12/12/2014 Pre-Conference Nurse’s Course Mr Ricky Gellissen Imperial College Healthcare NHS Trust, London How will new treatments affect nursing practice? Ricky Gellissen ([email protected]) Imperial College Healthcare NHS Trust, London H.I.V. H.C.V. 1 12/12/2014 Glossary • • • • Sustained Virological Response (SVR), or Viral Cure - A term used when a patient’s HCV RNA remains undetectable six months after stopping treatment. SVR is also known as viral cure. Rapid Virological Response (RVR) -Measure of treatment response at week 4. Indicated by undetectable HCV RNA (confirmed by HCV PCR) after 4 weeks of treatment. Reaching RVR predicts a higher likelihood of SVR (viral cure). Extended Rapid Virological Response (eRVR) - occurs when a patient has undetectable HCV RNA at weeks 4 and 12. Early Virological Response (EVR) - Measurement of response to hepatitis C treatment at week 12. Occurs when HCV RNA cannot be detected in a patient’s blood or decreases by more than 2 log (100 times) from the starting level by week 12. Glossary • • Genotype - The genetic make-up of an organism or a virus. HCV has six genotypes and many subtypes. A person’s HCV genotype may be important in determining the severity of the disease and predicting response to treatment. CD4 Count - A laboratory test that measures the number of CD4 T lymphocytes (CD4 cells) in a sample of blood. In people with HIV, the CD4 count is the most important laboratory indicator of immune function and the strongest predictor of HIV progression. The CD4 count is one of the factors used to determine when to start antiretroviral therapy (ART). The CD4 count is also used to monitor response to ART. 2 12/12/2014 Data 100 1986 1998 2001 2002 2011 2013 2014 90 80 70 60 50 40 30 20 10 0 3 12/12/2014 When to treat and what combination? • Pegylated interferon Acute HCV co-infection: • Ribavirin • Treat now? • Boceprevir • Wait for NICE approval on new agents? • Telaprevir • Simeprevir • Sofosbuvir Improved treatment options for patients with cirrhosis, and pre and post liver transplant • Ledipasvir • Daclatasvir SOME ANTIRALS ARE BETTER THAN OTHERS 4 12/12/2014 Simeprevir - OLYSIO 150mg hard capsules https://www.medicines.org.uk/emc/medicine/28888/SPC/OLYSIO+150mg+hard+capsules/ Olysio - Simepravir NS3/4A protease inhibitor Simeprevir + peginterferon alfa + ribavirin: 24 weeks therapy (12 weeks triple therapy followed by 12 weeks peg/riba) • treatment naïve and prior relapsers, G1 or G4, without cirrhosis Simeprevir + peginterferon alfa + ribavirin: 48 weeks therapy (12 weeks triple therapy followed by 36 weeks peg/riba) • For treatment-naïve and prior relapse HIV coinfected patients with cirrhosis • for prior non-responder patients (including partial and null responders), G1 or G4, with or without cirrhosis 5 12/12/2014 Dosing considerations • Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended (will be paid for by the company) Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism Must be taken with food as a whole tablet, daily. • • Stopping Rules HCV RNA Action Treatment week 4: ≥ Discontinue Simeprevir, peginterferon alfa and 25 IU/ml ribavirin Treatment week 12: detectable1 Discontinue peginterferon alfa and ribavirin (treatment with Simeprevir is complete at week 12) Treatment week 24: detectable1 Discontinue peginterferon alfa and ribavirin 1 Re-evaluation of HCV RNA is recommended in case of detectable HCV RNA after previous undetectable HCV RNA to confirm HCV RNA levels prior to discontinuing HCV treatment. 