Dr John Perry. Gastroenterologist Waitemata DHB Waitemata Gastroenterology Waitemata Endoscopy. 7:00-7:55 Abbvie Breakfast Session

Transcription

1 Dr John Perry Gastroenterologist Waitemata DHB Waitemata Gastroenterology Waitemata Endoscopy 7:00-7:55 Abbvie Breakfast Session

2 Hepatitis C in New Zealand: New Treatment for use in primary care

3 Disclaimer The views and opinions expressed in the following presentations are those of the presenter and do not necessarily reflect those of AbbVie Ltd. AbbVie Ltd does not endorse the use of unregistered products or products outside of their registered indications. Please refer to the Product Information or Data Sheet for licensed instructions.

4 Hepatitis C what is it? RNA virus (Flavivirus) Discovered 1989 in post-transfusion nona, nonb hepatitis Blood-to-blood transmission HCV has only 1% infectivity of HBV

5 HCV Symptoms Many have none Fatigue, brain fog A few have a cryoglobulin rash, renal disease Symptoms and signs of advanced liver disease If left untreated Progressive fatigue Liver disease cirrhosis hepatocelluar carcinoma Increase in all-cause mortality It s curable!!!!! 5

6 Natural History of Chronic Hepatitis C 100% 80% 60% 40% 68% 37% 35% Stage 0-1 fibrosis Stage 2-3 fibrosis 20% 24% 30% Cirrhosis 0% 8% Duration of infection (years) 10% Death

7 Hepatitis C who is at risk?

8 Hepatitis C how is it transmitted? 1. Transmission through blood products Since no post-transfusion hepatitis Immigrants from countries where HCV is endemic may have been exposed via this route 2. ~90% HCV in NZ through injecting drug use» Peak age of infection years» Peak incidence <5% via unsafe tattooing or body piercing 4. Mother-to-child transmission in 5% No impact of mode of delivery Test all children of HCV+ women Wait until >12 months (maternal anti-hcv) 5. Sexual transmission negligible unless: MSM HIV+ Trauma, menstruation Gane E, et al. NZ Med J ; 1407: Total number infected >50,000 Estimated undiagnosed = 40 50%

9 Hepatitis C 7 Key Questions 1. Have you ever injected drugs? 2. Have you received blood transfusion prior to 1992? 3. Have you ever been in prison? 4. Have you ever had jaundice or abnormal liver fn? 5. Have you ever lived in or received health care in SE Asia, Indian subcontinent, Middle East or Eastern Europe? 6. Does your mother or household member have chronic HCV infection? 7. Have you ever received a tattoo or body piercing using unsterile equipment?

10 Proportion of HCV+ve tests (%) Total Viremic Infected (2013) Hepatitis C Age in NZ Ministry of Health Ministry of Health modeling HCV Pilots ,000 7,000 6,000 5,000 4,000 Median age at diagnosis = 47 years Duration of infection 3,000 >25 years 2,000 1,000 - Age (years) Hepatitis Foundation Report Nov Age (years) Gane E, et al. NZ Med J ; 1407:61 74.

11 Hepatitis C Disease severity in NZ Ministry of Health HCV Pilot in Bay of Plenty and Wellington: 788 Fibroscans 11% have established cirrhosis 23% have at least severe fibrosis Hepatitis Foundation Report Nov 2014.

12 The WHO has spoken! To eliminate HCV as a public threat by 2030 Large scale reductions in new transmissions of HCV People becoming ill from or dying from HCV To a level where HCV no longer represents a major health concern Numerically: 65% reduction in HCV-related mortality 80% eligible people receive Hep C treatment 90% reduction in HCV transmission

13 New treatments could eliminate HCV in New Zealand within 15 years Total numbers living with chronic HCV 60,000 50,000 40,000 30,000 20,000 10,000-1% treated 50% cured 2% treated (i.e. only cirrhotics) 90% cured 10% treated 90% cured Gane E, et al. NZ Med J ; 1407:61 74.

