis 2014;58: El-Kamary S, et al. Clin Infect Dis Jul 15; 53(2):

16 Consequences of not treating 8,000 Cirrhosis 1,200 Decompensation 7,000 6,000 5,000 1, , ,000 2,000 1, % treated (status quo) 50% cure rate HCC Liver-related Deaths 10% treated 90% cure rate New treatments could eliminate HCV in NZ by 2030 Gane E, et al. NZ Med J 2014;127(1407):

17 What will it take to eliminate HCV from NZ? Identify the 30,000 patients who remain undiagnosed Target testing in primary care, including point-of-care testing in Prisons, Needle Exchanges, Community Alcohol and Drug Services. Improve access to safe and effective treatments Treat the sickest patients in secondary care, with follow-up monitoring. Offer assessment and treatment for most patients in primary care. Broaden funding to include effective treatment for non-1 genotypes Prevent transmission and reinfection Broaden access to sterile equipment for high-risk activities, and provide education and support to reduce risk factors. Gane E, et al. NZ Med J 2014;127(1407):

18 A brighter future for your patients with Hepatitis C achieving cure in General Practice TOPIC What is hepatitis C and who should be tested? 5 Why should we treat hepatitis C? 5 How to assess patients for treatment 5 What is the treatment and how is it prescribed? 5 How to manage side effects and drug interactions 5 Questions? 5 TIME 18

19 Algorithm for community treatment Treatment is not currently reimbursed for non-cirrhotic patients with genotypes 2 6. No cirrhosis Primary Care Anti-HCV+ HCV RNA+ Fibroscan HCV Genotype Cirrhosis Refer to Secondary Care Genotypes 2-6 Genotype 1 VIEKIRA PAK 2-5% relapse 95-98% cured Refer for specialist assessment, treatment, and monitoring, with long-term follow-up for hepatocellular carcinoma (HCC). Annual review to discuss access. 3 yearly Fibroscan Discharge (avoid reinfection) Ministry of Health HCV Implementation Committee. Clinical pathway for hepatitis C. June

20 Pre-treatment assessment: Fibroscan Non-invasive liver staging Patients with liver stiffness measurement (LSM) >10.5 kpa on Fibroscan or shear wave elastography: refer to secondary care 10.5 kpa 12.5 kpa Non-cirrhotic F1, F2 Transition to cirrhosis F3 Cirrhosis F4 All patients with cirrhosis, or in transition to cirrhosis, should be referred to secondary care for treatment and follow-up. Gane, Stedman. NZSG Treatment Guidelines Available at Accessed December AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version10: May

21 How to assess cirrhosis without a Fibroscan 21 Liver biopsy APRI test (AST to Platelet Ratio Index) Blood count Liver function tests Results from a previous biopsy (within 5 years): refer patients with cirrhosis to secondary care If a FibroScan is unavailable or unsuccessful, test serum markers. Use the free online calculator, and if APRI 1.0 refer to Secondary Care Low platelet count (<100 cells x10 9 L) suggests portal hypertension and risk of AEs: refer to secondary care Low albumin (<35 g/l) suggests cirrhosis: refer to secondary care. All patients with cirrhosis, or in transition to cirrhosis, should be referred to secondary care for treatment and follow-up. Free online APRI calculator at AST= aspartate aminotransferase. 21

22 Pre-treatment assessment: comorbidities Gane, Stedman. NZSG Treatment Guidelines Accessed December AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May University of Liverpool website: Accessed December

23 Pre-treatment assessment: contraindications for VIEKIRA PAK Severe hepatic impairment (Child-Pugh C). Co-administration with drugs that are highly dependent on CYP3A for clearance, are moderate or strong inducers of CYP3A, or are strong inducers or inhibitors of CYP2C8. Hypersensitivity to components or excipients of VIEKIRA PAK. Additional contraindications for VIEKIRA PAK-RBV Pregnancy (including of a partner). History of severe, unstable, or uncontrolled cardiac disease in previous 6 months Haemoglobinopathies (e.g. thalassaemia, sickle-cell anaemia). AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

24 Pre-treatment assessment: pregnancy and contraception Pregnancy is not recommended while using VIEKIRA PAK (Category B3) and contraindicated while using VIEKIRA PAK-RBV (Category X). Talk to all patients about the risks of pregnancy or breastfeeding (for themselves or their female partners). Discuss contraceptive options patients on VIEKIRA PAK-RBV will need two forms of contraception.* *Note: Contraceptives containing ethinyl oestradiol are contraindicated with VIEKIRA PAK and VIEKIRA PAK-RBV. Change any contraceptives well before starting treatment to ensure full coverage. Ensure adequate contraception throughout treatment. Continue contraception for 6 months after the end of treatment. Female patients must have a negative pregnancy test before starting treatment. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