6 12/12/2014 It is not recommended to co-administer Simeprevir with: HIV products: • Efavirenz • Delavirdine • Etravirine • Nevirapine • Darunavir • Ritonavir • It is not recommended to co-administer Simeprevir with any HIV PI, with or without ritonavir. Sofosbuvir - Sovaldi 400 mg film coated tablets https://www.medicines.org.uk/emc/medicine/28539 7 12/12/2014 Recommended co-administered medicinal product(s) and treatment duration for Sovaldi combination therapy • G1,4,5 or 6 : Sovaldi + ribavirin + peginterferon alfa for 12 weeks • G1, 4, 5 or 6 and ineligible or intolerant to peginterferon alfa: Sovaldi + ribavirin for 24 weeks • G2: Sovaldi + ribavirin for 12 weeks • G3: Sovaldi + ribavirin + peginterferon alfa for 12 weeks Or Sovaldi + ribavirin for 12 weeks Patients with CHC awaiting liver transplantation on Sovaldi + ribavirin until liver transplantation Co-administration is not recommended with: • • • • • • • • • Modafinil Carbamazepine Phenytoin Phenobarbital Oxcarbazepine Rifabutin Rifampicin Rifapentine St. John's wort No clinically significant DDIs observed between SOF and the following ARVs: • • • • • • Efavirenz Emtricitabine Tenofovir Rilpivirine Darunavir boosted with ritonavir Raltegravir 8 12/12/2014 Ledipasvir/Sofosbuvir - Harvoni 90 mg/400 mg film-coated tablets https://www.medicines.org.uk/emc/medicine/29471 Recommended treatment duration for Harvoni and the recommended use of co-administered ribavirin for certain subgroups G1 or 4, without cirrhosis, on Harvoni: • 12 weeks • 8 weeks may be considered in previously untreated genotype 1-infected patients. • 24 weeks should be considered for previously treated patients with uncertain subsequent retreatment options. With compensated cirrhosis, on Harvoni: • 24 weeks • 12 weeks may be considered for patients deemed at low risk for clinical disease progression and who have subsequent retreatment options. Patients with decompensated cirrhosis or who are pre-/post-liver transplant • Harvoni + ribavirin for 24 weeks G3 with cirrhosis and/or prior treatment failure • Harvoni + ribavirin for 24 weeks • G1, 4, 5 or 6 : Only for use in patients ineligible or intolerant to 9 12/12/2014 Co-administration is not recommended with: • • • • • • • • • • • Carbamazepine Phenytoin Phenobarbital Oxcarbazepine Rifabutin Rifampicin Rifapentine Rosuvastatin Simeprevir St. John's wort Tipranavir No clinically significant DDIs observed between SOF and the following ARVs: • • • • • • • • Abacavir Efavirenz Emtricitabine Lamivudine Tenofovir Rilpivirine Darunavir boosted with ritonavir Raltegravir Daclatasvir - Daklinza film-coated tablets https://www.medicines.org.uk/emc/medicine/29129 10 12/12/2014 HCV/HIV co-infection • The safety and efficacy of Daklinza in the treatment of HCV infection in patients who are co-infected with HIV have not been established. 11 12/12/2014 Recommended regimens and treatment duration for Daklinza • G1 or 4, without cirrhosis - Daklinza + sofosbuvir - 12 weeks • G1 or 4, with compensated cirrhosis - Daklinza + sofosbuvir - 24 weeks • G3, with compensated cirrhosis and/or treatment experienced - Daklinza + sofosbuvir + ribavirin – 24 weeks • G4, 24 weeks of Daklinza in combination with 24-48 weeks of peginterferon alfa and ribavirin. Interactions and dose recommendations • Coadministration of Daklinza with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, systemic dexamethasone, St. John's wort or other strong inducers of CYP3A4 is contraindicated. • An oral contraceptive containing ethinylestradiol 35 μg and norgestimate 0.180/0.215/0.250 mg is recommended with Daklinza. Other oral contraceptives have not been studied. • It is not known whether daclatasvir is excreted in human milk. Available pharmacokinetic and toxicological data in animals have shown excretion of daclatasvir and metabolites in milk. A risk to the newborn/infant cannot be excluded. Mothers should be instructed not to breastfeed if they are taking Daklinza. 