14 July August September October November December January February March April May June Number treated with VIEKIRA PAK Treatment Uptake Trends by month Numbers per month (total period July 2016-June 2017) AVHEC, August 2017

15 What will it take to eliminate HCV from NZ? Total number infected >50,000 Estimated undiagnosed = 40 50% Identify those who remain undiagnosed Targeted testing in Primary Care Point-of-care testing in Prisons, Needle Exchange (NEX), Community Alcohol and Drug Services (CADS) Full funding of treatment, and quadruple numbers treated by 2020 (2,000 patients per annum) by moving treatment out to the community GPs NEX, CADS, Prisons treatment as prevention

16 TESTING FOR HEPATITIS C

17 Hepatitis C tests HCV Antibody test Exposure to virus, remains positive after virus cleared or cured, some false positives, HCV RNA Indicates current infection HCV Genotype Subtype of the virus, determines eligibility for treatment with funded drugs Testing for HCV: In some areas you now only need to request the HCV Antibody test

18 Test of cure One test at 12 weeks following end of treatment We will be checking and testing will only be done if timing is correct On request form: HCV treatment completed.... /.... /.... HCV RNA on.... /.... /....

19 Treatments for hepatitis C: prescribing and monitoring guidelines

20 What s New??? No more interferon! Two new Direct Acting Antivirals (DAAs) funded in NZ: Viekira Pak for Genotype 1 Harvoni for decompensated cirrhosis Who can prescribe it? Viekira Pak You!!! Harvoni secondary care Funding is available for GPs depending on your DHB 21

21 Auckland Regional HealthPathways

22 Ministry of Health e-learning

23 Ministry of Health BPAC

24 HCV Genotype distribution in New Zealand 6130 patients genotyped at LabPlus ( ) 56% have genotype 1 VIEKIRA PAK and VIEKIRA PAK-RBV are only licensed for genotype 1. Gane E, et al. NZ Med J ; 1407:61 74 AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August 2016.

25 VIEKIRA PAK: mode of action 1. EARLY INHIBITION NS3/4A protease inhibitor Paritaprevir (PTV) Translation and polyprotein processing HCV Receptor binding and endocytosis Fusion and uncoating (+) RNA ER ER Transport and release GOLGI RNA replication 3. MID-/LATE LIFECYCLE INHIBITION NS5A inhibitor Ombitasvir (OBV) Replication, virion assembly, and egress 2. MID-LIFECYCLE INHIBITION non-nucleoside NS5B polymerase inhibitor Dasabuvir (DSV) Lindenbach & Rice. Nature 2005:436; AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August

26 VIEKIRA PAK: Indication 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; August 2016.

27 VIEKIRA PAK: Pre-treatment assessment HCV GENOTYPE eligible for PHARMAC funded Rx VIEKIRA PAK-RBV in subtype 1a VIEKIRA PAK in subtype 1b FIBROSCAN if <10.5 KPa suitable for GP treatment FULL BLOOD COUNT: Low Hb monitor Hb closely. MEDICINES REVIEW: Consider potential drug-drug interactions between VIEKIRA PAK and usual medications PREGNANCY: VIEKIRA PAK and RBV contraindicated Women during treatment Men during treatment, and for 6 months after if taking ribavirin COMORBIDITIES: RBV is contraindicated in severe or unstable cardiac disease and haemoglobinopathies

28 Fibroscan (Transient Elastography) Ultrasound transducer Mild amplitude, 50 Hz Elastic sheer wave Velocity correlates with stiffness, fibrosis mins Available by ereferral by GPs for HCV Results 4 5 kpa = normal >10.5 kpa= advanced fibrosis >12.5 kpa = cirrhosis

29 VIEKIRA PAK: MEDSAFE LABEL Type of hepatitis C (HCV) Treatment Duration Genotype 1a (or mixed/unsubtypeable GT1) VIEKIRA PAK-RBV* 12 weeks Genotype 1b VIEKIRA PAK 8 weeks AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August 2016.