25 A brighter future for your patients with Hepatitis C achieving cure in General Practice TOPIC What is hepatitis C and who should be tested? 5 Why should we treat hepatitis C? 5 How to assess patients for treatment 5 What is the treatment and how is it prescribed? 5 How to manage side effects and drug interactions 5 Questions? 5 TIME 25

26 What treatment is funded for hepatitis C in NZ? VIEKIRA PAK and VIEKIRA PAK-RBV are indicated for the treatment of genotype 1 chronic hepatitis C, including patients with compensated cirrhosis. Duration of therapy and addition of ribavirin are dependent on patient population. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

27 NZ Medsafe-approved regimen: non-cirrhotic patients Type of hepatitis C (HCV) Treatment Duration Genotype 1a (or mixed/unsubtypeable GT1) VIEKIRA PAK-RBV* 12 weeks Genotype 1b VIEKIRA PAK 12 weeks *VIEKIRA PAK (without RBV) can be considered for non-cirrhotic treatment-naïve patients with genotype 1a; however, addition of RBV is recommended for most GT1a patients to maximise antiviral efficacy. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

28 Constituents of VIEKIRA PAK Co-formulated paritaprevir/ritonavir (PTV/r) 75 mg/50 mg plus ombitasvir (OBV) 12.5 mg tablets Dasabuvir (DSV) 250 mg tablets VIEKIRA PAK is taken with food, as three tablets in the morning and one in the evening. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

29 Constituents of VIEKIRA PAK-RBV Co-formulated paritaprevir/ritonavir (PTV/r) 75 mg/50 mg plus ombitasvir (OBV) 12.5 mg tablets Dasabuvir (DSV) 250 mg tablets Ribavirin, weight-based dose, 200 mg tablets Example: 1000mg RBV dose for a patient 75kg Ribavirin is a synthetic nucleoside analogue with HCV antiviral activity. Most patients should start on 1000 or 1200 mg per day, depending on bodyweight. Some (e.g. with renal dysfunction or vascular disease) should start with a lower dose. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

30 SVR12 (%) Efficacy in HCV genotype 1 patients without cirrhosis / / 33 Prior relapse 36/ 36 26/ / 87 32/ / / 210 Prior relapse Prior partial response Prior null response Treatment-naïve GT1a GT1b SVR12 is sustained virological response, defined as undetectable HCV RNA 12 weeks after the end of treatment. Patients who reach SVR12 can be said to have achieved cure of their HCV. Prior partial response Prior null response Previous treatment with pegifn/rbv Treatmentnaïve Pooled trial data from 1025 patients. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

31 SVR12 (%) Efficacy in HCV genotype 1 patients without cirrhosis GT1a GT1b / 50 33/ 33 Prior relapse 36/ 36 26/ 26 Prior partial response 83/ 87 32/ 32 Prior null response 403/ / 210 Treatmentnaïve Prior relapse Prior partial response Prior null response Treatment-naïve Previous treatment with pegifn/rbv Overall SVR12 was 97% with the recommended regimen in noncirrhotic patients: GT1a: 96% GT1b: 100% Pooled trial data from 1025 patients. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

32 Access to treatment All prescribers, including GPs, can access fully funded VIEKIRA PAK or VIEKIRA PAK-RBV for patients with GT1 HCV. AbbVieCare Pharmacies have been trained and accredited to dispense these treatments, to provide relevant information about the medication to the patient, check for potential drug-drug interactions, and support patients on treatment. Patient do not need to pay any pharmacy charges associated with accessing VIEKIRA PAK. 32

33 Process for access to VIEKIRA PAK 1 Select the most convenient AbbVie Care Pharmacy for your patient from the list on or More than 280 pharmacies are currently accredited. If a patient cannot access an AbbVie Care pharmacy please contact PHARMAC at Viekira@pharmac.govt.nz or

34 Process for access to VIEKIRA PAK 1 Select the most convenient AbbVie Care Pharmacy for your patient 2 Complete PHARMAC s Request Form online at or print and fax the form. 34