12 12/12/2014 Interactions and dose recommendations • The dose of Daklinza should be reduced to 30 mg once daily when coadministered with atazanavir/ritonavir or other strong inhibitors of CYP3A4 • Due to the lack of data, coadministration of Daklinza and darunavir or lopinavir is not recommended. • The dose of Daklinza should be increased to 90 mg once daily when coadministered with efavirenz. • Due to the lack of data, coadministration of Daklinza and etravirine or nevirapine is not recommended. • The dose of Daklinza should be reduced to 30 mg once daily when coadministered with cobicistat or other strong inhibitors of CYP3A4. Drug-Drug-Interactions 13 12/12/2014 Drug-Drug-Interactions Changes? Managing patient expectations Move towards community care or shared care? Managing adverse effects Frequency of visits and duration of treatment 14 12/12/2014 • • • • Reviewing written materials with each patient and describing technical terms that may be used so that the patient does not find him/herself in an uncomfortable situation where literacy deficits have to be revealed. Providing patients with pictorial or verbal information, and with models or diagrams to supplement written materials. Displaying materials in both private and public areas creates a safe space for a person to view the materials and may prompt a person to speak with a clinician about the issues raised in the printed material. Words, figures or pictures which should represent the exact number of pills a person is taking and should correspond to the appropriate dose. Similarly indicate when & how the medication is to be taken (e.g., symbol for morning for A.M. dose and symbol for food when medication is required to be taken with food). Use of medication aids e.g. pill boxes, SMS text services, alarms 15 12/12/2014 • • • Discussing possible side effects (e.g., potential drug and food interactions) prior to a person beginning a particular medication and concentrating efforts to plan for and to manage side effects at times when a new drug or regimen is being started and thus medication side effects are most likely to occur. Giving prompt attention to medication problems. Initiating a discussion regarding an individual’s side effects can assist those who may be hesitant to address such issues, especially when the subjects are perceived as embarrassing or socially unacceptable. Referring to peer educators and/or group meetings as good sources for individuals to share practical management tips. 16 12/12/2014 The following applies if a scheduled dose of Daclatasvir is missed: • If the missed dose is remembered within 20 hours of the scheduled dose time, the dose should be taken as soon as possible. The following applies if a scheduled dose of Sofosbuvir/Ledipasvir is missed: • If the missed dose is remembered within 18 hours of the scheduled dose time, the dose should be taken as soon as possible. The following applies if a scheduled dose of Simeprevir is missed: • If the missed dose is remembered within 12 hours of the scheduled dose time, the dose should be taken with food as soon as possible. My Medication Passport 17 12/12/2014 Medication Passport App 18 12/12/2014 What are we waiting for? DAA + PR (2014) SIMEPREVIR + PR IFN-FREE (2014) SOFOSBUVIR + SIMEPREVIR FUTURE IFN-FREE (2015–2016) Abbvie PARATAPREVIR/r + OMBITASVIR + DASABUVIR DACLATASVIR + PR SOFOSBUVIR + DACLATASVIR Gilead SOFOSBUVIR + GS-5816 SOFOSBUVIR + PR SOFOSBUVIR + RIBAVIRIN Merck GRAZOPREVIR+ ELBASVIR SOFOSBUVIR + LEDIPASVIR BMS DACLATASVIR + ASUNAPREVIR + BACLABUVIR Janssen SIMEPREVIR + TMC647055 +IDX719 FDC: fixed-dose combination Acknowledgments: • Paul Gilvarry, Lead Pharmacist, Hepatology, Imperial College Healthcare NHS Trust • Ashley Brown, Consultant Hepatologist, Imperial College Healthcare NHS Trust • Louise Campbell, Senior Nurse, Liver Unit, Imperial College Healthcare NHS Trust • Susan Kidger, Lead Nurse Hepatitis, North Manchester General Hospital 19