30 SVR12 = CURE (%) VIEKIRA PAK: Efficacy of recommended regimen in HCV GT 1 without cirrhosis / 50 GT1a GT1b Overall Cure was 97% 33/ 33 96% in GT 1a 100% in GT 1b 36/ 36 26/ 26 83/ 87 32/ / 210/ Prior relapse Prior partial response Prior null response Treatment-naïve Previous treatment with pegifn/rbv

31 SVR (% of patients) Treatment-naïve non-cirrhotic patients: VIEKIRA PAK±RBV GT 1a GT 1b % 90.2% % 99.0% Adding RBV improves SVR rates for patients with GT1a / /205 VIEKIRA PAK-RBV VIEKIRA PAK 0 209/ /209 VIEKIRA PAK-RBV VIEKIRA PAK Ferenci P, et al. N Eng J Med 2014;370:

32 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. Paritaprevir is boosted with ritonavir (a CYP3A inhibitor that increases systemic exposure of paritaprevir). AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August 2016.

33 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 (patient 75kg) Ribavirin is a synthetic nucleoside analogue with HCV antiviral activity. Most patients should start on 1000 or 1200 mg, depending on bodyweight: < 75 kg = 1000mg (400mg breakfast, 600mg dinner) >= 75 kg = 1200mg (600mg bd)

34 VIEKIRA PAK-RBV: Safety Monitoring Ribavirin (RBV) can cause dose-related haemolysis and anaemia Haemoglobin should be monitored during treatment, and the dose of RBV reduced if necessary. Some patients should start with a lower dose.* Consult Data Sheets and Guidelines for recommendations on starting dose of RBV, monitoring during treatment, and dose reduction or discontinuation.* 8.5% of patients required RBV dose to be reduced due to anaemia. The rate of SVR12 in these patients was 99% (i.e. dose reduction did not affect effectiveness). Usual dose adjustment is: Hb drops to <100 g/l = 400mg bd Hb drops to <85 g/l = stop Ribavirin, weekly FBC, restart 200mg bd when >100 g/l *RBV should be used with caution in certain patients, such as those with renal dysfunction, severe vascular disease, or recent transplant. Reduce starting dose and monitor according to recommendations.

35 VIEKIRA PAK-RBV: Safety Monitoring during 12 week course Genotype 1a Check FBC for Hb - weeks 2, 4, 8 If Hb < 100 adjust ribavirin dose (see guidelines) Genotype 1b No monitoring required 12 weeks after treatment HCV RNA to check for cure

36 VIEKIRA PAK-RBV: How to manage side-effects of the ribavirin (RBV) Fatigue: Check haemoglobin and adjust RBV dosage Nausea: Consider ondansetron. Skin rash: Use 10% urea cream, Pinetarsol, or fatty cream. Consult DermNet NZ. Insomnia: Consider advice on improved sleep hygiene. If severe, then consider temazepam at full recommended dose OR zopiclone at half the recommended dose. Depression (comorbidity): Citalopram/escitalopram are allowed. Gane, Stedman. NZ Society of Gastroenterology HCV Treatment Guidelines Available at: Accessed July 2016.

37 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 regimen, with low rates of discontinuations due to adverse events (1.0%) *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; August

38 Management Algorithm for Patients with HCV Primary Care Secondary Care Discharge (avoid reinfection) Ministry of Health HCV Implementation Committee. Clinical pathway for hepatitis C. June 2016.

39 What about Patients infected with HCV GT 2 6? Self-funded generic daclatasvir-sofosbuvir for 12 weeks available for patients ineligible for PHARMAC funded treatment Import via internet-based organisations such as the Fix HepC Buyers Club ( Chance of cure will be 95% Simple GP guide on HealthPathways, e-learning and BPAC

40 Treatments for hepatitis C: management of drug interactions

41 VIEKIRA PAK: Drug drug interactions 42 All direct-acting antivirals interact with drug metabolising enzymes or transporters. Ribavirin is associated with additional 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; August University of Liverpool website: Gane, Stedman. NZSG Treatment Guidelines Available at

42 Patients with hep C often have many comorbidities with associated medications Cirrhosis Depression Renal disease Substance misuse Chronic pain Cognitive impairment Respiratory disease/ COPD Hypertension Cardiovascular disease Hyperlipidaemia HIV co-infection Louie, KS. BMC Infect Dis. 2012; 12: 86. Psychosis Diabetes

43 Where to find information on interactions 1. Medsafe-approved Data Sheets: Please first refer to the New Zealand label for all contraindicated medications, drug interactions, and precautions. 2. University of Liverpool website: Searchable by alphabetical list of drugs or by drug class. Mobile apps are available. 3. AbbVie Medical Information: , AbbVie can answer questions based on Data on File, built up through the clinical development programme and post-marketing experience.