35 PHARMAC online request form 35

36 PHARMAC form to print or fax 36

37 Process for access to VIEKIRA PAK 1 Select the most convenient AbbVie Care Pharmacy for your patient 2 Complete PHARMAC s Request Form online or print and fax it. Write a prescription for VIEKIRA PAK or VIEKIRA PAK-RBV for your patient to take to the selected AbbVie Care Pharmacy. Advise the patient that the pharmacist will call to let them know when the medicine has arrived and is ready for collection. (It may take up to a week). They will need to take their prescription to the AbbVieCare pharmacy. Dispensing will be on a monthly basis. 37

38 A brighter future for your patients with Hepatitis C achieving cure in General Practice TOPIC What is hepatitis C and who should be tested? 5 Why should we treat hepatitis C? 5 How to assess patients for treatment 5 What is the treatment and how is it prescribed? 5 How to manage side effects and drug interactions 5 Questions? 5 TIME 38

39 Likelihood of common side effects VIEKIRA PAK VIEKIRA PAK-RBV Based on adverse events that occurred 5% more often with VIEKIRA PAK and VIEKIRA PAK-RBV than with placebo. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

40 Monitoring during treatment: uncomplicated non-cirrhotic patients Week 2 Week 4 Week 8 Week 12 Week 24 GT1a GT1b FBC FBC FBC - LFTs VIRAL LOAD Undetectable virus = SVR12 = CURE During treatment, check adherence, ask about side effects, and check any new comedications for potential drug interactions. End of treatment Haemoglobin levels should be monitored in patients taking VIEKIRA PAK-RBV. Modify RBV dose according to Data Sheet and Guidelines for patients who develop anaemia. FBC= Full Blood Count VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May Gane, Stedman. NZ Society of Gastroenterology HCV Treatment Guidelines

41 Monitoring during treatment: uncomplicated non-cirrhotic patients Week 2 Week 4 Week 8 Week 12 Week 24 GT1a GT1b FBC FBC FBC - LFTs Test viral load Undetectable virus = SVR12 = CURE End of treatment Haemoglobin levels should be monitored in patients taking VIEKIRA PAK-RBV. Modify RBV dose according to Data Sheet and Guidelines for patients who develop anaemia. FBC= Full Blood Count VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May Gane, Stedman. NZ Society of Gastroenterology HCV Treatment Guidelines

42 Management of side effects Fatigue: Check haemoglobin level and adjust ribavirin dosage accordingly. Nausea: Consider ondansetron at the standard recommended dosage. Insomnia: Consider advice on improved sleep hygiene. If severe, consider using temazepam 10 mg or zopiclone 3.75 mg when required. Skin rash: Continue treatment. Use 10% urea cream, Pinetarsol, or fatty cream. Consult DermNet NZ. Management of common comorbidities Depression: Citalopram or escitalopram are allowed. Gane, Stedman. NZ Society of Gastroenterology HCV Treatment Guidelines Accessed December

43 AbbVie reporting of adverse events An adverse event is any untoward medical occurrence in a patient given a medicinal product, including death, hospitalisation, surgery, or any worsening of a patient s condition; overdose, abuse, or misuse; inadvertent, accidental, or occupational exposure; use during pregnancy or breastfeeding; lack of effect; medication error; suspected transmission of an infectious agent via a medicinal product; off-label use with an adverse event; and unexpected benefit. Please report any adverse event regarding VIEKIRA PAK or VIEKIRA PAK-RBV anzpv@abbvie.com or phone: or NZ s National Centre for Adverse Reactions Monitoring (CARM): carmnz@otago.ac.nz 43

44 Patients with hepatitis C often have many comorbidities with associated medications Depression Cirrhosis Renal disease Substance misuse Chronic pain Cognitive impairment Respiratory disease/ COPD Hypertension Cardiovascular disease Hyperlipidaemia HIV co-infection Psychosis Diabetes Louie, KS. BMC Infect Dis. 2012; 12:

45 VIEKIRA PAK: drug interactions All direct-acting antivirals interact with drug metabolising enzymes or transporters. Ribavirin is also associated with drug interactions. Drug interactions could reduce clinical efficacy and/or cause adverse events. All patients need a careful medicines review before treatment. Most potential drug interactions can be managed by adjustment of dose and/or monitoring during treatment for any potential adverse reactions. No dose adjustment is needed for VIEKIRA PAK itself. Some medications are contraindicated, and must be stopped, or substituted with alternatives, during treatment. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May University of Liverpool website: Gane, Stedman. NZSG Treatment Guidelines Accessed December