44 NZ Data Sheet: drug interactions with VIEKIRA PAK Refer to the Data Sheet and the University of Liverpool website for full information No restrictions Abacavir Buprenorphine Dolutegravir Duloxetine Emtricitabine Escitalopram Lamivudine Metformin Methadone Naloxone Norethisterone Paracetamol Raltegravir Sulfamethoxazole Tenofovir Trimethoprim * Contraindicated for treatment of pulmonary arterial hypertension; for erectile dysfunction, reduced dose frequency is recommended. Contraindicated in Liverpool website but not NZ Data Sheet. Caution / dose adjustment / clinical monitoring Alprazolam Amiodarone Amlodipine Atazanavir Atorvastatin Cyclosporine Darunavir Diazepam Digoxin Fluticasone Flecainide Furosemide Ketoconazole Lidocaine (systemic) Mexiletine Omeprazole Pravastatin Propafenone Rosuvastatin Tacrolimus Quetiapine Contraindicated/ not recommended Carbamazepine Colchicine in renal or hepatic impairment Efavirenz Ergotamine and its derivatives Ethinyloestradiol-containing products Fusidic Acid Gemfibrozil Oral Midazolam Phenobarbital Phenytoin Rifampicin Rilpivirine Ritonavir Sildenafil * Simvastatin Salmeterol St. John s Wort (Hypericum Perforatum) Terfenadine Triazolam AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August University of Liverpool website: 45

45 VIEKIRA PAK drug-drug interactions: University of Liverpool Website Liverpool HIV & HEPATITIS Pharmacology Group. Hepatitis Drug Interactions. (Accessed July 2016).

46 AbbVie Care Pharmacy Programme

47 PHARMAC Request form

48 49

49 Case studies

50 Case #1: Sarah 34 yr old woman Mother of 2 Very fatigued Brief period IVDU aged 19 Wonders if might have Hepatitis C

51 Case #1: Sarah 34 yr old woman HCV Ab +ve HCV RNA 5.6 log IU/mL Genotype 1a Can you treat her?

52 VIEKIRA PAK: Pre-treatment assessment HCV ANTIBODY TEST exposure to virus HCV RNA PCR TEST active HCV infection HCV GENOTYPE eligible for PHARMAC funded Rx VIEKIRA PAK-RBV in subtype 1a VIEKIRA PAK in subtype 1b FIBROSCAN if <10.5 KPa suitable for GP treatment FULL BLOOD COUNT: Low Hb monitor Hb closely. MEDICINES REVIEW: Consider potential drug-drug interactions between VIEKIRA PAK and usual medications PREGNANCY: VIEKIRA PAK and RBV contraindicated Women during treatment Men during treatment, and for 6 months after if taking ribavirin COMORBIDITIES: RBV is contraindicated in severe or unstable cardiac disease and haemoglobinopathies

53 Case #1: Sarah 34 yr old woman HCV Ab +ve HCV RNA 5.6 log IU/mL Genotype 1a Hb 137 Fibroscan 5.6 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care)

54 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 AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August 2016.

55 SVR12 (%) Non-cirrhotic patients: efficacy with NZ s recommended regimen / / 33 Prior relapse 36/ 36 26/ 26 Prior partial response Prior relapse Prior partial response Prior null response Treatment-naïve 95 83/ / 32 Prior null response 403/ 420 Previous treatment with pegifn/rbv / 210 Treatmentnaïve GT1a GT1b AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August Overall SVR12 was 97% with the recommended regimen in noncirrhotic patients: GT1a: 96% GT1b: 100% Pooled trial data

56 VIEKIRA PAK: Pre-treatment assessment HCV ANTIBODY TEST exposure to virus HCV RNA PCR TEST active HCV infection HCV GENOTYPE eligible for PHARMAC funded Rx VIEKIRA PAK-RBV in subtype 1a VIEKIRA PAK in subtype 1b FIBROSCAN if <10.5 KPa suitable for GP treatment FULL BLOOD COUNT: Low Hb monitor Hb closely. MEDICINES REVIEW: Consider potential drug-drug interactions between VIEKIRA PAK and usual medications PREGNANCY: VIEKIRA PAK and RBV contraindicated Women during treatment Men during treatment, and for 6 months after if taking ribavirin COMORBIDITIES: RBV is contraindicated in severe or unstable cardiac disease and haemoglobinopathies