46 Where to find information on interactions Medsafe-approved Data Sheets: Please first refer to the New Zealand label for all contraindicated medications, drug interactions, and precautions. University of Liverpool website: Searchable by alphabetical list of drugs or by drug class. AbbVie Medical Information: , AbbVie can answer questions based on Data on File, built up through the clinical development programme and post-marketing experience. 46

47 Printed resource: AbbVie Guide to Managing DDIs 47

48 NZ Data Sheet: drug interactions with VIEKIRA PAK This is not an exhaustive list. Please refer to the full Data Sheets and the University of Liverpool s Hep-Drug Interaction website. * Contraindicated for treatment of pulmonary arterial hypertension; for erectile dysfunction, reduced dose frequency is recommended. Contraindicated in Liverpool website but not NZ Data Sheet. Weak interaction. AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May University of Liverpool HIV & HEPATITIS Pharmacology Group. Hepatitis Drug Interactions. 48

49 Online resource: University of Liverpool s website Liverpool HIV & HEPATITIS Pharmacology Group. Hepatitis Drug Interactions. Accessed July

50 Example of drug-interaction search: methadone Search by either generic abbreviations (OBV/PTV/r + DSV) or Trade name (VIEKIRA PAK) Liverpool HIV & HEPATITIS Pharmacology Group. Hepatitis Drug Interactions. Accessed July

51 Example of drug-interaction search: atorvastatin Liverpool HIV & HEPATITIS Pharmacology Group. Hepatitis Drug Interactions. Accessed July

52 For more information, links, and resources: username GT1, password GT1 52

53 BPAC NZ Treatment Guidelines: primary care Best Practice Journal. Treatment of hepatitis C has changed. September 2016; Best Practice Journal. Hepatitis C: you can t treat it if you don t test for it. June 2017;

54 NZ Treatment Guidelines endorsed by NZSG, ASID, and RNZCGPS. Available at: Gane, Stedman. NZ Society of Gastroenterology HCV Treatment Guidelines Accessed December

55 Webinar for GPs Goodfellow webinar, available from: 55

56 NZ Doctor e-learning

57 PHARMAC information for clinicians Video: How one Auckland practice identifies patients for treatment PHARMAC. 28 July

58 Ministry of Health Ministry of Health e-learning. Available at: 58

59 Summary: VIEKIRA PAK and VIEKIRA PAK-RBV High certainty of cure* EFFICACY: SVR12 = 97% for patients with genotype 1 HCV, including cirrhotics and those who previously failed with pegifn/rbv. Low rates of failure RESISTANCE PROFILE: Low rates of virologic failure (<2%) Low rates of discontinuation SAFETY: Well-tolerated, with low rates of discontinuations due to adverse events (1%) *Cure defined as 25 IU/mL HCV RNA 12 weeks after end of treatment (SVR12). SVR12 for VIEKIRA PAK and VIEKIRA PAK-RBV was 97% in patients with GT1 HCV (with or without cirrhosis; pooled analysis Phase III trial cohorts; n=1088). AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; version 10: May

60 A brighter future for your patients with Hepatitis C achieving cure in General Practice TOPIC What is hepatitis C and who should be tested? 5 Why should we treat hepatitis C? 5 How to assess patients for treatment 5 What is the treatment and how is it prescribed? 5 How to manage side effects and drug interactions 5 Questions? 5 TIME 60