57 Case #1: Sarah 34 yr old woman HCV Ab +ve HCV RNA 5.6 log IU/mL Genotype 1a Hb 137 Fibroscan 5.6 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care) Comorbidities Medications Treated Depression Mild gastroesophageal reflux disease Citalopram 10mg od Omeprazole 20mg od PRN

58 Drug-drug interactions: Liverpool app University of Liverpool HIV & HEPATITIS Pharmacology Group. Hepatitis Drug Interactions. (Accessed Feb 2016).

59 Drug drug interactions Antidepressants VIEKIRA PAK Citalopram Gastrointestinal agents Omeprazole VIEKIRA PAK Monitor patients for decreased efficacy of omeprazole. Consider increasing omeprazole dose in patients whose symptoms are not well controlled; avoid >40 mg per day. No clinically significant interaction expected. Potential interaction may require monitoring, alteration of drug dosage or timing of administration

60 Case #1: Sarah 34 yr old woman HCV Ab +ve HCV RNA 5.6 log IU/mL Genotype 1a Hb 137 Fibroscan 5.6 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care) Comorbidities Medications Depression Gastroesophageal reflux disease Citalopram 10mg od Omeprazole 20mg PRN Plan: Viekira Pak + Ribavirin 12 weeks FBC 2, 4, 8 weeks Use contraception throughout Progress: No Hb drop weeks 2, 4, 8 HCV RNA negative at 24 weeks Cured!

61 Case #2: Kevin 47 yr old man Part-time carpenter, father Fatigue ++ IVDU aged Some Marijuana now

62 Case #2: Kevin 47 yr old man HCV Ab +ve HCV RNA 4.7 log IU/mL Genotype 1a Hb 143 Fibroscan 7.8 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care)

63 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 AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August 2016.

64 Case #2: Kevin 47 yr old man HCV Ab +ve HCV RNA 4.7 log IU/mL Genotype 1a Hb 143 Fibroscan 7.8 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care) Comorbidities Medications Gout Hypertension Dyslipidaemia Allopurinol 300mg od Cilazapril 5mg od Metoprolol 47.5mg od Simvastatin 20mg nocte

65 Drug drug interactions Beta blockers Metoprolol Anti-Hypertensives Cilazapril Gout Allopurinol Statins Simvastatin VIEKIRA PAK No clinically significant interaction expected. No clinically significant interaction No clinically significant interaction expected Contraindicated: Do not co-administer Causes rhabdomyolysis So stop the statin for 12 weeks of treatment, plus 2 weeks after University of Liverpool. AbbVie Ltd. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe NZ; August 2016.

66 Case #2: Kevin 47 yr old man HCV Ab +ve HCV RNA 4.7 log IU/mL Genotype 1a HB143 Fibroscan 7.8 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care) Comorbidities Medications Gout Hypertension Dyslipidaemia Allopurinol 300mg od Cilazapril 5mg od Metoprolol 47.5mg od Simvastatin 20mg nocte

67 Case #2: Kevin 47 yr old man Plan: 12 weeks Vieikira Pak mg Ribavirin Ribavirin dosing: <75 kg = 400mg mane, 600mg nocte (1000mg) >=75 kg = 600mg bd (1200mg) Contraception important for males too during treatment and for 6 months after 68

68 Drug Caution: illicit/ recreational drugs Interaction Benzodiazepines Midazolam (oral) and triazolam CONTRAINDICATED Concentration of others (e.g. zopiclone) will generally be increased. These need monitoring and possible dose reduction. Temazepam Monitor Consider dose reduction No clinically significant interaction / Heroin University of Liverpool. AbbVie Ltd. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe NZ; August 2016.