61 Thank you 61

62 VIEKIRA PAK and VIEKIRA PAK-RBV are fully funded prescription medicines on the Pharmaceutical Schedule with an alternative Xpharm distribution arrangement. Please review full Data Sheets before prescribing. These are available from AbbVie Limited at and from Medsafe at VIEKIRA PAK is a combination therapy containing ombitasvir/paritaprevir/ritonavir (12.5/75/50/ mg) tablets and dasabuvir (250 mg) tablets. VIEKIRA PAK-RBV contains VIEKIRA PAK, plus ribavirin (200 mg*) tablets. INDICATIONS: VIEKIRA PAK and VIEKIRA PAK-RBV are indicated for the treatment of genotype 1 chronic hepatitis C (including patients with compensated cirrhosis (Child-Pugh A), co-infection with HIV-1, and those who have had a liver transplant). CONTRAINDICATIONS: Severe hepatic impairment (Child-Pugh C); Hypersensitivity to components or excipients of VIEKIRA PAK or VIEKIRA PAK- RBV; or Concomitant administration with atorvastatin, carbamazepine, colchicine (in renal or hepatic impairment), efavirenz, ergotamine or its derivatives, ethinyloestradiol-containing medicines (e.g. oral contraceptives), fusidic acid, gemfibrozil, oral midazolam, phenobarbital, phenytoin, ranolazine, rifampicin, St. John s wort (Hypericum perforatum), salmeterol, sildenafil (when used for pulmonary arterial hypertension), simvastatin, terfenadine, or triazolam. Please refer to the full Data Sheets for a complete list of contraindicated medicines. VIEKIRA PAK-RBV: As above, and: Pregnancy, including men whose partners are pregnant (Category X); Severe cardiac disease in previous 6 months; or Haemoglobinopathies (e.g. thalassaemia or sickle-cell anaemia). PRECAUTIONS: Not recommended for patients with moderate hepatic impairment (Child-Pugh B); For patients with compensated cirrhosis, monitor for clinical signs and symptoms of hepatic decompensation (such as ascites, hepatic encephalopathy, or variceal haemorrhage), and monitor liver function including bilirubin and alanine transaminase (ALT) according to local recommendations; Discontinue treatment in patients who develop evidence of hepatic decompensation or if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalised ratio (INR); Not recommended for concomitant use with atazanavir/ritonavir, everolimus, fluticasone or other glucocorticoids metabolised by CYP3A, lopinavir/ritonavir, quetiapine, rilpivirine, sirolimus, or tacrolimus; Not recommended for patients with HCV genotypes other than 1; Not studied in patients previously treated with VIEKIRA PAK or other direct-acting antiviral agents; Not studied in patients younger than 18 or older than 70 years; Not recommended in pregnancy (Category B3); Discontinue breastfeeding prior to initiation; and Screen all patients for hepatitis B (HBV) before initiation of treatment and monitor coinfected patients and those with past HBV infection according to current clinical guidelines. VIEKIRA PAK-RBV: As above, and: Obtain a negative pregnancy test prior to initiation of therapy; Ensure patients use two forms of contraception during treatment and for 6 months after treatment (with monthly pregnancy tests during this time); Monitor haemoglobin in patients with preexisting cardiac disease; Monitor uric acid in patients predisposed to gout; and Reduce dose of ribavirin and monitor haemoglobin in patients with renal impairment. INTERACTIONS: See Data Sheets for medicines for which dose adjustment and/or monitoring should be considered. ADVERSE EFFECTS: Fatigue, nausea, pruritus, insomnia and asthenia. VIEKIRA PAK-RBV: As above, and: anaemia, diarrhoea, vomiting, decreased appetite, dizziness, headache, sleep disorder, cough, dyspnoea, dry skin, and rash. DOSAGE AND ADMINISTRATION: The recommended dose is two ombitasvir/paritaprevir/ritonavir (12.5/75/50/ mg) tablets once daily (in the morning) and one dasabuvir (250 mg) tablet taken with food twice daily (morning and evening) for 12 weeks. VIEKIRA PAK-RBV: As above, for 12 or 24 weeks, with ribavirin. The recommended dose of ribavirin depends on a patient's bodyweight (<75 kg = 1000 mg; 75 kg = 1200 mg), and should be taken with food in two divided doses (morning and evening). Ribavirin monotherapy is not effective and ribavirin must only be used in combination with VIEKIRA PAK. See full Data Sheets for additional information on duration of therapy and use in special populations. *Other presentations, including ribavirin 400 mg and 600 mgtablets, are not currently available in New Zealand. AbbVie is a registered Trademark of AbbVie Inc. VIEKIRA PAK is a registered Trademark of AbbVie Ireland Unlimited Company AbbVie Limited, PO Box 11437, Manners Street, Wellington 6142, New Zealand. NZ-HCV TAPS PP8614. August 2017.

63 Who is at risk for HCV infection in NZ? In NZ, ~90% of people with chronic HCV were infected via injecting drug use. Most were years old between 1970 and Hepatitis C has not been transmitted via blood transfusion in NZ since Immigrants from countries with endemic HCV may have been infected more recently (e.g. South East Asia, India, the Middle East, or Eastern Europe). Unsafe tattooing or body piercing, or other blood-blood contact (e.g. sporting, sexual, violent, or occupational activities). Mother to child transmission during birth (5% risk), and occasional transmission within households. All children of women with chronic HCV should be tested (>1 year old). Prison inmates have relatively high rates of infection with HCV. Anyone with a history of jaundice or abnormal liver function should consider a test, particularly if they also have other risk factors. Gane E, et al. NZ Med J 2014;127(1407):