69 Case #2: Kevin 47 yr old man Plan: 12 weeks Vieikira Pak mg Ribavirin Ribavirin dosing: <75 kg = 400mg mane, 600mg nocte (1000mg) >=75 kg = 600mg bd (1200mg) Contraception important for males too during treatment and for 6 months after Limit Marijuana use Monitoring on treatment: FBC weeks 2, 4, 8. Hb baseline 143 Week Week Week

70 Case #2: Kevin 47 yr old man Plan: 12 weeks Vieikira Pak mg Ribavirin Ribavirin dosing: <75 kg = 400mg mane, 600mg nocte (1000mg) >=75 kg = 600mg bd (1200mg) Contraception important for males too during treatment and for 6 months after Limit Marijuana use Monitoring on treatment: FBC weeks 2, 4, 8. Hb baseline 143 Week Week Week If Hb <100 g/l then decrease Ribavirin to 400mg bd If Hb <85 g/l stop Ribavirin, weekly Hb, restart 200mg bd once Hb >100 HCV RNA 12 weeks post Rx negative Cured! 71

71 Case #3: Chen 53 yr old man 72 Baker Grew up in Cambodia 3 kids No recalled needle exposure Struggling with fatigue and 3 am starts

72 Case #3: Chen 53 yr old man HCV Ab +ve HCV RNA 4.7 log IU/mL Genotype 1b Hb 157 g/l Fibroscan 4.5 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care) Comorbidities Medications Asthma Flixotide inhaler BD Ventolin inhaler PRN Viagra 100mg PRN

73 Drug drug interactions Bronchodilator Salbutamol Ventolin VIEKIRA PAK No clinically significant interaction expected. Corticosteroid Fluticasone propionate Flixotide Erectile dysfunction Sildenafil Viagra Not recommended unless potential benefits outweigh the risk of systemic corticosteroid effects. Fluticasone is a substrate of CYP3A4; exposure expected to increase, reducing plasma cortisol. Cushing's syndrome and adrenal suppression have been reported with ritonavir. Use beclomethasone as an alternative. Coadministration has not been studied. Sildenafil is a substrate of CYP3A4 and its exposure may increase due to CYP3A4 inhibition by ritonavir resulting in increased potential for sildenafil-associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope. Use sildenafil for the treatment of erectile dysfunction with caution at reduced doses of 25 mg every 48 hours with increased monitoring for adverse events. University of Liverpool. AbbVie Ltd. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe NZ; August 2016.

74 Steroids Beclazone, QVAR Eumovate cream University of Liverpool.

75 Case #3: Chen 53 yr old man HCV Ab +ve HCV RNA 4.7 log IU/mL Genotype 1b Hb 157 g/l Fibroscan 4.5 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care) Comorbidities Medications Asthma Flixotide inhaler BD switch to QVAR Ventolin inhaler PRN Viagra 100mg PRN decrease to 25mg carefully

76 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 8 weeks AbbVie Limited. VIEKIRA PAK and VIEKIRA PAK-RBV Data Sheets. Medsafe New Zealand; August 2016.

77 VIEKIRA PAK-RBV: Safety Monitoring during 12 week course in noncirrhotic patients Week 2 Week 4 Week 8 Week 12 Week 24 GT1a Hb Hb Hb - TEST VIRAL LOAD GT1b SVR12 = CURE During treatment, check adherence, ask about side effects, and look up any new co-medications (for potential DDIs). Gane, Stedman. NZSG Treatment Guidelines Available at Hb = haemoglobin. LFT = liver function tests. End of treatment

78 Case #3: Chen 53 yr old man HCV Ab +ve HCV RNA 4.7 log IU/mL Genotype 1b Hb 157 g/l Fibroscan 4.5 kpa (= mild fibrosis, <10.5 is suitable for treatment in primary care) Comorbidities Medications Asthma Flixotide inhaler BD switch to QVAR Ventolin inhaler PRN Viagra 100mg PRN decrease to 25mg carefully Plan: 8 weeks Viekira Pak No bloods until 12 week post treatment HCV RNA Cured!

79 Summary Hepatitis C is a curable disease Test for it if History of IVDU Other risk factors Reflex testing for HCV RNA and genotype Genotype 1 patients without cirrhosis can be treated in primary care from October 1 st Viekira Pak: Minimal side-effects High certainty of a cure Avoid drug interactions Without treatment in primary care we will only scratch the surface. 80

80 It s going to get a lot easier 81

81 TO ELIMINATE HCV FROM NZ